Actonel Combi film-coated tablets + effervescent granules


1. Name Of The Medicinal Product

Actonel Combi 35 mg + 1000 mg / 880 IU film-coated tablets + effervescent granules

2. Qualitative And Quantitative Composition

Each film-coated tablet contains 35 mg risedronate sodium, (equivalent to 32.5 mg risedronic acid).

Each sachet of effervescent granules contains 2500 mg calcium carbonate equivalent to 1000 mg calcium and 22 micrograms (880 IU) colecalciferol (vitamin D3).

Excipients: Each film-coated tablet contains lactose. Each sachet of effervescent granules contains potassium (163 mg), sucrose, soya-bean oil and sorbitol.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Film-coated tablet.

Risedronate tablets: Oval, light-orange, film-coated tablet with RSN on one side and 35 mg on the other.

Effervescent granules

Calcium carbonate/colecalciferol, white effervescent granules.

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures.

Treatment of established postmenopausal osteoporosis, to reduce the risk of hip fractures (see section 5.1).

Actonel Combi is only intended for use in assessed patients for whom the amount of calcium and vitamin D3 included is considered to provide adequate supplementation.

4.2 Posology And Method Of Administration

A weekly unit of Actonel Combi consists of 1 Actonel 35 mg film-coated tablet and 6 calcium/vitamin D3 sachets in a box.

The recommended dose in adults is 1 Actonel 35 mg tablet on the first day followed on the next day by 1 calcium/vitamin D3 sachet daily for 6 days. This 7-day sequence is then repeated each week starting with Actonel 35 mg tablet.

Actonel 35 mg (light-orange tablet):

The Actonel 35 mg tablet should be taken orally on the same day each week.

The absorption of risedronate sodium is affected by food, thus to ensure adequate absorption, patients should take the Actonel 35 mg tablet

• Before breakfast: at least 30 minutes before the first food, other medicinal product or drink (other than plain water) of the day.

The tablet must be swallowed whole and not sucked or chewed. To aid delivery of the tablet to the stomach the Actonel 35 mg tablet is to be taken while in an upright position with a glass of plain water (>120 ml). Patients should not lie down for 30 minutes after taking the tablet (see section 4.4).

Calcium/vitamin D3 (sachet):

Calcium/vitamin D3 sachet should be taken each day for 6 days per week starting on the day after the Actonel 35 mg tablet is taken. The contents of the sachet should be poured into a glass of plain water, stirred and drunk immediately once the fizzing has subsided.

In case the Actonel 35 mg tablet dose is missed, patients should be instructed that the Actonel 35 mg tablet should be taken on the next day in the morning according to the dosing instructions. In this particular instance, patients should then take their calcium/vitamin D3 sachet on the following day. Patients should be instructed that they should never take the tablet and the sachet the same day.

If the calcium/vitamin D3 sachet dose is missed, the patient should be instructed to continue taking one sachet each day beginning on the day the missed dose is remembered. Patient should be instructed that they should not take two sachets on the same day. Any remaining calcium/vitamin D3 sachet at the end of the weekly cycle should be discarded.

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of risedronate on an individual patient basis, particularly after 5 or more years of use.

Elderly: No dosage adjustment is necessary since bioavailability, distribution and elimination were similar in elderly (>60 years of age) compared to younger subjects. This has also been shown in the very elderly, 75 years old and above in postmenopausal population.

Renal Impairment: No dosage adjustment is required for those patients with mild to moderate renal impairment. The use of risedronate sodium and calcium/vitamin D3 is contraindicated in patients with severe renal impairment (creatinine clearance lower than 30ml/min) (see sections 4.3 and 5.2).

Paediatric population: Risedronate sodium is not recommended for use in children below age 18 due to insufficient data on safety and efficacy (also see section 5.1).

4.3 Contraindications

Hypersensitivity to risedronate sodium, calcium carbonate, colecalciferol or to any of the excipients (in particular soya-bean oil).

Hypocalcaemia (see section 4.4)

Hypercalcaemia.

Hypercalciuria

Diseases and/or conditions (such as prolonged immobilization) associated with hypercalcaemia and/or hypercalciuria

Nephrolithiasis

Pregnancy and lactation.

Severe renal impairment (creatinine clearance <30ml/min).

Hypervitaminosis D

4.4 Special Warnings And Precautions For Use

Risedronate sodium:

Foods, drinks (other than plain water) and medicinal products containing polyvalent cations (such as calcium, magnesium, iron and aluminium) may interfere with the absorption of risedronate sodium and should not be taken at the same time (see section 4.5). Therefore the risedronate sodium tablet (light-orange tablet) should be taken at least 30 minutes before the first food, other medicinal product or drink of the day (see section 4.2).

Efficacy of bisphosphonates in the treatment of postmenopausal osteoporosis is related to the presence of low bone mineral density (BMD) [T-score at hip or lumbar spine

High age or clinical risk factors for fracture alone are not sufficient reasons to initiate treatment of osteoporosis with a bisphosphonate. The evidence to support efficacy of bisphosphonates including risedronate sodium in very elderly women (>80 years) is limited (see section 5.1).

Bisphosphonates have been associated with oesophagitis, gastritis, oesophageal ulcerations and gastroduodenal ulcerations. Thus, caution should be used:

• In patients who have a history of oesophageal disorders which delay oesophageal transit or emptying e.g. stricture or achalasia.

• In patients who are unable to stay in the upright position for at least 30 minutes after taking the tablet.

• If risedronate is given to patients with active or recent oesophageal or upper gastrointestinal problems.

Prescribers should emphasise to patients the importance of paying attention to the dosing instructions and be alert to any signs and symptoms of possible oesophageal reaction. The patients should be instructed to seek timely medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing, retrosternal pain or new/worsened heartburn.

Hypocalcaemia should be treated before starting Actonel Combi therapy. Other disturbances of bone and mineral metabolism (i.e. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting Actonel Combi therapy.

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

In patients with mild to moderate renal impairment or a history of absorptive or renal hypercalciuria, nephrocalcinosis, kidney stone formation, or hypophosphataemia, renal function, serum and urinary calcium and phosphate should be monitored regularly.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Calcium carbonate/vitamin D3:

Vitamin D3 should be used with caution in patients with impairment of renal function and the effect on calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be taken into account. In patients with severe renal insufficiency, vitamin D in the form of colecalciferol is not metabolised normally and another form of vitamin D should be used (see section 4.3)

During long-term treatment, serum and urinary calcium levels should be followed and renal function should be monitored through measurement of serum creatinine. Monitoring is especially important in elderly patients on concomitant treatment with cardiac glycosides or diuretics (see section 4.5) and in patients with a high tendency to calculus formation. Treatment must be reduced or suspended if urinary calcium exceeds 7.5 mmol/24 hour (300 mg/24 hour). In case of hypercalcaemia or signs of impaired renal function, treatment with calcium/vitamin D3 sachets should be discontinued.

The dose of vitamin D3 in the sachets should be considered when prescribing other drugs containing vitamin D. Additional doses of calcium or vitamin D should be taken under close medical supervision. In such cases it is necessary to monitor serum calcium levels and urinary calcium excretion frequently.

Calcium/vitamin D3 sachets should be used with caution in patients suffering from sarcoidosis because of the risk of increased metabolism of vitamin D to its active metabolite. In these patients, serum calcium levels and urinary calcium excretion must be monitored.

Calcium/vitamin D3 sachets should be used with caution in immobilised patients with osteoporosis due to the increased risk of hypercalcaemia. The calcium/vitamin D3 treatment might be discontinued in prolonged immobilization and should only be resumed once the patient becomes mobile again.

This medicinal product contains sorbitol and sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Risedronate sodium:

No formal interaction studies have been performed with risedronate sodium, however no clinically relevant interactions with other medicinal products were found during clinical trials. In the risedronate sodium Phase III osteoporosis studies with daily dosing, acetyl salicylic acid or non-steroidal anti-inflammatory drug (NSAID) use was reported by 33% and 45% of patients respectively. In the Phase III once a week study, acetyl salicylic acid or NSAID use was reported by 57% and 40% of patients respectively. Among regular acetyl salicylic acid or NSAID users (3 or more days per week) the incidence of upper gastrointestinal adverse events in risedronate sodium treated patients was similar to that in control patients.

If considered appropriate risedronate sodium may be used concomitantly with oestrogen supplementation.

Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium) will interfere with the absorption of risedronate sodium (see section 4.4).

Risedronate sodium is not systemically metabolised, does not induce cytochrome P450 enzymes, and has low protein binding.

Calcium carbonate/vitamin D3:

Thiazide diuretics reduce the urinary excretion of calcium. Due to increased risk of hypercalcemia serum calcium should be regularly monitored during concomitant use of thiazide diuretics.

