Tenofovir


Pronunciation: ten-OF-oh-vir
Generic Name: Tenofovir
Brand Name: Viread

Severe and sometimes fatal lactic acidosis (a buildup of lactic acid in the blood) and liver problems have occurred with this type of medicine. The risk may be greater in women, patients who are very overweight, or patients who have been taking nucleoside medicines (eg, emtricitabine, tenofovir) for a long time.

Tell your doctor right away if you develop symptoms of lactic acidosis (eg, unusual weakness or tiredness; unusual muscle pain; fast or difficult breathing; stomach pain with nausea and vomiting; feeling cold, especially in the arms and legs; dizziness or lightheadedness; fast or irregular heartbeat). Tell your doctor right away if you develop symptoms of liver problems (eg, yellowing of the skin or eyes, dark urine, pale stools, persistent loss of appetite, nausea, stomach pain).

Some patients with hepatitis B virus (HBV) infection who took Tenofovir had severe worsening of HBV infection after they stopped taking it. Patients who have HBV infection need close medical follow-up to check for worsening liver problems for at least several months after they stop Tenofovir. Keep all doctor and lab appointments. Do not stop taking Tenofovir without checking with your doctor.


Tenofovir is used for:

Treating HIV infection in combination with other medicines. It is also used to treat chronic hepatitis B infection. It may also be used for other conditions as determined by your doctor.

Tenofovir is an antiviral reverse transcriptase inhibitor. It works to treat HIV infection by reducing the amount of HIV (the virus that causes AIDS) in the body by blocking the ability of the virus to multiply. It works to treat HBV infection by reducing the amount of HBV in the body by blocking the ability of the virus to multiply and infect new liver cells. Tenofovir is not a cure for HIV or AIDS.

Do NOT use Tenofovir if: you are allergic to any ingredient in Tenofovir you have severe liver problems (eg, an enlarged liver) or lactic acidosis you take adefovir or other medicines that contain tenofovir you take a medicine that may harm your kidneys (eg, an aminoglycoside antibiotic [eg, gentamicin], amphotericin B, cyclosporine, a nonsteroidal anti-inflammatory drug [NSAID] [eg, ibuprofen], tacrolimus, vancomycin). Ask your doctor if you are not sure if any of your medicines might harm your kidneys

Contact your doctor or health care provider right away if any of these apply to you.

Before using Tenofovir:

Some medical conditions may interact with Tenofovir. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have a history of bone problems or kidney problems (including dialysis treatment), or if you are overweight if you have abnormal liver function tests or liver problems, including HBV infection if you have HIV infection

Some MEDICINES MAY INTERACT with Tenofovir. Tell your health care provider if you are taking any other medicines, especially any of the following:

Medicines that may harm the kidney (eg, aminoglycoside antibiotics [eg, gentamicin], amphotericin B, cyclosporine, NSAIDs [eg, ibuprofen], tacrolimus, vancomycin) because they may increase the risk of Tenofovir's side effects. Ask your doctor if you are not sure if any of your medicines might harm your kidneys Certain antiviral medicines (eg, acyclovir, cidofovir, ganciclovir) because they may increase the risk of Tenofovir's side effects Adefovir, HIV protease inhibitors (eg, atazanavir), lopinavir/ritonavir, or medicines that contain tenofovir because they may increase the risk of Tenofovir's side effects Didanosine because the risk of its side effects may be increased by Tenofovir

This may not be a complete list of all interactions that may occur. Ask your health care provider if Tenofovir may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Tenofovir:

Use Tenofovir as directed by your doctor. Check the label on the medicine for exact dosing instructions.

An extra patient leaflet is available with Tenofovir. Talk to your pharmacist if you have questions about this information. Take Tenofovir by mouth with or without food. Continue to take Tenofovir even if you feel well. Do not miss any doses. Taking Tenofovir at the same time each day will help you remember to take it. Do not suddenly stop taking Tenofovir without checking with your doctor. This may cause the virus to become less sensitive to this or other medicines. Some conditions (eg, hepatitis B) could become worse if you suddenly stop taking Tenofovir. If you miss a dose of Tenofovir, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Tenofovir.

Important safety information: Tenofovir may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Tenofovir with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it. If you have HIV infection, you should be tested for HBV infection before you start to take Tenofovir. If you have HBV infection, you should be tested for HIV infection before you start to take Tenofovir. Keep a list of all the medicines that you take. Make a new list each time medicines are added or stopped. Find out about medicines that should not be taken while you are using Tenofovir. Be sure that each of your health care providers know all the medicines that you are taking. When your medicine supply is low, get more from your doctor or pharmacist as soon as you can. Do not stop taking Tenofovir, even for a short period of time. If you do, the virus may grow resistant to the medicine and become harder to treat. Tenofovir is not a cure for HIV infection. Patients may still get illnesses and infections associated with HIV. Remain under the care of your doctor. Tenofovir does not stop the spread of HIV or HBV to others through blood or sexual contact. Use barrier methods of birth control (eg, condoms) if you have HIV infection. Do not share needles, injection supplies, or items like toothbrushes or razors. If you have HBV infection, you will need close medical follow-up for several months after stopping treatment with Tenofovir. Follow-up includes medical exams and blood tests to check for HBV infection that could be getting worse. Tenofovir may improve immune system function. This may reveal hidden infections in some patients. Tell your doctor right away if you notice symptoms of infection (eg, fever, sore throat, weakness, cough, shortness of breath) after you start Tenofovir. Check with your doctor to see if you should take a calcium and vitamin D supplement while you are taking Tenofovir. Changes in body fat (eg, an increased amount of fat in the upper back, neck, breast, and trunk, and loss of fat from the legs, arms, and face) may occur in some patients taking Tenofovir. The cause and long-term effects of these changes are unknown. Discuss any concerns with your doctor. Lab tests, including liver and kidney function and bone mineral density, may be performed while you use Tenofovir. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments. Use Tenofovir with extreme caution in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Tenofovir while you are pregnant. It is not known if Tenofovir is found in breast milk. Mothers infected with HIV should not breast-feed. There is a risk of passing the HIV infection or Tenofovir to the baby. Do not breast-feed while taking Tenofovir. Possible side effects of Tenofovir:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Abnormal skin sensations; back pain; diarrhea; dizziness; gas; headache; indigestion; loss of appetite; nausea; sleeplessness; sweating; vomiting; weakness; weight loss.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); anxiety; bone pain; chest pain; fever, chills, or sore throat; mental or mood changes (eg, depression); numbness, burning, pain, or tingling in the hands or feet; pneumonia; severe or persistent nausea or vomiting; shortness of breath; stomach pain; symptoms of kidney problems (eg, increased or decreased urination, increased thirst); symptoms of lactic acidosis (eg, unusual weakness or tiredness; unusual muscle pain; fast or difficult breathing; stomach pain with nausea and vomiting; feeling cold, especially in the arms and legs; dizziness or lightheadedness; fast or irregular heartbeat); symptoms of liver problems (eg, yellowing of the skin or eyes; dark urine; pale stools; persistent loss of appetite).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Tenofovir side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Tenofovir:

Store Tenofovir at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Do not use Tenofovir if the seal over the bottle opening is broken or missing. Keep Tenofovir in its original container and keep the container tightly closed. Do not keep medicine that is out of date or that you no longer need. If you throw any medicines away, make sure that children or pets cannot find them. Keep Tenofovir out of the reach of children and away from pets.

General information: If you have any questions about Tenofovir, please talk with your doctor, pharmacist, or other health care provider. Tenofovir is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Tenofovir. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Tenofovir resources Tenofovir Side Effects (in more detail) Tenofovir Use in Pregnancy & Breastfeeding Tenofovir Drug Interactions Tenofovir Support Group 2 Reviews for Tenofovir - Add your own review/rating tenofovir Advanced Consumer (Micromedex) - Includes Dosage Information Tenofovir Disoproxil Fumarate Monograph (AHFS DI) Viread Prescribing Information (FDA) Viread Consumer Overview Compare Tenofovir with other medications Hepatitis B HIV Infection Nonoccupational Exposure


More




AccessPak for HIV PEP Basic


Generic Name: emtricitabine and tenofovir (em trye SYE ta been and ten OF oh vir)
Brand Names: AccessPak for HIV PEP Basic, Truvada

What is AccessPak for HIV PEP Basic (emtricitabine and tenofovir)?

Emtricitabine and tenofovir are antiviral drugs that work by preventing HIV (human immunodeficiency virus) cells from multiplying in the body.

The combination of emtricitabine and tenofovir is used to treat HIV, which causes acquired immunodeficiency syndrome (AIDS). Emtricitabine and tenofovir is not a cure for HIV or AIDS.

Emtricitabine and tenofovir may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about AccessPak for HIV PEP Basic (emtricitabine and tenofovir)? You should not take this medication if you are allergic to emtricitabine (Emtriva) or tenofovir (Viread).

Do not take this medication with other medicines that also contain emtricitabine or tenofovir (Atripla, Emtriva, Viread), or lamivudine (Combivir, Epivir, Epzicom, or Trizivir).

Some people develop lactic acidosis while taking emtricitabine and tenofovir. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Emtricitabine and tenofovir can cause severe or fatal liver problems. Call your doctor at once if you have symptoms such as nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). What should I discuss with my healthcare provider before taking AccessPak for HIV PEP Basic (emtricitabine and tenofovir)? You should not take this medication if you are allergic to emtricitabine (Emtriva) or tenofovir (Viread). Do not take this medication with other medicines that also contain emtricitabine or tenofovir (Atripla, Emtriva, Viread), or lamivudine (Combivir, Epivir, Epzicom, or Trizivir).

If you have any of these other conditions, you may need an emtricitabine and tenofovir dose adjustment or special tests:

liver or kidney disease;

osteopenia (low bone mineral density); or

if you also have hepatitis B infection.

Some people develop a life-threatening condition called lactic acidosis while taking emtricitabine and tenofovir. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk. FDA pregnancy category B. Emtricitabine and tenofovir is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of emtricitabine and tenofovir on the baby.

Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. Do not give this medicine to anyone under 18 without the advice of a doctor. How should I take AccessPak for HIV PEP Basic (emtricitabine and tenofovir)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

You may take this medication with or without food.

Use emtricitabine and tenofovir regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

To be sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your kidney and liver function or bone density may also need to be tested. Visit your doctor regularly.

If you have hepatitis B you may develop liver symptoms after you stop taking emtricitabine and tenofovir, even months after stopping. Your doctor may want to check your liver function at regular visits for several months after you stop using the medicine. Do not miss any follow-up visits to your doctor.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store at room temperature away from moisture and heat. Keep the tablets in their original container, along with the packet of moisture-absorbing preservative that comes with emtricitabine and tenofovir. What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. What should I avoid while taking AccessPak for HIV PEP Basic (emtricitabine and tenofovir)? Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. AccessPak for HIV PEP Basic (emtricitabine and tenofovir) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. This medication may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as:

muscle pain or weakness;

numb or cold feeling in your arms and legs;

trouble breathing;

feeling dizzy, light-headed, tired, or very weak;

stomach pain, nausea with vomiting; or

fast or uneven heart rate.

Call your doctor at once if you have any of these other serious side effects:

signs of liver damage - nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

increased thirst, urinating more or less than usual or not at all;

swelling, rapid weight gain, feeling short of breath; or

signs of infection such as fever, chills, skin lesions, or cough with yellow or green mucus.

Less serious side effects may include:

diarrhea, mild nausea;

headache, tired feeling;

dizziness, depressed mood;

sleep problems (insomnia), strange dreams;

mild itching or skin rash;

runny or stuffy nose, cough; or

changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect AccessPak for HIV PEP Basic (emtricitabine and tenofovir)?

Emtricitabine and tenofovir can harm your kidneys. This effect is increased when you also use other medicines harmful to the kidneys. You may need dose adjustments or special tests if you have recently used:

lithium (Lithobid);

methotrexate (Rheumatrex, Trexall);

pain or arthritis medicines such as aspirin (Anacin, Excedrin), acetaminophen (Tylenol), diclofenac (Cataflam, Voltaren), etodolac (Lodine), ibuprofen (Advil, Motrin), indomethacin (Indocin), naproxen (Aleve, Naprosyn), and others;

medicines used to prevent organ transplant rejection, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune) or tacrolimus (Prograf);

an IV antibiotic such as gentamicin (Garamycin), vancomycin (Vancocin, Vancoled), and others;

antiviral medicines such as adefovir (Hepsera), cidofovir (Vistide), or foscarnet (Foscavir); or

cancer medicine such as aldesleukin (Proleukin), carmustine (BiCNU, Gliadel), cisplatin (Platinol), ifosfamide (Ifex), oxaliplatin (Eloxatin), plicamycin (Mithracin), streptozocin (Zanosar), or tretinoin (Vesanoid).

You may need dose adjustments or special tests when taking any of these medications together with emtricitabine and tenofovir.

Other medications that can affect emtricitabine and tenofovir include:

the herpes medications acyclovir (Zovirax) or valacyclovir (Valtrex);

medications to treat cytomegalovirus (CMV) such as cidofovir (Vistide), ganciclovir (Cytovene) or valganciclovir (Valcyte); or

certain other HIV medicines such as atazanavir (Reyataz), didanosine (Videx), indinavir (Crixivan), saquinavir (Invirase), lopinavir/ritonavir (Kaletra), or ritonavir (Norvir).

This list is not complete and other drugs may interact with emtricitabine and tenofovir. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More AccessPak for HIV PEP Basic resources AccessPak for HIV PEP Basic Side Effects (in more detail) AccessPak for HIV PEP Basic Use in Pregnancy & Breastfeeding AccessPak for HIV PEP Basic Drug Interactions 0 Reviews for AccessPak for HIV PEP Basic - Add your own review/rating Truvada Prescribing Information (FDA) Truvada Advanced Consumer (Micromedex) - Includes Dosage Information Truvada MedFacts Consumer Leaflet (Wolters Kluwer) Truvada Consumer Overview Compare AccessPak for HIV PEP Basic with other medications HIV Infection Nonoccupational Exposure Where can I get more information? Your pharmacist can provide more information about emtricitabine and tenofovir.

See also: AccessPak for HIV PEP Basic side effects (in more detail)


More




efavirenz, emtricitabine, and tenofovir


Generic Name: efavirenz, emtricitabine, and tenofovir (ef AV ir enz, em trye SYE ta been, and ten OF oh vir)
Brand Names: Atripla

What is efavirenz, emtricitabine, and tenofovir?

Efavirenz, emtricitabine, and tenofovir is an antiviral medication that prevents human immunodeficiency virus (HIV) from reproducing in your body.

Efavirenz, emtricitabine, and tenofovir treats HIV, which causes acquired immunodeficiency syndrome (AIDS). This medication is not a cure for HIV or AIDS.

Efavirenz, emtricitabine, and tenofovir may also be used for purposes not listed in this medication guide.

What is the most important information I should know about efavirenz, emtricitabine, and tenofovir? Do not use efavirenz, emtricitabine, and tenofovir if you are pregnant. It could harm the unborn baby. Do not take this medication if you are also taking cisapride (Propulsid), midazolam (Versed), triazolam (Halcion), St. John's wort, voriconazole (Vfend), or an ergot medicine such as dihydroergotamine (D.H.E. 45, Migranal), ergonovine (Ergotrate), ergotamine (Ergomar), or methylergonovine (Methergine). Do not take this medication with other medicines that also contain efavirenz, emtricitabine, or tenofovir (Complera, Sustiva, Emtriva, Truvada, Viread), or lamivudine (Combivir, Epivir, Epzicom, Trizivir).

There are many other drugs that can cause serious or life-threatening medical problems if you take them together with efavirenz, emtricitabine, and tenofovir. Tell your doctor about all medications you use.

Some people develop lactic acidosis while taking efavirenz, emtricitabine, and tenofovir. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Efavirenz, emtricitabine, and tenofovir can cause severe or fatal liver problems. Call your doctor at once if you have symptoms such as nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). What should I discuss with my healthcare provider before taking efavirenz, emtricitabine, and tenofovir? You should not take this medication if you are allergic to efavirenz (Sustiva), emtricitabine (Emtriva), or tenofovir (Viread), or if you are taking any of the following drugs:

cisapride (Propulsid);

midazolam (Versed) or triazolam (Halcion);

St. John's wort;

voriconazole (Vfend);

an ergot medicine such as dihydroergotamine (D.H.E. 45, Migranal), ergonovine (Ergotrate), ergotamine (Ergomar), or methylergonovine (Methergine);

lamivudine (Combivir, Epivir, Epzicom, or Trizivir); or

any other medicines that also contain efavirenz, emtricitabine, or tenofovir (such as Complera, Sustiva, Emtriva, Truvada, or Viread).

To make sure you can safely take this medication, tell your doctor if you have any of these other conditions:

liver or kidney disease;

a history of mental illness, use of antipsychotic medication, or injection drug use;

epilepsy or other seizure disorder;

osteopenia (low bone mineral density); or

hepatitis B or C infection.

FDA pregnancy category D. Do not use this medication if you are pregnant. It could harm the unborn baby. Tell your doctor if you become pregnant during treatment. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide) while you are using this medication and for at least 12 weeks after your treatment ends. HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection. Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. Some people develop a life-threatening condition called lactic acidosis while taking efavirenz, emtricitabine, and tenofovir. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk. How should I take efavirenz, emtricitabine, and tenofovir?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.

Take this medication on an empty stomach at bedtime.

Use this medication regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

To be sure this medicine is helping your condition, your blood will need to be tested often. Your liver function may also need to be tested. Visit your doctor regularly.

If you have hepatitis B you may develop liver symptoms after you stop taking this medication, even months after stopping. Your doctor may want to check your liver function for several months after you stop using efavirenz, emtricitabine, and tenofovir.

This medication can cause you to have a false positive drug screening test. If you provide a urine sample for drug screening, tell the laboratory staff that you are taking efavirenz, emtricitabine, and tenofovir.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store in the original container at room temperature, away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

See also: Efavirenz, emtricitabine, and tenofovir dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose can cause uncontrolled muscle movements. What should I avoid while taking efavirenz, emtricitabine, and tenofovir? Drinking alcohol can increase certain side effects of this medication. This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. Efavirenz, emtricitabine, and tenofovir side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. This medication may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Stop using this medication and call your doctor at once if you have any other serious side effects such as:

signs of liver damage - nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

urinating less than usual or not at all;

fever, chills, body aches, flu symptoms;

unusual thoughts or behavior, anger, severe depression, thoughts of hurting yourself or others, hallucinations;

severe blistering, peeling, and red skin rash; or

seizure (convulsions).

Less serious side effects may include:

mild nausea, vomiting, diarrhea, gas, upset stomach;

headache, dizziness, drowsiness, tired feeling;

trouble concentrating;

sleep problems (insomnia), strange dreams;

darkened skin on the palms of your hands or the soles of your feet; or

changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Efavirenz, emtricitabine, and tenofovir Dosing Information

Usual Adult Dose for HIV Infection:

1 tablet orally once a day at bedtime on an empty stomach

What other drugs will affect efavirenz, emtricitabine, and tenofovir?

Many drugs can interact with efavirenz, emtricitabine, and tenofovir. Below is just a partial list. Tell your doctor if you are using:

acyclovir (Zovirax), ganciclovir (Cytovene), valacyclovir (Valtrex), or valganciclovir (Valcyte);

adefovir (Hepsera) or cidofovir (Vistide);

maraviroc (Selzentry);

methadone (Methadose);

sertraline (Zoloft);

a blood thinner such as warfarin (Coumadin, Jantoven);

cholesterol medications such as atorvastatin (Lipitor, Caduet), pravastatin (Pravachol), or simvastatin (Zocor, Simcor, Vytorin);

an antibiotic such as clarithromycin (Biaxin), rifabutin (Mycobutin), or rifampin (Rifater, Rifamate);

antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), or posaconazole (Noxafil);

heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nicardipine (Cardene), nifedipine (Procardia, Adalat), verapamil (Calan, Covera, Isoptin, Verelan), and others;

medicines used to prevent organ transplant rejection, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune), or tacrolimus (Prograf);

seizure medication such as carbamazepine (Carbatrol, Equetro, Tegretol), phenytoin (Dilantin), phenobarbital (Solfoton); or

certain other HIV medicines such as atazanavir (Reyataz), didanosine (Videx), indinavir (Crixivan), saquinavir (Invirase), lopinavir/ritonavir (Kaletra), fosamprenavir (Lexiva), or ritonavir (Norvir, Kaletra).

This list is not complete and there are many other drugs that can interact with efavirenz, emtricitabine, and tenofovir. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. More efavirenz, emtricitabine, and tenofovir resources Efavirenz, emtricitabine, and tenofovir Side Effects (in more detail) Efavirenz, emtricitabine, and tenofovir Dosage Efavirenz, emtricitabine, and tenofovir Use in Pregnancy & Breastfeeding Efavirenz, emtricitabine, and tenofovir Drug Interactions Efavirenz, emtricitabine, and tenofovir Support Group 34 Reviews for Efavirenz, emtricitabine, and tenofovir - Add your own review/rating Compare efavirenz, emtricitabine, and tenofovir with other medications HIV Infection Where can I get more information? Your pharmacist can provide more information about efavirenz, emtricitabine, and tenofovir.

See also: efavirenz, emtricitabine, and tenofovir side effects (in more detail)


More




Efavirenz/Emtricitabine/Tenofovir


Pronunciation: EF-a-VIR-enz/EM-trye-SYE-ta-been/ten-OF-oh-vir
Generic Name: Efavirenz/Emtricitabine/Tenofovir
Brand Name: Atripla

Severe and sometimes fatal lactic acidosis (a buildup of lactic acid in the blood) and liver problems have occurred with this type of medicine. The risk may be greater in women, patients who are very overweight, or patients who have been taking nucleoside medicines (eg, emtricitabine, tenofovir) for a long time.

Tell your doctor right away if you develop symptoms of lactic acidosis (eg, unusual weakness or tiredness; unusual muscle pain; fast or difficult breathing; stomach pain with nausea and vomiting; feeling cold, especially in the arms and legs; dizziness or light-headedness; fast or irregular heartbeat). Tell your doctor right away if you develop symptoms of liver problems (eg, yellowing of the skin or eyes, dark urine, pale stools, persistent loss of appetite, nausea, stomach pain).

Efavirenz/Emtricitabine/Tenofovir is not approved to treat hepatitis B virus (HBV) infection. Safety and effectiveness have not been confirmed in patients who both HIV and HBV. Some patients with HBV who were treated with similar medicines have had severe worsening of liver problems after they stopped treatment. Patients with both HIV and HBV who take Efavirenz/Emtricitabine/Tenofovir should have medical exams and liver function tests performed for at least several months after they stop taking Efavirenz/Emtricitabine/Tenofovir.


Efavirenz/Emtricitabine/Tenofovir is used for:

Treating HIV infection alone or along with other medicines.

Efavirenz/Emtricitabine/Tenofovir is an antiviral combination of 3 reverse transcriptase inhibitors. It works by slowing the growth of HIV, the virus that causes AIDS. Efavirenz/Emtricitabine/Tenofovir is not a cure for HIV or AIDS.

Do NOT use Efavirenz/Emtricitabine/Tenofovir if: you are allergic to any ingredient in Efavirenz/Emtricitabine/Tenofovir you have developed red, swollen, blistered, or peeling skin after taking efavirenz, a component of Efavirenz/Emtricitabine/Tenofovir you have moderate to severe kidney problems you have moderate to severe liver problems or lactic acidosis you are taking adefovir, astemizole, atazanavir, bepridil, cabazitaxel, cisapride, an ergot derivative (eg, dihydroergotamine, ergotamine), ixabepilone, lurasidone, midazolam, nevirapine, pimozide, St. John's wort, terfenadine, ticagrelor, triazolam, vandetanib, or voriconazole you are taking a medicine that contains lamivudine, or another medicine that contains efavirenz, emtricitabine, or tenofovir you take a medicine that may harm your kidneys (eg, an aminoglycoside antibiotic [eg, gentamicin], amphotericin B, cyclosporine, a nonsteroidal anti-inflammatory drug [NSAID] [eg, ibuprofen], tacrolimus, vancomycin). Ask your doctor if you are not sure if any of your medicines might harm your kidneys

Contact your doctor or health care provider right away if any of these apply to you.

Before using Efavirenz/Emtricitabine/Tenofovir:

Some medical conditions may interact with Efavirenz/Emtricitabine/Tenofovir. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have a history of bone problems (eg, fracture, osteoporosis), seizures, diabetes, high cholesterol, kidney problems (including dialysis treatment), lactic acidosis, or liver problems (eg, hepatitis, abnormal liver function tests) if you have a history of mental or mood problems (eg, depression), suicidal thoughts or actions, or alcohol or other substance abuse or dependence if you are very overweight

Some MEDICINES MAY INTERACT with Efavirenz/Emtricitabine/Tenofovir. Tell your health care provider if you are taking any other medicines, especially any of the following:

Astemizole, bepridil, cisapride, ergot derivatives (eg, dihydroergotamine, ergotamine), midazolam, pimozide, terfenadine, or triazolam because the risk of irregular heartbeat, severe drowsiness, or breathing problems may be increased Adefovir or other medicines that may harm the kidneys (eg, aminoglycoside antibiotics [eg, gentamicin], amphotericin B, cyclosporine, NSAIDs [eg, ibuprofen], tacrolimus, vancomycin) because they may increase the risk of Efavirenz/Emtricitabine/Tenofovir's side effects. Ask your doctor or pharmacist if you are not sure if any of your medicines may harm the kidneys A medicine that contains lamivudine or other medicines that contain efavirenz, emtricitabine, or tenofovir because they may increase the risk of Efavirenz/Emtricitabine/Tenofovir's side effects Atazanavir because its effectiveness may be decreased by Efavirenz/Emtricitabine/Tenofovir or it may increase the risk of Efavirenz/Emtricitabine/Tenofovir's side effects Nevirapine or St. John's wort because they may decrease Efavirenz/Emtricitabine/Tenofovir's effectiveness Cabazitaxel, ixabepilone, lurasidone, ticagrelor, vandetanib, or voriconazole because their effectiveness may be decreased by Efavirenz/Emtricitabine/Tenofovir Medicines that may harm the liver (eg, acetaminophen, methotrexate, ketoconazole, isoniazid, certain medicines for HIV infection) because the risk of liver side effects may be increased. Ask your doctor if you are unsure if any of your medicines might harm the liver Many prescription and nonprescription medicines (eg, used for infections, HIV, hepatitis C, blood thinning, inflammation, aches and pains, high blood pressure, high cholesterol, seizures, emergency contraception, heart problems, immune system suppression, birth control, mental or mood problems), multivitamin products, and herbal or dietary supplements (eg, herbal teas, coenzyme Q10, garlic, ginseng, ginkgo) may interact with Efavirenz/Emtricitabine/Tenofovir, increasing the risk of side effects or decreasing effectiveness

This may not be a complete list of all interactions that may occur. Ask your health care provider if Efavirenz/Emtricitabine/Tenofovir may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Efavirenz/Emtricitabine/Tenofovir:

Use Efavirenz/Emtricitabine/Tenofovir as directed by your doctor. Check the label on the medicine for exact dosing instructions.