Systemic corticosteroids reduce calcium absorption. During concomitant use, it may be necessary to increase the dose of calcium.

Calcium carbonate may interfere with the absorption of concomitant administered tetracycline preparations. For this reason, tetracycline preparations should be administered at least two hours before or four to six hours after oral intake of calcium carbonate/vitamin D3.

Hypercalcaemia may increase the toxicity of digitalis and other cardiac glycosides (risk of dysrhythmia) during treatment with calcium combined with vitamin D3. Such patients should be monitored with regard to electrocardiogram (ECG) and serum calcium levels.

If sodium fluoride is used concomitantly, this preparation should be administered at least three hours before intake of calcium carbonate/vitamin D3 since gastrointestinal absorption may be reduced.

Oxalic acid (found in spinach and rhubarb) and phytic acid (found in whole cereals) may inhibit calcium absorption through formation of insoluble compounds with calcium ions. The patient should not take calcium products within two hours of eating foods with high concentration of oxalic acid and phytic acid.

Simultaneous treatment with ion exchange resins such as cholestyramine or laxatives such as paraffin oil may reduce the gastrointestinal absorption of vitamin D.

4.6 Pregnancy And Lactation

This medicinal product is contraindicated during pregnancy and lactation (see section 4.3).

Risedronate sodium:

There are no adequate data from use of risedronate sodium in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk to humans is unknown. Studies in animals indicate that a small amount of risedronate sodium pass into breast milk. Risedronate sodium must not be used during pregnancy or by breast-feeding women.

Calcium carbonate/vitamin D3:

During pregnancy the daily intake should not exceed 1500 mg calcium and 600 IU colecalciferol (15?g vitamin D3). There are no indications that vitamin D at therapeutic doses is teratogenic in humans. Studies in animals have shown reproductive toxicity with high doses of vitamin D. In pregnant women, overdoses of calcium and vitamin D should be avoided as permanent hypercalcaemia has been related to adverse effects on the developing foetus. Calcium and vitamin D 3 pass into breast milk. Calcium carbonate 2500 mg/vitamin D3 880 IU dose granules must not be used during pregnancy and lactation.

4.7 Effects On Ability To Drive And Use Machines

No effects on ability to drive and use machines have been observed.

4.8 Undesirable Effects

Risedronate sodium:

Risedronate sodium has been studied in phase III clinical trials involving more than 15,000 patients. The majority of undesirable effects observed in clinical trials were mild to moderate in severity and usually did not require cessation of therapy.

Adverse experiences reported in phase III clinical trials in postmenopausal women with osteoporosis treated for up to 36 months with risedronate sodium 5mg/day (n=5020) or placebo (n=5048) and considered possibly or probably related to risedronate sodium are listed below using the following convention (incidences versus placebo are shown in brackets): very common (

Nervous system disorders:

Common: headache (1.8% vs. 1.4%)

Eye disorders:

Uncommon: iritis*

Gastrointestinal disorders:

Common: constipation (5.0% vs. 4.8%), dyspepsia (4.5% vs. 4.1%), nausea (4.3% vs. 4.0%), abdominal pain (3.5% vs. 3.3%), diarrhoea (3.0% vs. 2.7%)

Uncommon: gastritis (0.9% vs. 0.7%), oesophagitis (0.9% vs. 0.9%), dysphagia (0.4% vs. 0.2%), duodenitis (0.2% vs. 0.1%), oesophageal ulcer (0.2% vs. 0.2%)

Rare: glossitis (<0.1% vs. 0.1%), oesophageal stricture (<0.1% vs. 0.0%),

Musculoskeletal and connective tissues disorders:

Common: musculoskeletal pain (2.1% vs. 1.9%)

Investigations:

Rare: abnormal liver function tests*

* No relevant incidences from Phase III osteoporosis studies; frequency based on adverse event/laboratory/rechallenge findings in earlier clinical trials.

In a one-year, double-blind, multicentre study comparing risedronate 5 mg daily (n= 480) and risedronate sodium 35 mg weekly (n=485) in postmenopausal women with osteoporosis, the overall safety and tolerability profiles were similar. The following additional adverse experiences considered possibly or probably drug related by investigators have been reported (incidence greater in risedronate 35 mg than in risedronate sodium 5 mg group): gastrointestinal disorder (1.6% vs. 1.0%) and pain (1.2% vs. 0.8%).

Laboratory findings: Early, transient, asymptomatic and mild decreases in serum calcium and phosphate levels have been observed in some patients.

The following additional adverse reactions have been reported during post-marketing use (frequency unknown):

Eye disorders:

iritis, uveitis

Muskuloskeletal and connective tissues disorders:

osteonecrosis of the jaw

Skin and subcutaneous tissue disorders:

hypersensitivity and skin reactions, including angioedema, generalised rash, urticaria and bullous skin reactions, some severe including isolated reports of Stevens-Johnson syndrome, toxic epidermal necrolysis and leukocytoclastic vasculitis

hair loss.

Immune system disorders:

anaphylactic reaction

Hepatobiliary disorders:

serious hepatic disorders. In most of the reported cases the patients were also treated with other products known to cause hepatic disorders.

During post-marketing experience the following reactions have been reported (frequency rare):

Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).

Calcium carbonate/vitamin D3

Adverse reactions are listed below, by system organ class and frequency following convention: very common (

Metabolism and nutrition disorders

Uncommon: Hypercalcaemia and hypercalciuria.

Gastrointestinal disorders

Rare: Constipation, flatulence, nausea, abdominal pain and diarrhoea.

Skin and subcutaneous disorders

Rare: Pruritus, rash and urticaria.

4.9 Overdose

Risedronate sodium:

No specific information is available on the treatment of acute overdose with risedronate sodium.

Decreases in serum calcium following substantial overdose may be expected. Signs and symptoms of hypocalcaemia may also occur in some of these patients.

Milk or antacids containing magnesium, calcium or aluminium should be given to bind risedronate sodium and reduce absorption of risedronate sodium. In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed risedronate sodium.

Calcium carbonate/vitamin D3:

Overdose can lead to hypervitaminosis, hypercalciura and hypercalcaemia. Symptoms of hypercalcaemia may include anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, renal calculi and in severe cases, cardiac arrhythmias. Extreme hypercalcaemia may result in coma and death. Persistently high calcium levels may lead to irreversible renal damage and soft tissue calcification.

Treatment of hypercalcaemia: The treatment with calcium must be discontinued. Treatment with thiazide diuretics, lithium, vitamin A, vitamin D3 and cardiac glycosides must also be discontinued. Emptying of the stomach in patients with impaired consciousness. Rehydration, and, according to severity, isolated or combined treatment with loop diuretics, bisphosphonates, calcitonin and corticosteroids. Serum electrolytes, renal function and diuresis must be monitored. In severe cases, ECG and central venous pressure should be followed.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmaco-therapeutic group: Bisphosphonates, combinations,

ATC Code: M05BB04.

Risedronate sodium:

Risedronate sodium is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoclast-mediated bone resorption. The bone turnover is reduced while the osteoblast activity and bone mineralisation is preserved. In preclinical studies risedronate sodium demonstrated potent anti-osteoclast and antiresorptive activity, and dose dependently increased bone mass and biomechanical skeletal strength. The activity of risedronate sodium was confirmed by measuring biochemical markers for bone turnover during pharmacodynamic and clinical studies. Decreases in biochemical markers of bone turnover were observed within 1 month and reached a maximum in 3-6 months. Decreases in biochemical markers of bone turnover were similar with risedronate sodium 35 mg weekly and risedronate sodium 5 mg daily at 12 months.

Treatment of Postmenopausal Osteoporosis:

A number of risk factors are associated with postmenopausal osteoporosis including low bone mass, low bone mineral density, early menopause, a history of smoking and a family history of osteoporosis. The clinical consequence of osteoporosis is fractures. The risk of fractures is increased with the number of risk factors.

Based on effects on mean change in lumbar spine bone mineral density (BMD), risedronate sodium 35 mg weekly (n=485) was shown to be equivalent to risedronate sodium 5 mg daily (n=480) in a one-year, double-blind, multicentre study of postmenopausal women with osteoporosis.

The clinical programme for risedronate sodium administered once daily studied the effect of risedronate sodium on the risk of hip and vertebral fractures and contained early and late postmenopausal women with and without fracture. Daily doses of 2.5 mg and 5 mg were studied and all groups, including the control groups, received calcium and vitamin D (if baseline levels were low). The absolute and relative risk of new vertebral and hip fractures were estimated by use of a time-to-first event analysis.

• Two placebo-controlled trials (n=3661) enrolled postmenopausal women under 85 years with vertebral fractures at baseline. Risedronate sodium 5 mg daily given for 3 years reduced the risk of new vertebral fractures relative to the control group. In women with respectively at least 2 or at least 1 vertebral fractures, the relative risk reduction was 49% and 41% respectively (incidence of new vertebral fractures with risedronate sodium 18.1% and 11.3%, with placebo 29.0% and 16.3%, respectively). The effect of treatment was seen as early as the end of the first year of treatment. Benefits were also demonstrated in women with multiple fractures at baseline. Risedronate sodium 5 mg daily also reduced the yearly height loss compared to the control group.

• Two further placebo controlled trials enrolled postmenopausal women above 70 years with or without vertebral fractures at baseline. Women 70-79 years were enrolled with femoral neck BMD T-score <-3 SD (manufacturer's range, i.e. -2.5 SD using NHANES III) and at least one additional risk factor. Women

- In the subgroup of patients with femoral neck BMD T-score

- Data suggest that a more limited protection than this may be observed in the very elderly (

In these trials, data analysed as a secondary endpoint indicated a decrease in the risk of new vertebral fractures in patients with low femoral neck BMD without vertebral fracture and in patients with low femoral neck BMD with or without vertebral fracture.

• Risedronate sodium 5 mg daily given for 3 years increased BMD relative to control at the lumbar spine, femoral neck, trochanter and wrist and maintained bone density at the mid-shaft radius.

• In a one-year follow-up off therapy after three years treatment with risedronate sodium 5 mg daily there was rapid reversibility of the suppressing effect of risedronate sodium on bone turnover rate.

• Bone biopsy samples from postmenopausal women treated with risedronate sodium 5 mg daily for 2 to 3 years, showed an expected moderate decrease in bone turnover. Bone formed during risedronate sodium treatment was of normal lamellar structure and bone mineralisation. These data together with the decreased incidence of osteoporosis related fractures at vertebral sites in women with osteoporosis appear to indicate no detrimental effect on bone quality.

• Endoscopic findings from a number of patients with a number of moderate to severe gastrointestinal complaints in both risedronate sodium and control patients indicated no evidence of treatment related gastric, duodenal or oesophageal ulcers in either group, although duodenitis was uncommonly observed in the risedronate sodium group.

Calcium carbonate/vitamin D3:

In case of calcium deficiency, oral intake of calcium supplementation supports the remineralisation of the skeleton. Vitamin D3 increases the intestinal absorption of calcium.

Administration of calcium and vitamin D3 counteracts the increase in parathyroid hormone (PTH) which is caused by calcium deficiency which causes increased bone resorption.

A clinical study of institutionalised patients suffering from vitamin D deficiency indicated that a daily intake of effervescent granules of 1000 mg calcium/880 IU colecalciferol for six months normalised the value of the 25-hydoxylated metabolite of vitamin D3 and reduced secondary hyperparathyroidism.

Paediatric population: The safety and efficacy of risedronate sodium is being investigated in an on-going study of paediatric patients aged 4 to less than 16 years with osteogenesis imperfecta. After completion of its one-year randomized, double-blind, placebo controlled phase, a statistically significant increase in lumbar spine BMD in the risedronate group versus placebo group was demonstrated; however an increased number of at least 1 new morphometric (identified by x-ray) vertebral fracture was found in the risedronate group compared to placebo. Overall, results do not support the use of risedronate sodium in paediatric patients with osteogenesis imperfecta.

5.2 Pharmacokinetic Properties

Risedronate sodium:

Absorption: risedronate sodium absorption after an oral dose is relatively rapid (tmax ~1 hour) and is independent of dose over the range studied (single dose study, 2.5 to 30 mg; multiple dose studies, 2.5 to 5 mg daily and up to 50 mg dosed weekly). Mean oral bioavailability of the tablet is 0.63% and is decreased when risedronate sodium is administered with food. Bioavailability was similar in men and women.

Distribution: The mean steady state volume of distribution of risedronate sodium is 6.3 l/kg in humans. Plasma protein binding is about 24%.

Metabolism: There is no evidence of systemic metabolism of risedronate sodium.

Elimination: Approximately half of the absorbed risedronate sodium dose is excreted in urine within 24 hours, and 85% of an intravenous dose is recovered in the urine after 28 days. Mean renal clearance is 105 ml/min and mean total clearance is 122 ml/min, with the difference probably attributed to clearance due to adsorption to bone. The renal clearance is not concentration dependent, and there is a linear relationship between renal clearance and creatinine clearance. Unabsorbed risedronate sodium is eliminated unchanged in faeces. After oral administration the concentration-time profile shows three elimination phases with a terminal half-life of 480 hours.

Special Populations

Elderly: no dosage adjustment is necessary.

Acetyl salicylic acid/ NSAID users: Among regular acetyl salicylic acid or NSAID users (3 or more days per week) the incidence of upper gastrointestinal adverse events in risedronate sodium treated patients was similar to that in control patients.

Calcium carbonate:

Absorption: During dissolution the calcium salt contained in the effervescent granules is transformed into calcium citrate. Calcium citrate is well absorbed, approximately 30% to 40% of the ingested dose.

Distribution and metabolism: 99% of calcium in the body is concentrated in the hard structure of bones and teeth. The remaining 1% is present in the intra- and extracellular fluids. About 50% of the total blood calcium content is physiologically active ionised form with approximately 10% being complexed to citrate, phosphate or other anions, the remaining 40% being bound to proteins, principally albumin.

Elimination: Calcium is eliminated through faeces, urine and sweat. Renal excretion depends on glomerular filtration and calcium tubular reabsorption.

Vitamin D3:

Absorption: Vitamin D is readily absorbed in the small intestine.

Distribution and metabolism: Colecalciferol and its metabolites circulate in the blood bound to a specific globulin. Colecalciferol is converted in the liver by hydroxylation to the active form 25-hydroxycolecalciferol. It is then further converted in the kidneys to 1,25 hydroxycolecalciferol. 1,25 hydroxycolecalciferol is the metabolite responsible for increasing calcium absorption. Vitamin D that is not metabolised is stored in adipose and muscle tissues.

Elimination: Vitamin D is excreted in faeces and urine.

5.3 Preclinical Safety Data

Risedronate sodium:

In toxicological studies in rat and dog dose dependent liver toxic effects of risedronate sodium were seen, primarily as enzyme increases with histological changes in rat. The clinical relevance of these observations is unknown. Testicular toxicity occurred in rat and dog at exposures considered in excess of the human therapeutic exposure. Dose related incidences of upper airway irritation were frequently noted in rodents. Similar effects have been seen with other bisphosphonates. Lower respiratory tract effects were also seen in longer term studies in rodents, but the clinical significance of these findings is unclear. In reproduction toxicity studies at exposures close to clinical exposure ossification changes were seen in sternum and/or skull of foetuses from treated rats and hypocalcemia and mortality in pregnant females allowed to deliver. There was no evidence of teratogenesis at 3.2mg/kg/day in rat and 10mg/kg/day in rabbit, although data are only available on a small number of rabbits. Maternal toxicity prevented testing of higher doses. Studies on genotoxicity and carcinogenesis did not show any particular risk for humans.

Calcium carbonate/vitamin D3:

At doses far higher than the human therapeutic range, teratogenicity has been observed in animal studies (see section 4.6). There is no further information of relevance to the safety assessment in addition to what is stated in other parts of the SPC.

6. Pharmaceutical Particulars 6.1 List Of Excipients Film-coated tablet:       Tablet core: Lactose monohydrate,   Cellulose microcrystalline,   Crospovidone A,   Magnesium stearate.     Film coating: Hypromellose,   Macrogol   Hyprolose   Silicon dioxide   Titanium dioxide (E171), ,   Iron oxide yellow (E172),   Iron oxide red (E172).     Effervescent granules:         Citric acid anhydrous   Malic acid,   Gluconolactone,   Maltodextrin,   Sodium cyclamate,   Saccharin sodium,   Sorbitol E420,   Mannitol E421,   Gluconolactone,   Dextrin, acacia,   Lemon oils   Lime flavour   Rice starch,   Potassium carbonate,   All-rac-?-Tocopherol,   Soya-bean oil, hydrogenated   Gelatin,   Sucrose,   Maize starch. 6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

This medicinal product does not require any special storage conditions.

6.5 Nature And Contents Of Container

Combination pack constituted of an outer carton pack containing weekly unit(s) (carton boxes).