An extra patient leaflet is available with Efavirenz/Emtricitabine/Tenofovir. Talk to your pharmacist if you have questions about this information. Take Efavirenz/Emtricitabine/Tenofovir by mouth on an empty stomach at least 1 hour before or 2 hours after eating. Take Efavirenz/Emtricitabine/Tenofovir with a full glass of water (8 oz/240 mL). Do not take Efavirenz/Emtricitabine/Tenofovir if the seal over the bottle opening is broken or missing. Continue to take Efavirenz/Emtricitabine/Tenofovir even if you feel well. Do not miss any doses. Take Efavirenz/Emtricitabine/Tenofovir at the same time each day, preferably at bedtime, unless otherwise directed by your doctor. Do not suddenly stop taking Efavirenz/Emtricitabine/Tenofovir without checking with your doctor. This may cause the virus to become less sensitive to this or other medicines. Also, some conditions (eg, hepatitis B) could become worse if you suddenly stop taking Efavirenz/Emtricitabine/Tenofovir. If you miss a dose of Efavirenz/Emtricitabine/Tenofovir, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Efavirenz/Emtricitabine/Tenofovir.

Important safety information: Efavirenz/Emtricitabine/Tenofovir may cause drowsiness, dizziness, or trouble concentrating. These effects may be worse if you take it with alcohol or certain medicines. Use Efavirenz/Emtricitabine/Tenofovir with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it. Check with your doctor before you drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Efavirenz/Emtricitabine/Tenofovir; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness. Efavirenz/Emtricitabine/Tenofovir may cause dizziness, drowsiness, trouble sleeping, trouble concentrating, or unusual dreams. These effects usually go away after you have taken Efavirenz/Emtricitabine/Tenofovir for about 2 to 4 weeks. Taking it at bedtime may help to decrease these effects. Check with your doctor if they continue or are severe. Do NOT take more than the recommended dose, change your dose, or stop taking Efavirenz/Emtricitabine/Tenofovir without checking with your doctor. Taking more than the recommended dose may not provide additional benefits and may increase the risk of side effects. You should be tested for HBV infection before you start to take Efavirenz/Emtricitabine/Tenofovir. Keep a list of all the medicines that you take. Make a new list each time medicines are added or stopped. Find out about medicines that should not be taken while you are using Efavirenz/Emtricitabine/Tenofovir. Be sure that each of your health care providers knows all the medicines that you are taking. Efavirenz/Emtricitabine/Tenofovir is not a cure for HIV infection. Patients may still get illnesses and infections associated with HIV. Remain under the care of your doctor. Efavirenz/Emtricitabine/Tenofovir does not stop the spread of HIV to others through blood or sexual contact. Use barrier methods of birth control (eg, condoms) if you have HIV infection. Do not share needles, injection supplies, or items like toothbrushes or razors. When your medicine supply is low, get more from your doctor or pharmacist as soon as you can. Do not stop taking Efavirenz/Emtricitabine/Tenofovir, even for a short period of time. If you do, the virus may grow resistant to the medicine and become harder to treat. Changes in body fat (eg, an increased amount of fat in the upper back, neck, breast, and trunk, and loss of fat from the legs, arms, and face) may occur in some patients taking Efavirenz/Emtricitabine/Tenofovir. The cause and long-term effects of these changes are unknown. Discuss any concerns with your doctor. Efavirenz/Emtricitabine/Tenofovir may improve immune system function. This may reveal hidden infections in some patients. Tell your doctor right away if you notice symptoms of infection (eg, fever, sore throat, weakness, cough, shortness of breath) after you start Efavirenz/Emtricitabine/Tenofovir. Check with your doctor to see if you should take a calcium and vitamin D supplement while you are taking Efavirenz/Emtricitabine/Tenofovir. Diabetes patients - Efavirenz/Emtricitabine/Tenofovir may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine. Women who may become pregnant should have a negative pregnancy test before they start to take Efavirenz/Emtricitabine/Tenofovir. Discuss any questions or concerns with your doctor. If you may become pregnant, you must use an effective form of birth control while you take Efavirenz/Emtricitabine/Tenofovir and for 12 weeks after you stop taking it. Hormonal birth control (eg, birth control pills) may not work as well while you are using Efavirenz/Emtricitabine/Tenofovir. You should always use a barrier form of birth control (eg, condoms), even if you already use another method of birth control (eg, hormonal birth control). If you have questions about effective birth control, talk with your doctor. Efavirenz/Emtricitabine/Tenofovir may affect certain lab tests, including drug tests. Be sure your doctor and lab personnel know you are taking Efavirenz/Emtricitabine/Tenofovir. Lab tests, including liver and kidney function, cholesterol and triglyceride levels, and bone density, may be performed while you use Efavirenz/Emtricitabine/Tenofovir. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments. Use Efavirenz/Emtricitabine/Tenofovir with caution in the ELDERLY; they may be more sensitive to its effects. Efavirenz/Emtricitabine/Tenofovir should not be used in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed. PREGNANCY and BREAST-FEEDING: Efavirenz/Emtricitabine/Tenofovir may cause harm to the fetus. Do not become pregnant while you take Efavirenz/Emtricitabine/Tenofovir and for 12 weeks after you stop taking it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Efavirenz/Emtricitabine/Tenofovir while you are pregnant. It is not known if Efavirenz/Emtricitabine/Tenofovir is found in breast milk. Do not breast-feed while taking Efavirenz/Emtricitabine/Tenofovir. Mothers infected with HIV should not breast-feed. There is a risk of passing the HIV infection or Efavirenz/Emtricitabine/Tenofovir to the baby. Possible side effects of Efavirenz/Emtricitabine/Tenofovir:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Back pain; cough; darkened skin color on the palms of hands or soles of feet; diarrhea; dizziness; drowsiness; gas or indigestion; headache; loss of appetite; mild stomach pain; muscle or joint aches; nausea; skin discoloration (small spots or freckles); stomach upset; strange dreams; stuffy or runny nose; tiredness; trouble concentrating; trouble sleeping; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bone pain; change in personality; chest pain; confusion; decreased coordination; delusions; fever, chills, or persistent sore throat; hallucinations; memory loss; mental, mood, or behavior changes (eg, abnormal thoughts, agitation, aggression, anxiety, depression, nervousness, paranoia); muscle pain or weakness; numbness, burning, pain, or tingling of the hands, feet, or skin; red, swollen, blistered, or peeling skin; seizures; severe or persistent stomach pain, nausea, or vomiting; shortness of breath; suicidal thoughts or actions; symptoms of kidney problems (eg, increased or decreased urination, increased thirst); symptoms of lactic acidosis (eg, dizziness or lightheadedness; fast or difficult breathing; fast or irregular heartbeat; feeling cold, especially in the arms and legs; stomach pain with nausea and vomiting; unusual muscle pain; unusual weakness or tiredness); symptoms of liver problems (eg, dark urine; pale stools; persistent loss of appetite; yellowing of the skin or eyes).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Efavirenz/Emtricitabine/Tenofovir side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include hallucinations; muscle twitching; severe dizziness, drowsiness, or coordination problems; trouble concentrating; trouble sleeping.

Proper storage of Efavirenz/Emtricitabine/Tenofovir:

Store Efavirenz/Emtricitabine/Tenofovir at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Store only in original container and keep it tightly closed. Do not store in the bathroom. Do not use Efavirenz/Emtricitabine/Tenofovir if it is past the expiration date on the bottle. Keep Efavirenz/Emtricitabine/Tenofovir out of the reach of children and away from pets.

General information: If you have any questions about Efavirenz/Emtricitabine/Tenofovir, please talk with your doctor, pharmacist, or other health care provider. Efavirenz/Emtricitabine/Tenofovir is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Efavirenz/Emtricitabine/Tenofovir. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Efavirenz/Emtricitabine/Tenofovir resources Efavirenz/Emtricitabine/Tenofovir Side Effects (in more detail) Efavirenz/Emtricitabine/Tenofovir Use in Pregnancy & Breastfeeding Efavirenz/Emtricitabine/Tenofovir Drug Interactions Efavirenz/Emtricitabine/Tenofovir Support Group 34 Reviews for Efavirenz/Emtricitabine/Tenofovir - Add your own review/rating Atripla Prescribing Information (FDA) Atripla Advanced Consumer (Micromedex) - Includes Dosage Information Atripla Consumer Overview Compare Efavirenz/Emtricitabine/Tenofovir with other medications HIV Infection


More




Truvada


Generic Name: emtricitabine and tenofovir disoproxil fumarate
Dosage Form: tablet, film coated
FULL PRESCRIBING INFORMATION WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including VIREAD, a component of Truvada, in combination with other antiretrovirals [See Warnings and Precautions (5.1)].

Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Truvada have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Truvada. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Truvada. If appropriate, initiation of anti-hepatitis B therapy may be warranted [See Warnings and Precautions (5.2)].

Indications and Usage for Truvada

 Truvada®, a combination of EMTRIVA® and VIREAD®, is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older.

The following points should be considered when initiating therapy with Truvada for the treatment of HIV-1 infection:

It is not recommended that Truvada be used as a component of a triple nucleoside regimen. Truvada should not be coadministered with ATRIPLA®, EMTRIVA, VIREAD or lamivudine-containing products [See Warnings and Precautions (5.4)]. In treatment experienced patients, the use of Truvada should be guided by laboratory testing and treatment history [See Clinical Pharmacology (12.4)]. Truvada Dosage and Administration Recommended Dose

 The dose of Truvada for adults and pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg (greater than or equal to 77 lb) is one tablet (containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) once daily taken orally with or without food.

Dose Adjustment for Renal Impairment

Significantly increased drug exposures occurred when EMTRIVA or VIREAD were administered to subjects with moderate to severe renal impairment [see EMTRIVA or VIREAD Package Insert]. Therefore, the dosing interval of Truvada should be adjusted in patients with baseline creatinine clearance 30–49 mL/min using the recommendations in Table 1. These dosing interval recommendations are based on modeling of single-dose pharmacokinetic data in non-HIV infected subjects. The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated in patients with moderate renal impairment, therefore clinical response to treatment and renal function should be closely monitored in these patients [See Warnings and Precautions (5.3)].

No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50–80 mL/min). Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients with mild renal impairment [See Warnings and Precautions (5.3)].

Table 1 Dosage Adjustment for Patients with Altered Creatinine Clearance Creatinine Clearance (mL/min)* ?50 30–49 <30
(Including Patients Requiring Hemodialysis) * Calculated using ideal (lean) body weight Recommended Dosing Interval Every 24 hours Every 48 hours Truvada should not be administered.

 No data are available to make dose recommendations in pediatric patients 12 years of age and older with renal impairment.

Dosage Forms and Strengths

Truvada is available as tablets. Each tablet contains 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil). The tablets are blue, capsule-shaped, film-coated, debossed with "GILEAD" on one side and with "701" on the other side.

Contraindications

None.

Warnings and Precautions Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including VIREAD, a component of Truvada, in combination with other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Truvada should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Patients Coinfected with HIV-1 and HBV

It is recommended that all patients with HIV-1 be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy. Truvada is not approved for the treatment of chronic HBV infection and the safety and efficacy of Truvada have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Truvada. In some patients infected with HBV and treated with EMTRIVA, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Patients who are coinfected with HIV-1 and HBV should be closely monitored with both clinical and laboratory follow up for at least several months after stopping treatment with Truvada. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

New Onset or Worsening Renal Impairment

Emtricitabine and tenofovir are principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of VIREAD [See Adverse Reactions (6.2)].

It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy and as clinically appropriate during therapy with Truvada. Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving HEPSERA.

Dosing interval adjustment of Truvada and close monitoring of renal function are recommended in all patients with creatinine clearance 30–49 mL/min, [See Dosage and Administration (2.2)]. No safety or efficacy data are available in patients with renal impairment who received Truvada using these dosing guidelines, so the potential benefit of Truvada therapy should be assessed against the potential risk of renal toxicity. Truvada should not be administered to patients with creatinine clearance below 30 mL/min or patients requiring hemodialysis.

Truvada should be avoided with concurrent or recent use of a nephrotoxic agent.

Coadministration with Other Products

Truvada is a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate. Truvada should not be coadministered with ATRIPLA, EMTRIVA, or VIREAD. Due to similarities between emtricitabine and lamivudine, Truvada should not be coadministered with other drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine).

Truvada should not be administered with HEPSERA® (adefovir dipivoxil).

Decreases in Bone Mineral Density

 Assessment of bone mineral density (BMD) should be considered for HIV-1 infected adults and pediatric patients 12 years of age and older who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected then appropriate consultation should be obtained.

Tenofovir Disoproxil Fumarate: In a 144-week trial of treatment-naive adult subjects, decreases in BMD were seen at the lumbar spine and hip in both arms of the trial. At Week 144, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in subjects receiving VIREAD + lamivudine + efavirenz compared with subjects receiving stavudine + lamivudine + efavirenz. Changes in BMD at the hip were similar between the two treatment groups. In both groups, the majority of the reduction in BMD occurred in the first 24–48 weeks of the trial and this reduction was sustained through 144 weeks. Twenty-eight percent of VIREAD-treated subjects vs. 21% of the comparator subjects lost at least 5% of BMD at the spine or 7% of BMD at the hip. Clinically relevant fractures (excluding fingers and toes) were reported in 4 subjects in the VIREAD group and 6 subjects in the comparator group. Tenofovir disoproxil fumarate was associated with significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide, and urinary N-telopeptide), suggesting increased bone turnover. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving VIREAD.

 In a clinical trial of HIV-1 infected pediatric subjects 12 years of age and older (Study 321), bone effects were similar to adult subjects. Under normal circumstances BMD increases rapidly in this age group. In this trial, the mean rate of bone gain was less in the VIREAD-treated group compared to the placebo group. Six VIREAD treated subjects and one placebo treated subject had significant (greater than 4%) lumbar spine BMD loss in 48 weeks. Among 28 subjects receiving 96 weeks of VIREAD, Z-scores declined by -0.341 for lumbar spine and -0.458 for total body. Skeletal growth (height) appeared to be unaffected. Markers of bone turnover in VIREAD-treated pediatric subjects 12 years of age and older suggest increased bone turnover, consistent with the effects observed in adults.

The effects of VIREAD-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. For additional information, please consult the VIREAD prescribing information.

Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of VIREAD [See Adverse Reactions (6.2)].

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Truvada. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.

Early Virologic Failure

Clinical trials in HIV-infected subjects have demonstrated that certain regimens that only contain three nucleoside reverse transcriptase inhibitors (NRTI) are generally less effective than triple drug regimens containing two NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor or a HIV-1 protease inhibitor. In particular, early virological failure and high rates of resistance substitutions have been reported. Triple nucleoside regimens should therefore be used with caution. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.

Adverse Reactions

The following adverse reactions are discussed in other sections of the labeling:

Lactic Acidosis/Severe Hepatomegaly with Steatosis [See Boxed Warning, Warnings and Precautions (5.1)]. Severe Acute Exacerbations of hepatitis B [See Boxed Warning, Warnings and Precautions (5.2)]. New Onset or Worsening Renal Impairment [See Warnings and Precautions (5.3)]. Decreases in Bone Mineral Density [See Warnings and Precautions (5.5)]. Immune Reconstitution Syndrome [See Warnings and Precautions (5.7)]. Adverse Reactions from Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials in Adult Subjects

The most common adverse reactions (incidence greater than or equal to 10%, any severity) occurring in Study 934, an active-controlled clinical trial of efavirenz, emtricitabine, and tenofovir disoproxil fumarate, include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. See also Table 2 for the frequency of treatment-emergent adverse reactions (Grade 2–4) occurring in greater than or equal to 5% of subjects treated with efavirenz, emtricitabine, and tenofovir disoproxil fumarate in this trial.

Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naive subjects received either VIREAD + EMTRIVA administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this trial were generally consistent with those seen in other trials in treatment-experienced or treatment-naive subjects receiving VIREAD and/or EMTRIVA (Table 2).

Table 2 Selected Treatment-Emergent Adverse Reactions* (Grades 2–4) Reported in ?5% in Any Treatment Group in Study 934 (0–144 Weeks) FTC + TDF + EFV† AZT/3TC + EFV N=257 N=254 * Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. † From Weeks 96 to 144 of the trial, subjects received Truvada with efavirenz in place of VIREAD + EMTRIVA with efavirenz. ‡ Rash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular. Gastrointestinal Disorder   Diarrhea 9% 5%   Nausea 9% 7%   Vomiting 2% 5% General Disorders and Administration Site Condition   Fatigue 9% 8% Infections and Infestations   Sinusitis 8% 4%   Upper respiratory tract infections 8% 5%   Nasopharyngitis 5% 3% Nervous System Disorders   Headache 6% 5%   Dizziness 8% 7% Psychiatric Disorders   Depression 9% 7%   Insomnia 5% 7% Skin and Subcutaneous Tissue Disorders   Rash event‡ 7% 9%

Laboratory Abnormalities: Laboratory abnormalities observed in this trial were generally consistent with those seen in other trials of VIREAD and/or EMTRIVA (Table 3).

Table 3 Significant Laboratory Abnormalities Reported in ?1% of Subjects in Any Treatment Group in Study 934 (0–144 Weeks) FTC + TDF + EFV* AZT/3TC + EFV N=257 N=254 * From Weeks 96 to 144 of the trial, subjects received Truvada with efavirenz in place of VIREAD + EMTRIVA with efavirenz. Any ? Grade 3 Laboratory Abnormality 30% 26% Fasting Cholesterol (>240 mg/dL) 22% 24% Creatine Kinase
(M: >990 U/L)
(F: >845 U/L) 9% 7% Serum Amylase (>175 U/L) 8% 4% Alkaline Phosphatase (>550 U/L) 1% 0% AST
(M: >180 U/L)
(F: >170 U/L) 3% 3% ALT
(M: >215 U/L)
(F: >170 U/L) 2% 3% Hemoglobin (<8.0 mg/dL) 0% 4% Hyperglycemia (>250 mg/dL) 2% 1% Hematuria (>75 RBC/HPF) 3% 2% Glycosuria (?3+) <1% 1% Neutrophils (<750/mm3) 3% 5% Fasting Triglycerides (>750 mg/dL) 4% 2%

In addition to the events described above for Study 934, other adverse reactions that occurred in at least 5% of subjects receiving EMTRIVA or VIREAD with other antiretroviral agents in clinical trials include anxiety, arthralgia, increased cough, dyspepsia, fever, myalgia, pain, abdominal pain, back pain, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), pneumonia, and rhinitis.

In addition to the laboratory abnormalities described above for Study 934, Grade 3/4 laboratory abnormalities of increased bilirubin (>2.5 ? ULN), increased pancreatic amylase (>2.0 ? ULN), increased or decreased serum glucose (<40 or >250 mg/dL), and increased serum lipase (>2.0 ? ULN) occurred in up to 3% of subjects treated with EMTRIVA or VIREAD with other antiretroviral agents in clinical trials.

Clinical Trials in Pediatric Subjects 12 Years of Age and Older

Emtricitabine: In addition to the adverse reactions reported in adults, anemia and hyperpigmentation were observed in 7% and 32%, respectively, of pediatric subjects (3 months to less than 18 years of age) who received treatment with EMTRIVA in the larger of two open-label, uncontrolled pediatric trials (N=116). For additional information, please consult the EMTRIVA prescribing information.

Tenofovir Disoproxil Fumarate: In a pediatric clinical trial conducted in subjects 12 to less than 18 years of age, the adverse reactions observed in pediatric subjects who received treatment with VIREAD were consistent with those observed in clinical trials of VIREAD in adults [See Warnings and Precautions (5.5)].

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of VIREAD. No additional adverse reactions have been identified during postapproval use of EMTRIVA. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders
allergic reaction, including angioedema

Metabolism and Nutrition Disorders
lactic acidosis, hypokalemia, hypophosphatemia

Respiratory, Thoracic, and Mediastinal Disorders
dyspnea

Gastrointestinal Disorders
pancreatitis, increased amylase, abdominal pain

Hepatobiliary Disorders
hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)

Skin and Subcutaneous Tissue Disorders
rash

Musculoskeletal and Connective Tissue Disorders
rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy

Renal and Urinary Disorders
acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

General Disorders and Administration Site Conditions
asthenia

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

Drug Interactions

No drug interaction trials have been conducted using Truvada tablets. Drug interaction trials have been conducted with emtricitabine and tenofovir disoproxil fumarate, the components of Truvada. This section describes clinically relevant drug interactions observed with emtricitabine and tenofovir disoproxil fumarate [See Clinical Pharmacology (12.3)].

Didanosine

Coadministration of Truvada and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse reactions. Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions.

When tenofovir disoproxil fumarate was administered with didanosine the Cmax and AUC of didanosine administered as either the buffered or enteric-coated formulation increased significantly [See Clinical Pharmacology (12.3)]. The mechanism of this interaction is unknown. Higher didanosine concentrations could potentiate didanosine-associated adverse reactions, including pancreatitis, and neuropathy. Suppression of CD4+ cell counts has been observed in patients receiving tenofovir DF with didanosine 400 mg daily.

In patients weighing greater than 60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with Truvada. Data are not available to recommend a dose adjustment of didanosine for adult or pediatric patients weighing less than 60 kg. When coadministered, Truvada and Videx EC may be taken under fasted conditions or with a light meal (less than 400 kcal, 20% fat). Coadministration of didanosine buffered tablet formulation with Truvada should be under fasted conditions.

Atazanavir

Atazanavir has been shown to increase tenofovir concentrations [See Clinical Pharmacology (12.3)]. The mechanism of this interaction is unknown. Patients receiving atazanavir and Truvada should be monitored for Truvada-associated adverse reactions. Truvada should be discontinued in patients who develop Truvada-associated adverse reactions.

Tenofovir decreases the AUC and Cmin of atazanavir [See Clinical Pharmacology (12.3)]. When coadministered with Truvada, it is recommended that atazanavir 300 mg is given with ritonavir 100 mg. Atazanavir without ritonavir should not be coadministered with Truvada.

Lopinavir/Ritonavir

Lopinavir/ritonavir has been shown to increase tenofovir concentrations [See Clinical Pharmacology (12.3)]. The mechanism of this interaction is unknown. Patients receiving lopinavir/ritonavir and Truvada should be monitored for Truvada-associated adverse reactions. Truvada should be discontinued in patients who develop Truvada-associated adverse reactions.

Drugs Affecting Renal Function

Emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion [See Clinical Pharmacology (12.3)]. No drug-drug interactions due to competition for renal excretion have been observed; however, coadministration of Truvada with drugs that are eliminated by active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the coadministered drug. Some examples include, but are not limited to acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, and valganciclovir. Drugs that decrease renal function may increase concentrations of emtricitabine and/or tenofovir.

USE IN SPECIFIC POPULATIONS Pregnancy

Pregnancy Category B

Emtricitabine: The incidence of fetal variations and malformations was not increased in embryofetal toxicity studies performed with emtricitabine in mice at exposures (AUC) approximately 60-fold higher and in rabbits at approximately 120-fold higher than human exposures at the recommended daily dose.

Tenofovir Disoproxil Fumarate: Reproduction studies have been performed in rats and rabbits at doses up to 14 and 19 times the human dose based on body surface area comparisons and revealed no evidence of impaired fertility or harm to the fetus due to tenofovir.

There are, however, no adequate and well-controlled trials in pregnant women. Because animal reproduction studies are not always predictive of human response, Truvada should be used during pregnancy only if clearly needed.

Antiretroviral Pregnancy Registry: To monitor fetal outcomes of pregnant women exposed to Truvada, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients by calling 1-800-258-4263.

Nursing Mothers

Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV-1. Studies in rats have demonstrated that tenofovir is secreted in milk. It is not known whether tenofovir is excreted in human milk. It is not known whether emtricitabine is excreted in human milk. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving Truvada.

Pediatric Use

Truvada should only be administered to pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg (greater than or equal to 77 lb) because it is a fixed-dose combination tablet containing a component, VIREAD, for which safety and efficacy have not been established in pediatric patients less than 12 years of age or weighing less than 35 kg (less than 77 lb) [See Warnings and Precautions (5.5), Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].

Geriatric Use

Clinical trials of EMTRIVA or VIREAD did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for the elderly patients should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Patients with Impaired Renal Function

It is recommended that the dosing interval for Truvada be modified in patients with creatinine clearance 30–49 mL/min. Truvada should not be used in patients with creatinine clearance below 30 mL/min and in patients with end-stage renal disease requiring dialysis [See Dosage and Administration (2.2)].

Overdosage

If overdose occurs the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.

Emtricitabine: Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA. In one clinical pharmacology trials single doses of emtricitabine 1200 mg were administered to 11 subjects. No severe adverse reactions were reported.

Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.

Tenofovir Disoproxil Fumarate: Limited clinical experience at doses higher than the therapeutic dose of VIREAD 300 mg is available. In one trial, 600 mg tenofovir disoproxil fumarate was administered to 8 subjects orally for 28 days, and no severe adverse reactions were reported. The effects of higher doses are not known.

Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of VIREAD, a four-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.

Truvada Description

Truvada tablets are fixed dose combination tablets containing emtricitabine and tenofovir disoproxil fumarate. EMTRIVA is the brand name for emtricitabine, a synthetic nucleoside analog of cytidine. Tenofovir disoproxil fumarate (tenofovir DF) is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Both emtricitabine and tenofovir exhibit inhibitory activity against HIV-1 reverse transcriptase.

Emtricitabine: The chemical name of emtricitabine is 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position.

It has a molecular formula of C8H10FN3O3S and a molecular weight of 247.24. It has the following structural formula:

Emtricitabine is a white to off-white crystalline powder with a solubility of approximately 112 mg/mL in water at 25 °C. The partition coefficient (log p) for emtricitabine is -0.43 and the pKa is 2.65.

Tenofovir Disoproxil Fumarate: Tenofovir disoproxil fumarate is a fumaric acid salt of the bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir. The chemical name of tenofovir disoproxil fumarate is 9-[(R)-2 [[bis[[(isopropoxycarbonyl)oxy]- methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of C19H30N5O10P • C4H4O4 and a molecular weight of 635.52. It has the following structural formula:

Tenofovir disoproxil fumarate is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in water at 25 °C. The partition coefficient (log p) for tenofovir disoproxil is 1.25 and the pKa is 3.75. All dosages are expressed in terms of tenofovir disoproxil fumarate except where otherwise noted.

Truvada tablets are for oral administration. Each film-coated tablet contains 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate, (which is equivalent to 245 mg of tenofovir disoproxil), as active ingredients. The tablets also include the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch (gluten free). The tablets are coated with Opadry II Blue Y-30-10701, which contains FD&C Blue #2 aluminum lake, hydroxypropyl methylcellulose 2910, lactose monohydrate, titanium dioxide, and triacetin.

Truvada - Clinical Pharmacology

For additional information on Mechanism of Action, Antiviral Activity, Resistance and Cross Resistance, please consult the EMTRIVA and VIREAD prescribing information.

Mechanism of Action

Truvada is a fixed-dose combination of antiviral drugs emtricitabine and tenofovir disoproxil fumarate. [See Clinical Pharmacology (12.4)].

Pharmacokinetics

Truvada: One Truvada tablet was bioequivalent to one EMTRIVA capsule (200 mg) plus one VIREAD tablet (300 mg) following single-dose administration to fasting healthy subjects (N=39).