Each weekly unit contains:

Clear PVC/aluminium foil blister containing one tablet

Six sachets (laminated aluminium paper foil) containing effervescent granules

Pack sizes:

1 weekly unit: 1x(1 film-coated tablet + effervescent granules in 6 sachets)

2 weekly units: 2x(1 film-coated tablet + effervescent granules in 6 sachets)

4 weekly units: 4x(1 film-coated tablet + effervescent granules in 6 sachets)

3x4 weekly units: 12x(1 film-coated tablet + effervescent granules in 6 sachets)

4x4 weekly units: 16x(1 film-coated tablet + effervescent granules in 6 sachets)

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Warner Chilcott UK Limited

Old Belfast Road,

Millbrook,

Larne,

County Antrim,

BT40 2SH

8. Marketing Authorisation Number(S)

PL 10947/0007

9. Date Of First Authorisation/Renewal Of The Authorisation

2006-10-13

10. Date Of Revision Of The Text

2011-08-18


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Vitamin B Complex



Dosage Form: injection, solution
Vitamin B Complex Description Vitamin B-Complex 100 Injection is a sterile solution for intramuscular or slow intravenous injection comprised of vitamins which may be categorized as belonging to the Vitamin B Complex group.

Each mL contains: Thiamine Hydrochloride 100 mg, Riboflavin 5’ Phosphate Sodium 2 mg, Pyridoxine Hydrochloride 2 mg, Dexpanthenol 2 mg, Niacinamide 100 mg, with Benzyl Alcohol 2% as preservative, in Water for Injection. Sodium Hydroxide and/or Hydrochloric acid may have been used to adjust the pH.

INDICATIONS & USAGE

In disorders requiring parenteral administration of vitamins, i.e. pre- and post-operative treatment, when requirements are increased as in fever, severe burns, increased metabolism, pregnancy, gastrointestinal disorders interfering with intake or absorption of vitamins, prolonged or wasting diseases, alcoholism and where other deficiencies exist.

Contraindications

Sensitivity to the ingredients listed.

Warnings

Anaphylactogenesis may occur with parenteral thiamine. Use with caution. An intradermal test dose is recommended prior to administration in patients suspected of being sensitive to the drug.

Precautions

The usual precautions for parenteral administration should be observed. Do not inject if precipitate occurs. Inject slowly by the intravenous route. High concentrations should be diluted using Normal Saline Injection when giving intravenously.

Adverse Reactions

Mild transient diarrhea, polycythemia vera, peripheral vascular thrombosis, itching transitory exanthema, feeling of swelling of entire body, anaphylactic shock and death. Sensitivity to the ingredients listed may occur (See WARNINGS). Use should be discontinued upon observance of any untoward reaction. Pain upon intramuscular injection may be noted.

DOSAGE & ADMINISTRATION

Usually 0.25 to 2 mL by intramuscular or slow intravenous injection. High concentrations given intravenously may be diluted using parenteral infusion solutions. (See PRECAUTIONS).
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit (See HOW SUPPLIED).

How is Vitamin B Complex Supplied

Vitamin B-Complex 100 Injection is available in a 30 ml multiple dose vial individually boxed (NDC 67157-108-30) or in a 5 vial shelf pack (NDC 67157-108-31).
Phase separation due to reduced solubility can occur under certain conditions of shipping or storage (e.g. accidental freezing), which may produce visible particles. Do not use product if these do not re-dissolve on warming to body temperature and shaking well.
Refrigeration of the product may cause darkening of the solution due to the riboflavin content. The color does not affect the safety or efficacy of the product.

PROTECT FROM LIGHT:

Store in carton until contents are used. Store under refrigeration 2oC – 8oC (36oF – 46oF). Do not permit to freeze.

Rx ONLY

Manufactured By:

McGuff Pharmaceuticals, Inc. Santa Ana, CA 92704 U.S.A. 

MD381-0024 rev: NEW 8/2009


VITAMIN B-COMPLEX 
thiamine hydrochloride, riboflavin 5 phosphate sodium, pyridoxine hydrochloride, dexpanthenol, niacinamide  injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67157-108 Route of Administration INTRAMUSCULAR, INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength THIAMINE HYDROCHLORIDE (THIAMINE) THIAMINE HYDROCHLORIDE 100 mg  in 1 mL RIBOFLAVIN 5'-PHOSPHATE SODIUM (RIBOFLAVIN) RIBOFLAVIN 5'-PHOSPHATE SODIUM 2 mg  in 1 mL PYRIDOXINE HYDROCHLORIDE (PYRIDOXINE) PYRIDOXINE HYDROCHLORIDE 2 mg  in 1 mL DEXPANTHENOL (DEXPANTHENOL) DEXPANTHENOL 2 mg  in 1 mL NIACINAMIDE (NIACINAMIDE) NIACINAMIDE 100 mg  in 1 mL Inactive Ingredients Ingredient Name Strength BENZYL ALCOHOL 2 mL  in 100 mL WATER   SODIUM HYDROXIDE   HYDROCHLORIC ACID   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 67157-108-30 1 VIAL In 1 PACKAGE contains a VIAL, MULTI-DOSE 1 30 mL In 1 VIAL, MULTI-DOSE This package is contained within the PACKAGE (67157-108-30) 2 67157-108-31 5 VIAL In 1 PACKAGE contains a VIAL, MULTI-DOSE 2 30 mL In 1 VIAL, MULTI-DOSE This package is contained within the PACKAGE (67157-108-31)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 01/25/2010
Labeler - McGuff Pharmaceuticals Inc. (134632103) Establishment Name Address ID/FEI Operations McGuff Pharmaceuticals Inc. 134632103 manufacture Revised: 01/2010McGuff Pharmaceuticals Inc. More Vitamin B Complex resources Vitamin B Complex Use in Pregnancy & Breastfeeding Vitamin B Complex Drug Interactions Vitamin B Complex Support Group 4 Reviews for Vitamin B Complex - Add your own review/rating multivitamin Concise Consumer Information (Cerner Multum) Multivitamin Drops MedFacts Consumer Leaflet (Wolters Kluwer) Balanced B-50 Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer) Cardiotek-RX MedFacts Consumer Leaflet (Wolters Kluwer) Cerefolin MedFacts Consumer Leaflet (Wolters Kluwer) Cholinoid MedFacts Consumer Leaflet (Wolters Kluwer) Diatx MedFacts Consumer Leaflet (Wolters Kluwer) Folbee Plus MedFacts Consumer Leaflet (Wolters Kluwer) Folcaps MedFacts Consumer Leaflet (Wolters Kluwer) Foltrate MedFacts Consumer Leaflet (Wolters Kluwer) Ivites Rx MedFacts Consumer Leaflet (Wolters Kluwer) Metanx MedFacts Consumer Leaflet (Wolters Kluwer) Nephrocaps Protegra MedFacts Consumer Leaflet (Wolters Kluwer) Tri-Vi-Sol MedFacts Consumer Leaflet (Wolters Kluwer) Vitamin A Monograph (AHFS DI) Compare Vitamin B Complex with other medications Dietary Supplementation Hyperhomocysteinemia
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Mycelex-7 Combo Pack Cream


Pronunciation: kloe-TRIM-a-zole
Generic Name: Clotrimazole
Brand Name: Mycelex-7 Combo Pack
Mycelex-7 Combo Pack Cream is used for:

Treating vaginal yeast infections and relieving external vulvar itching and irritation associated with yeast infection.

Mycelex-7 Combo Pack Cream is an antifungal agent. It works by weakening the cell membrane of the fungus, resulting in the death of the fungus.

Do NOT use Mycelex-7 Combo Pack Cream if: you are allergic to any ingredient in Mycelex-7 Combo Pack Cream you have never had a vaginal yeast infection diagnosed by a doctor you have itching caused by a condition other than a yeast infection you have stomach, shoulder, or lower back pain; fever; chills; nausea; foul-smelling vaginal discharge; or vomiting

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

Before using Mycelex-7 Combo Pack Cream:

Some medical conditions may interact with Mycelex-7 Combo Pack Cream. 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 the blood disease porphyria or a history of liver disease or diabetes, or you have been exposed to HIV if this is the first time you have had vaginal itching and discomfort if you have vaginal yeast infections often (eg, your symptoms return within 2 months) or your symptoms do not clear up with treatment if you are taking antibiotics

Some MEDICINES MAY INTERACT with Mycelex-7 Combo Pack Cream. However, no specific interactions with Mycelex-7 Combo Pack Cream are known at this time.

Ask your health care provider if Mycelex-7 Combo Pack Cream 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 Mycelex-7 Combo Pack Cream:

Use Mycelex-7 Combo Pack Cream as directed by your doctor. Check the label on the medicine for exact dosing instructions.

An extra patient leaflet is available with Mycelex-7 Combo Pack Cream. Talk to your pharmacist if you have questions about this information. Mycelex-7 Combo Pack Cream is for vaginal use only. Do not use it rectally or take by mouth. Suppositories - Using the applicator provided, insert 1 suppository high into the vagina at bedtime for 7 days. Mycelex-7 Combo Pack Cream comes with one applicator to be used for all 7 days of treatment. Do not throw away applicator after use. Separate the pieces of the applicator and wash with warm, soapy water immediately after use. Rinse thoroughly. Make sure the applicator is completely dry before the next use. External cream - Squeeze a small amount of cream onto your finger and gently spread the cream onto the itchy, irritated skin outside the vagina as directed by your doctor or on the packaging. Wash your hands immediately after using Mycelex-7 Combo Pack Cream. To clear up your infection completely, use Mycelex-7 Combo Pack Cream for the full course of treatment. Keep using it even if you feel better in a few days. If you miss a dose of Mycelex-7 Combo Pack Cream, use 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 use 2 doses at once.

Ask your health care provider any questions you may have about how to use Mycelex-7 Combo Pack Cream.

Important safety information: Mycelex-7 Combo Pack Cream is for vaginal use only. Avoid contact with the eyes, nose, or mouth. If you get Mycelex-7 Combo Pack Cream in your eyes, flush with a generous amount of cool water. Be sure to use Mycelex-7 Combo Pack Cream for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future. If your symptoms do not improve within 3 days, if they last more than 7 days, or if they get worse, check with your doctor. Do not use Mycelex-7 Combo Pack Cream for itching caused by other conditions. Dry the outside vaginal area completely after showering, bathing, or swimming. Do not go swimming for at least 9 to 12 hours after applying Mycelex-7 Combo Pack Cream. Change out of wet bathing suits or damp workout clothes as soon as possible. Continue using Mycelex-7 Combo Pack Cream even during your menstrual period. Do not use tampons while you are using Mycelex-7 Combo Pack Cream or until all of your symptoms go away. Use unscented pads or pantiliners. Do not have vaginal sexual intercourse while you are using Mycelex-7 Combo Pack Cream. Mycelex-7 Combo Pack Cream may decrease the effectiveness of condoms and diaphragms, increasing the chance of pregnancy or risk of sexually transmitted disease. Do not use tampons, douches, spermicides, or other vaginal products while using Mycelex-7 Combo Pack Cream. If you use topical products too often, your condition may become worse. Mycelex-7 Combo Pack Cream should not be used in CHILDREN younger than 12 years old; 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 using Mycelex-7 Combo Pack Cream while you are pregnant. It is not known if Mycelex-7 Combo Pack Cream is found in breast milk. If you are or will be breast-feeding while you use Mycelex-7 Combo Pack Cream, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Mycelex-7 Combo Pack Cream:

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:

Headache; mild vaginal burning, irritation, or itching; stomach cramps.

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); fever or chills; foul-smelling vaginal discharge; nausea; severe or prolonged vaginal burning, irritation, or itching; stomach pain; swelling; vomiting.

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: Mycelex-7 Combo Pack 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 Mycelex-7 Combo Pack Cream:

Store Mycelex-7 Combo Pack Cream at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Avoid temperatures above 86 degrees F (30 degrees C). Avoid freezing. Store away from heat, moisture, and light. Do not store in the bathroom. Do not use if the wrapper on the applicator or suppository is torn or damaged. Keep Mycelex-7 Combo Pack Cream out of the reach of children and away from pets.

General information: If you have any questions about Mycelex-7 Combo Pack Cream, please talk with your doctor, pharmacist, or other health care provider. Mycelex-7 Combo Pack Cream 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 Mycelex-7 Combo Pack Cream. 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 Mycelex-7 Combo Pack resources Mycelex-7 Combo Pack Side Effects (in more detail) Mycelex-7 Combo Pack Use in Pregnancy & Breastfeeding Mycelex-7 Combo Pack Support Group 0 Reviews for Mycelex-7 Combo Pack - Add your own review/rating Compare Mycelex-7 Combo Pack with other medications Cutaneous Candidiasis Tinea Corporis Tinea Cruris Tinea Pedis Tinea Versicolor Vaginal Yeast Infection
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Pronto with Metal Comb


Generic Name: piperonyl butoxide and pyrethrins topical (pi PER o nil bue TOX ide and pye RETH rins)
Brand Names: A-200 Lice Control, A-200 Lice Treatment, Good Sense Lice Killing Shampoo, Step 1, Lice Treatment Maximum Strength, Pronto Lice Kill System, Pronto Shampoo & Cream Rinse, Pronto Shampoo Kit, Pronto Spray, Pronto with Metal Comb, R & C Lice Treatment Kit, Rid Pediculicide, Tegrin-LT Lice Spray, Tegrin-LT Lice Treatment Kit, Tegrin-LT Shampoo, Triple X Pediculicide

What is Pronto with Metal Comb (piperonyl butoxide and pyrethrins topical)?

Piperonyl butoxide and pyrethrins are insecticide chemicals.

Piperonyl butoxide and pyrethrins topical (for the skin) is used to treat lice.

Piperonyl butoxide and pyrethrins topical may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Pronto with Metal Comb (piperonyl butoxide and pyrethrins topical)? You should not use this medication if you are allergic to piperonyl butoxide and pyrethrins, or if you have an allergy to chrysanthemums or ragweed.

Check all household members for signs of lice. Lice can be spread from person to person by sharing a hairbrush, a comb, hats, or headbands. It can also be spread through head-to-head contact.

Use this medication for the full prescribed length of time. Your symptoms may improve before the lice infestation is completely cleared. Call your doctor if your condition does not improve, or if your symptoms get worse while using this medication.

Stop using piperonyl butoxide and pyrethrins and call your doctor at once if you have severe stinging, burning, itching, swelling, or irritation where the medication is applied.

To prevent reinfection with lice, wash all clothing, hats, bed linens, stuffed toys, hair brushes, and combs in hot water with a strong cleanser to remove any mites or eggs. You may need to use a special lice control spray to treat furniture, mattresses, sports helmets, headphones, and other non-washable items. Ask your doctor of pharmacist about disinfecting your home.

What should I discuss with my healthcare provider before using Pronto with Metal Comb (piperonyl butoxide and pyrethrins topical)? You should not use this medication if you are allergic to piperonyl butoxide and pyrethrins topical, or if you have an allergy to chrysanthemums or ragweed. It is not known whether piperonyl butoxide and pyrethrins topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Piperonyl butoxide and pyrethrins can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How should I use Pronto with Metal Comb (piperonyl butoxide and pyrethrins topical)?

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

Check for signs of lice on all household members. They may also need to be treated for lice. Lice can be spread from person to person by sharing a hairbrush, a comb, hats, or headbands. It can also be spread through head-to-head contact.

Apply the shampoo form of this medication to dry hair. Wetting the hair first may make the medication less effective. Apply the shampoo to all areas of the scalp, including behind the ears and neck. Treat hair from the roots to the ends and leave the shampoo in the hair for 10 minutes. Add warm water to form a lather and shampoo. Then rinse thoroughly with warm water. Piperonyl butoxide and pyrethrins shampoo is usually used once every 7 to 10 days.

You may need to use a larger amount of the shampoo if you have long hair. Follow the directions on the product label.

Keep your eyes tightly closed while using the shampoo, foam, or spray, and while rinsing it out of your hair. You may use a washcloth or towel to protect your eyes while applying the medication to your head.

Do not apply this medication to your eyebrows or eyelashes. Call your doctor if these areas become infected with lice.

Avoid inhaling the vapors from this medication. Use in a well-ventilated area.

You will need to remove any eggs (nits) from the hair shafts with a special comb. Some piperonyl butoxide and pyrethrins products come provided with a nit comb. If you do not have such a comb, ask your pharmacist where you can get one. Nits may not be removed effectively with a regular fine-tooth comb.

Use this medication for the full prescribed length of time. Your symptoms may improve before the lice infestation is completely cleared. Call your doctor if your condition does not improve, or if your symptoms get worse while using this medication.

To prevent reinfection with lice, wash all clothing, hats, bed linens, stuffed toys, hair brushes, and combs in hot water with a strong cleanser to remove any mites or eggs. You may need to use a special lice control spray to treat furniture, mattresses, sports helmets, headphones, and other non-washable items. Ask your doctor of pharmacist about disinfecting your home.

Store this medication at room temperature away from moisture and heat. Keep the medicine canister away from open flame or high heat. The canister may explode if it gets too hot. Do not puncture or incinerate the can, the contents are under pressure. 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.

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 using Pronto with Metal Comb (piperonyl butoxide and pyrethrins topical)?

Avoid using other medications or skin products on the areas you treat with piperonyl butoxide and pyrethrins topical, unless you doctor tells you to.