Emtricitabine: The pharmacokinetic properties of emtricitabine are summarized in Table 4. Following oral administration of EMTRIVA, emtricitabine is rapidly absorbed with peak plasma concentrations occurring at 1–2 hours post-dose. Less than 4% of emtricitabine binds to human plasma proteins in vitro and the binding is independent of concentration over the range of 0.02–200 µg/mL. Following administration of radiolabelled emtricitabine, approximately 86% is recovered in the urine and 13% is recovered as metabolites. The metabolites of emtricitabine include 3'-sulfoxide diastereomers and their glucuronic acid conjugate. Emtricitabine is eliminated by a combination of glomerular filtration and active tubular secretion. Following a single oral dose of EMTRIVA, the plasma emtricitabine half-life is approximately 10 hours.

Tenofovir Disoproxil Fumarate: The pharmacokinetic properties of tenofovir disoproxil fumarate are summarized in Table 4. Following oral administration of VIREAD, maximum tenofovir serum concentrations are achieved in 1.0 ± 0.4 hour. Less than 0.7% of tenofovir binds to human plasma proteins in vitro and the binding is independent of concentration over the range of 0.01–25 µg/mL. Approximately 70–80% of the intravenous dose of tenofovir is recovered as unchanged drug in the urine. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. Following a single oral dose of VIREAD, the terminal elimination half-life of tenofovir is approximately 17 hours.

Table 4 Single Dose Pharmacokinetic Parameters for Emtricitabine and Tenofovir in Adults* Emtricitabine Tenofovir * NC = Not calculated † Median (range) ‡ Mean (± SD) § Data presented as steady state values. Fasted Oral Bioavailability† (%) 92 (83.1–106.4) 25 (NC–45.0) Plasma Terminal Elimination Half-Life† (hr) 10 (7.4–18.0) 17 (12.0–25.7) Cmax‡ (µg/mL) 1.8 ± 0.72§ 0.30 ± 0.09 AUC‡ (µg?hr/mL) 10.0 ± 3.12§ 2.29 ± 0.69 CL/F‡ (mL/min) 302 ± 94 1043 ± 115 CLrenal‡ (mL/min) 213 ± 89 243 ± 33

Effects of Food on Oral Absorption

Truvada may be administered with or without food. Administration of Truvada following a high fat meal (784 kcal; 49 grams of fat) or a light meal (373 kcal; 8 grams of fat) delayed the time of tenofovir Cmax by approximately 0.75 hour. The mean increases in tenofovir AUC and Cmax were approximately 35% and 15%, respectively, when administered with a high fat or light meal, compared to administration in the fasted state. In previous safety and efficacy trials, VIREAD (tenofovir) was taken under fed conditions. Emtricitabine systemic exposures (AUC and Cmax) were unaffected when Truvada was administered with either a high fat or a light meal.

Special Populations

Race

Emtricitabine: No pharmacokinetic differences due to race have been identified following the administration of EMTRIVA.

Tenofovir Disoproxil Fumarate: There were insufficient numbers from racial and ethnic groups other than Caucasian to adequately determine potential pharmacokinetic differences among these populations following the administration of VIREAD.

Gender

Emtricitabine and Tenofovir Disoproxil Fumarate: Emtricitabine and tenofovir pharmacokinetics are similar in male and female subjects.

Pediatric Patients

Truvada should not be administered to pediatric patients less than 12 years of age or weighing less than 35 kg (less than 77 lb).

Emtricitabine: The pharmacokinetics of emtricitabine at steady state were determined in 27 HIV-1-infected pediatric subjects 13 to 17 years of age receiving a daily dose of 6 mg/kg up to a maximum dose of 240 mg oral solution or a 200 mg capsule; 26 of 27 subjects in this age group received the 200 mg EMTRIVA capsule. Mean (± SD) Cmax and AUC were 2.7 ± 0.9 ?g/mL and 12.6 ± 5.4 ?g•hr/mL, respectively. Exposures achieved in pediatric subjects 12 to less than 18 years of age were similar to those achieved in adults receiving a once daily dose of 200 mg.

Tenofovir Disoproxil Fumarate: Steady-state pharmacokinetics of tenofovir were evaluated in 8 HIV-1 infected pediatric subjects (12 to less than 18 years). Mean (± SD) Cmax and AUCtau are 0.38 ± 0.13 ?g/mL and 3.39 ± 1.22 ?g•hr/mL, respectively. Tenofovir exposure achieved in these pediatric subjects receiving oral daily doses of VIREAD 300 mg was similar to exposures achieved in adults receiving once-daily doses of VIREAD 300 mg.

Geriatric Patients

Pharmacokinetics of emtricitabine and tenofovir have not been fully evaluated in the elderly (65 years of age and older).

Patients with Impaired Renal Function

The pharmacokinetics of emtricitabine and tenofovir are altered in subjects with renal impairment [See Warnings and Precautions (5.3)]. In adult subjects with creatinine clearance below 50 mL/min, Cmax, and AUC0–? of emtricitabine and tenofovir were increased. It is recommended that the dosing interval for Truvada be modified in patients with creatinine clearance 30–49 mL/min. Truvada should not be used in patients with creatinine clearance below 30 mL/min and in patients with end-stage renal disease requiring dialysis [See Dosage and Administration (2.2)].

Patients with Hepatic Impairment

The pharmacokinetics of tenofovir following a 300 mg dose of VIREAD have been studied in non-HIV infected subjects with moderate to severe hepatic impairment. There were no substantial alterations in tenofovir pharmacokinetics in subjects with hepatic impairment compared with unimpaired subjects. The pharmacokinetics of Truvada or emtricitabine have not been studied in subjects with hepatic impairment; however, emtricitabine is not significantly metabolized by liver enzymes, so the impact of liver impairment should be limited.

Assessment of Drug Interactions

The steady state pharmacokinetics of emtricitabine and tenofovir were unaffected when emtricitabine and tenofovir disoproxil fumarate were administered together versus each agent dosed alone.

In vitro studies and clinical pharmacokinetic drug-drug interaction trials have shown that the potential for CYP mediated interactions involving emtricitabine and tenofovir with other medicinal products is low.

No clinically significant drug interactions have been observed between emtricitabine and famciclovir, indinavir, stavudine, tenofovir disoproxil fumarate, and zidovudine (see Tables 5 and 6). Similarly, no clinically significant drug interactions have been observed between tenofovir disoproxil fumarate and abacavir, efavirenz, emtricitabine, entecavir, indinavir, lamivudine, lopinavir/ritonavir, methadone, nelfinavir, oral contraceptives, ribavirin, saquinavir/ritonavir, and tacrolimus in trials conducted in healthy volunteers (see Tables 7 and 8).

Table 5 Drug Interactions: Changes in Pharmacokinetic Parameters for Emtricitabine in the Presence of the Coadministered Drug


More




Complera


Generic Name: emtricitabine, rilpivirine, and tenofovir (Oral route)

em-trye-SYE-ta-been, ril-pi-VIR-een hye-droe-KLOR-ide, ten-OF-oh-vir dye-soe-PROX-il FUE-ma-rate

Oral route(Tablet)

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including tenofovir disoproxil fumarate, a component of emtricitabine/rilpivirine hydrochloride/tenofovir disoproxil fumarate. Not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy have not been established in patients co-infected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with HBV and HIV-1 and have discontinued emtricitabine/rilpivirine hydrochloride/tenofovir; monitor hepatic function upon discontinuation of therapy .

Commonly used brand name(s)

In the U.S.

Complera

Available Dosage Forms:

Tablet

Pharmacologic Class: Nucleoside Reverse Transcriptase Inhibitor

Uses For Complera

Emtricitabine, rilpivirine, and tenofovir combination is used to treat human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS). This medicine is usually given to patients who have not received any HIV treatment in the past.

This medicine will not cure HIV infection or AIDS. It works by lowering the amount of HIV in the blood. The medicine will also help your immune system. This may help delay problems that usually result from AIDS or HIV disease. It will not keep you from spreading HIV to other people. People who receive this medicine may continue to have some of the problems usually related to AIDS or HIV disease.

This medicine is available only with your doctor's prescription.

Before Using Complera

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Emtricitabine, rilpivirine, and tenofovir combination is not recommended for children. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of emtricitabine, rilpivirine, and tenofovir combination in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving emtricitabine, rilpivirine, and tenofovir combination.

Pregnancy Pregnancy Category Explanation All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus. Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Carbamazepine Dexamethasone Esomeprazole Lansoprazole Omeprazole Oxcarbazepine Pantoprazole Phenobarbital Phenytoin Rabeprazole Rifabutin Rifampin Rifapentine St John's Wort

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Adefovir Dipivoxil Aluminum Carbonate, Basic Aluminum Hydroxide Aluminum Phosphate Atazanavir Calcium Carbonate Cimetidine Delavirdine Didanosine Dihydroxyaluminum Aminoacetate Dihydroxyaluminum Sodium Carbonate Efavirenz Etravirine Famotidine Magaldrate Magnesium Carbonate Magnesium Hydroxide Magnesium Oxide Magnesium Trisilicate Nevirapine Nizatidine Ranitidine Telaprevir

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Ketoconazole Lopinavir Methadone Ritonavir Tipranavir Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

Bone problems, history of or Depression, or history of or Fanconi syndrome (type of kidney disease) or Hepatitis B infection or Liver disease or Osteomalacia (soft bones) or Osteoporosis (weak or brittle bones)—Use with caution. May make these conditions worse. Kidney disease—Should not be used in patients with this condition. Proper Use of Complera

Take this medicine exactly as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

Keep taking this medicine for the full time of treatment, even if you begin to feel better. Do not stop taking it without checking first with your doctor. When your supply of the medicine is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of the medicine.

This medicine comes with a patient information leaflet. Read and follow the instructions in the leaflet carefully. Ask your doctor if you have any questions.

It is best to take this medicine with food.

If you are taking antacids that contain aluminum, magnesium, or calcium, take the antacid at least 2 hours before or 4 hours after this medicine.

If you are taking a stomach medicine for heartburn or ulcers (such as cimetidine, famotidine, nizatidine, ranitidine, Axid®, Pepcid®, Tagamet®, or Zantac®), take the heartburn medicine at least 12 hours before or 4 hours after this medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets): For treatment of HIV infection: Adults—One tablet once a day. Children—Use is not recommended. Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose or forget to use your medicine and it is less than 12 hours since your last dose, take it as soon as you can and take your next dose at the normal time. If you miss a dose or forget to use it, and it is more than 12 hours since your last dose, wait and take your next dose at the normal time. Do not use extra medicine to make up for a missed dose.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Complera

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

This medicine does not decrease the risk of transmitting HIV infection to others through sexual contact or by contamination through blood. HIV may be acquired from or spread to others through infected body fluids, including blood, vaginal fluid, or semen. If you are infected, it is best to avoid any sexual activity involving an exchange of body fluids with other people. If you do have sex, always wear (or have your partner wear) a condom (“rubber”). Only use condoms made of latex or polyurethane and use them every time you have contact with semen, vaginal secretions, or blood. Also, do not share needles or equipment with anyone or use dirty needles. If you have any questions about this, check with your doctor.

This medicine may cause a rare, but serious, unwanted effect called lactic acidosis. This is a condition where the blood has too much acid. Stop using this medicine and call your doctor right away if you have more than one of these symptoms: abdominal or stomach discomfort; a decreased appetite; diarrhea; fast, shallow breathing; a general feeling of discomfort; muscle pain or cramping; nausea; shortness of breath; sleepiness; or unusual tiredness or weakness.

This medicine may cause rare, but serious, liver problems. This may occur in patients with a history of hepatitis B infection. Stop using this medicine and check with your doctor right away if you have more than one of these symptoms: clay-colored stools; dark urine; a decreased appetite; fever; headache; itching; nausea and vomiting; skin rash; stomach pain or tenderness; swelling of the feet or lower legs; unusual tiredness or weakness; or yellow eyes or skin.

Tell your doctor right away if you start to feel depressed and have thoughts about hurting yourself. Report any unusual thoughts or behavior that troubles you, especially if they are new or get worse quickly.

This medicine may cause your bones to get thin. This could increase your risk for broken bones (fractures). Ask your doctor about this if you have any concerns.

This medicine may cause you to have extra body fat. Tell your doctor if you notice changes in your body shape, such as an increased amount of fat in the upper back and neck, or around the chest and stomach area. You might also lose fat from your legs, arms, or face.

When you start taking HIV medicines, your immune system may get stronger. If you already have pneumonia or tuberculosis, you may notice new symptoms when your body tries to fight the infections. If this occurs, be sure to tell your doctor.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

This medicine should not be used together with adefovir (Hepsera®), dexamethasone (Decadron®), lamivudine (Combivir®, Epivir®, Epivir-HBV®, Epzicom™, Trizivir®), or certain seizure medicines (such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, Dilantin®, Tegretol®, or Trileptal®).

Do not use this medicine together with medicines for tuberculosis (such as rifabutin, rifampin, rifapentine, Mycobutin®, Priftin®, Rifadin®, or Rimactane®), certain stomach medicines (such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, Aciphex®, Nexium®, Prevacid®, Prilosec®, or Protonix®). or St. John's wort.

The medicines in this combination tablet are also available as Atripla®, Emtriva®, Edurant®, Truvada®, and Viread®. Do not take the emtricitabine, rilpivirine, and tenofovir combination with any of these medicines.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Complera Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common Discouragement feeling sad or empty irritability lack of appetite loss of interest or pleasure mental depression thoughts of killing oneself tiredness trouble concentrating trouble sleeping Less common Body aches or pain burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings chest pain cough difficulty with breathing ear congestion fever or chills headache loss of voice runny or stuffy nose shortness of breath sneezing sore throat tightness in the chest troubled breathing unsteadiness or awkwardness unusual tiredness or weakness weakness in the arms, hands, legs, or feet wheezing Incidence not known Abdominal or stomach discomfort agitation bloating bloody or cloudy urine bone pain broken bones, especially the thigh bone changes in behavior confusion constipation dark urine decreased appetite decrease in amount of urine diarrhea difficulty with swallowing dizziness dry mouth fast heartbeat fast, shallow breathing frequent urination general tiredness and weakness headache hives hostility increased thirst indigestion irritability itching large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs lethargy light-colored stools loss of appetite muscle pain or cramps muscle tenderness, wasting, or weakness nausea or vomiting numbness or tingling in the hands, feet, or lips pain in the stomach, side, or abdomen, possibly radiating to the back rapid weight gain seizures skin rash sleepiness swelling of the face, ankles, hands, feet, or lower legs upper right stomach pain vomiting yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common Abnormal dreams sleeplessness trouble sleeping unable to sleep Less common Acid or sour stomach back pain belching difficulty with moving heartburn pain in the joints pain or tenderness around the eyes and cheekbones sneezing stomach discomfort or upset Incidence not known Lack or loss of strength

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.


More




Emtricitabine


Class: Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: 5-Fluoro-1-(2R, 5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine
Molecular Formula: C8H10FN3O3S
CAS Number: 143491-57-0
Brands: Atripla, Emtriva, Truvada

Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported rarely in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals.1 (See Hepatic Effects and Lactic Acidosis under Cautions.)

Single entity or fixed-combination preparations containing emtricitabine not indicated for treatment of chronic hepatitis B virus (HBV) infection; safety and efficacy not established for treatment of HIV infection in patients coinfected with HBV.1

Severe, acute exacerbations of HBV reported following discontinuance of emtricitabine.1 Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after emtricitabine is discontinued in patients coinfected with HBV and HIV.1 If appropriate, initiation of treatment for HBV infection may be warranted.1

Introduction

Antiretroviral; nucleoside reverse transcriptase inhibitor (NRTI).1

Uses for Emtricitabine Treatment of HIV Infection

Treatment of HIV-1 infection in conjunction with other antiretrovirals.1 2 3

A preferred or alternative NRTI for use in multiple-drug antiretroviral regimens for initial therapy in adults.4

Fixed-combination preparation containing emtricitabine and tenofovir (Truvada) used in conjunction with other antiretrovirals.10 Can be used to decrease pill burden,4 but should not be used as a component of a triple NRTI regimen.10

Fixed-combination preparation containing efavirenz, emtricitabine, and tenofovir (Atripla) used alone or in conjunction with other antiretrovirals.14 Used to decrease pill burden and improve compliance.14

Base decision to use emtricitabine in previously treated adults on laboratory testing (e.g., genotype testing, phenotype testing) and treatment history.1

For treatment of HIV in patients coinfected with hepatitis B virus (HBV), some experts recommend an NRTI combination of tenofovir and (emtricitabine or lamivudine); avoid use of only 1 of these antiretrovirals (may increase risk of HBV resistance).4 17

Postexposure Prophylaxis following Occupational Exposure to HIV

Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.13 Used in conjunction with other antiretrovirals.13

Postexposure Prophylaxis following Nonoccupational Exposure to HIV

Postexposure prophylaxis of HIV infection† in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.12 Used in conjunction with other antiretrovirals.12

Emtricitabine Dosage and Administration Administration Oral Administration

Administer single-entity preparation (Emtriva) or fixed-combination preparation (Truvada) orally without regard to meals.1 10 Administer fixed-combination preparation (Atripla) orally once daily on an empty stomach, preferably at bedtime.14

Because the dosage of emtricitabine and tenofovir cannot be adjusted individually, the fixed combination containing emtricitabine and tenofovir (Truvada) should not be used in pediatric patients; patients with severe renal impairment (Clcr <30 mL/minute); or patients who experience dose-limiting adverse effects.10

Because the dosage of efavirenz, emtricitabine, and tenofovir cannot be adjusted individually, the fixed combination containing efavirenz, emtricitabine, and tenofovir (Atripla) should not be used in patients with moderate to severe renal impairment (Clcr <50 mL/minute).14

Dosage

Emtricitabine capsules and oral solution are not bioequivalent.1 (See Bioavailability under Pharmacokinetics.)

Emtriva and Truvada must be given in conjunction with other antiretrovirals.1 10 Atripla may be used alone or in conjunction with other antiretrovirals.14

Dosage of Truvada and Atripla expressed as number of tablets.10 14

Pediatric Patients Treatment of HIV Infection Oral

Infants 0–3 months of age: 3 mg/kg (as the oral solution) once daily.1

Children 3 months to 17 years of age: 6 mg/kg (up to a maximum of 240 mg as the oral solution) once daily.1 11

Children weighing >33 kg who can swallow an intact capsule: 200 mg (as the capsule) once daily.1 11

Adults Treatment of HIV Infection Oral

200 mg (as the capsule) once daily.1 Alternatively, 240 mg (as the oral solution) once daily.1 4

Truvada: 1 tablet once daily.4 10

Atripla: 1 tablet once daily.4 14

Postexposure Prophylaxis following Occupational Exposure to HIV† Oral

200 mg (as the capsule) once daily.13

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.13

Postexposure Prophylaxis following Nonoccupational Exposure to HIV† Oral

200 mg (as the capsule) once daily.12

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ?72 hours after exposure) and continue for 28 days.12

Prescribing Limits Pediatric Patients Treatment of HIV Infection Oral

Children 3 months to 17 years of age: Maximum 240 mg (as the oral solution) once daily.1

Special Populations Renal Impairment Treatment of HIV Infection Oral

Reduce dosage in adults with Clcr <50 mL/minute (see tables).1

Data insufficient to make specific dosage recommendations for pediatric patients with renal impairment; consider reducing dose and/or increasing dosing interval.1

Table 1. Emtriva Dosage in Adults with Renal Impairment14

Clcr (mL/minute)

Dosage of Capsules

Dosage of Oral Solution

?50

200 mg every 24 hours

240 mg every 24 hours

30–49

200 mg every 48 hours

120 mg every 24 hours

15–29

200 mg every 72 hours

80 mg every 24 hours

<15

200 mg every 96 hours

60 mg every 24 hours

Hemodialysis patients

200 mg every 96 hours; on day of dialysis, give dose after the procedure

60 mg every 24 hours; give dose after hemodialysis

Table 2. Truvada Dosage in Adults with Renal Impairment10

Clcr (mL/minute)

Dose and Dosing Interval

?50

One tablet every 24 hours

30–49

One tablet every 48 hours (monitor clinical response and renal function since dosage has not been evaluated clinically)

<30 (including hemodialysis patients)

Not recommended

Atripla: Dosage adjustment not necessary in patients with Clcr ?50 mL/minute.14 Not recommended in patients with Clcr < 50 mL/minute.14

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Cautions for Emtricitabine Contraindications

Known hypersensitivity to emtricitabine or any ingredient in the formulation.1

Warnings/Precautions Warnings Hepatic Effects and Lactic Acidosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving emtricitabine.1 Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.1 Has been reported in patients with no known risk factors.1

Use with caution in patients with known risk factors for liver disease.1

Interrupt therapy if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).1

HIV-infected Individuals Coinfected with Hepatitis B Virus (HBV)

Test all HIV patients for presence of HBV before initiating antiretroviral therapy.1

Not indicated for treatment of chronic HBV infection.1

Safety and efficacy not established for treatment of HIV infection in patients coinfected with HBV.1 (See Treatment of HIV Infection under Uses.)

Severe acute exacerbations of HBV reported following discontinuance of emtricitabine.1 Exacerbations of HBV have been associated with hepatic decompensation and hepatic failure.1 If used in those coinfected with HIV and HBV, closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after emtricitabine is discontinued.1 If appropriate, initiation of treatment for HBV infection may be warranted.1

General Precautions

Do not use multiple emtricitabine-containing preparations concomitantly.1

Emtricitabine should not be administered with lamivudine or fixed-combination preparations containing lamivudine (Combivir, Epivir, Epivir-HBV, Epzicom, Trizivir).1

Use of Fixed Combinations

When used in fixed combination with tenofovir (Truvada), consider the cautions, precautions, and contraindications associated with tenofovir.10

When used in fixed combination with tenofovir and efavirenz (Atripla), consider the cautions, precautions, and contraindications associated with the concomitant agents.14

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]);1 this may necessitate further evaluation and treatment.1

Specific Populations Pregnancy

Category B.1

Antiretroviral Pregnancy Registry at 800-258-4263.1

Some experts state that emtricitabine is an alternative (not a preferred) NRTI for use in multiple-drug antiretroviral regimens in pregnant women.16

Lactation

Not known whether distributed into human milk.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1

Pediatric Use

Emtriva: Safety and efficacy in pediatric patients 3 months through 21 years of age supported by evidence from studies in pediatric patients.1

Pharmacokinetics evaluated in a limited number of neonates born to HIV-infected mothers; efficacy in preventing or treating HIV infection in these neonates not determined.1 20

Adverse effects reported in children similar to adults.1

Truvada: Safety and efficacy not established in children <18 years of age.8 10

Atripla: Safety and efficacy not established in children <18 years of age.14

Geriatric Use

Insufficient experience in those ?65 years of age to determine whether they respond differently than younger adults.1

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Renal Impairment

Dosage adjustment necessary based on degree of renal impairment.1 Monitor clinical response and renal function in patients with renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Emtricitabine not metabolized by liver enzymes; any impact of hepatic impairment expected to be limited.1

Use with caution in patients with known risk factors for liver disease.1

Common Adverse Effects

Mild to moderate headache; GI effects (diarrhea, nausea); rash.1

Interactions for Emtricitabine

Emtricitabine does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, or CYP3A4.1 Interactions with drugs metabolized by these CYP isoenzymes unlikely.1

Emtricitabine does not inhibit glucuronosyltransferase (uridine diphosphoglucuronosyltransferase, UDP-glucuronate ?-d-glucuronosyltransferase [acceptor-unspecific]), an enzyme responsible for glucuronidation.1 Pharmacokinetic interactions unlikely.1

Specific Drugs

Drug

Interaction

Comments

Abacavir

In vitro evidence of additive or synergistic antiretroviral effects1

Darunavir

Pharmacokinetic interaction unlikely18

Delavirdine

In vitro evidence of additive or synergistic antiretroviral effects1

Efavirenz

In vitro evidence of additive or synergistic antiretroviral effects1

Famciclovir

Pharmacokinetic interaction unlikely1

Indinavir

Pharmacokinetic interaction unlikely1

Lamivudine

Do not use concomitantly;1 4 no potential benefit since emtricitabine is an analog of lamivudine and has the same resistance profile4

Nelfinavir

In vitro evidence of additive or synergistic antiretroviral effects1

Nevirapine

In vitro evidence of additive or synergistic antiretroviral effects1

Ritonavir

In vitro evidence of additive or synergistic antiretroviral effects1

Saquinavir

In vitro evidence of additive or synergistic antiretroviral effects1

Stavudine

Pharmacokinetic interaction unlikely1

In vitro evidence of additive or synergistic antiretroviral effects1

Tenofovir

Pharmacokinetic interaction unlikely1

In vitro evidence of additive or synergistic antiretroviral effects1

Tipranavir

In vitro evidence of additive antiretroviral effects19

Zidovudine

In vitro evidence of additive or synergistic antiretroviral effects1

Emtricitabine Pharmacokinetics Absorption Bioavailability

Rapidly and extensively absorbed; peak plasma concentrations attained within 1–2 hours.1

Capsules: Bioavailability is 93%.1

Oral solution: Bioavailability is 75%.1

Fixed-combination tablet containing emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg (Truvada) is bioequivalent to a 200-mg capsule of emtricitabine and a 300-mg tablet of tenofovir disoproxil fumarate given simultaneously.10

Fixed-combination tablet containing efavirenz 600 mg, tenofovir disoproxil fumarate 300 mg, and emtricitabine 200 mg (Atripla) is bioequivalent to a 600-mg tablet of efavirenz, a 300-mg tablet of tenofovir disoproxil fumarate, and a 200-mg capsule of emtricitabine given simultaneously.14

Food

Food does not appear to affect absorption.1

Special Populations

Peak plasma concentrations and AUC increased in patients with renal impairment due to a reduction in renal clearance of the drug.1 Dosage adjustment needed.1

AUC reported in pediatric patients 3 months to 17 years of age receiving the recommended dosage (6 mg/kg daily [up to 240 mg daily] as the oral solution or 200-mg capsule once daily) similar to that reported in adults receiving 200 mg daily.1 AUC reported in neonates receiving 3 mg/kg daily for 4 days similar to that reported in children 3 months to 17 years of age receiving the recommended dosage.1

Distribution Extent

Not well characterized.1

Not known whether crosses the placenta or is distributed into milk.1

Plasma Protein Binding

<4 %.1

Elimination Metabolism

Undergoes oxidation and conjugation with glucuronic acid.1

Intracellularly, emtricitabine is phosphorylated and converted by cellular enzymes to the active metabolite, emtricitabine 5?-triphosphate.1

Elimination Route

Excreted in urine (86%) and feces (14%).1 Eliminated by glomerular filtration and active tubular secretion.1

Removed by hemodialysis; not known whether removed by peritoneal dialysis.1

Half-life

10 hours.1

Special Populations

Renal impairment reduces renal clearance.1

Stability Storage Oral Capsules

Emtriva: 25°C (may be exposed to 15–30°C).1

Solution

Emtriva: 2–8°C until dispensed.1 For patient use, store at 25°C (may be exposed to 15–30°C); use within 3 months.1

Tablets

Truvada: 25°C (may be exposed to 15–30°C).10

Atripla: 25°C (may be exposed to 15–30°C).14

Actions and SpectrumActions

Thio analog of cytidine.1

Pharmacologically related to other NRTIs (e.g., abacavir, didanosine, lamivudine, stavudine, zidovudine); differs structurally from these drugs; also differs pharmacologically and structurally from other currently available antiretroviral agents.1

Active in vitro against HIV-1 and HIV-2.1 Also has some activity against HBV.5 7

Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).1

Strains of HIV-1 with reduced susceptibility to emtricitabine have been produced in vitro and have emerged during therapy with the drug.1

Strains of HIV resistant to emtricitabine may be cross-resistant to some other NRTIs (e.g., lamivudine).1

Cross-resistance between emtricitabine and PIs is highly unlikely since the drugs have different target enzymes.4 Cross-resistance between emtricitabine and NNRTIs is considered to be low since the drugs bind at different sites on reverse transcriptase and have different mechanisms of action.4

Advice to Patients

Critical nature of compliance with HIV therapy.1 Importance of using emtricitabine in conjunction with other antiretrovirals—not for monotherapy.1

Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.1 HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.1

Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Emtricitabine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg

Emtriva

Gilead

Solution

10 mg/mL

Emtriva

Gilead

Emtricitabine Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

200 mg with Tenofovir Disoproxil Fumarate 300 mg

Truvada

Gilead

200 mg with Tenofovir Disoproxil Fumarate 300 mg and Efavirenz 600 mg

Atripla

Bristol-Myers Squibb and Gilead

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Atripla 600-200-300MG Tablets (BRISTOL-MYERS SQUIBB/GILEAD): 30/$1795.72 or 90/$5154.14

Emtriva 200MG Capsules (GILEAD SCIENCES): 30/$466 or 60/$883.01

Truvada 200-300MG Tablets (GILEAD SCIENCES): 30/$1071.69 or 90/$3180.65

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 01, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Gilead Sciences, Inc. Emtriva (emtricitabine) capsules prescribing information. Foster City, CA; 2008 May.