Avoid getting this medication in your eyes, nose, mouth, or vagina. If this does happen, rinse with water. Do not use piperonyl butoxide and pyrethrins topical on sunburned, windburned, dry, chapped, irritated, or broken skin.

Avoid close contact with others until the infection has been cured. Also avoid sharing hair combs, hair accessories, hats, clothing, bed linens, pillows, and other items of personal use. Lice infestations are highly contagious.

Pronto with Metal Comb (piperonyl butoxide and pyrethrins topical) 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 piperonyl butoxide and pyrethrins and call your doctor at once if you have severe stinging, burning, itching, swelling, or irritation where the medication is applied.

Less serious side effects may include:

mild itching, burning, or stinging;

mild skin rash; or

numbness or tingly feeling.

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 Pronto with Metal Comb (piperonyl butoxide and pyrethrins topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied piperonyl butoxide and pyrethrins. But many drugs can interact with each other. 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 Pronto with Metal Comb resources Pronto with Metal Comb Use in Pregnancy & Breastfeeding Pronto with Metal Comb Support Group 0 Reviews for Pronto with Metal Comb - Add your own review/rating Compare Pronto with Metal Comb with other medications Head Lice Where can I get more information? Your pharmacist can provide more information about piperonyl butoxide and pyrethrins.
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Combivent Respimat


Generic Name: ipratropium and albuterol (Inhalation route)

ip-ra-TROE-pee-um BROE-mide, al-BUE-ter-ol SUL-fate

Commonly used brand name(s)

In the U.S.

Combivent Combivent Respimat Duoneb

In Canada

Ratio-Ipra Sal Udv

Available Dosage Forms:

Aerosol Powder Solution Spray Aerosol Liquid

Therapeutic Class: Bronchodilator

Pharmacologic Class: Ipratropium

Uses For Combivent Respimat

Ipratropium and albuterol combination is used to help control the symptoms of lung diseases, such as asthma, chronic bronchitis, and emphysema. It is also used to treat air flow blockage and prevent the worsening of chronic obstructive pulmonary disease (COPD) in patients who need another medicine.

Ipratropium and albuterol belong to the family of medicines known as bronchodilators. Bronchodilators are medicines that are breathed in through the mouth to open up the bronchial tubes (air passages) in the lungs.

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

Before Using Combivent Respimat

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

Appropriate studies have not been performed on the relationship of age to the effects of ipratropium and albuterol combination in the pediatric population. 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 Combivent® Respimat® spray in the elderly.

No information is available on the relationship of age to the effects of Combivent® in geriatric patients.

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 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.

Acebutolol Alprenolol Arotinolol Atenolol Atomoxetine Befunolol Betaxolol Bevantolol Bisoprolol Bopindolol Brofaromine Bucindolol Bupranolol Carteolol Carvedilol Celiprolol Clorgyline Dilevalol Esmolol Furazolidone Iproniazid Isocarboxazid Labetalol Landiolol Lazabemide Levobetaxolol Levobunolol Linezolid Mepindolol Metipranolol Metoprolol Moclobemide Nadolol Nebivolol Nialamide Nipradilol Oxprenolol Pargyline Penbutolol Phenelzine Pindolol Procarbazine Propranolol Rasagiline Selegiline Sotalol Talinolol Tertatolol Timolol Toloxatone Tranylcypromine

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.

Betel Nut 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:

Allergy to soya lecithin, soybean, or peanuts, history of—Combivent® brand should not be used in patients with this condition. Blood circulation problems or Heart or blood vessel disease or Heart rhythm problems (e.g., arrhythmia) or Hypertension (high blood pressure)—Use with caution. May increase risk for serious side effects. Diabetes or Difficult urination or Enlarged prostate or Hyperthyroidism (an overactive thyroid) or Hypokalemia (low potassium in the blood) or Narrow-angle glaucoma or Seizures or Urinary bladder blockage—Use with caution. May make these conditions worse. Proper Use of ipratropium and albuterol

This section provides information on the proper use of a number of products that contain ipratropium and albuterol. It may not be specific to Combivent Respimat. Please read with care.

This medicine usually comes with patient directions or instructions. Read them carefully before using the medicine. If you do not understand the directions or you are not sure how to use the inhaler or nebulizer, ask your doctor to show you how to use it.

Use this medicine only as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. Also, do not stop using this medicine without telling your doctor. To do so may cause your lung condition to become worse.

When you use the inhalation solution, make sure you use a jet nebulizer that is connected to an air compressor with a good air flow. Use a face mask or mouthpiece to inhale the medicine.

Keep the spray away from your eyes. This medicine may cause eye pain or discomfort, irritation, blurred vision, or start seeing halos or odd colors when you look at things. If it does come into contact with your eyes, check with your doctor right away.

To use the Combivent® inhaler:

Insert the metal canister firmly and fully into the clear end of the Combivent® Inhalation Aerosol mouthpiece. This mouthpiece should not be used with other inhaled medicines. Remove the cap and look at the mouthpiece to make sure it is clean. Shake the inhaler for at least 10 seconds and test spray it in the air 3 times before using it for the first time or if the inhaler has not been used for 24 hours. To inhale this medicine, breathe out fully, trying to get as much air out of the lungs as possible. Put the mouthpiece just in front of your mouth with the canister upright. Open your mouth and breathe in slowly and deeply (like yawning), and at the same time firmly press down once on the top of the canister. Hold your breath for about 10 seconds, then breathe out slowly. If you are supposed to use more than one puff, wait 1 to 2 minutes before inhaling the second puff. Repeat these steps for the second puff, starting with shaking the inhaler. When you have finished all of your doses, rinse your mouth with water. Clean the inhaler mouthpiece every day with hot water. Dry it thoroughly before use.

To use the Combivent® Respimat® spray:

Insert the cartridge into the Combivent® Respimat® inhaler. Before using the inhaler, prime it by spraying the medicine towards the ground (away from your face), until an aerosol cloud is visible. Repeat 3 more times. The inhaler is now ready for use. If the inhaler is not used for more than 3 days, prime the inhaler once to prepare it for use. If it not used for more than 21 days, prime the inhaler 3 times. To inhale this medicine, breathe out fully, trying to get as much air out of the lungs as possible. Open your mouth and breathe in slowly and deeply (like yawning), and at the same time firmly press down once the release button of the inhaler. Hold your breath for about 10 seconds, then breathe out slowly. After using the inhaler, clean the mouthpiece with a damp cloth or tissue at least once a week. This inhaler has a dose indicator window that shows how much medicine is left. When the pointer enters the red area of the scale, it is time that you need to refill your prescription. Throw away the inhaler 3 months from its first use or when the inhaler is locked (after 120 puffs).

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

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 symptoms of chronic obstructive pulmonary disease (COPD): For inhalation aerosol dosage form (used with an inhaler): Adults—2 puffs four times a day and as needed. Do not use more than 12 puffs in any 24-hour period. Children—Use and dose must be determined by your doctor. For inhalation solution dosage form (used with a nebulizer): Adults—Use one 3 milliliter (mL) vial in the nebulizer four times a day. You may use 2 additional treatments per day if needed. Children—Use and dose must be determined by your doctor. For inhalation spray dosage form (used with an inhaler): Adults—One puff four times a day. You may take additional doses per day if needed. Do not use more than 6 puffs in any 24-hour period. Children—Use and dose must be determined by your doctor. 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.

Storage

Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.

Keep the medicine in the foil pouch until you are ready to use it. Store at room temperature, away from heat and direct light. Do not freeze.

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 Combivent Respimat

It is very important that your doctor check your progress closely while you are using this medicine to see if it is working properly and to help reduce any unwanted effects.

This medicine may cause paradoxical bronchospasm, which means your breathing or wheezing will get worse. Paradoxical bronchospasm may be life-threatening. Stop using this medicine and check with your doctor right away if you have coughing, difficulty breathing, shortness of breath, or wheezing after using this medicine.

Check with your doctor at once if difficulty with breathing continues after using a dose of this medicine or if your condition gets worse.

This medicine may cause serious types of allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash; itching; hives; hoarseness; trouble with breathing; trouble with swallowing; or any swelling of your hands, face, or mouth while you are using this medicine.

Tell your doctor right away if you feel chest pain, notice any changes in your blood pressure (such as feeling lightheaded or changes in vision), or notice your heart beating faster or slower .

Take all of your COPD medicines as your doctor ordered. If you use any type of corticosteroid medicine to control your breathing, keep using it as ordered by your doctor. This includes corticosteroid medicines that are taken by mouth or inhaled (such as prednisone, Azmacort®, or Flovent®). If any of your COPD medicines do not seem to be working as well as usual, call your doctor right away. Do not change your doses or stop using your medicines without asking your doctor.

This medicine may cause dizziness, blurred vision, or trouble in seeing clearly. Make sure you know how you react to this medicine before you drive, use machines, or do other jobs that require you to be alert, well-coordinated, or able to see well.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, and herbal or vitamin supplements. .

Combivent Respimat 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 Body aches or pain chills cough cough producing mucus difficulty with breathing ear congestion fever headache loss of voice runny nose shortness of breath sneezing sore throat stuffy nose tightness in the chest unusual tiredness or weakness wheezing Less common Bladder pain bloody or cloudy urine blurred vision burning while urinating burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings chest pain congestion diarrhea difficult, burning, or painful urination dizziness fainting fast, slow, irregular, pounding, or racing heartbeat or pulse frequent urge to urinate general feeling of discomfort or illness hoarseness increased sputum joint pain loss of appetite lower back or side pain muscle aches and pains nausea nervousness noisy breathing pain pain or tenderness around the eyes and cheekbones pounding in the ears shakiness in the legs, arms, hands, or feet shivering sweating swelling tender, swollen glands in the neck trembling or shaking of the hands or feet trouble with sleeping trouble with swallowing voice changes vomiting Rare Skin rash or hives swelling of the face, lips, eyelids, mouth, or throat Incidence not known Chest discomfort decrease in the frequency of urination decrease in urine volume difficulty in passing urine (dribbling) difficulty with swallowing itching skin large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs pain or discomfort in the arms, jaw, back, or neck puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue redness of the skin welts

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:

Less common Acid or sour stomach bad, unusual, or unpleasant (after) taste belching change in taste diarrhea difficulty with moving dry mouth heartburn hoarseness indigestion muscle pain or stiffness sleeplessness stomach discomfort, upset, or pain trouble sleeping unable to sleep voice changes Less common or rare Nervousness tremor Incidence not known Bigger, dilated, or enlarged pupils (black part of the eye) blindness change in near or distance vision decreased vision difficulty in focusing eyes dry throat eye pain increased sensitivity of the eyes to light itching, redness, tearing, or other sign of eye irritation not present before use of this medicine or becoming worse during use lack or loss of strength noisy breathing redness of the white part of the eyes or inside of the eyelids swelling of the eye swelling or inflammation of the mouth tearing

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 Combivent Respimat resources Combivent Respimat Use in Pregnancy & Breastfeeding Combivent Respimat Drug Interactions 0 Reviews for Combivent Respimat - Add your own review/rating Compare Combivent Respimat with other medications COPD, Maintenance
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Antidiabetic combinations


A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.

Antidiabetic combinations are medicines with two or more classes of antidiabetic agents (with different mechanisms of action) in one pill or dose. Just having one pill may improve compliance and better glycemic control.

See also

Medical conditions associated with antidiabetic combinations:

Cardiovascular Risk Reduction Diabetes, Type 2 High Cholesterol High Cholesterol, Familial Heterozygous High Cholesterol, Familial Homozygous Drug List: Actoplus-Met-Xr-Extended-Release-Tablets Duetact Kombiglyze-Xr Avandaryl Janumet Glucovance Actoplus_Met Avandamet Juvisync Metaglip Prandimet
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High Potency Multi B Complex



Dosage Form: FOR ANIMAL USE ONLY
HIGH POTENCY VITAMIN B COMPLEX INDICATIONS

For use as a supplement source of B complex vitamins in cattle, swine and sheep.

Precautions

Allergic-type reactions following the injection of products containing thiamine have been reported. Administer with caution and keep treated animals under close observation.

High Potency Multi B Complex Dosage and Administration

Inject intramuscularly. May be administered subcutaneously or intravenously if recommended by your veterinarian. The following are suggested dosages, depending on the condition of the animal and the desired response.

Adult Cattle--1 to 2 mL per 100 pounds body weight.
Calves, Swine and Sheep--5 mL per 100 pounds of body weight.

May be repeated daily, if indicated.

TAKE TIME OBSERVE LABEL DIRECTIONS

COMPOSITION

Each mL of sterile aqueous solution contains:

Thiamine Hydrochloride (B1) . . . . . . . . . . . . . 100 mg
Riboflavin (B2) . . . . . . . . . . . . . . . . . . . . . . . . .5 mg
  (as Riboflavin 5'--Phosphate Sodium)
Niacinamide . . . . . . . . . . . . . . . . . . . . . . . . .100 mg
Pyridoxine Hydrochloride (B6) . . . . . . . . . . . . . 10 mg
d-Panthenol . . . . . . . . . . . . . . . . . . . . . . . . . .10 mg
Cyanocobalamin (B12) . . . . . . . . . . . . . . . . .100 mcg
With Citric Acid and Benzyl Alcohol 1.5% v/v (preservative)

Store at controlled room temperature between 15o and 30oC (59o-86oF)

Protect from light


High Potency Multi B Complex 
cyanocobalamin, niacinamide, dexpanthenol, p yridoxine hydrochloride, riboflavin 5 phosphate sodium, thiamine hydrochloride  injection Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58005-606 Route of Administration INTRAMUSCULAR, SUBCUTANEOUS, INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CYANOCOBALAMIN (CYANOCOBALAMIN) CYANOCOBALAMIN 100 ug  in 1 mL NIACINAMIDE (NIACINAMIDE) NIACINAMIDE 100 mg  in 1 mL DEXPANTHENOL (DEXPANTHENOL) DEXPANTHENOL 10 mg  in 1 mL PYRIDOXINE HYDROCHLORIDE (PYRIDOXINE) PYRIDOXINE HYDROCHLORIDE 10 mg  in 1 mL RIBOFLAVIN 5'-PHOSPHATE SODIUM (RIBOFLAVIN) RIBOFLAVIN 5'-PHOSPHATE SODIUM 5 mg  in 1 mL THIAMINE HYDROCHLORIDE (THIAMINE) THIAMINE HYDROCHLORIDE 100 mg  in 1 mL Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 58005-606-04 100 mL In 1 VIAL None 2 58005-606-05 250 mL In 1 VIAL None 3 58005-606-06 500 mL In 1 VIAL None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 07/01/1996
Labeler - Sparhawk Laboratories, Inc. (958829558) Revised: 08/2010Sparhawk Laboratories, Inc.

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Comtan


Generic Name: Entacapone
Class: Catechol-O-Methyltransferase (COMT) Inhibitors
VA Class: CN500
Chemical Name: (E)-?-Cyano-N,N-diethyl-1,3,4-dihydroxy-5-nitrocinnamamide
Molecular Formula: C14H15N3O5
CAS Number: 130929-57-6

Introduction

Selective, reversible inhibitor of catechol-O-methyltransferase (COMT).1 2 3 7

Uses for Comtan Parkinsonian Syndrome

Adjunct to levodopa-carbidopa in the symptomatic treatment of idiopathic parkinsonian syndrome in patients with manifestations of end-of-dose “wearing-off.”1 4

Not evaluated systematically in patients without manifestations of end-of-dose “wearing-off.”1

Comtan Dosage and Administration Administration Oral Administration

Administer orally without regard to meals.1

Administer in conjunction with levodopa-carbidopa (conventional tablets, orally disintegrating tablets, or extended-release preparations) or as a fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo).1 8

Administer one tablet of the fixed-combination preparation (Stalevo) per dosing interval; do not divide the tablets.8

Dosage Adults Parkinsonian Syndrome Oral

200 mg with each levodopa-carbidopa dose.1

May need to reduce daily levodopa dosage or administration frequency to optimize patient response.1 In clinical studies, most patients receiving ?800 mg of levodopa daily or experiencing moderate or severe dyskinesias before initiating entacapone therapy required a reduction (average 25%) in levodopa dosage.1

Transferring to the Fixed-combination Preparation (Stalevo) Oral

Patients receiving levodopa-carbidopa conventional tablets containing a 1:4 ratio of carbidopa to levodopa: Switch to the corresponding strength of Stalevo.8

No information on transferring patients receiving extended-release levodopa-carbidopa preparation or levodopa-carbidopa preparations containing a 1:10 ratio of carbidopa to levodopa.8

Initiating Entacapone Using the Fixed-combination Preparation (Stalevo) Oral

Patients receiving levodopa >600 mg daily or with history of moderate or severe dyskinesias: Administer levodopa-carbidopa (1:4 ratio) and entacapone as separate preparations to determine optimum maintenance dosage and then switch to corresponding strength of Stalevo.8

Patients receiving levodopa <600 mg daily (conventional tablet, 1:4 ratio) with no dyskinesias: Switch to the strength of Stalevo that corresponds to the dosage of levodopa-carbidopa being taken.8 Further adjustment may be needed.8

Prescribing Limits Adults Parkinsonian Syndrome Oral

Entacapone: Maximum of 8 doses (1.6 g) daily; clinical experience with dosages >1.6 g daily is limited.1 8

Fixed-combination preparations containing levodopa 50–150 mg, carbidopa 12.5–37.5 mg, and entacapone 200 mg (Stalevo 50, 75, 100, 125, and 150): Maximum of 8 tablets daily; clinical experience with entacapone dosages >1.6 g daily is limited.8

Fixed-combination preparation containing levodopa 200 mg, carbidopa 50 mg, and entacapone 200 mg (Stalevo 200): Maximum of 6 tablets daily; clinical experience with carbidopa dosages >300 mg daily is limited.8

Cautions for Comtan Contraindications

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

When entacapone is used in fixed combination with levodopa-carbidopa, consider the contraindications associated with levodopa-carbidopa.8

Warnings/Precautions Warnings Concomitant Use with MAO Inhibitors

Possible inhibition of principal pathways involved in the metabolism of catecholamines if used concomitantly with a nonselective MAO inhibitor (e.g., phenelzine, tranylcypromine); concomitant use not recommended.1 (See Specific Drugs under Interactions.)