2. Saag M, Cahn P, Raffi F et al. A randomized, double-blind, multicenter comparison of emtricitabine QD to stavudine BID. Proceedings of ICAAC San Diego 2002. Abstract No. LB-1.

3. Sanne I, van der Horst C, Shaw A et al. Two randomized, controlled, equivalence trials of emtricitabine (FTC) to lamivudine (3TC). Poster presented at the XIV International AIDS Conference. Barcelona, Spain: 2002 Jul 7-12.

4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (November 3, 2008). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website.

5. Seigneres B, Martin P, Werle B et al. Effects of pyrimidine and purine analog combinations in the duck hepatitis B virus infection model. Antimicrob Agents Chemother. 2003; 47:1842-52. [PubMed 12760857]

6. AIDSinfo Drugs Database. Emtricitabine. From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) web site. Accessed 7 Oct 2003.

7. Gish RG, Leung NWY, Wright TL et al. Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection. Antimicrob Agents Chemother. 2002; 46:1734-40. [IDIS 481640] [PubMed 12019083]

8. Gilead, Foster City, CA: Personal communication.

9. Saez-Llorens X, Violari A, Ndiweni D et al. Once daily emtricitabine (FTC) in HIV-infected pediatric patients with other antiretroviral agents. Poster presented at the 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA: 2003 Feb 10-4.

10. Gilead Sciences, Inc. Truvada (emtricitabine and tenofovir disoproxil fumarate) tablet prescribing information. Foster City, CA; 2005 Jan.

11. Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children of the National Resource Center at the Fran?ois-Xavier Bagnoud Center, Health Resources and Services Administration (HRSA), and National Institutes of Health (NIH). Guidelines for the use of antiretroviral agents in pediatric HIV infection (February 23, 2009). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website.

12. Center for Disease Control and Prevention. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: Recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2005; 54(No. RR-2):1-19.

13. Center for Disease Control and Prevention. Updated U.S. public health service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005; 54(No. RR-9):1-17.

14. Bristol-Myers Squibb and Gilead. Atripla (efavirenz 600 mg/emtricitabine 200mg /tenofovir disoproxil fumarate 300mg) tablets prescribing information. Foster City, CA; 2006 Jul.

15. Gallant JE, DeJesus E, Arribas JR et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006; 354:251-60. [PubMed 16421366]

16. Perinatal HIV Guidelines Working Group. US Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States (April 29, 2009). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website.

17. Hammer SM, Saag MS, Schechter M et al. Treatment of adult HIV infection: 2006 recommendations of the International AIDS Society–USA panel. JAMA. 2006; 296:827-43. [PubMed 16905788]

18. Tibotec. Prezista (darunavir) prescribing information. Raritan, NJ; 2006 Jun.

19. Boehringer Ingelheim. Aptivus (tipranavir) capsules prescribing information. Ridgefield, CT; 2006 Jun 27.

20. Blum MR, Ndiweni D, Chittick G et al. Steady-state pharmacokinetic evaluation of emtricitabine in neonates exposed to HIV in utero. Poster presented at the 13th Conference on Retroviruses and Opportunistic Infections. Denver, CO: 2006 Feb 5-9.

More Emtricitabine resources Emtricitabine Side Effects (in more detail) Emtricitabine Use in Pregnancy & Breastfeeding Emtricitabine Drug Interactions Emtricitabine Support Group 0 Reviews for Emtricitabine - Add your own review/rating Emtricitabine MedFacts Consumer Leaflet (Wolters Kluwer) Emtricitabine Professional Patient Advice (Wolters Kluwer) emtricitabine Advanced Consumer (Micromedex) - Includes Dosage Information Emtriva Prescribing Information (FDA) Emtriva Consumer Overview Compare Emtricitabine with other medications HIV Infection Nonoccupational Exposure


More




Atripla


Generic Name: efavirenz, emtricitabine, and tenofovir disoproxil fumarate
Dosage Form: tablet, film coated
FULL PRESCRIBING INFORMATION WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS B

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of Atripla, in combination with other antiretrovirals [See Warnings and Precautions (5.1)].

Atripla is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Atripla have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA or VIREAD, which are components of Atripla. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Atripla. If appropriate, initiation of anti-hepatitis B therapy may be warranted [See Warnings and Precautions (5.2)].

Indications and Usage for Atripla

Atripla® is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.

Atripla Dosage and Administration

Adults: The dose of Atripla is one tablet once daily taken orally on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms.

Pediatrics: Atripla is not recommended for use in patients less than 18 years of age.

Renal Impairment: Because Atripla is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment such as those with moderate or severe renal impairment (creatinine clearance below 50 mL/min).

Dosage Forms and Strengths

Atripla is available as tablets. Each tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (tenofovir DF, which is equivalent to 245 mg of tenofovir disoproxil). The tablets are pink, capsule-shaped, film-coated, debossed with "123" on one side and plain-faced on the other side.

Contraindications Hypersensitivity

Atripla is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of Atripla.

Contraindicated Drugs

For some drugs, competition for CYP3A by efavirenz could result in inhibition of their metabolism and create the potential for serious and/or life-threatening adverse reactions (e.g., cardiac arrhythmias, prolonged sedation, or respiratory depression). Drugs that are contraindicated with Atripla are listed in Table 1.

Table 1 Drugs That Are Contraindicated or Not Recommended for Use With Atripla Drug Class: Drug Name Clinical Comment Antifungal: voriconazole Efavirenz significantly decreases voriconazole plasma concentrations, and coadministration may decrease the therapeutic effectiveness of voriconazole. Also, voriconazole significantly increases efavirenz plasma concentrations, which may increase the risk of efavirenz-associated side effects. Because Atripla is a fixed-dose combination product, the dose of efavirenz cannot be altered. [See Clinical Pharmacology (12.3) Tables 5 and 6] Ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine) Potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Benzodiazepines: midazolam, triazolam Potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Calcium channel blocker: bepridil Potential for serious and/or life-threatening reactions such as cardiac arrhythmias. GI motility agent: cisapride Potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Neuroleptic: pimozide Potential for serious and/or life-threatening reactions such as cardiac arrhythmias. St. John's wort (Hypericum perforatum) May lead to loss of virologic response and possible resistance to efavirenz or to the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Warnings and Precautions Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs including tenofovir DF, a component of Atripla, in combination with other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Atripla should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Patients Coinfected with HIV-1 and HBV

It is recommended that all patients with HIV-1 be tested for the presence of chronic HBV before initiating antiretroviral therapy. Atripla is not approved for the treatment of chronic HBV infection, and the safety and efficacy of Atripla have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir DF, two of the components of Atripla. In some patients infected with HBV and treated with emtricitabine, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Patients who are coinfected with HIV-1 and HBV should be closely monitored with both clinical and laboratory follow up for at least several months after stopping treatment with Atripla. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Atripla should not be administered with HEPSERA® (adefovir dipivoxil) [See Drug Interactions (7.2)].

Drug Interactions

Efavirenz plasma concentrations may be altered by substrates, inhibitors, or inducers of CYP3A. Likewise, efavirenz may alter plasma concentrations of drugs metabolized by CYP3A [See Contraindications (4.2), Drug Interactions (7.1)].

Coadministration with Related Products

 Related drugs not for coadministration with Atripla include COMPLERA (emtricitabine/rilpivirine/tenofovir DF), EMTRIVA (emtricitabine), SUSTIVA (efavirenz), TRUVADA (emtricitabine/tenofovir DF), and VIREAD (tenofovir DF), which contain the same active components as Atripla. Due to similarities between emtricitabine and lamivudine, Atripla should not be coadministered with drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Epivir, or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine).

Psychiatric Symptoms

Serious psychiatric adverse experiences have been reported in patients treated with efavirenz. In controlled trials of 1008 subjects treated with regimens containing efavirenz for a mean of 2.1 years and 635 subjects treated with control regimens for a mean of 1.5 years, the frequency (regardless of causality) of specific serious psychiatric events among subjects who received efavirenz or control regimens, respectively, were: severe depression (2.4%, 0.9%), suicidal ideation (0.7%, 0.3%), nonfatal suicide attempts (0.5%, 0%), aggressive behavior (0.4%, 0.5%), paranoid reactions (0.4%, 0.3%), and manic reactions (0.2%, 0.3%). When psychiatric symptoms similar to those noted above were combined and evaluated as a group in a multifactorial analysis of data from Study AI266006 (006), treatment with efavirenz was associated with an increase in the occurrence of these selected psychiatric symptoms. Other factors associated with an increase in the occurrence of these psychiatric symptoms were history of injection drug use, psychiatric history, and receipt of psychiatric medication at trial entry; similar associations were observed in both the efavirenz and control treatment groups. In Study 006, onset of new serious psychiatric symptoms occurred throughout the trial for both efavirenz-treated and control-treated subjects. One percent of efavirenz-treated subjects discontinued or interrupted treatment because of one or more of these selected psychiatric symptoms. There have also been occasional postmarketing reports of death by suicide, delusions, and psychosis-like behavior, although a causal relationship to the use of efavirenz cannot be determined from these reports. Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risks of continued therapy outweigh the benefits [See Adverse Reactions (6)].

Nervous System Symptoms

Fifty-three percent (531/1008) of subjects receiving efavirenz in controlled trials reported central nervous system symptoms (any grade, regardless of causality) compared to 25% (156/635) of subjects receiving control regimens. These symptoms included dizziness (28.1% of the 1008 subjects), insomnia (16.3%), impaired concentration (8.3%), somnolence (7.0%), abnormal dreams (6.2%), and hallucinations (1.2%). Other reported symptoms were euphoria, confusion, agitation, amnesia, stupor, abnormal thinking, and depersonalization. The majority of these symptoms were mild-moderate (50.7%); symptoms were severe in 2.0% of subjects. Overall, 2.1% of subjects discontinued therapy as a result. These symptoms usually begin during the first or second day of therapy and generally resolve after the first 2–4 weeks of therapy. After 4 weeks of therapy, the prevalence of nervous system symptoms of at least moderate severity ranged from 5% to 9% in subjects treated with regimens containing efavirenz and from 3% to 5% in subjects treated with a control regimen. Patients should be informed that these common symptoms were likely to improve with continued therapy and were not predictive of subsequent onset of the less frequent psychiatric symptoms [See Warnings and Precautions (5.5)]. Dosing at bedtime may improve the tolerability of these nervous system symptoms [See Dosage and Administration (2)].

Analysis of long-term data from Study 006, (median follow-up 180 weeks, 102 weeks, and 76 weeks for subjects treated with efavirenz + zidovudine + lamivudine, efavirenz + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among efavirenz-treated subjects were generally similar to those in the indinavir-containing control arm.

Patients receiving Atripla should be alerted to the potential for additive central nervous system effects when Atripla is used concomitantly with alcohol or psychoactive drugs.

Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.

New Onset or Worsening Renal Impairment

Emtricitabine and tenofovir are principally eliminated by the kidney; however, efavirenz is not. Since Atripla is a combination product and the dose of the individual components cannot be altered, patients with creatinine clearance below 50 mL/min should not receive Atripla.

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir DF [See Adverse Reactions (6.3)].

It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy and as clinically appropriate during therapy with Atripla. Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving HEPSERA.

Atripla should be avoided with concurrent or recent use of a nephrotoxic agent.

Reproductive Risk Potential

Pregnancy Category D: Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. Pregnancy should be avoided in women receiving Atripla. Barrier contraception must always be used in combination with other methods of contraception (e.g., oral or other hormonal contraceptives). Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of Atripla is recommended. Women of childbearing potential should undergo pregnancy testing before initiation of Atripla. If this drug is used during the first trimester of pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.

There are no adequate and well-controlled trials of Atripla in pregnant women. Atripla should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options.

Antiretroviral Pregnancy Registry: To monitor fetal outcomes of pregnant women, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients who become pregnant by calling (800) 258-4263.

Efavirenz: As of July 2009, the Antiretroviral Pregnancy Registry has received prospective reports of 661 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first-trimester exposures (606 pregnancies). Birth defects occurred in 14 of 501 live births (first-trimester exposure) and 2 of 55 live births (second/third-trimester exposure). One of these prospectively reported defects with first-trimester exposure was a neural tube defect. A single case of anophthalmia with first-trimester exposure to efavirenz has also been prospectively reported; however, this case included severe oblique facial clefts and amniotic banding, a known association with anophthalmia. There have been six retrospective reports of findings consistent with neural tube defects, including meningomyelocele. All mothers were exposed to efavirenz-containing regimens in the first trimester. Although a causal relationship of these events to the use of efavirenz has not been established, similar defects have been observed in preclinical studies of efavirenz.

Malformations have been observed in 3 of 20 fetuses/infants from efavirenz-treated cynomolgus monkeys (versus 0 of 20 concomitant controls) in a developmental toxicity study. The pregnant monkeys were dosed throughout pregnancy (postcoital days 20–150) with efavirenz 60 mg/kg daily, a dose which resulted in plasma drug concentrations similar to those in humans given 600 mg/day of efavirenz. Anencephaly and unilateral anophthalmia were observed in one fetus, microophthalmia was observed in another fetus, and cleft palate was observed in a third fetus. Efavirenz crosses the placenta in cynomolgus monkeys and produces fetal blood concentrations similar to maternal blood concentrations. Efavirenz has been shown to cross the placenta in rats and rabbits and produces fetal blood concentrations of efavirenz similar to maternal concentrations. An increase in fetal resorptions was observed in rats at efavirenz doses that produced peak plasma concentrations and AUC values in female rats equivalent to or lower than those achieved in humans given 600 mg once daily of efavirenz. Efavirenz produced no reproductive toxicities when given to pregnant rabbits at doses that produced peak plasma concentrations similar to and AUC values approximately half of those achieved in humans given 600 mg once daily of efavirenz.

Rash

In controlled clinical trials, 26% (266/1008) of subjects treated with 600 mg efavirenz experienced new-onset skin rash compared with 17% (111/635) of subjects treated in control groups. Rash associated with blistering, moist desquamation, or ulceration occurred in 0.9% (9/1008) of subjects treated with efavirenz. The incidence of Grade 4 rash (e.g., erythema multiforme, Stevens-Johnson syndrome) in subjects treated with efavirenz in all trials and expanded access was 0.1%. Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 2 weeks of initiating therapy with efavirenz (median time to onset of rash in adults was 11 days) and, in most subjects continuing therapy with efavirenz, rash resolves within 1 month (median duration, 16 days). The discontinuation rate for rash in clinical trials was 1.7% (17/1008). Atripla can be reinitiated in patients interrupting therapy because of rash. Atripla should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash.

Experience with efavirenz in subjects who discontinued other antiretroviral agents of the NNRTI class is limited. Nineteen subjects who discontinued nevirapine because of rash have been treated with efavirenz. Nine of these subjects developed mild-to-moderate rash while receiving therapy with efavirenz, and two of these subjects discontinued because of rash.

Hepatotoxicity

Monitoring of liver enzymes before and during treatment is recommended for patients with underlying hepatic disease, including hepatitis B or C infection; patients with marked transaminase elevations; and patients treated with other medications associated with liver toxicity [See also Warnings and Precautions (5.2)]. A few of the postmarketing reports of hepatic failure occurred in patients with no pre-existing hepatic disease or other identifiable risk factors [See Adverse Reactions (6.3)]. Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. In patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range, the benefit of continued therapy with Atripla needs to be weighed against the unknown risks of significant liver toxicity [See Adverse Reactions (6.2)].

Decreases in Bone Mineral Density

Bone mineral density (BMD) monitoring should be considered for HIV-1 infected subjects who have a history of pathologic bone fracture or are at risk for osteopenia. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected then appropriate consultation should be obtained.

In a 144-week trial of treatment-naive subjects receiving tenofovir DF, decreases in BMD were seen at the lumbar spine and hip in both arms of the trial. At Week 144, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in subjects receiving tenofovir DF + lamivudine + efavirenz compared with subjects receiving stavudine + lamivudine + efavirenz. Changes in BMD at the hip were similar between the two treatment groups. In both groups, the majority of the reduction in BMD occurred in the first 24–48 weeks of the trial and this reduction was sustained through 144 weeks. Twenty-eight percent of tenofovir DF-treated subjects vs. 21% of the comparator subjects lost at least 5% of BMD at the spine or 7% of BMD at the hip. Clinically relevant fractures (excluding fingers and toes) were reported in 4 subjects in the tenofovir DF group and 6 subjects in the comparator group. Tenofovir DF was associated with significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide, and urinary N-telopeptide), suggesting increased bone turnover. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving tenofovir DF. The effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. For additional information, consult the tenofovir DF prescribing information.

Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of tenofovir DF [See Adverse Reactions (6.3)].

Convulsions

Convulsions have been observed in patients receiving efavirenz, generally in the presence of known medical history of seizures. Caution must be taken in any patient with a history of seizures.

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [See Drug Interactions (7.3)].

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of Atripla. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Adverse Reactions

Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate: The following adverse reactions are discussed in other sections of the labeling:

Lactic Acidosis/Severe Hepatomegaly with Steatosis [See Boxed Warning, Warnings and Precautions (5.1)]. Severe Acute Exacerbations of Hepatitis B [See Boxed Warning, Warnings and Precautions (5.2)]. Psychiatric Symptoms [See Warnings and Precautions (5.5)]. Nervous System Symptoms [See Warnings and Precautions (5.6)]. New Onset or Worsening Renal Impairment [See Warnings and Precautions (5.7)]. Rash [See Warnings and Precautions (5.9)]. Hepatotoxicity [See Warnings and Precautions (5.10)]. Decreases in Bone Mineral Density [See Warnings and Precautions (5.11)]. Immune Reconstitution Syndrome [See Warnings and Precautions (5.13)]. Drug Interactions [See Contraindications (4.2), Warnings and Precautions (5.3) and Drug Interactions (7)].

For additional safety information about SUSTIVA (efavirenz), EMTRIVA (emtricitabine), or VIREAD (tenofovir DF) in combination with other antiretroviral agents, consult the prescribing information for these products.

Adverse Reactions from Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Study 934

Study 934 was an open-label active-controlled trial in which 511 antiretroviral-naive subjects received either emtricitabine + tenofovir DF administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254).

The most common adverse reactions (incidence greater than or equal to 10%, any severity) occurring in Study 934 include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. Adverse reactions observed in Study 934 were generally consistent with those seen in previous trials of the individual components (Table 2).

Table 2 Selected Treatment-Emergent Adverse Reactions* (Grades 2–4) Reported in ?5% in Either Treatment Group in Study 934 (0–144 Weeks) FTC + TDF + EFV† AZT/3TC + EFV N=257 N=254 * Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. † From Weeks 96 to 144 of the trial, subjects received emtricitabine/tenofovir DF administered in combination with efavirenz in place of emtricitabine + tenofovir DF with efavirenz. ‡ Rash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular. Gastrointestinal Disorder   Diarrhea 9% 5%   Nausea 9% 7%   Vomiting 2% 5% General Disorders and Administration Site Condition   Fatigue 9% 8% Infections and Infestations   Sinusitis 8% 4%   Upper respiratory tract infections 8% 5%   Nasopharyngitis 5% 3% Nervous System Disorders   Headache 6% 5%   Dizziness 8% 7% Psychiatric Disorders   Anxiety 5% 4%   Depression 9% 7%   Insomnia 5% 7% Skin and Subcutaneous Tissue Disorders   Rash Event‡ 7% 9%

Study 073

In Study 073, subjects with stable, virologic suppression on antiretroviral therapy and no history of virologic failure were randomized to receive Atripla or to stay on their baseline regimen. The adverse reactions observed in Study 073 were generally consistent with those seen in Study 934 and those seen with the individual components of Atripla when each was administered in combination with other antiretroviral agents.

Efavirenz, Emtricitabine, or Tenofovir Disoproxil Fumarate

In addition to the adverse reactions in Study 934 and Study 073 the following adverse reactions were observed in clinical trials of efavirenz, emtricitabine, or tenofovir DF in combination with other antiretroviral agents.

Efavirenz: The most significant adverse reactions observed in subjects treated with efavirenz are nervous system symptoms [See Warnings and Precautions (5.6)], psychiatric symptoms [See Warnings and Precautions (5.5)], and rash [See Warnings and Precautions (5.9)].

Selected adverse reactions of moderate-severe intensity observed in greater than or equal to 2% of efavirenz-treated subjects in two controlled clinical trials included pain, impaired concentration, abnormal dreams, somnolence, anorexia, dyspepsia, abdominal pain, nervousness, and pruritus.

Pancreatitis has also been reported, although a causal relationship with efavirenz has not been established. Asymptomatic increases in serum amylase levels were observed in a significantly higher number of subjects treated with efavirenz 600 mg than in control subjects.

Emtricitabine and Tenofovir Disoproxil Fumarate: Adverse reactions that occurred in at least 5% of treatment-experienced or treatment-naive subjects receiving emtricitabine or tenofovir DF with other antiretroviral agents in clinical trials include arthralgia, increased cough, dyspepsia, fever, myalgia, pain, abdominal pain, back pain, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), pneumonia, rhinitis and rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash and allergic reaction).

Skin discoloration has been reported with higher frequency among emtricitabine-treated subjects; it was manifested by hyperpigmentation on the palms and/or soles and was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Laboratory Abnormalities

Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate: Laboratory abnormalities observed in Study 934 were generally consistent with those seen in previous trials (Table 3).

Table 3 Significant Laboratory Abnormalities Reported in ?1% of Subjects in Either Treatment Group in Study 934 (0–144 Weeks) FTC + TDF + EFV* AZT/3TC + EFV N=257 N=254 * From Weeks 96 to 144 of the trial, subjects received emtricitabine/tenofovir DF administered in combination with efavirenz in place of emtricitabine + tenofovir DF with efavirenz. Any ? Grade 3 Laboratory Abnormality 30% 26% Fasting Cholesterol (>240 mg/dL) 22% 24% Creatine Kinase
(M: >990 U/L)
(F: >845 U/L) 9% 7% Serum Amylase (>175 U/L) 8% 4% Alkaline Phosphatase (>550 U/L) 1% 0% AST
(M: >180 U/L)
(F: >170 U/L) 3% 3% ALT
(M: >215 U/L)
(F: >170 U/L) 2% 3% Hemoglobin (<8.0 mg/dL) 0% 4% Hyperglycemia (>250 mg/dL) 2% 1% Hematuria (>75 RBC/HPF) 3% 2% Glycosuria (?3+) <1% 1% Neutrophils (<750/mm3) 3% 5% Fasting Triglycerides (>750 mg/dL) 4% 2%

Laboratory abnormalities observed in Study 073 were generally consistent with those in Study 934.

In addition to the laboratory abnormalities described for Study 934 (Table 3), Grade 3/4 laboratory abnomalities of increased bilirubin (>2.5 ? ULN), increased pancreatic amylase (>2.0 ? ULN), increased or decreased serum glucose (<40 or >250 mg/dL), and increased serum lipase (>2.0 ? ULN) occurred in up to 3% of subjects treated with emtricitabine or tenofovir DF with other antiretroviral agents in clinical trials.

Hepatic Events: In Study 934, 19 subjects treated with efavirenz, emtricitabine, and tenofovir DF and 20 subjects treated with efavirenz and fixed-dose zidovudine/lamivudine were hepatitis B surface antigen or hepatitis C antibody positive. Among these coinfected subjects, one subject (1/19) in the efavirenz, emtricitabine and tenofovir DF arm had elevations in transaminases to greater than five times ULN through 144 weeks. In the fixed-dose zidovudine/lamivudine arm, two subjects (2/20) had elevations in transaminases to greater than five times ULN through 144 weeks. No HBV and/or HCV coinfected subject discontinued from the trial due to hepatobiliary disorders [See Warnings and Precautions (5.10)].

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of efavirenz, emtricitabine, or tenofovir DF. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Efavirenz:

Cardiac Disorders
Palpitations

Ear and Labyrinth Disorders
Tinnitus, vertigo

Endocrine Disorders
Gynecomastia

Eye Disorders
Abnormal vision

Gastrointestinal Disorders
Constipation, malabsorption

General Disorders and Administration Site Conditions
Asthenia

Hepatobiliary Disorders
Hepatic enzyme increase, hepatic failure, hepatitis. A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing in some cases to transplantation or death.

Immune System Disorders
Allergic reactions

Metabolism and Nutrition Disorders
Redistribution/accumulation of body fat [See Warnings and Precautions (5.14)], hypercholesterolemia, hypertriglyceridemia

Musculoskeletal and Connective Tissue Disorders
Arthralgia, myalgia, myopathy

Nervous System Disorders
Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor

Psychiatric Disorders
Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide

Respiratory, Thoracic and Mediastinal Disorders
Dyspnea

Skin and Subcutaneous Tissue Disorders
Flushing, erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome

Emtricitabine: No postmarketing adverse reactions have been identified for inclusion in this section.

Tenofovir Disoproxil Fumarate:

Immune System Disorders
Allergic reaction, including angioedema

Metabolism and Nutrition Disorders
Lactic acidosis, hypokalemia, hypophosphatemia

Respiratory, Thoracic, and Mediastinal Disorders
Dyspnea

Gastrointestinal Disorders
Pancreatitis, increased amylase, abdominal pain

Hepatobiliary Disorders
Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT, gamma GT)

Skin and Subcutaneous Tissue Disorders
Rash

Musculoskeletal and Connective Tissue Disorders
Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy

Renal and Urinary Disorders
Acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

General Disorders and Administration Site Conditions
Asthenia

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

Drug Interactions

This section describes clinically relevant drug interactions with Atripla. Drug interaction trials are described elsewhere in the labeling [See Clinical Pharmacology (12.3)].