Concomitant Use with Drugs Metabolized by Catechol-O-methyltransferase

Possible increased heart rate, arrhythmias, and excessive changes in BP when used concomitantly with drugs metabolized by catechol-O-methyltransferase (COMT).1 (See Specific Drugs under Interactions.)

Potential Risk of Prostate Cancer

Higher incidence of prostate cancer was observed in one long-term, randomized, controlled study in patients initiating levodopa therapy with levodopa, carbidopa, and entacapone (Stalevo) compared with those initiating therapy with conventional levodopa-carbidopa formulation.11 13 Increased risk of prostate cancer not observed in other shorter-term controlled studies evaluating entacapone as an adjunct to levodopa-carbidopa.11 13 FDA is continuing to review available data related to this safety concern.11

FDA advises patients receiving entacapone as an adjunct to levodopa-carbidopa (either separately or as a fixed-combination preparation) to continue taking the drugs as prescribed unless otherwise instructed by a clinician.11 Men receiving such therapy should continue to be monitored for development of prostate cancer according to current prostate cancer screening guidelines.11

Major Toxicities Cardiovascular Effects

Enhances levodopa availability; possible increased occurrence of orthostatic hypotension or syncope when administered with levodopa-carbidopa.1

Findings from an FDA-conducted meta-analysis suggest that patients receiving combined therapy with levodopa, carbidopa, and entacapone may be at increased risk of adverse cardiovascular events (i.e., MI, stroke, cardiovascular death) compared with those receiving levodopa-carbidopa.12 However, several limitations of the meta-analysis preclude definite conclusions.12 FDA is continuing to review available data related to this safety concern.12 FDA advises patients receiving entacapone as an adjunct to levodopa-carbidopa (either separately or as a fixed-combination preparation) to continue taking the drugs as prescribed unless otherwise instructed by a clinician.12 Clinicians should monitor cardiac function regularly, particularly in patients with a history of cardiovascular disease.12

GI Effects

Possible mild to moderate diarrhea; rarely may be severe.1 Generally occurs during first 4–12 weeks of therapy; may occur as early as first week or as late as several months following initiation and resolves following discontinuance.1

Hallucinations

Possible hallucinations, sometimes resulting in hospitalization.1

Dyskinesia

May potentiate adverse dopaminergic effects of levodopa and may cause or exacerbate dyskinesias.1 3 4

Reduction of levodopa dosage may ameliorate dyskinesias; however, many patients in clinical studies continued to experience frequent dyskinesias.1 Discontinuance of therapy may be required.1

Rhabdomyolysis

Severe rhabdomyolysis reported rarely.1 4 7

Nervous System and Muscular Effects

Symptom complex resembling neuroleptic malignant syndrome (NMS) (elevated temperature, muscular rigidity, altered consciousness, elevated CPK) reported in association with abrupt withdrawal or dosage lowering of other dopaminergic agents.1 Similar episodes possible with entacapone.1 4 7 (See Withdrawal of Therapy under Cautions.)

Respiratory Effects

Retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and thickening of the pleura reported with ergot-derivative dopamine receptor agonists (e.g., bromocriptine, pergolide); possibility exists that nonergot-derived drugs that increase dopaminergic activity (e.g., entacapone) may induce similar pulmonary changes.1

General Precautions Use of Fixed Combination

When the fixed combination containing levodopa, carbidopa, and entacapone (Stalevo) is used, observe the usual precautions and contraindications associated with all the drugs in the preparation.8

Withdrawal of Therapy

Slow withdrawal is recommended.1

If entacapone therapy is discontinued, closely monitor patient and adjust dosage of dopaminergic therapy accordingly.1

If hyperpyrexia or severe rigidity occurs, consider possibility of symptom complex resembling NMS.1

Melanoma

Epidemiologic studies indicate patients with parkinsonian syndrome have a twofold to approximately sixfold higher risk of developing melanoma than the general population.1 8 Unclear whether increased risk is due to parkinsonian syndrome or other factors (e.g., drugs used to treat the disease).1 8

Monitor for melanoma on a frequent and regular basis.1 8 Manufacturer recommends periodic skin examinations performed by appropriately qualified individuals (e.g., dermatologists).1 8

Intense Urges

Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including entacapone).1 8 Although causal relationship not established, urges stopped in some cases when dosage was reduced or drug was discontinued.1 8

Consider reducing dosage or discontinuing entacapone if a patient develops such urges.1 8

Specific Populations Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Caution if used in nursing women.1

Pediatric Use

Not indicated.1

Geriatric Use

No substantial differences in safety or pharmacokinetics relative to younger adults.1 3 7

Hepatic Impairment

Use with caution.1 (See Special Populations under Pharmacokinetics.)

Biliary Obstruction

Use with caution.1

Common Adverse Effects

Dyskinesia, nausea, hyperkinesia, diarrhea, urine discoloration, hypokinesia, dizziness, abdominal pain, constipation, fatigue.1

Interactions for Comtan

Inhibits CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A only at very high concentrations.1 Inhibition of these isoenzymes not expected during clinical use.1

Drugs Metabolized by Catechol-O-methyltransferase

Possible increased heart rate, arrhythmias, and excessive changes in BP.1

Drugs Interfering with Biliary Excretion, Glucuronidation, and Intestinal ?-Glucuronidase

Decreased entacapone excretion.1 7

Protein-bound Drugs

No binding displacement between entacapone and other highly protein bound drugs (e.g., warfarin, salicylic acid, phenylbutazone, diazepam).1

Specific Drugs

Drug

Interaction

Comments

Anti-infective agents (e.g., ampicillin, chloramphenicol, erythromycin, rifampin)

Possible decreased entacapone excretion1 7

Use with caution1

Apomorphine

Possible increased heart rate, arrhythmias, and excessive changes in BP1

Cholestyramine

Possible decreased entacapone excretion1

Use with caution1

CNS depressants

Additive sedative effects1

Imipramine

Pharmacologic interaction unlikely1

Levodopa

Increased plasma levodopa concentrations, resulting in enhanced therapeutic effects1

Increased risk of levodopa-induced cardiovascular effects and dyskinesia1

MAO inhibitors

Potential inhibition of catecholamine metabolism when used concomitantly with nonselective MAO inhibitors (e.g., phenelzine, tranylcypromine)1

Pharmacologic interaction unlikely with selective MAO-B inhibitors (e.g., selegiline)1

Avoid concomitant use with nonselective MAO inhibitors1

Methyldopa

Possible increased heart rate, arrhythmias, and excessive changes in BP1

Probenecid

Possible decreased entacapone excretion1

Use with caution1

Sympathomimetic (adrenergic) agents (e.g., dobutamine, dopamine, epinephrine, isoetharine, isoproterenol, norepinephrine)

Possible increased heart rate, arrhythmias, and excessive changes in BP1

Comtan Pharmacokinetics Absorption Bioavailability

Rapidly absorbed following oral administration, with peak plasma concentrations attained within approximately 1 hour.1

Absolute bioavailability is 35%.1 a

Food

Food does not affect pharmacokinetics.1

Special Populations

Increased peak plasma concentrations and AUC in patients with mild to moderate hepatic impairment.1

Distribution Extent

Does not distribute widely into tissues.1

Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

98% (mainly albumin).1

Elimination Metabolism

Almost completely metabolized, principally by isomerization followed by glucuronidation to an inactive conjugate.1

Elimination Route

Entacapone and its metabolites are eliminated principally in feces (90%) via biliary excretion and