Efavirenz

Efavirenz has been shown in vivo to induce CYP3A. Other compounds that are substrates of CYP3A may have decreased plasma concentrations when coadministered with efavirenz. In vitro studies have demonstrated that efavirenz inhibits CYP2C9, 2C19, and 3A4 isozymes in the range of observed efavirenz plasma concentrations. Coadministration of efavirenz with drugs primarily metabolized by these isozymes may result in altered plasma concentrations of the coadministered drug. Therefore, appropriate dose adjustments may be necessary for these drugs.

Drugs that induce CYP3A activity (e.g., phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of efavirenz resulting in lowered plasma concentrations.

Emtricitabine and Tenofovir Disoproxil Fumarate

Since emtricitabine and tenofovir are primarily eliminated by the kidneys, coadministration of Atripla with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine, tenofovir, and/or other renally eliminated drugs. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, and valganciclovir.

Coadministration of tenofovir DF and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse reactions. Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions [for didanosine dosing adjustment recommendations, see Table 4]. Suppression of CD4+ cell counts has been observed in patients receiving tenofovir DF with didanosine 400 mg daily.

Lopinavir/ritonavir has been shown to increase tenofovir concentrations. The mechanism of this interaction is unknown. Patients receiving lopinavir/ritonavir with Atripla should be monitored for tenofovir-associated adverse reactions. Atripla should be discontinued in patients who develop tenofovir-associated adverse reactions [See Table 4].

Coadministration of atazanavir with Atripla is not recommended since coadministration of atazanavir with either efavirenz or tenofovir DF has been shown to decrease plasma concentrations of atazanavir. Also, atazanavir has been shown to increase tenofovir concentrations. There are insufficient data to support dosing recommendations for atazanavir or atazanavir/ritonavir in combination with Atripla [See Table 4].

Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate

Other important drug interaction information for Atripla is summarized in Table 1 and Table 4. The drug interactions described are based on trials conducted with efavirenz, emtricitabine or tenofovir DF as individual agents or are potential drug interactions; no drug interaction trials have been conducted using Atripla [for pharmacokinetics data see Clinical Pharmacology (12.3), Tables 5–9]. The tables include potentially significant interactions, but are not all inclusive.

Table 4 Established and Other Potentially Significant* Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Trials or Predicted Interaction Concomitant Drug Class: Drug Name Effect Clinical Comment * This table is not all inclusive. Antiretroviral agents Protease inhibitor:
  atazanavir ?atazanavir concentration
? tenofovir concentration Coadministration of atazanavir with Atripla is not recommended. Coadministration of atazanavir with either efavirenz or tenofovir DF decreases plasma concentrations of atazanavir. The combined effect of efavirenz plus tenofovir DF on atazanavir plasma concentrations is not known. Also, atazanavir has been shown to increase tenofovir concentrations. There are insufficient data to support dosing recommendations for atazanavir or atazanavir/ritonavir in combination with Atripla. Protease inhibitor:
  fosamprenavir calcium ? amprenavir concentration Fosamprenavir (unboosted): Appropriate doses of fosamprenavir and Atripla with respect to safety and efficacy have not been established.
 
Fosamprenavir/ritonavir: An additional 100 mg/day (300 mg total) of ritonavir is recommended when Atripla is administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when Atripla is administered with fosamprenavir plus ritonavir twice daily. Protease inhibitor:
  indinavir ? indinavir concentration The optimal dose of indinavir, when given in combination with efavirenz, is not known. Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to efavirenz. Protease inhibitor:
  lopinavir/ritonavir ? lopinavir concentration
? tenofovir concentration A dose increase of lopinavir/ritonavir to 600/150 mg (3 tablets) twice daily may be considered when used in combination with efavirenz in treatment-experienced patients where decreased susceptibility to lopinavir is clinically suspected (by treatment history or laboratory evidence). Patients should be monitored for tenofovir-associated adverse reactions. Atripla should be discontinued in patients who develop tenofovir-associated adverse reactions. Protease inhibitor:
  ritonavir ? ritonavir concentration
? efavirenz concentration When ritonavir 500 mg every 12 hours was coadministered with efavirenz 600 mg once d


More




efavirenz


Generic Name: efavirenz (e FAV ir enz)
Brand Names: Sustiva

What is efavirenz?

Efavirenz is an antiviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in your body.

Efavirenz is used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). Efavirenz is not a cure for HIV or AIDS.

Efavirenz may also be used for purposes not listed in this medication guide.

What is the most important information I should know about efavirenz? Do not use efavirenz if you are pregnant. It could harm the unborn baby. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide gel) while you are taking efavirenz, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment.

Efavirenz may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.

Do not take efavirenz with cisapride (Propulsid), pimozide (Orap), midazolam (Versed), triazolam (Halcion), or ergot medicines such as dihydroergotamine (D.H.E. 45), ergonovine (Ergotrate), ergotamine (Ergomar, Cafergot, Wigraine), or methylergonovine (Methergine). These drugs can cause life-threatening side effects if you use them while you are taking efavirenz.

There are many other medicines that can interact with efavirenz, or make it less effective. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Taking this medication will not prevent you from passing HIV to other people. Talk with your doctor about safe methods of preventing HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. What should I discuss with my healthcare provider before taking efavirenz? You should not use this medication if you are allergic to efavirenz, if you have moderate to severe liver problems, or if you are using any of the following drugs:

cisapride (Propulsid);

midazolam (Versed) or triazolam (Halcion);

pimozide (Orap); or

ergot medicine such as ergotamine (Ergomar, Ergostat, Cafergot, Ercaf, Wigraine), dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), or methylergonovine (Methergine).

Using any of these medicines while you are taking efavirenz can cause serious medical problems or death.

To make sure you can safely take efavirenz, tell your doctor if you have any of these other conditions:

liver disease (including hepatitis B or C);

high cholesterol or triglycerides; or

if you have ever taken delavirdine (Rescriptor) or nevirapine (Viramune) and they were not effective in treating your condition.

FDA pregnancy category D. Do not use efavirenz if you are pregnant. It could harm the unborn baby. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide gel) while you are taking efavirenz, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment. HIV can be passed to the baby if the mother is not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection while you are pregnant.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of efavirenz on the baby.

Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. How should I take efavirenz?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take efavirenz on an empty stomach at bedtime, unless your doctor tells you otherwise.

Efavirenz can cause side effects such as mood or behavior changes. These symptoms may improve the longer you take the medication. Taking efavirenz at bedtime may also lessen these effects. Contact your doctor if you have more serious symptoms such as severe depression or thoughts of hurting yourself.

Take efavirenz regularly to get the most benefit. Get your prescriptions refilled before you run out of medicine completely.

Do not take efavirenz as your only HIV medication. HIV/AIDS is usually treated with a combination of different drugs. Your disease may become resistant to efavirenz if you do not take it in combination with other HIV medicines your doctor has prescribed. Use all of your medications as directed by your doctor. Do not change your doses or medication schedule without advice from your doctor. Every person with HIV or AIDS should remain under the care of a doctor.

To be sure efavirenz is helping your condition and not causing harmful effects, your blood and liver function may need to be tested often. Visit your doctor regularly.

This medication can cause you to have a false positive drug-screening test. If you provide a urine sample for drug-screening, tell the laboratory staff that you are taking efavirenz.

Store at room temperature away from moisture and heat.

See also: Efavirenz dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause confusion, lack of balance or coordination, severe mood or behavior changes, or thoughts of suicide.

What should I avoid while taking efavirenz? Efavirenz may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of efavirenz. Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. Efavirenz side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Efavirenz may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.

Call your doctor at once if you have a serious side effect such as:

fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;

nausea, stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

fever, chills, body aches, flu symptoms; or

any other signs of new infection.

Less serious side effects may include:

mild nausea, vomiting, or stomach pain, diarrhea or constipation;

cough;

blurred vision;

headache, tired feeling, dizziness, spinning sensation;

trouble concentrating, problems with balance or coordination;

muscle or joint pain;

sleep problems (insomnia), unusual dreams; or

changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Efavirenz Dosing Information

Usual Adult Dose for HIV Infection:

600 mg orally once a day

Usual Adult Dose for Nonoccupational Exposure:

(Not approved by FDA)
Centers for Disease Control and Prevention (CDC) recommendations: 600 mg orally once a day, in combination with (lamivudine or emtricitabine) plus (zidovudine or tenofovir)
Duration: 28 days
Prophylaxis should be initiated as soon as possible, within 72 hours of exposure.

Usual Adult Dose for Occupational Exposure:

(Not approved by FDA)
CDC recommendations:
Alternate expanded regimen for HIV postexposure prophylaxis: 600 mg orally once a day, in combination with (lamivudine plus zidovudine) or (emtricitabine plus zidovudine) or (lamivudine plus tenofovir) or (emtricitabine plus tenofovir)
Duration: Generally 28 days; however, the exact duration of therapy may differ based on the institution's protocol.
Prophylaxis should be initiated immediately, preferably within hours after exposure.

Usual Pediatric Dose for HIV Infection:

3 years or older:
10 to less than 15 kg: 200 mg orally once a day
15 to less than 20 kg: 250 mg orally once a day
20 to less than 25 kg: 300 mg orally once a day
25 to less than 32.5 kg: 350 mg orally once a day
32.5 to less than 40 kg: 400 mg orally once a day
40 kg or more: 600 mg orally once a day

What other drugs will affect efavirenz? Cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by efavirenz. Tell your doctor if you regularly use any of these medicines.

There are many other medicines that can interact with efavirenz, or make it less effective. Before taking efavirenz, tell your doctor if you are using any of the following drugs:

bupropion (Aplenzin, Budeprion, Wellbutrin, Zyban);

cyclosporine (Gengraf, Neoral, Sandimmune);

itraconazole (Sporanox), posaconazole (Noxafil);

maraviroc (Selzentry);

sirolimus (Rapamune), tacrolimus (Prograf);

St. John's wort;

voriconazole (Vfend);

a blood thinner such as warfarin (Coumadin, Jantoven);

a cholesterol medication such as Lipitor or Zocor;

an antibiotic such as clarithromycin (Biaxin), rifabutin (Mycobutin), or rifampin (Rifadin, Rifater, Rifamate, Rimactane);

heart or blood pressure medications such as amlodipine (Norvasc), diltiazem (Tiazac, Cartia, Cardizem), felodipine (Plendil), nicardipine (Cardene), nifedipine (Procardia, Adalat), or verapamil (Calan, Covera, Isoptin, Verelan);

other HIV medicines such as atazanavir (Reyataz), indinavir (Crixivan), lopinavir/ritonavir (Kaletra), nevirapine (Viramune), ritonavir (Norvir), or saquinavir (Invirase); or

seizure medications such as phenytoin (Dilantin) or carbamazepine (Tegretol).

This list is not complete and there are many other drugs that can interact with efavirenz. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. More efavirenz resources Efavirenz Side Effects (in more detail) Efavirenz Dosage Efavirenz Use in Pregnancy & Breastfeeding Efavirenz Drug Interactions Efavirenz Support Group 2 Reviews for Efavirenz - Add your own review/rating efavirenz Advanced Consumer (Micromedex) - Includes Dosage Information Efavirenz Professional Patient Advice (Wolters Kluwer) Efavirenz MedFacts Consumer Leaflet (Wolters Kluwer) Efavirenz Monograph (AHFS DI) Sustiva Prescribing Information (FDA) Sustiva Consumer Overview Compare efavirenz with other medications HIV Infection Nonoccupational Exposure Occupational Exposure Where can I get more information? Your pharmacist can provide more information about efavirenz.

See also: efavirenz side effects (in more detail)


More




Videx


didanosine
Dosage Form: powder for oral solution
FULL PRESCRIBING INFORMATION WARNING: PANCREATITIS, LACTIC ACIDOSIS and HEPATOMEGALY with STEATOSIS

Fatal and nonfatal pancreatitis has occurred during therapy with Videx used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Videx should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis [see Warnings and Precautions (5.1)].

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk [see Warnings and Precautions (5.2)].

Indications and Usage for Videx

Videx® (didanosine, USP), also known as ddI, in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus (HIV)-1 infection [see Clinical Studies (14)].

Videx Dosage and Administration

Videx should be administered on an empty stomach, at least 30 minutes before or 2 hours after eating.

Recommended Dosage (Adult and Pediatric Patients)

The preferred dosing frequency of Videx is twice daily because there is more evidence to support the effectiveness of this dosing regimen. Once-daily dosing should be considered only for patients whose management requires once-daily dosing of Videx [see Clinical Studies (14)]. The recommended adult total daily dose is based on body weight (kg) (see Table 1).

Table 1: Recommended Dosage (Adult) at least 60 kg less than 60 kg Preferred dosing 200 mg twice daily 125 mg twice daily Dosing for patients whose management requires once-daily frequency 400 mg once daily 250 mg once daily

Pediatric Patients (2 weeks old to 18 years old): The recommended dose of Videx (didanosine) in pediatric patients between 2 weeks old and 8 months old is 100 mg/m2 twice daily, and the recommended Videx dose for pediatric patients greater than 8 months old is 120 mg/m2 twice daily but not to exceed the adult dosing recommendation.

Dosing recommendations in patients less than 2 weeks of age cannot be made because the pharmacokinetics of didanosine in these children are too variable to determine an appropriate dose. There are no data on once-daily dosing of Videx in pediatric patients.

Renal Impairment Adult Patients

In adult patients with impaired renal function, the dose of Videx should be adjusted to compensate for the slower rate of elimination. The recommended doses and dosing intervals of Videx in adult patients with renal insufficiency are presented in Table 2.

Table 2: Recommended Dosage in Patients with Renal Impairment Creatinine Clearance
(mL/min) Recommended Videx Dose by Patient Weight at least 60 kg less than 60 kg a 400 mg once daily (at least 60 kg) or 250 mg once daily (less than 60 kg) for patients whose management requires once-daily frequency of administration. at least 60 200 mg twice dailya 125 mg twice dailya 30-59 200 mg once daily
or 100 mg twice daily 150 mg once daily
or 75 mg twice daily 10-29 150 mg once daily 100 mg once daily less than 10 100 mg once daily 75 mg once daily Pediatric Patients

Urinary excretion is also a major route of elimination of didanosine in pediatric patients, therefore the clearance of didanosine may be altered in pediatric patients with renal impairment. Although there are insufficient data to recommend a specific dose adjustment of Videx in this patient population, a reduction in the dose should be considered (see Table 2).

Patients Requiring Continuous Ambulatory Peritoneal Dialysis (CAPD) or Hemodialysis

For patients requiring CAPD or hemodialysis, follow dosing recommendations for patients with creatinine clearance of less than 10 mL/min, shown in Table 2. It is not necessary to administer a supplemental dose of Videx following hemodialysis.

Dosage Adjustment Concomitant Therapy with Tenofovir Disoproxil Fumarate

In patients who are also taking tenofovir disoproxil fumarate, a dose reduction of Videx to 250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min) or 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min) once daily is recommended. Videx and tenofovir disoproxil fumarate may be taken together in the fasted state. Alternatively, if tenofovir disoproxil fumarate is taken with food, Videx should be taken on an empty stomach (at least 30 minutes before food or 2 hours after food). The appropriate dose of Videx coadministered with tenofovir disoproxil fumarate in patients with creatinine clearance of less than 60 mL/min has not been established. ([See Drug Interactions (7) and Clinical Pharmacology (12.3)]; see the complete prescribing information for Videx EC (enteric-coated formulation of didanosine) for results of drug interaction studies of tenofovir disoproxil fumarate with reduced doses of the enteric-coated formulation of didanosine.)

Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

Dosage Forms and Strengths

Videx (didanosine, USP) Pediatric Powder for Oral Solution is supplied in 4- and 8-ounce glass bottles containing 2 g or 4 g of Videx, respectively.

Contraindications

These recommendations are based on either drug interaction studies or observed clinical toxicities.

Allopurinol

Coadministration of didanosine and allopurinol is contraindicated because systemic exposures of didanosine are increased, which may increase didanosine-associated toxicity [see Clinical Pharmacology (12.3)].

Ribavirin

Coadministration of didanosine and ribavirin is contraindicated because exposures of the active metabolite of didanosine (dideoxyadenosine 5?-triphosphate) are increased. Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving both didanosine and ribavirin.

Warnings and Precautions Pancreatitis

Fatal and nonfatal pancreatitis has occurred during therapy with Videx used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Videx should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Patients treated with Videx in combination with stavudine may be at increased risk for pancreatitis.

When treatment with life-sustaining drugs known to cause pancreatic toxicity is required, suspension of Videx (didanosine) therapy is recommended. In patients with risk factors for pancreatitis, Videx should be used with extreme caution and only if clearly indicated. Patients with advanced HIV-1 infection, especially the elderly, are at increased risk of pancreatitis and should be followed closely. Patients with renal impairment may be at greater risk for pancreatitis if treated without dose adjustment. The frequency of pancreatitis is dose related. [See Adverse Reactions (6).]

Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk [see Use in Specific Populations (8.1)]. Particular caution should be exercised when administering Videx to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Videx should be suspended in any patient who develops clinical signs or symptoms with or without laboratory findings consistent with symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Hepatic Toxicity

The safety and efficacy of Videx have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.

Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. This combination should be avoided. [See Adverse Reactions (6).]

Non-cirrhotic Portal Hypertension

Postmarketing cases of non-cirrhotic portal hypertension have been reported, including cases leading to liver transplantation or death. Cases of didanosine-associated non-cirrhotic portal hypertension were confirmed by liver biopsy in patients with no evidence of viral hepatitis. Onset of signs and symptoms ranged from months to years after start of didanosine therapy. Common presenting features included elevated liver enzymes, esophageal varices, hematemesis, ascites, and splenomegaly.

Patients receiving Videx should be monitored for early signs of portal hypertension (eg, thrombocytopenia and splenomegaly) during routine medical visits. Appropriate laboratory testing including liver enzymes, serum bilirubin, albumin, complete blood count, and international normalized ratio (INR) and ultrasonography should be considered. Videx should be discontinued in patients with evidence of non-cirrhotic portal hypertension.

Peripheral Neuropathy

Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients receiving Videx therapy. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, in patients with a history of neuropathy, or in patients being treated with neurotoxic drug therapy, including stavudine. Discontinuation of Videx should be considered in patients who develop peripheral neuropathy. [See Adverse Reactions (6).]

Retinal Changes and Optic Neuritis

Retinal changes and optic neuritis have been reported in adult and pediatric patients. Periodic retinal examinations should be considered for patients receiving Videx [see Adverse Reactions (6)].

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Videx. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

 Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barr? syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections:

Pancreatitis [see Boxed Warning, Warnings and Precautions (5.1)] Lactic acidosis/severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.2)] Hepatic toxicity [see Warnings and Precautions (5.3)] Non-cirrhotic portal hypertension [see Warnings and Precautions (5.4)] Peripheral neuropathy [see Warnings and Precautions (5.5)] Retinal changes and optic neuritis [see Warnings and Precautions (5.6)] Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

Selected clinical adverse reactions that occurred in adult patients in clinical studies with Videx are provided in Tables 3 and 4.

Table 3: Selected Clinical Adverse Reactions from Monotherapy Studies   Percent of Patients*   ACTG 116A ACTG 116B/117 Adverse Reactions Videx
n=197 zidovudine
n=212 Videx
n=298 zidovudine
n=304 *  The incidences reported included all severity grades and all reactions regardless of causality. Diarrhea 19 15 28 21 Peripheral Neurologic
  Symptoms/Neuropathy 17 14 20 12 Abdominal Pain 13 8 7 8 Rash/Pruritus 7 8 9 5 Pancreatitis 7 3 6 2 Table 4: Selected Clinical Adverse Reactions from Combination Studies   Percent of Patientsa,c   AI454-148b START 2b
Adverse Reactions Videx +
stavudine +
nelfinavir
n=482 zidovudine +
lamivudine +
nelfinavir
n=248 Videx +
stavudine +
indinavir
n=102 zidovudine +
lamivudine +
indinavir
n=103 a  Percentages based on treated subjects. b  Median duration of treatment 48 weeks. c  The incidences reported included all severity grades and all reactions regardless of causality. *  This event was not observed in this study arm. Diarrhea 70 60 45 39 Nausea 28 40 53 67 Peripheral Neurologic
  Symptoms/Neuropathy 26 6 21 10 Headache 21 30 46 37 Rash 13 16 30 18 Vomiting 12 14 30 35 Pancreatitis (see below) 1 * less than 1 *

Pancreatitis resulting in death was observed in one patient who received Videx (didanosine) plus stavudine plus nelfinavir in Study Al454-148 and in one patient who received Videx plus stavudine plus indinavir in the START 2 study. In addition, pancreatitis resulting in death was observed in 2 of 68 patients who received Videx plus stavudine plus indinavir plus hydroxyurea in an ACTG clinical trial [see Warnings and Precautions (5)].

The frequency of pancreatitis is dose related. In phase 3 studies, incidence ranged from 1% to 10% with doses higher than are currently recommended and from 1% to 7% with recommended dose.

Selected laboratory abnormalities in clinical studies with Videx are shown in Tables 5-7.

Table 5: Selected Laboratory Abnormalities from Monotherapy Studies   Percent of Patients   ACTG 116A ACTG 116B/117 Parameter Videx
n=197 zidovudine
n=212 Videx
n=298 zidovudine
n=304 ULN = upper limit of normal. SGOT (AST) (greater than 5 x ULN) 9 4 7 6 SGPT (ALT) (greater than 5 x ULN) 9 6 6 6 Alkaline phosphatase (greater than 5 x ULN) 4 1 1 1 Amylase (at least 1.4 x ULN) 17 12 15 5 Uric acid (greater than 12 mg/dL) 3 1 2 1 Table 6: Selected Laboratory Abnormalities from Combination Studies (Grades 3-4)   Percent of Patientsa   AI454-148b START 2b Parameter Videx +
stavudine +
nelfinavir
n=482 zidovudine +
lamivudine +
nelfinavir
n=248 Videx +
stavudine +
indinavir
n=102 zidovudine +
lamivudine +
indinavir
n=103 ULN = upper limit of normal. NC = Not Collected. a  Percentages based on treated subjects. b  Median duration of treatment 48 weeks. Bilirubin (greater than 2.6 x ULN) less than 1 less than 1 16 8 SGOT (AST) (greater than 5 x ULN) 3 2 7 7 SGPT (ALT) (greater than 5 x ULN) 3 3 8 5 GGT (greater than 5 x ULN) NC NC 5 2 Lipase (greater than 2 x ULN) 7 2 5 5 Amylase (greater than 2 x ULN) NC NC 8 2 Table 7: Selected Laboratory Abnormalities from Combination Studies (All Grades)   Percent of Patientsa   AI454-148b START 2b Parameter Videx +
stavudine +
nelfinavir
n=482 zidovudine +
lamivudine +
nelfinavir
n=248 Videx +
stavudine +
indinavir
n=102 zidovudine +
lamivudine +
indinavir
n=103 NC = Not Collected. a  Percentages based on treated subjects. b  Median duration of treatment 48 weeks. Bilirubin 7 3 68 55 SGOT (AST) 42 23 53 20 SGPT (ALT) 37 24 50 18 GGT NC NC 28 12 Lipase 17 11 26 19 Amylase NC NC 31 17 Pediatric Patients

In clinical trials, 743 pediatric patients between 2 weeks and 18 years of age have been treated with didanosine. Adverse reactions and laboratory abnormalities reported to occur in these patients were generally consistent with the safety profile of didanosine in adults.

In pediatric phase 1 studies, pancreatitis occurred in 2 of 60 (3%) patients treated at entry doses below 300 mg/m2/day and in 5 of 38 (13%) patients treated at higher doses. In study ACTG 152, pancreatitis occurred in none of the 281 pediatric patients who received didanosine 120 mg/m2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg/m2 every 12 hours in combination with zidovudine [see Clinical Studies (14)].

Retinal changes and optic neuritis have been reported in pediatric patients.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of didanosine. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to Videx, or a combination of these factors.

  Blood and Lymphatic System Disorders – anemia, leukopenia, and thrombocytopenia.      Body as a Whole – alopecia, anaphylactoid reaction, asthenia, chills/fever, pain, and redistribution/accumulation of body fat [see Warnings and Precautions (5.8)].      Digestive Disorders – anorexia, dyspepsia, and flatulence.      Exocrine Gland Disorders – pancreatitis (including fatal cases) [see Boxed Warning, Warnings and Precautions (5.1)], sialoadenitis, parotid gland enlargement, dry mouth, and dry eyes.      Hepatobiliary Disorders – symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [see Boxed Warning, Warnings and Precautions (5.2)]; non-cirrhotic portal hypertension [see Warnings and Precautions (5.4)]; hepatitis and liver failure.      Metabolic Disorders – diabetes mellitus, hypoglycemia, and hyperglycemia.      Musculoskeletal Disorders – myalgia (with or without increases in creatine kinase), rhabdomyolysis including acute renal failure and hemodialysis, arthralgia, and myopathy.      Ophthalmologic Disorders – retinal depigmentation and optic neuritis [see Warnings and Precautions (5.6)]. Use with Stavudine- and Hydroxyurea-Based Regimens

When didanosine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when didanosine is used alone. Thus, patients treated with Videx in combination with stavudine, with or without hydroxyurea, may be at increased risk for pancreatitis and hepatotoxicity, which may be fatal, and severe peripheral neuropathy [see Warnings and Precautions (5)]. The combination of Videx and hydroxyurea, with or without stavudine, should be avoided.

Drug Interactions Established Drug Interactions

Clinical recommendations based on the results of drug interaction studies are listed in Table 8. Pharmacokinetic results of drug interaction studies are shown in Tables 12 and 13 [see Contraindications (4.1 and 4.2), Clinical Pharmacology (12.3)]. 

Table 8: Established Drug Interactions with Videx Drug Effect Clinical Comment ?  Indicates increase. ?  Indicates decrease. a  The dosing recommendation for coadministration of Videx EC and tenofovir disoproxil fumarate with respect to meal consumption differs from that of Videx. See the complete prescribing information for Videx EC. ciprofloxacin ? ciprofloxacin concentration Administer Videx at least 2 hours after or 6 hours before ciprofloxacin. delavirdine ? delavirdine concentration Administer Videx 1 hour after delavirdine. ganciclovir ? didanosine concentration If there is no suitable alternative to ganciclovir, then use in combination with Videx with caution. Monitor for didanosine-associated toxicity. indinavir ? indinavir concentration Administer Videx 1 hour after indinavir. methadone ? didanosine concentration Do not coadminister methadone with Videx pediatric powder due to significant decreases in didanosine concentrations. If coadministration of methadone and didanosine is necessary, the recommended formulation of didanosine is Videx EC. Patients should be closely monitored for adequate clinical response when Videx EC is coadministered with methadone, including monitoring for changes in HIV RNA viral load. nelfinavir No interaction 1 hour after didanosine Administer nelfinavir 1 hour after Videx. tenofovir disoproxil fumarate ? didanosine concentration A dose reduction of Videx to the following dosage once daily is recommended.a
250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min) 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min) Videx and tenofovir disoproxil fumarate may be taken together in the fasted state. If tenofovir disoproxil fumarate is taken with food, Videx should be taken on an empty stomach (at least 30 minutes before food or 2 hours after food). Patients should be monitored for didanosine-associated toxicities and clinical response.

Exposure to didanosine is increased when coadministered with tenofovir disoproxil fumarate [Table 8 and see Clinical Pharmacokinetics (12.3, Table 12)]. Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Coadministration of tenofovir disoproxil fumarate with Videx should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities and clinical response. Videx should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop [see Dosage and Administration (2.3), Warnings and Precautions (5)]. Suppression of CD4 cell counts has been observed in patients receiving tenofovir disoproxil fumarate with didanosine at a dose of 400 mg daily.

Predicted Drug Interactions

Predicted drug interactions with Videx are listed in Table 9.

Table 9: Predicted Drug Interactions with Videx Drug or Drug Class Effect Clinical Comment ?  Indicates increase. ?  Indicates decrease. a  Only if other drugs are not available and if clearly indicated. If treatment with life-sustaining drugs that cause pancreatic toxicity is required, suspension of Videx is recommended [see Warnings and Precautions (5.1)]. b  [See Warnings and Precautions (5.6).] Drugs that may cause pancreatic toxicity ? risk of pancreatitis Use only with extreme cautiona Neurotoxic drugs ? risk of neuropathy Use with cautionb Antacids containing magnesium or aluminum ? side effects associated with antacid components Use caution with Videx Pediatric Powder for Oral Solution Azole antifungals ? ketoconazole or itraconazole concentration Administer drugs such as ketoconazole or itraconazole at least 2 hours before Videx. Quinolone antibiotics (see also ciprofloxacin in Table 8) ? quinolone concentration Consult package insert of the quinolone. Tetracycline antibiotics ? antibiotic concentration Consult package insert of the tetracycline. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B

Reproduction studies have been performed in rats and rabbits at doses up to 12 and 14.2 times the estimated human exposure (based upon plasma levels), respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to didanosine. At approximately 12 times the estimated human exposure, didanosine was slightly toxic to female rats and their pups during mid and late lactation. These rats showed reduced food intake and body weight gains but the physical and functional development of the offspring was not impaired and there were no major changes in the F2 generation. A study in rats showed that didanosine and/or its metabolites are transferred to the fetus through the placenta. Animal reproduction studies are not always predictive of human response.

There are no adequate and well-controlled studies of didanosine in pregnant women. Didanosine should be used during pregnancy only if the potential benefit justifies the potential risk.

Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. It is unclear if pregnancy augments the risk of lactic acidosis/hepatic steatosis syndrome reported in nonpregnant individuals receiving nucleoside analogues [see Warnings and Precautions (5.2)]. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk. Healthcare providers caring for HIV-infected pregnant women receiving didanosine should be alert for early diagnosis of lactic acidosis/hepatic steatosis syndrome.

Antiretroviral Pregnancy Registry

To monitor maternal-fetal outcomes of pregnant women exposed to didanosine and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

Nursing Mothers

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. A study in rats showed that following oral administration, didanosine and/or its metabolites were excreted into the milk of lactating rats. It is not known if didanosine is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving didanosine.

Pediatric Use

Use of didanosine in pediatric patients from 2 weeks of age through adolescence is supported by evidence from adequate and well-controlled studies of Videx in adult and pediatric patients [see Dosage and Administration (2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

Geriatric Use

In an Expanded Access Program for patients with advanced HIV infection, patients aged 65 years and older had a higher frequency of pancreatitis (10%) than younger patients (5%) [see Warnings and Precautions (5.1)]. Clinical studies of didanosine did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently than younger subjects. Didanosine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. In addition, renal function should be monitored and dosage adjustments should be made accordingly [see Dosage and Administration (2.2)].

Renal Impairment

Patients with renal impairment (creatinine clearance of less than 60 mL/min) may be at greater risk of toxicity from didanosine due to decreased drug clearance [see Clinical Pharmacology (12.3)]. A dose reduction is recommended for these patients [see Dosage and Administration (2)].

Overdosage

There is no known antidote for Videx (didanosine) overdosage. In phase 1 studies, in which Videx was initially administered at doses ten times the currently recommended dose, toxicities included: pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia, and hepatic dysfunction. Didanosine is not dialyzable by peritoneal dialysis, although there is some clearance by hemodialysis [see Clinical Pharmacology (12.3)].

Videx Description

Videx® is a brand name for didanosine, USP, a synthetic purine nucleoside analogue active against HIV-1.

Didanosine is available as Videx, a Pediatric Powder for Oral Solution [see How Supplied/Storage and Handling (16)] and as Videx® EC Delayed-Release Capsules, containing enteric-coated beadlets [consult prescribing information for Videx EC (didanosine)].

The chemical name for didanosine is 2?,3?-dideoxyinosine. The structural formula is:

Didanosine is a white crystalline powder with the molecular formula C10H12N4O3 and a molecular weight of 236.2. The aqueous solubility of didanosine at 25° C and pH of approximately 6 is 27.3 mg/mL. Didanosine is unstable in acidic solutions. For example, at pH less than 3 and 37° C, 10% of didanosine decomposes to hypoxanthine in less than 2 minutes.

Videx - Clinical Pharmacology Mechanism of Action

Didanosine is an antiviral agent [see Clinical Pharmacology (12.4)].

Pharmacokinetics

The pharmacokinetic parameters of didanosine are summarized in Table 10. Didanosine is rapidly absorbed, with peak plasma concentrations generally observed from 0.25 to 1.50 hours following oral dosing. Increases in plasma didanosine concentrations were dos


More




Sanctura XR


Generic Name: trospium (tros PEE um)
Brand Names: Sanctura, Sanctura XR

What is Sanctura XR (trospium)?

Trospium relieves spasms of the bladder.

Trospium is used to treat overactive bladder and symptoms of urinary incontinence, frequency, and urgency.

Trospium may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Sanctura XR (trospium)? You should not take this medicine if you are allergic to trospium, or if you have untreated or uncontrolled narrow-angle glaucoma, a blockage in your digestive system, or if you are unable to urinate. Take trospium on an empty stomach, at least 1 hour before a meal. Avoid drinking alcohol within 2 hours before or after you take trospium. Drinking alcohol can increase certain side effects of trospium.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Trospium can decrease sweating, which makes it easier for you to have heat stroke. Drink plenty of fluids while you are taking this medication.

Before using trospium, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by trospium. What should I discuss with my healthcare provider before taking Sanctura XR (trospium)? You should not use trospium if you are allergic to it, or if you have:

untreated or uncontrolled narrow-angle glaucoma;

a blockage in your digestive system; or

if you are unable to urinate.

FDA pregnancy category C. It is not known whether trospium will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

To make sure you can safely take trospium, tell your doctor if you have any of these other conditions:

glaucoma;

liver disease;

kidney disease;

a stomach or intestinal disorder such as ulcerative colitis;

a muscle disorder such as myasthenia gravis; or

an enlarged prostate.

It is not known whether trospium passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Older adults may be more likely to have side effects from this medicine.

How should I take Sanctura XR (trospium)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take trospium on an empty stomach, at least 1 hour before a meal. Extended-release trospium (Sanctura XR) should be taken once each morning, at least 1 hour before a meal. Do not crush, chew, break, or open an extended-release capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time. Store at room temperature away from moisture and heat. What happens if I miss a dose?

Take the missed dose 1 hour before your next meal. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking Sanctura XR (trospium)? This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly. Avoid drinking alcohol within 2 hours before or after you take trospium. Drinking alcohol can increase certain side effects of trospium.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Trospium can decrease sweating, which makes it easier for you to have heat stroke. Drink plenty of fluids while you are taking this medication.

Sanctura XR (trospium) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using trospium and call your doctor at once if you have a serious side effect such as:

severe stomach pain or bloating;

severe constipation; or

urinating less than usual or not at all.

Less serious side effects may include:

dry mouth or throat;

headache;

mild constipation;

upset stomach, gas;

drowsiness, or

dry eyes.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Sanctura XR (trospium)? Before using trospium, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by trospium.

Tell your doctor about all other medicines you use, especially:

atropine (Atreza, Sal-Tropine, and others);

belladonna (Donnatal, and others);

benztropine (Cogentin);

dicyclomine (Bentyl);

dimenhydrinate (Dramamine);

metformin (Actoplus Met, Avandamet, Glucophage, Glucovance, Janumet, Kombiglyze, Metaglip, PrandiMet);

morphine (Kadian, MS Contin, Oramorph);

procainamide (Procanbid, Pronestyl);

tenofovir (Viread);

vancomycin (Vancocin);

bronchodilators such as ipratropium (Atrovent) or tiotropium (Spiriva);

bladder or urinary medications such as darifenacin (Enablex), flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare);

irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Hyomax), or propantheline (Pro Banthine); or

ulcer medications such as glycopyrrolate (Robinul) or mepenzolate (Cantil).

This list is not complete and other drugs may interact with trospium. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Sanctura XR resources Sanctura XR Side Effects (in more detail) Sanctura XR Use in Pregnancy & Breastfeeding Sanctura XR Drug Interactions Sanctura XR Support Group 5 Reviews for Sanctura XR - Add your own review/rating Sanctura XR Extended-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer) Sanctura XR Prescribing Information (FDA) Sanctura Prescribing Information (FDA) Sanctura Monograph (AHFS DI) Sanctura Advanced Consumer (Micromedex) - Includes Dosage Information Sanctura MedFacts Consumer Leaflet (Wolters Kluwer) Sanctura Consumer Overview Compare Sanctura XR with other medications Interstitial Cystitis Overactive Bladder Urinary Incontinence Where can I get more information? Your pharmacist can provide more information about trospium.

See also: Sanctura XR side effects (in more detail)


More




icodextrin LVP solution


Generic Name: icodextrin (LVP solution) (EYE koe dex trin (LVP soe LOO tion))
Brand Names: Extraneal

What is icodextrin (LVP solution)?

Icodextrin is a dialysis solution that draws fluid and wastes from your bloodstream into your peritoneal cavity (the space around the organs in your abdomen). These fluids and wastes are removed when the dialysis solution is drained.

Icodextrin is used in peritoneal dialysis that lasts 8 hours or longer (also called the long dwell exchange).

Icodextrin may also be used for purposes not listed in this medication guide.

What is the most important information I should know about icodextrin (LVP solution)? If you have diabetes and you test your blood sugar using a glucose monitor and test strips, ask a doctor or pharmacist about the best type to use. Certain glucose monitors and test strips must not be used while you are being treated with icodextrin. Tell any doctor who treats you that you are using icodextrin. You should not use this medication if you are allergic to icodextrin or cornstarch, or if you have maltose or isomaltose intolerance, severe lactic acidosis, or a glycogen storage disease (an inherited metabolic disorder). Before using icodextrin, tell your doctor if any of the following conditions have recently affected your stomach area: surgery, tumors, hernia, infection, or open wounds.

Also tell your doctor about all of your medical conditions and about all other medicines you use.

Drink plenty of liquids while you are using icodextrin. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough. What should I discuss with my healthcare provider before using icodextrin (LVP solution)? You should not use this medication if you are allergic to icodextrin or cornstarch, or if you have:

maltose or isomaltose intolerance;

severe lactic acidosis; or

a glycogen storage disease (an inherited metabolic disorder).

If you have diabetes and you test your blood sugar using a glucose monitor and test strips, ask a doctor or pharmacist about the best type to use. Certain glucose monitors and test strips must not be used while you are being treated with icodextrin. Tell any doctor who treats you that you are using icodextrin. Before using icodextrin, tell your doctor if any of the following conditions have recently affected your stomach area: surgery, tumors, hernia, infection, or open wounds.

To make sure you can safely use icodextrin, tell your doctor if you have any of these other conditions:

a breathing disorder;

an electrolyte imbalance (such as low levels of potassium or magnesium in your blood;)

high levels of calcium in your blood;

high blood pressure, congestive heart failure;

a stomach or intestinal condition such as inflammatory bowel disease, diverticulitis, or if you have a colostomy or ileostomy;

if you are malnourished or cannot eat; or

if you have recently had aortic graft surgery.

FDA pregnancy category C. It is not known whether icodextrin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether icodextrin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How is icodextrin (LVP solution) given?

Icodextrin is used in peritoneal dialysis during the long dwell exchange (8 to 16 hours). Icodextrin is given during the night-time exchange if you are on continuous peritoneal dialysis. Icodextrin is given during the daytime exchange if you are using automated peritoneal dialysis (a cycler).

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Prepare your dose only when you are ready to give the medicine.

You may warm the medication with a heating pad to make it more comfortable to use during dialysis. Do not heat icodextrin with hot water or in a microwave. High heat can ruin the medicine.

Do not use the medication if it looks cloudy or has particles in it. Call your doctor for a new prescription. Drink plenty of liquids while you are using icodextrin. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

You will need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly.

Store at room temperature away from moisture and heat. Do not freeze. Keep the medicine in its moisture-proof pouch until you are ready to prepare your dose.

Throw away any unused icodextrin after the expiration date on the label has passed.

What happens if I miss a dose?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Do not use icodextrin more than once in a 24 hour period. What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Using too much icodextrin can cause swelling or puffiness in your stomach, feeling of fullness, feeling short of breath. Drain the solution from your peritoneal cavity if you have any of these symptoms.

What should I avoid while using icodextrin (LVP solution)?

Avoid becoming dehydrated (heavy sweating, hot and dry skin, feeling very thirsty or hot, being unable to urinate). Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Icodextrin (LVP solution) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using icodextrin and call your doctor at once if you have a serious side effect such as:

fever, stomach pain, redness, or cloudy drained fluid;

flu symptoms;

chest pain;

high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss); or

severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects may include:

mild stomach pain, nausea;

headache; or

new or worsening cough.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect icodextrin (LVP solution)?

Tell your doctor about all other medicines you use, especially:

adefovir (Hepsera);

blood pressure medication;

digoxin (Lanoxin, Lanoxicaps);

entecavir (Baraclude);

insulin;

metformin (Glucophage, Actoplus Met, Avandamet, Glucovance, Janumet, Kombiglyze, Metaglip, PrandiMet); or

HIV or AIDS medications such as abacavir (Ziagen), didanosine (Videx), emtricitabine (Atripla, Emtriva), lamivudine (Combivir, Epzicom), stavudine (Zerit), tenofovir (Truvada, Viread), or zidovudine (Retrovir, Trizivir).

There may be other drugs that can interact with icodextrin. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More icodextrin resources Icodextrin Support Group 0 Reviews for Icodextrin - Add your own review/rating Compare icodextrin with other medications Fluid Retention Where can I get more information? Your pharmacist can provide more information about icodextrin (LVP solution).


More




Trospium Extended-Release Capsules


Pronunciation: TROSE-pee-um
Generic Name: Trospium
Brand Name: Sanctura XR
Trospium Extended-Release Capsules are used for:

Treating overactive bladder with symptoms such as urinary incontinence, urgency, and frequency.

Trospium Extended-Release Capsules are an antispasmodic and antimuscarinic agent. It works by reducing muscle tone of the bladder, which decreases urinary spasm and frequency.

Do NOT use Trospium Extended-Release Capsules if: you are allergic to any ingredient in Trospium Extended-Release Capsules you have delayed or slow emptying of the stomach or uncontrolled narrow-angle glaucoma, you are unable to urinate, or you are at risk of developing these conditions you have severe kidney problems you are taking a solid oral potassium product (eg, tablet)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Trospium Extended-Release Capsules:

Some medical conditions may interact with Trospium Extended-Release Capsules. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you use alcohol or have a history of alcohol abuse if you have liver or kidney problems, or glaucoma or increased pressure in the eye if you have stomach or bowel problems (eg, inflammation, constipation, blockage, problems with the muscles in your intestines), myasthenia gravis, bladder blockage, or trouble urinating

Some MEDICINES MAY INTERACT with Trospium Extended-Release Capsules. Tell your health care provider if you are taking any other medicines, especially any of the following:

Solid oral potassium products (eg, tablets) because the risk of stomach or bowel irritation may be increased by Trospium Extended-Release Capsules Anticholinergic medicines (eg, scopolamine), metformin, morphine, procainamide, tenofovir, or vancomycin because they may increase the risk of Trospium Extended-Release Capsules's side effects Phenothiazines (eg, thioridazine) because their effectiveness may be decreased by Trospium Extended-Release Capsules

This may not be a complete list of all interactions that may occur. Ask your health care provider if Trospium Extended-Release Capsules may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Trospium Extended-Release Capsules:

Use Trospium Extended-Release Capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

An extra patient leaflet is available with Trospium Extended-Release Capsules. Talk to your pharmacist if you have questions about this information. Take Trospium Extended-Release Capsules by mouth with water on an empty stomach at least 1 hour before eating, preferably in the morning or as directed by your doctor. If you miss a dose of Trospium Extended-Release Capsules, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Trospium Extended-Release Capsules.

Important safety information: Trospium Extended-Release Capsules may cause drowsiness or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Trospium Extended-Release Capsules with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it. Do not drink alcohol within 2 hours before or after you take Trospium Extended-Release Capsules. Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Trospium Extended-Release Capsules; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness. Trospium Extended-Release Capsules may cause dry mouth. To relieve dry mouth, suck on sugarless hard candy or ice chips, chew sugarless gum, drink water, or use a saliva substitute. Do not become overheated in hot weather or while you are being active; heatstroke may occur. Tell your doctor or dentist that you take Trospium Extended-Release Capsules before you receive any medical or dental care, emergency care, or surgery. A severe and sometimes life-threatening side effect called angioedema has been reported with Trospium Extended-Release Capsules. Contact your doctor at once if you develop swelling of the hands, face, lips, eyes, throat, or tongue; difficulty swallowing or breathing; or hoarseness. Use Trospium Extended-Release Capsules with caution in the ELDERLY; they may be more sensitive to its effects, especially dry mouth, constipation, stomach pain or upset, and trouble urinating. Trospium Extended-Release Capsules should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Trospium Extended-Release Capsules while you are pregnant. It is not known if Trospium Extended-Release Capsules are found in breast milk. If you are or will be breast-feeding while you take Trospium Extended-Release Capsules, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Trospium Extended-Release Capsules:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; dry mouth or eyes; gas; nasal dryness; nausea; upset stomach.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty swallowing or breathing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue; unusual hoarseness); chest pain; dark urine; difficulty urinating; fainting; fast or irregular heartbeat; hallucinations; mental or mood changes; muscle pain or weakness; red, swollen, peeling, or blistered skin; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Trospium side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center ( http://www.aapcc.org), or emergency room immediately. Symptoms may include fast or irregular heartbeat.

Proper storage of Trospium Extended-Release Capsules:

Store Trospium Extended-Release Capsules at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Trospium Extended-Release Capsules out of the reach of children and away from pets.

General information: If you have any questions about Trospium Extended-Release Capsules, please talk with your doctor, pharmacist, or other health care provider. Trospium Extended-Release Capsules are to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Trospium Extended-Release Capsules. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Trospium resources Trospium Side Effects (in more detail) Trospium Dosage Trospium Use in Pregnancy & Breastfeeding Drug Images Trospium Drug Interactions Trospium Support Group 17 Reviews for Trospium - Add your own review/rating Compare Trospium with other medications Interstitial Cystitis Overactive Bladder Urinary Incontinence


More




Kaletra 80mg / 20mg Oral Solution


1. Name Of The Medicinal Product

Kaletra (80 mg + 20 mg) / ml oral solution

2. Qualitative And Quantitative Composition

Each 5 ml of Kaletra oral solution contains 400 mg of lopinavir co-formulated with 100 mg of ritonavir as a pharmacokinetic enhancer.

Excipients:

Each 5 ml contains 356.3 mg of alcohol (42% v/v), 168.6 mg of high fructose corn syrup, 152.7 mg of propylene glycol (see section 4.3), 10.2 mg of polyoxyl 40 hydrogenated castor oil and 4.1 mg of acesulfame potassium (see section 4.4).

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Oral solution

The solution is light yellow to golden.

4. Clinical Particulars 4.1 Therapeutic Indications

Kaletra is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infected adults, adolescents and children above the age of 2 years.

The choice of Kaletra to treat protease inhibitor experienced HIV-1 infected patients should be based on individual viral resistance testing and treatment history of patients (see sections 4.4 and 5.1).

4.2 Posology And Method Of Administration

Kaletra should be prescribed by physicians who are experienced in the treatment of HIV infection.

Posology

Adult and adolescent use: the recommended dosage of Kaletra is 5 ml of oral solution (400/100 mg) twice daily taken with food.

Paediatric use (2 years of age and above): the recommended dosage of Kaletra is 230/57.5 mg/m2 twice daily taken with food, up to a maximum dose of 400/100 mg twice daily. The 230/57.5 mg/m2 dosage might be insufficient in some children when co-administered with nevirapine or efavirenz. An increase of the dose of Kaletra to 300/75 mg/m2 should be considered in these patients. Dose should be administered using a calibrated oral dosing syringe.

The oral solution is the recommended option for the most accurate dosing in children based on body surface area. However, if it is judged necessary to resort to soft capsules in children, they should be used with particular caution since they are associated with less precise dosing capabilities. Therefore, children receiving soft capsules might have higher exposure (with the risk of increased toxicity) or suboptimal exposure (with the risk of insufficient efficacy). Consequently when dosing children with soft capsules, therapeutic drug monitoring may be a useful tool to ensure appropriate lopinavir exposure in an individual patient.

Paediatric dosing guidelines for the dose 230/57.5 mg/m2

   

Body Surface Area* (m2)

Twice daily oral solution dose (dose in mg)

Twice daily soft capsule dose (dose in mg)

0.25

0.7 ml (57.5/14.4 mg)

NA

0.40

1.2 ml (96/24 mg)

1 soft capsule (133.3/33.3 mg)

0.50

1.4 ml (115/28.8 mg)

1 soft capsule (133.3/33.3 mg)

0.75

2.2 ml (172.5/43.1 mg)

1 soft capsule (133.3/33.3 mg)

0.80

2.3 ml (184/46 mg)

2 soft capsules (266.6/66.6 mg)

1.00

2.9 ml (230/57.5 mg)

2 soft capsules (266.6/66.6 mg)

1.25

3.6 ml (287.5/71.9 mg)

2 soft capsules (266.6/66.6 mg)

1.3

3.7 ml (299/74.8 mg)

2 soft capsules (266.6/66.6 mg)

1.4

4.0 ml (322/80.5 mg)

3 soft capsules (400/100 mg)

1.5

4.3 ml (345/86.3 mg)

3 soft capsules (400/100 mg)

1.7

5 ml (402.5/100.6 mg)

3 soft capsules (400/100 mg)

* Body surface area can be calculated with the following equation

BSA (m2) = ? (Height (cm) X Weight (kg) / 3600)

Children less than 2 years of age: the safety and efficacy of Kaletra in children aged less than 2 years have not yet been established. Currently available data are described in section 5.2 but no recommendation on the posology can be made.

Hepatic impairment: In HIV-infected patients with mild to moderate hepatic impairment, an increase of approximately 30% in lopinavir exposure has been observed but is not expected to be of clinical relevance. (see section 5.2). No data are available in patients with severe hepatic impairment. Kaletra must not be given to these patients (see section 4.3).

Renal impairment: since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment. Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis.

Method of administration

Kaletra is administered orally and should always be taken with food (see section 5.2).

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients.

Severe hepatic insufficiency.

Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A. Kaletra should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life threatening events. These medicinal products include astemizole, terfenadine, oral midazolam (for caution on parenterally administered midazolam, see section 4.5), triazolam, cisapride, pimozide, amiodarone, ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergonovine and methylergonovine) lovastatin, simvastatin, sildenafil used for the treatment of pulmonary arterial hypertension (for the use of sildenafil in patients with erectile dysfunction, see section 4.5) and vardenafil.

Herbal preparations containing St John's wort (Hypericum perforatum) must not be used while taking lopinavir and ritonavir due to the risk of decreased plasma concentrations and reduced clinical effects of lopinavir and ritonavir (see section 4.5).

Kaletra oral solution is contraindicated in children below the age of 2 years, pregnant women, patients with hepatic or renal failure and patients treated with disulfiram or metronidazole due to the potential risk of toxicity from the excipient propylene glycol (see section 4.4).

4.4 Special Warnings And Precautions For Use

Patients with coexisting conditions

Hepatic impairment: the safety and efficacy of Kaletra has not been established in patients with significant underlying liver disorders. Kaletra is contraindicated in patients with severe liver impairment (see section 4.3). Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions. In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products.

Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered.

Elevated transaminases with or without elevated bilirubin levels have been reported in HIV-1 mono-infected and in individuals treated for post-exposure prophylaxis as early as 7 days after the initiation of lopinavir/ritonavir in conjunction with other antiretroviral agents. In some cases the hepatic dysfunction was serious.

Appropriate laboratory testing should be conducted prior to initiating therapy with lopinavir/ritonavir and close monitoring should be performed during treatment.

Renal impairment: since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment. Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis.

Haemophilia: there have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis in patients with haemophilia type A and B treated with protease inhibitors. In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship had been evoked, although the mechanism of action had not been elucidated. Haemophiliac patients should therefore be made aware of the possibility of increased bleeding.

Lipid elevations

Treatment with Kaletra has resulted in increases, sometimes marked, in the concentration of total cholesterol and triglycerides. Triglyceride and cholesterol testing is to be performed prior to initiating Kaletra therapy and at periodic intervals during therapy. Particular caution should be paid to patients with high values at baseline and with history of lipid disorders. Lipid disorders are to be managed as clinically appropriate (see also section 4.5 for additional information on potential interactions with HMG-CoA reductase inhibitors).

Pancreatitis

Cases of pancreatitis have been reported in patients receiving Kaletra, including those who developed hypertriglyceridaemia. In most of these cases patients have had a prior history of pancreatitis and/or concurrent therapy with other medicinal products associated with pancreatitis. Marked triglyceride elevation is a risk factor for development of pancreatitis. Patients with advanced HIV disease may be at risk of elevated triglycerides and pancreatitis.

Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should occur. Patients who exhibit these signs or symptoms should be evaluated and Kaletra therapy should be suspended if a diagnosis of pancreatitis is made (see section 4.8).

Hyperglycaemia

New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors. In some of these the hyperglycaemia was severe and in some cases also associated with ketoacidosis. Many patients had confounding medical conditions some of which required therapy with agents that have been associated with the development of diabetes mellitus or hyperglycaemia.

Fat redistribution & metabolic disorders

Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients. The long-term consequences of these events are currently unknown. Knowledge about the mechanism is incomplete. A connection between visceral lipomatosis and protease inhibitors (PIs) and lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs) has been hypothesised. A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances. Clinical examination should include evaluation for physical signs of fat redistribution. Consideration should be given to measurement of fasting serum lipids and blood glucose. Lipid disorders should be managed as clinically appropriate (see section 4.8).

Immune Reactivation Syndrome

In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jiroveci pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary.

Osteonecrosis

Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

PR interval prolongation

Lopinavir/ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects. Rare reports of 2nd or 3rd degree atroventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving drugs known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving lopinavir/ritonavir. Kaletra should be used with caution in such patients (see section 5.1).

Interactions with medicinal products

Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A. Kaletra is likely to increase plasma concentrations of medicinal products that are primarily metabolised by CYP3A. These increases of plasma concentrations of co-administered medicinal products could increase or prolong their therapeutic effect and adverse events (see sections 4.3 and 4.5).

The combination of Kaletra with atorvastatin is not recommended. If the use of atorvastatin is considered strictly necessary, the lowest possible dose of atorvastatin should be administered with careful safety monitoring. Caution must also be exercised and reduced doses should be considered if Kaletra is used concurrently with rosuvastatin. If treatment with an HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended (see section 4.5).

PDE5 inhibitors: particular caution should be used when prescribing sildenafil or tadalafil for the treatment of erectile dysfunction in patients receiving Kaletra. Co-administration of Kaletra with these medicinal products is expected to substantially increase their concentrations and may result in associated adverse events such as hypotension, syncope, visual changes and prolonged erection (see section 4.5). Concomitant use of vardenafil and lopinavir/ritonavir is contraindicated (see section 4.3). Concomitant use of sildenafil prescribed for the treatment of pulmonary arterial hypertension with Kaletra is contraindicated (see section 4.3).

Particular caution must be used when prescribing Kaletra and medicinal products known to induce QT interval prolongation such as: chlorpheniramine, quinidine, erythromycin, clarithromycin. Indeed, Kaletra could increase concentrations of the co-administered medicinal products and this may result in an increase of their associated cardiac adverse reactions. Cardiac events have been reported with Kaletra in preclinical studies; therefore, the potential cardiac effects of Kaletra cannot be currently ruled out (see sections 4.8 and 5.3).

Co-administration of Kaletra with rifampicin is not recommended. Rifampicin in combination with Kaletra causes large decreases in lopinavir concentrations which may in turn significantly decrease the lopinavir therapeutic effect. Adequate exposure to lopinavir/ritonavir may be achieved when a higher dose of Kaletra is used but this is associated with a higher risk of liver and gastrointestinal toxicity. Therefore, this co-administration should be avoided unless judged strictly necessary (see section 4.5).

Concomitant use of Kaletra and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression (see section 4.5).

Other

Patients taking the oral solution, particularly those with renal impairment or with decreased ability to metabolise propylene glycol (e.g. those of Asian origin), should be monitored for adverse reactions potentially related to propylene glycol toxicity (i.e. seizures, stupor, tachycardia, hyperosmolarity, lactic acidosis, renal toxicity, haemolysis) (see section 4.3).

Kaletra is not a cure for HIV infection or AIDS. It does not reduce the risk of passing HIV to others through sexual contact or contamination with blood. Appropriate precautions should be taken. People taking Kaletra may still develop infections or other illnesses associated with HIV disease and AIDS.

Besides propylene glycol as described above, Kaletra oral solution contains alcohol (42% v/v) which is potentially harmful for those suffering from liver disease, alcoholism, epilepsy, brain injury or disease as well as for pregnant women and children. It may modify or increase the effects of other medicines. Kaletra oral solution contains up to 0.8 g of fructose per dose when taken according to the dosage recommendations. This may be unsuitable in hereditary fructose intolerance. Kaletra oral solution contains up to 0.3 g of glycerol per dose. Only at high inadvertent doses, it can cause headache and gastrointestinal upset. Furthermore, polyoxol 40 hydrogenated castor oil and potassium present in Kaletra oral solution may cause only at high inadvertent doses gastrointestinal upset. Patients on a low potassium diet should be cautioned.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A in vitro. Co-administration of Kaletra and medicinal products primarily metabolised by CYP3A may result in increased plasma concentrations of the other medicinal product, which could increase or prolong its therapeutic and adverse reactions. Kaletra does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 or CYP1A2 at clinically relevant concentrations (see section 4.3).

Kaletra has been shown in vivo to induce its own metabolism and to increase the biotransformation of some medicinal products metabolised by cytochrome P450 enzymes (including CYP2C9 and CYP2C19) and by glucuronidation. This may result in lowered plasma concentrations and potential decrease of efficacy of co-administered medicinal products.

Medicinal products that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events are listed in section 4.3.

Known and theoretical interactions with selected antiretrovirals and non-antiretroviral medicinal products are listed in the table below.

Interaction table

Interactions between Kaletra and co-administered medicinal products are listed in the table below (increase is indicated as “?”, decrease as “

Unless otherwise stated, studies detailed below have been performed with the recommended dosage of lopinavir/ritonavir (i.e. 400/100 mg twice daily).

Co-administered drug by therapeutic Area

Effects on drug levels

Geometric Mean Change (%) in AUC, Cmax, Cmin

Mechanism of interaction

Clinical recommendation concerning co-administration with Kaletra

Antiretroviral Agents

   

Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTIs)

   

Stavudine, Lamivudine

Lopinavir: ?

No dose adjustment necessary.

Abacavir, Zidovudine

Abacavir, Zidovudine:

Concentrations may be reduced due to increased glucuronidation by Kaletra.

The clinical significance of reduced abacavir and zidovudine concentrations is unknown.

Tenofovir, 300 mg QD

Tenofovir:

AUC: ? 32%

Cmax: ?

Cmin: ? 51%

Lopinavir: ?

No dose adjustment necessary.

Higher tenofovir concentrations could potentiate tenofovir associated adverse events, including renal disorders.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

   

Efavirenz, 600 mg QD

Lopinavir:

AUC:

Cmax:

Cmin:

The Kaletra tablets dosage should be increased to 500/125 mg twice daily when co-administered with efavirenz.

Efavirenz, 600 mg QD

(Lopinavir/ritonavir 500/125 mg BID)

Lopinavir: ?

(Relative to 400/100 mg BID administered alone)

 

Nevirapine, 200 mg BID

Lopinavir:

AUC:

Cmax:

Cmin:

The Kaletra tablets dosage should be increased to 500/125 mg twice daily when co-administered with nevirapine.

Co-administration with other HIV protease inhibitors (PIs)

According to current treatment guidelines, dual therapy with protease inhibitors is generally not recommended.

   

Fosamprenavir/ritonavir (700/100 mg BID)

(Lopinavir/ritonavir 400/100 mg BID)

or

Fosamprenavir (1400 mg BID)

(Lopinavir/ritonavir 533/133 mg BID)

Fosamprenavir:

Amprenavir concentrations are significantly reduced.

Co-administration of increased doses of fosamprenavir (1400 mg BID) with lopinavir/ritonavir (533/133 mg BID) to protease inhibitor-experienced patients resulted in a higher incidence of gastrointestinal adverse events and elevations in triglycerides with the combination regimen without increases in virological efficacy, when compared with standard doses of fosamprenavir/ritonavir. Concomitant administration of these medicinal products is not recommended.

Indinavir, 600 mg BID

Indinavir:

AUC: ?

Cmin: ? 3.5-fold

Cmax:

(relative to indinavir 800 mg TID alone)

Lopinavir: ?

(relative to historical comparison)

The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

Nelfinavir

Lopinavir:

Concentrations

The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

Saquinavir 1000 mg BID

Saquinavir: ?

No dose adjustment necessary.

Tipranavir/ritonavir (500/100 mg BID)

Lopinavir:

AUC:

Cmin:

Cmax:

Concomitant administration of these medicinal products is not recommended.

Acid reducing agents

   

Omeprazole (40 mg QD)

Omeprazole: ?

Lopinavir: ?

No dose adjustment necessary

Ranitidine (150 mg single dose)

Ranitidine: ?

No dose adjustment necessary

Analgesics

   

Fentanyl

Fentanyl:

Increased risk of side-effects (respiratory depression, sedation) due to higher plasma concentrations because of CYP3A4 inhibition by Kaletra

Careful monitoring of adverse effects (notably respiratory depression but also sedation) is recommended when fentanyl is concomitantly administered with Kaletra.

Antiarrhythmics

   

Digoxin

Digoxin:

Plasma concentrations may be increased due to P-glycoprotein inhibition by Kaletra. The increased digoxin level may lessen over time as Pgp induction develops.

Caution is warranted and therapeutic drug monitoring of digoxin concentrations, if available, is recommended in case of co-administration of Kaletra and digoxin. Particular caution should be used when prescribing Kaletra in patients taking digoxin as the acute inhibitory effect of ritonavir on Pgp is expected to significantly increase digoxin levels. Initiation of digoxin in patients already taking Kaletra is likely to result in lower than expected increases of digoxin concentrations.

Bepridil, Systemic Lidocaine, and Quinidine

Bepridil, Systemic Lidocaine, Quinidine:

Concentrations may be increased when co-administered with Kaletra.

Caution is warranted and therapeutic drug concentration monitoring is recommended when available.

Antibiotics

   

Clarithromycin

Clarithromycin:

Moderate increases in clarithromycin AUC are expected due to CYP3A inhibition by Kaletra.

For patients with renal impairment (CrCL <30 ml/min) dose reduction of clarithromycin should be considered (see section 4.4). Caution should be exercised in administering clarithromycin with Kaletra to patients with impaired hepatic or renal function.

Anticancer agents

   

Most tyrosine kinase inhibitors such as dasatinib and nilotinib, Vincristine, Vinblastine

Most tyrosine kinase inhibitors such as dasatinib and nilotinib, also vincristine and vinblastine:

Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by Kaletra.

Careful monitoring of the tolerance of these anticancer agents.

Anticoagulants

   

Warfarin

Warfarin:

Concentrations may be affected when co-administered with Kaletra due to CYP2C9 induction.

It is recommended that INR (international normalised ratio) be monitored.

Anticonvulsants

   

Phenytoin

Phenytoin:

Steady-state concentrations were moderately decreased due to CYP2C9 and CYP2C19 induction by Kaletra.

Lopinavir:

Concentrations are decreased due to CYP3A induction by phenytoin.

Caution should be exercised in administering phenytoin with Kaletra.

Phenytoin levels should be monitored when co-administering with lopinavir/ritonavir.

When co-administered with phenytoin, an increase of Kaletra dosage may be envisaged. Dose adjustment has not been evaluated in clinical practice.

Carbamazepine and Phenobarbital

Carbamazepine:

Serum concentrations may be increased due to CYP3A inhibition by Kaletra.

Lopinavir:

Concentrations may be decreased due to CYP3A induction by carbamazepine and phenobarbital.

Caution should be exercised in administering carbamazepine or phenobarbital with Kaletra.

Carbamazepine and phenobarbital levels should be monitored when co-administering with lopinavir/ritonavir.

When co-administered with carbamazepine or phenobarbital, an increase of Kaletra dosage may be envisaged. Dose adjustment has not been evaluated in clinical practice

Antidepressants and Anxiolytics

   

Trazodone single dose

(Ritonavir, 200 mg BID)

Trazodone:

AUC: ? 2.4-fold

Adverse events of nausea, dizziness, hypotension and syncope were observed following co-administration of trazodone and ritonavir.

It is unknown whether the combination of lopinavir/ritonavir causes a similar increase in trazodone exposure. The combination should be used with caution and a lower dose of trazodone should be considered.

Antifungals

   

Ketoconazole and Itraconazole

Ketoconazole, Itraconazole:

Serum concentrations may be increased due to CYP3A inhibition by Kaletra.

High doses of ketoconazole and itraconazole (> 200 mg/day) are not recommended.

Voriconazole

Voriconazole:

Concentrations may be decreased.

Co-administration of voriconazole and low dose ritonavir (100 mg BID) as contained in Kaletra should be avoided unless an assessment of the benefit/risk to patient justifies the use of voriconazole.

Antimycobacterials

   

Rifabutin, 150 mg QD

Rifabutin (parent drug and active 25-O-desacetyl metabolite):

AUC: ? 5.7-fold

Cmax: ? 3.5-fold

When given with Kaletra the recommended dose of rifabutin is 150 mg 3 times per week on set days (for example Monday-Wednesday-Friday). Increased monitoring for rifabutin-associated adverse reactions including neutropenia and uveitis is warranted due to an expected increase in exposure to rifabutin. Further dosage reduction of rifabutin to 150 mg twice weekly on set days is recommended for patients in whom the 150 mg dose 3 times per week is not tolerated. It should be kept in mind that the twice weekly dosage of 150 mg may not provide an optimal exposure to rifabutin thus leading to a risk of rifamycin resistance and a treatment failure. No dose adjustment is needed for Kaletra.

Rifampicin

Lopinavir:

Large decreases in lopinavir concentrations may be observed due to CYP3A induction by rifampicin.

Co-administration of Kaletra with rifampicin is not recommended as the decrease in lopinavir concentrations may in turn significantly decrease the lopinavir therapeutic effect A dose adjustment of Kaletra 400 mg/400 mg (i.e. Kaletra 400/100 mg + ritonavir 300 mg) twice daily has allowed compensating for the CYP 3A4 inducer effect of rifampicin. However, such a dose adjustment might be associated with ALT/AST elevations and with increase in gastrointestinal disorders. Therefore, this co-administration should be avoided unless judged strictly necessary. If this co-administration is judged unavoidable, increased dose of Kaletra at 400 mg/400 mg twice daily may be administered with rifampicin under close safety and therapeutic drug monitoring. The Kaletra dose should be titrated upward only after rifampicin has been initiated (see section 4.4).

Benzodiazepines

   

Midazolam

Oral Midazolam:

AUC: ? 13-fold

Parenteral Midazolam:

AUC: ? 4-fold

Due to CYP3A inhibition by Kaletra

Kaletra must not be co-administered with oral midazolam (see section 4.3), whereas caution should be used with co-administration of Kaletra and parenteral midazolam. If Kaletra is co-administered with parenteral midazolam, it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage adjustment for midazolam should be considered especially if more than a single dose of midazolam is administered.

Calcium channel blockers

   

Felodipine, Nifedipine, and Nicardipine

Felodipine, Nifedipine, Nicardipine:

Concentrations may be increased due to CYP3A inhibition by Kaletra.

Clinical monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with Kaletra.

Corticosteroids

   

Dexamethasone

Lopinavir:

Concentrations may be decreased due to CYP3A induction by dexamethasone.

Clinical monitoring of antiviral efficacy is recommended when these medicines are concomitantly administered with Kaletra.

Fluticasone propionate, 50 ?g intranasal 4 times daily

(100 mg ritonavir BID)

Fluticasone propionate:

Plasma concentrations ?

Cortisol levels

Greater effects may be expected when fluticasone propionate is inhaled. Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway eg budesonide. Consequently, concomitant administration of Kaletra and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4). A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (eg beclomethasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.

Erectile Dysfunction, Phosphodiesterase(PDE5) inhibitors

   

Tadalafil

Tadalafil:

AUC: ? 2-fold

Due to CYP3A inhibition by Kaletra.

Particular caution must be used when prescribing sildenafil or tadalafil in patients receiving Kaletra with increased monitoring for adverse events including hypotension, syncope, visual changes and prolonged erection (see section


More




Videx EC


Generic Name: didanosine (dye DAN oh seen)
Brand Names: Videx, Videx EC

What is Videx EC (didanosine)?

Didanosine is an antiviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in your body.

Didanosine is used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). Didanosine is not a cure for HIV or AIDS.

Didanosine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Videx EC (didanosine)? Do not use didanosine if you are allergic to it. Do not take didanosine together with allopurinol (Zyloprim) or ribavirin (Rebetol, Ribasphere, Copegus Virazole).

There are many other medicines that can interact with didanosine. Tell your doctor about all medications you use.

Didanosine can cause life-threatening effects on your liver or pancreas. Call your doctor at once if you have any of these symptoms: severe pain in your upper stomach spreading to your back, swelling around your stomach, feeling of fullness, feeling short of breath, coughing up blood, fast heart rate, nausea and vomiting, loss of appetite, low fever, dark urine or stools, or jaundice (yellowing of the skin or eyes). Do not take didanosine without telling your doctor if you are pregnant. Some people develop lactic acidosis while taking didanosine. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Taking this medication will not prevent you from passing HIV to other people. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. What should I discuss with my healthcare provider before taking Videx EC (didanosine)? Do not use didanosine if you are allergic to it. Do not take didanosine together with allopurinol (Zyloprim) or ribavirin (Rebetol, Ribasphere, Copegus Virazole). Didanosine can cause severe or life-threatening effects on your liver or pancreas.

If you have any of these conditions, you may need a dose adjustment or special tests:

liver disease; kidney disease (or if you are on dialysis);

a history of pancreatitis; or

a history of peripheral neuropathy (numbness or tingling in your hands or feet).

Some people develop a life-threatening condition called lactic acidosis while taking didanosine. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk. Do not take didanosine without telling your doctor if you are pregnant. Didanosine may be more likely to cause pancreatitis or liver problems in a pregnant woman.

HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of didanosine on the baby.

Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. How should I take Videx EC (didanosine)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take didanosine on an empty stomach, at least 1 hour before or 2 hours after a meal. Do not crush, chew, break, or open a delayed-release capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time. Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

HIV/AIDS is usually treated with a combination of different drugs. Certain HIV medications or antibiotics should not be taken at the same time as didanosine because they can affect the levels of this medicine in your blood stream:

ciprofloxacin (Cipro) should be taken at least 2 hours before or 6 hours after you take didanosine.

delavirdine (Rescriptor) or indinavir (Crixivan) should be taken at least 1 hour before you take didanosine.

nelfinavir (Viracept) should be taken at least 1 hour after you take didanosine.

itraconazole (Sporanox) or ketoconazole (Nizoral) should be taken at least 2 hours before you take didanosine.

Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your vision and liver function may also need to be tested. Visit your doctor regularly.

Store at room temperature in a tightly closed container, away from moisture and heat. Store the liquid form of didanosine in the refrigerator. Throw away any leftover didanosine liquid that is more than 30 days old. What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include some of the serious side effects listed in this medication guide.

What should I avoid while taking Videx EC (didanosine)? Do not drink alcohol. It may increase your risk of liver damage or pancreatitis.

Avoid using antacids without your doctor's advice while taking didanosine. Use only the specific type of antacid your doctor recommends.

Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. Videx EC (didanosine) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Didanosine may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as:

muscle pain or weakness;

numb or cold feeling in your arms and legs;

trouble breathing;

feeling dizzy, light-headed, tired, or very weak;

stomach pain, nausea with vomiting; or

fast or uneven heart rate.

Stop using didanosine and call your doctor at once if you have any of these other serious side effects:

liver damage - nausea, stomach pain, low fever, loss of appetite, dark urine or stools, jaundice (yellowing of the skin or eyes);

pancreatitis - severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

swelling around your stomach, feeling of fullness, feeling short of breath, coughing up blood;

numbness, tingling, or pain in your hands or feet;

pale skin, easy bruising or bleeding, feeling light-headed, rapid heart rate, trouble concentrating;

fever, chills, body aches, flu symptoms; or

any other signs of new infection.

Less serious side effects may include:

mild stomach pain, diarrhea;

headache;

mild rash; or

changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Videx EC (didanosine)?

Tell your doctor about all other medicines you use, especially:

ganciclovir (Cytovene);

hydroxyurea (Droxie, Hydrea);

methadone (Dolophine, Methadose);

stavudine (Zerit); or

tenofovir (Viread).

This list is not complete and there are many other drugs that can interact with didanosine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. More Videx EC resources Videx EC Side Effects (in more detail) Videx EC Use in Pregnancy & Breastfeeding Drug Images Videx EC Drug Interactions Videx EC Support Group 0 Reviews for Videx EC - Add your own review/rating Videx EC Prescribing Information (FDA) Videx EC Advanced Consumer (Micromedex) - Includes Dosage Information Videx EC Delayed-Release Enteric-Coated Capsules MedFacts Consumer Leaflet (Wolters Kluwer) Didanosine Prescribing Information (FDA) Didanosine Monograph (AHFS DI) Didanosine Professional Patient Advice (Wolters Kluwer) Didanosine Chewable/Dispersible Buffered Tablets MedFacts Consumer Leaflet (Wolters Kluwer) Videx Prescribing Information (FDA) Compare Videx EC with other medications HIV Infection Nonoccupational Exposure Where can I get more information? Your pharmacist can provide more information about didanosine.

See also: Videx EC side effects (in more detail)


More




Zerit


Generic Name: stavudine (STA vue deen)
Brand Names: Zerit

What is stavudine?

Stavudine is an antiviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in your body.

Stavudine is used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). Stavudine is not a cure for HIV or AIDS.

Stavudine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about stavudine? Some people have developed a life-threatening condition called lactic acidosis while taking stavudine. Early signs of lactic acidosis generally get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Stavudine can also cause severe or life-threatening effects on your liver or pancreas. Call your doctor at once if you have any of these symptoms while taking stavudine: severe pain in your upper stomach spreading to your back, fast heart rate, nausea and vomiting, diarrhea, loss of appetite, low fever, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). Before taking stavudine, tell your doctor if you have kidney disease, liver disease, a history of pancreatitis, or if you have used a medicine similar to stavudine in the past, such as abacavir (Ziagen), didanosine (Videx), lamivudine (Epivir), tenofovir (Viread), zalcitabine (Hivid), or zidovudine (Retrovir). What should I discuss with my healthcare provider before taking stavudine? Do not use this medication if you are allergic to stavudine.

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before taking stavudine, tell your doctor if you are allergic to any drugs, or if you have:

kidney disease; liver disease;

diabetes; or

a history of pancreatitis.

Some people have developed a life-threatening condition called lactic acidosis while taking stavudine. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken certain HIV or AIDS medications for a long time. Talk with your doctor about your individual risk. Stavudine can also cause severe or life-threatening effects on your liver or pancreas. Call your doctor at once if you have any of these symptoms while taking stavudine: severe pain in your upper stomach spreading to your back, fast heart rate, nausea and vomiting, diarrhea, loss of appetite, low fever, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). FDA pregnancy category C. It is not known whether this medication is harmful to an unborn baby. HIV can be passed to the baby if the mother is not properly treated during pregnancy. Stavudine may also be more likely to cause lactic acidosis in a pregnant woman. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Take all of your HIV medicines as directed to control your infection while you are pregnant.

Your name may need to be listed on an antiviral pregnancy registry when you start using stavudine. The purpose of this registry is to track the outcome of the pregnancy and delivery to evaluate whether stavudine had any effect on the baby.

You should not breast-feed while you are using stavudine. Women with HIV or AIDS should not breast-feed at all. Even if your baby is born without HIV, you may still pass the virus to the baby in your breast milk.

If you have diabetes, you should know that the liquid form of this medication contains 50 milligrams (mg) of sucrose (sugar) per milliliter (mL). This is equal to 250 milligrams of sugar per teaspoon (5 mL) of stavudine liquid.

How should I take stavudine?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Take stavudine with a full glass of water.

Stavudine can be taken with or without food.

Shake the oral suspension (liquid) well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

It is important to use stavudine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

HIV/AIDS is usually treated with a combination of different drugs. To best treat your condition, use all of your medications as directed by your doctor. Be sure to read the medication guide or patient instructions provided with each of your medications. Do not change your doses or medication schedule without advice from your doctor. Every person with HIV or AIDS should remain under the care of a doctor.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis. Your liver function may also need to be tested. Do not miss any visits to your doctor.

Store this medication at room temperature away from moisture and heat. Keep the bottle tightly closed. Keep the oral liquid in the refrigerator but do not let it freeze. Throw away any leftover medication after 30 days.

Throw away any unused or expired stavudine in a closed container or sealed bag. You may also ask your pharmacist where to locate a community pharmaceutical take-back disposal program.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include numbness, burning, pain, or tingly feeling, nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). What should I avoid while taking stavudine? Avoid drinking alcohol while taking stavudine. Alcohol may increase the risk of damage to the pancreas and/or liver.

Taking stavudine will not prevent you from passing HIV to other people through unprotected sex or sharing of needles. Talk with your doctor about safe methods of preventing HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Stavudine side effects Stop using stavudine and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these other serious side effects:

liver damage - nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

lactic acidosis - muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired;

pancreatitis - severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

peripheral neuropathy - numbness, tingling, or pain in your hands or feet;

high blood sugar - increased thirst, fruity breath odor, increased urination, drowsiness, dry skin, nausea, and vomiting; or

any signs of infection such as fever, chills, sore throat, flu symptoms, easy bruising or bleeding (nosebleeds, bleeding gums), mouth sores, or unusual weakness.

Less serious side effects may include:

diarrhea;

muscle pain;

headache;

mild skin rash; or

changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and trunk).

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect stavudine?

Before taking this medication, tell your doctor if you are using any of the following drugs:

didanosine (Videx);

doxorubicin (Adriamycin);

hydroxyurea (Droxia, Hydrea);

interferon-alfa (Roferon, Intron, Rebetron);

ribavirin (Rebetol, Ribasphere, Copegus Virazole); or

zidovudine (Retrovir).

This list is not complete and there may be other drugs that can interact with stavudine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Zerit resources Zerit Side Effects (in more detail) Zerit Use in Pregnancy & Breastfeeding Drug Images Zerit Drug Interactions Zerit Support Group 0 Reviews for Zerit - Add your own review/rating Zerit Prescribing Information (FDA) Zerit Monograph (AHFS DI) Zerit Advanced Consumer (Micromedex) - Includes Dosage Information Zerit Consumer Overview Zerit MedFacts Consumer Leaflet (Wolters Kluwer) Stavudine Professional Patient Advice (Wolters Kluwer) Compare Zerit with other medications HIV Infection Nonoccupational Exposure Where can I get more information? Your pharmacist can provide more information about stavudine.

See also: Zerit side effects (in more detail)


More




thioguanine


Generic Name: thioguanine (THYE oh GWA neen)
Brand Names: Tabloid

What is thioguanine?

Thioguanine is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Thioguanine is used to treat certain types of leukemia. Thioguanine is sometimes given with other cancer medications.

Thioguanine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about thioguanine? Do not use thioguanine if you are pregnant. It could harm the unborn baby. You should not use thioguanine if you are allergic to it, or if you have ever used thioguanine or mercaptopurine (Purinethol) and they were not effective in treating your condition.

Before taking thioguanine, tell your doctor if you have liver or kidney disease, or any type of infection.

Stop taking this medication and call your doctor at once if you have easy bruising or bleeding, fever, flu symptoms, mouth sores, dark urine, upper stomach pain, jaundice (yellowing of the skin or eyes), or ongoing diarrhea.

Thioguanine can lower blood cells that help your body fight infections. Your blood cells, kidney function, and liver function may need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Do not miss any follow up visits to your doctor for blood or urine tests.

What should I discuss with my healthcare provider before taking thioguanine? You should not use thioguanine if you are allergic to it, or if you have ever used thioguanine or mercaptopurine (Purinethol) and they were not effective in treating your condition.

To make sure you can safely take thioguanine, tell your doctor if you have any of these other conditions:

liver disease; kidney disease; or

any type of viral, bacterial, or fungal infection.

FDA pregnancy category D. Do not use thioguanine if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. It is not known whether thioguanine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking thioguanine. How should I take thioguanine?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Thioguanine can lower blood cells that help your body fight infections. Your blood cells, kidney function, and liver function may need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Do not miss any follow up visits to your doctor for blood or urine tests.

Store at room temperature away from moisture and heat.

See also: Thioguanine dosage (in more detail)

What happens if I miss a dose?

Contact your doctor if you miss a dose of thioguanine.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include some of the serious side effects listed in this medication guide.

What should I avoid while taking thioguanine?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a live vaccine while using thioguanine. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), oral polio, rotavirus, typhoid, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine. Thioguanine side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using thioguanine and call your doctor at once if you have any of these serious side effects:

pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

fever, chills, body aches, flu symptoms, sores or white patches in your mouth and throat;

easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

severe vomiting, ongoing diarrhea;

severe pain in your upper stomach spreading to your back, fast heart rate;

bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or

nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

vomiting, mild diarrhea;

hair loss;

mild itching or skin rash; or

darkened skin color.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Thioguanine Dosing Information

Usual Adult Dose for Acute Nonlymphocytic Leukemia:

Single Agent Chemotherapy: Usual Initial dose: 2 mg/kg/day orally.
If, after 4 weeks on this dosage, there is no clinical improvement and no leukocyte or platelet depression, the dosage may be cautiously increased to 3 mg/kg per day. The total daily dose may be given at one time.
As a part of combination therapy for induction of remission in patients with acute nonlymphocytic leukemia: 75 to 200 mg/m2/day in 1 to 2 divided doses for 5 to 7 days or until remission is attained.

Usual Geriatric Dose for Acute Nonlymphocytic Leukemia:

Single Agent Chemotherapy: Usual Initial dose: 2 mg/kg/day orally.
If, after 4 weeks on this dosage, there is no clinical improvement and no leukocyte or platelet depression, the dosage may be cautiously increased to 3 mg/kg per day. The total daily dose may be given at one time.
As a part of combination therapy for induction of remission in patients with acute nonlymphocytic leukemia: 75 to 200 mg/m2/day in 1 to 2 divided doses for 5 to 7 days or until remission is attained.
Because clinical studies of thioguanine did not include sufficient numbers of subjects 65 years of age or over to determine whether they respond differently from younger subjects, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range.

Usual Pediatric Dose for Acute Nonlymphocytic Leukemia:


>1 year: As a part of combination therapy for induction of remission in patients with acute nonlymphocytic leukemia: 75 to 200 mg/m2/day in 1 to 2 divided doses for 5 to 7 days or until remission is attained.
Single Agent Chemotherapy: Usual Initial dose: 2 mg/kg/day orally.
If, after 4 weeks on this dosage, there is no clinical improvement and no leukocyte or platelet depression, the dosage may be cautiously increased to 3 mg/kg per day. The total daily dose may be given at one time.

What other drugs will affect thioguanine?

Tell your doctor about all other cancer treatments you are receiving. Also tell your doctor about all other medicines you use, especially:

acetaminophen (Tylenol);

auranofin (Ridaura);

azathioprine (Azasan, Imuran);

cyclosporine (Neoral, Sandimmune);

mercaptopurine (Pureinethol);

methotrexate (Rheumatrex, Trexall);

olsalazine (Dipentum), mesalamine (Pentasa, Rowasa, Asacol), or sulfasalazine (Azulfidine);

sulfamethoxazole and trimethoprim (Bactrim, Gantanol, Gantrisin, Septra, SMX-TMP, and others);

birth control pills or hormone replacement therapy;

a blood thinner such as warfarin (Coumadin);

tuberculosis medications;

cholesterol medications such as niacin (Advicor), atorvastatin (Lipitor), simvastatin (Zocor, Simcor, Vytorin), lovastatin (Mevacor), pravastatin (Pravachol), and others;

an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), diclofenac (Cataflam, Voltaren), etodolac (Lodine), indomethacin (Indocin), ketoprofen (Orudis), and others; or

an ACE inhibitor such as benazepril (Lotensin), enalapril (Vasotec), lisinopril (Prinivil, Zestril), quinapril (Accupril), ramipril (Altace), and others;

an antibiotic such as dapsone, erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), or rifampin (Rifater, Rifadin, Rifamate);

antifungal medication such as fluconazole (Diflucan), itraconazole (Sporanox), or ketoconazole (Extina, Ketozole, Nizoral, Xolegal);

seizure medications such as carbamazepine (Carbatrol, Tegretol), phenytoin (Dilantin), felbamate (Felbatol), valproic acid (Depakene); or

HIV/AIDS medications such as abacavir/lamivudine/zidovudine (Trizivir), lamivudine (Combivir, Epivir), nevirapine (Viramune), tenofovir (Viread), or zidovudine (Retrovir);

This list is not complete and other drugs may interact with thioguanine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More thioguanine resources Thioguanine Side Effects (in more detail) Thioguanine Dosage Thioguanine Use in Pregnancy & Breastfeeding Drug Images Thioguanine Drug Interactions Thioguanine Support Group 0 Reviews for Thioguanine - Add your own review/rating thioguanine Advanced Consumer (Micromedex) - Includes Dosage Information Thioguanine Prescribing Information (FDA) Thioguanine Professional Patient Advice (Wolters Kluwer) Thioguanine Monograph (AHFS DI) Thioguanine MedFacts Consumer Leaflet (Wolters Kluwer) Tabloid Prescribing Information (FDA) Compare thioguanine with other medications Acute Nonlymphocytic Leukemia Where can I get more information? Your doctor or pharmacist can provide more information about thioguanine.

See also: thioguanine side effects (in more detail)


More




Plaquenil Sulfate


Generic Name: hydroxychloroquine (hye drox ee KLOR oh kwin)
Brand Names: Plaquenil Sulfate

What is Plaquenil Sulfate (hydroxychloroquine)?

Hydroxychloroquine is used to treat or prevent malaria, a disease caused by parasites. Parasites that cause malaria typically enter the body through the bite of a mosquito. Malaria is common in areas such as Africa, South America, and Southern Asia.

Hydroxychloroquine is also used to treat symptoms of rheumatoid arthritis and discoid or systemic lupus erythematosus.

Hydroxychloroquine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Plaquenil Sulfate (hydroxychloroquine)? You should not use this medication if you are allergic to hydroxychloroquine, or if you have a history of vision changes or damage to your retina caused by hydroxychloroquine or similar anti-malaria medications.

Before using hydroxychloroquine, tell your doctor if you are allergic to any drugs, or if you have psoriasis, porphyria, liver disease, alcoholism, or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Call a poison control center at once and then seek emergency medical attention if you think you have used too much of this medicine. An overdose of hydroxychloroquine can be fatal, especially in children. Take this medicine for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Contact your doctor as soon as possible if you have been exposed to malaria, or if you have fever or other symptoms of illness during or after a stay in an area where malaria is common.

When treating lupus or arthritis, tell your doctor if your symptoms do not improve after 6 months of treatment.

If you take hydroxychloroquine long-term, your doctor may need to check your knee and ankle reflexes and also do blood tests on a regular basis to check for harmful side effects. Your vision may also need to be tested every 3 months. Do not miss any scheduled appointments.

Hydroxychloroquine should not be used for long-term treatment in children.

What should I discuss with my health care provider before taking Plaquenil Sulfate (hydroxychloroquine)? You should not use this medication if you are allergic to hydroxychloroquine, or if you have a history of vision changes or damage to your retina caused by hydroxychloroquine or similar anti-malaria medications.

Hydroxychloroquine should not be used for long-term treatment in children.

To make sure you can safely take hydroxychloroquine, tell your doctor if you have any of these other conditions:

psoriasis;

porphyria;

liver disease;

alcoholism; or

glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

It is not known whether hydroxychloroquine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Malaria is more likely to cause death in a pregnant woman. If you are pregnant, talk with your doctor about the risks of traveling to areas where malaria is common. It is not known whether hydroxychloroquine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How should I take Plaquenil Sulfate (hydroxychloroquine)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take hydroxychloroquine with a meal or a glass of milk, unless your doctor tells you otherwise.

Hydroxychloroquine is sometimes given only once per week. Choose the same day each week to take this medication if you are on a weekly dosing schedule.

To prevent malaria: Start taking the medicine 2 weeks before entering an area where malaria is common. Continue taking the medicine regularly during your stay and for at least 8 weeks after you leave the area.

To treat malaria: Your doctor may recommend a single dose, or a high starting dose followed by a smaller dose 6 to 8 hours later for 2 days in a row. Follow your doctor's instructions.

Take this medicine for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated.

In addition to taking hydroxychloroquine, use protective clothing, insect repellents, and mosquito netting around your bed to further prevent mosquito bites that could cause malaria.

Contact your doctor as soon as possible if you have been exposed to malaria, or if you have fever or other symptoms of illness during or after a stay in an area where malaria is common.

When treating lupus or arthritis, hydroxychloroquine is usually given daily for several weeks or months. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 months of treatment.

If you take hydroxychloroquine long-term, your doctor may need to check your knee and ankle reflexes and also do blood tests on a regular basis to check for harmful side effects. Your vision may also need to be tested every 3 months. Do not miss any scheduled appointments.

No medication is 100% effective in treating or preventing all types of malaria. For best results, keep using the medication as directed. Talk with your doctor if you have fever, vomiting, or diarrhea during your treatment.

Store at room temperature away from moisture, heat, and light. What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of hydroxychloroquine can be fatal, especially in children.

Treatment of a hydroxychloroquine overdose must be started quickly. You may be told to induce vomiting right away (at home, before transport to an emergency room). Ask the poison control center how to induce vomiting in the case of a hydroxychloroquine overdose.

Overdose symptoms may include headache, drowsiness, vision changes, slow heart rate, chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, seizure (convulsions), shallow breathing, or breathing that stops.

What should I avoid while taking Plaquenil Sulfate (hydroxychloroquine)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Plaquenil Sulfate (hydroxychloroquine) side effects Some people taking this medication over long periods of time or at high doses have developed irreversible damage to the retina of the eye. Stop taking hydroxychloroquine and call your doctor at once if you have trouble focusing, if you see light streaks or flashes in your vision, or if you notice any swelling or color changes in your eyes. Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

muscle weakness, twitching, or uncontrolled movement;

loss of balance or coordination;

blurred vision, light sensitivity, seeing halos around lights;

pale skin, easy bruising or bleeding;

confusion, unusual thoughts or behavior; or

seizure (convulsions).

Less serious side effects may include:

headache, ringing in your ears;

spinning sensation;

nausea, vomiting, stomach pain;

loss of appetite, weight loss;

mood changes, feeling nervous or irritable;

skin rash or itching; or

hair loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Plaquenil Sulfate (hydroxychloroquine)?

Hydroxychloroquine can harm your liver. This effect is increased when you also use other medicines harmful to the liver. You may need dose adjustments or special tests if you have recently used:

acetaminophen (Tylenol);

cancer medications;

tuberculosis medications;

birth control pills or hormone replacement therapy;

arthritis medications such as auranofin (Ridaura) or methotrexate (Rheumatrex, Trexall);

an ACE inhibitor such as benazepril (Lotensin), enalapril (Vasotec), lisinopril (Prinivil, Zestril), quinapril (Accupril), ramipril (Altace), and others;

an antibiotic such as dapsone, erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), or rifampin (Rifater, Rifadin, Rifamate);

an antifungal medication such as fluconazole (Diflucan), itraconazole (Sporanox), or ketoconazole (Nizoral);

cholesterol medications such as niacin (Advicor, Niaspan, Niacor, Simcor, Slo Niacin, and others), atorvastatin (Lipitor, Caduet), lovastatin (Mevacor, Altoprev, Advicor), simvastatin (Zocor, Simcor, Vytorin), and others;

HIV/AIDS medications such as lamivudine (Combivir, Epivir), abacavir/lamivudine/zidovudine (Trizivir), nevirapine (Viramune), tenofovir (Viread), or zidovudine (Retrovir);

an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others; or

seizure medications such as carbamazepine (Carbatrol, Tegretol), phenytoin (Dilantin), felbamate (Felbatol), valproic acid (Depakene).

This list is not complete and other drugs may interact with hydroxychloroquine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Plaquenil Sulfate resources Plaquenil Sulfate Side Effects (in more detail) Plaquenil Sulfate Use in Pregnancy & Breastfeeding Plaquenil Sulfate Drug Interactions Plaquenil Sulfate Support Group 35 Reviews for Plaquenil Sulfate - Add your own review/rating Hydroxychloroquine MedFacts Consumer Leaflet (Wolters Kluwer) hydroxychloroquine Advanced Consumer (Micromedex) - Includes Dosage Information Hydroxychloroquine Sulfate Monograph (AHFS DI) Compare Plaquenil Sulfate with other medications Dermatomyositis Lyme Disease, Arthritis Malaria Malaria Prevention Rheumatoid Arthritis Sjogren's Syndrome Systemic Lupus Erythematosus Undifferentiated Connective Tissue Disease Where can I get more information? Your pharmacist can provide more information about hydroxychloroquine.

See also: Plaquenil Sulfate side effects (in more detail)


More




Cataflam Immediate-Release Tablets


Pronunciation: dye-KLOE-fen-ak
Generic Name: Diclofenac
Brand Name: Cataflam

Cataflam Immediate-Release Tablets are a nonsteroidal anti-inflammatory drug (NSAID). It may cause an increased risk of serious and sometimes fatal heart and blood vessel problems (eg, a heart attack, stroke). The risk may be greater if you already have heart problems or if you take Cataflam Immediate-Release Tablets for a long time. Do not use Cataflam Immediate-Release Tablets right before or after bypass heart surgery.

Cataflam Immediate-Release Tablets may cause an increased risk of serious and sometimes fatal stomach ulcers and bleeding. Elderly patients may be at greater risk. This may occur without warning signs.


Cataflam Immediate-Release Tablets are used for:

Treating rheumatoid arthritis, osteoarthritis, menstrual pain, or mild to moderate pain. It may also be used for other conditions as determined by your doctor.

Cataflam Immediate-Release Tablets are an NSAID. Exactly how it works is not known. It may block certain substances in the body that are linked to inflammation. NSAIDs treat the symptoms of pain and inflammation. They do not treat the disease that causes those symptoms.

Do NOT use Cataflam Immediate-Release Tablets if: you are allergic to any ingredient in Cataflam Immediate-Release Tablets you have had a severe allergic reaction (eg, severe rash, hives, trouble breathing, growths in the nose, dizziness) to aspirin or another NSAID (eg, ibuprofen, celecoxib) you have recently had or will be having bypass heart surgery you have severe kidney problems you are in the last 3 months of pregnancy

Contact your doctor or health care provider right away if any of these apply to you.

Before using Cataflam Immediate-Release Tablets:

Some medical conditions may interact with Cataflam Immediate-Release Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have a history of kidney or liver problems, diabetes, or stomach or bowel problems (eg, bleeding, perforation, ulcers) if you have a history of swelling or fluid buildup, asthma, growths in the nose (nasal polyps), or mouth inflammation if you have high blood pressure, blood disorders (eg, porphyria), bleeding or clotting problems, heart problems (eg, heart failure), blood vessel disease, or if you are at risk of any of these diseases if you have poor health, dehydration or low fluid volume, low blood sodium levels, or you drink alcohol or have a history of alcohol abuse

Some MEDICINES MAY INTERACT with Cataflam Immediate-Release Tablets. Tell your health care provider if you are taking any other medicines, especially any of the following:

Anticoagulants (eg, warfarin), aspirin, clopidogrel, corticosteroids (eg, prednisone), direct factor Xa inhibitors (eg, rivaroxaban), heparin, prasugrel, or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the risk of bleeding, including stomach bleeding, may be increased Azole antifungals (eg, itraconazole, voriconazole), bisphosphonates (eg, risedronate), or probenecid because they may increase the risk of Cataflam Immediate-Release Tablets's side effects Rifamycins (eg, rifampin) because they may decrease Cataflam Immediate-Release Tablets's effectiveness Cyclosporine, lithium, methotrexate, other NSAIDs (eg, ibuprofen), quinolones (eg, ciprofloxacin), or tenofovir because the risk of their side effects may be increased by Cataflam Immediate-Release Tablets Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril) or diuretics (eg, furosemide, hydrochlorothiazide) because their effectiveness may be decreased by Cataflam Immediate-Release Tablets Medicines that may harm the liver (eg, acetaminophen, ketoconazole, isoniazid, certain medicines for HIV infection, certain antibiotics or seizure medicines) because the risk of liver side effects may be increased. Ask your doctor if you are unsure if any of your medicines might harm the liver

This may not be a complete list of all interactions that may occur. Ask your health care provider if Cataflam Immediate-Release Tablets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Cataflam Immediate-Release Tablets:

Use Cataflam Immediate-Release Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Cataflam Immediate-Release Tablets comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Cataflam Immediate-Release Tablets refilled. Take Cataflam Immediate-Release Tablets by mouth. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach or bowel problems (eg, bleeding, ulcers). Talk with your doctor or pharmacist if you have persistent stomach upset. Take Cataflam Immediate-Release Tablets with a full glass of water (8 oz/240 mL) as directed by your doctor. If you miss a dose of Cataflam Immediate-Release Tablets and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Cataflam Immediate-Release Tablets.

Important safety information: Cataflam Immediate-Release Tablets may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Cataflam Immediate-Release Tablets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it. Serious stomach ulcers or bleeding can occur with the use of Cataflam Immediate-Release Tablets. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking Cataflam Immediate-Release Tablets with food will NOT reduce the risk of these effects. Contact your doctor or emergency room at once if you develop severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling. Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor. Cataflam Immediate-Release Tablets are an NSAID. Before you start any new medicine, check the label to see if it has an NSAID (eg, ibuprofen) in it too. If it does or if you are not sure, check with your doctor or pharmacist. Do not take aspirin while you are using Cataflam Immediate-Release Tablets unless your doctor tells you to. Do not switch between different forms of Cataflam Immediate-Release Tablets (eg, enteric-coated tablets, immediate-release tablets) unless your doctor tells you to. They may not provide the same amount of medicine to your body. Lab tests, including kidney and liver function, blood electrolyte levels, complete blood cell counts, and blood pressure, may be performed while you use Cataflam Immediate-Release Tablets. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments. Use Cataflam Immediate-Release Tablets with caution in the ELDERLY; they may be more sensitive to its effects, especially stomach bleeding and kidney problems. Cataflam Immediate-Release Tablets should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed. PREGNANCY and BREAST-FEEDING: Cataflam Immediate-Release Tablets may cause harm to the fetus. Do not use it during the last 3 months of pregnancy. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Cataflam Immediate-Release Tablets while you are pregnant. It is not known if Cataflam Immediate-Release Tablets are found in breast milk. Do not breast-feed while taking Cataflam Immediate-Release Tablets. Possible side effects of Cataflam Immediate-Release Tablets:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; gas; headache; heartburn; nausea; stomach upset.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; mental or mood changes; numbness of an arm or leg; one-sided weakness; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe vomiting or diarrhea; shortness of breath; sudden or unexplained weight gain; swelling of the hands, legs, or feet; symptoms of liver problems (eg, dark urine, pale stools, persistent loss of appetite, yellowing of the skin or eyes); unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; vision or speech changes; vomit that looks like coffee grounds.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Cataflam side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include decreased urination; loss of consciousness; seizures; severe dizziness or drowsiness; severe nausea, vomiting, or stomach pain; slow or troubled breathing; tremor; unusual bleeding or bruising; vomit that looks like coffee grounds.

Proper storage of Cataflam Immediate-Release Tablets:

Store Cataflam Immediate-Release Tablets at room temperature, below 86 degrees F (30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Cataflam Immediate-Release Tablets out of the reach of children and away from pets.

General information: If you have any questions about Cataflam Immediate-Release Tablets, please talk with your doctor, pharmacist, or other health care provider. Cataflam Immediate-Release Tablets are to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Cataflam Immediate-Release Tablets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Cataflam resources Cataflam Side Effects (in more detail) Cataflam Use in Pregnancy & Breastfeeding Drug Images Cataflam Drug Interactions Cataflam Support Group 15 Reviews for Cataflam - Add your own review/rating Compare Cataflam with other medications Ankylosing Spondylitis Aseptic Necrosis Back Pain Frozen Shoulder Muscle Pain Osteoarthritis Pain Period Pain Rheumatoid Arthritis Sciatica


More




Cambia Powder Packets


Pronunciation: dye-KLOE-fen-ak poe-TAS-ee-um
Generic Name: Diclofenac Potassium
Brand Name: Cambia

Cambia Powder Packets are a nonsteroidal anti-inflammatory drug (NSAID). It may cause an increased risk of serious and sometimes fatal heart and blood vessel problems (eg, a heart attack, stroke). The risk may be greater if you already have heart problems or if you use Cambia Powder Packets for a long time. Do not use Cambia Powder Packets right before or after bypass heart surgery.

Cambia Powder Packets may cause an increased risk of serious and sometimes fatal stomach ulcers and bleeding. Elderly patients may be at greater risk. This may occur without warning signs.


Cambia Powder Packets are used for:

Treating migraine headache.

Cambia Powder Packets are an NSAID. Exactly how it works is not known. It may work by blocking certain substances in the body that are linked to inflammation. NSAIDs treat the symptoms of pain and inflammation. They do not treat the disease that causes those symptoms.

Do NOT use Cambia Powder Packets if: you are allergic to any ingredient in Cambia Powder Packets you have had a severe allergic reaction (eg, severe rash, hives, trouble breathing, growths in the nose, dizziness) to aspirin or another NSAID (eg, ibuprofen, celecoxib) you have recently had or will be having bypass heart surgery you have severe kidney problems you are in the last 3 months of pregnancy

Contact your doctor or health care provider right away if any of these apply to you.

Before using Cambia Powder Packets:

Some medical conditions may interact with Cambia Powder Packets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have other kinds of headaches (eg, cluster headaches) or you have a headache that is different from your usual migraine if you have a history of kidney or liver problems, diabetes, or stomach or bowel problems (eg, bleeding, perforation, ulcers) if you have a history of swelling or fluid buildup, asthma, growths in the nose (nasal polyps), or mouth inflammation if you have high blood pressure, blood disorders (eg, porphyria), bone marrow problems; bleeding or clotting problems, heart problems (eg, heart failure, irregular heartbeat, chest pain), blood vessel disease, or if you are at risk of any of these diseases if you have phenylketonuria, poor health, dehydration or low fluid volume, low blood sodium levels, you smoke or drink alcohol, or you have a history of alcohol abuse

Some MEDICINES MAY INTERACT with Cambia Powder Packets. Tell your health care provider if you are taking any other medicines, especially any of the following:

Anticoagulants (eg, warfarin), aspirin, clopidogrel, corticosteroids (eg, prednisone), direct factor Xa inhibitors (eg, rivaroxaban), heparin, prasugrel, or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the risk of bleeding, including stomach bleeding, may be increased Azole antifungals (eg, itraconazole, voriconazole), bisphosphonates (eg, risedronate), or probenecid because they may increase the risk of Cambia Powder Packets's side effects Rifamycins (eg, rifampin) because they may decrease Cambia Powder Packets's effectiveness Cyclosporine, lithium, methotrexate, other NSAIDs (eg, ibuprofen), quinolones (eg, ciprofloxacin), or tenofovir because the risk of their side effects may be increased by Cambia Powder Packets Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril) or diuretics (eg, furosemide, hydrochlorothiazide) because their effectiveness may be decreased by Cambia Powder Packets Medicines that may harm the liver (eg, acetaminophen, ketoconazole, isoniazid, certain medicines for HIV infection, certain antibiotics or seizure medicines) because the risk of liver side effects may be increased. Ask your doctor if you are unsure if any of your medicines might harm the liver

This may not be a complete list of all interactions that may occur. Ask your health care provider if Cambia Powder Packets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Cambia Powder Packets:

Use Cambia Powder Packets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Cambia Powder Packets comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Cambia Powder Packets refilled. Do not open a packet of Cambia Powder Packets until you are ready to take a dose. To use Cambia Powder Packets, mix the contents of 1 packet with 2 to 4 tablespoons (30 to 60 mL) water. Do not use a liquid other than water. Mix well and drink right away. Do not store the mixed medicine for future use. Cambia Powder Packets may be taken with food if it upsets your stomach. Taking it with food may make it less effective. Taking it with food may not lower the risk of stomach or bowel problems (eg, bleeding, ulcers). Talk with your doctor or pharmacist if you have persistent stomach upset. Only 1 dose of Cambia Powder Packets are required. If you miss your dose of Cambia Powder Packets and you still have a migraine, take it as soon as you remember.

Ask your health care provider any questions you may have about how to use Cambia Powder Packets.

Important safety information: Cambia Powder Packets may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Cambia Powder Packets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it. Serious stomach ulcers or bleeding can occur with the use of Cambia Powder Packets. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking Cambia Powder Packets with food will NOT reduce the risk of these effects. Contact your doctor or emergency room at once if you develop severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling. Cambia Powder Packets should not be used to prevent migraine headaches. Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor. Cambia Powder Packets are an NSAID. Before you start any new medicine, check the label to see if it has an NSAID (eg, ibuprofen) in it too. If it does or if you are not sure, check with your doctor or pharmacist. Do not take aspirin while you are using Cambia Powder Packets unless your doctor tells you to. Do not switch between different forms of Cambia Powder Packets (eg, enteric-coated tablets, immediate-release tablets) unless your doctor tells you to. They may not provide the same amount of medicine to your body. Some of these products contain phenylalanine. If you must have a diet that is low in phenylalanine, ask your pharmacist if it is in your product. Lab tests, including kidney and liver function, blood electrolyte levels, complete blood cell counts, and blood pressure, may be performed while you use Cambia Powder Packets. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments. Use Cambia Powder Packets with caution in the ELDERLY; they may be more sensitive to its effects, especially stomach bleeding and kidney problems. Cambia Powder Packets should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed. PREGNANCY and BREAST-FEEDING: Cambia Powder Packets may cause harm to the fetus. Do not take it during the last 3 months of pregnancy. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Cambia Powder Packets while you are pregnant. It is not known if Cambia Powder Packets are found in breast milk. Do not breast-feed while taking Cambia Powder Packets. Possible side effects of Cambia Powder Packets:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dizziness; nausea.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; mental or mood changes; numbness of an arm or leg; one-sided weakness; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe vomiting or diarrhea; shortness of breath; sudden or unexplained weight gain; swelling of the hands, legs, or feet; symptoms of liver problems (eg, dark urine, pale stools, persistent loss of appetite, yellowing of the skin or eyes); unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; vision or speech changes; vomit that looks like coffee grounds.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Cambia side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include decreased urination; loss of consciousness; seizures; severe dizziness or drowsiness; severe nausea, vomiting, or stomach pain; slow or troubled breathing; tremor; unusual bleeding or bruising; vomit that looks like coffee grounds.

Proper storage of Cambia Powder Packets:

Store Cambia Powder Packets at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Cambia Powder Packets and the empty packets out of the reach of children and away from pets.

General information: If you have any questions about Cambia Powder Packets, please talk with your doctor, pharmacist, or other health care provider. Cambia Powder Packets are to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Cambia Powder Packets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Cambia resources Cambia Side Effects (in more detail) Cambia Use in Pregnancy & Breastfeeding Cambia Drug Interactions Cambia Support Group 2 Reviews for Cambia - Add your own review/rating Compare Cambia with other medications Migraine


More




Cambia Powder Packets


Related Posts Tenofovir: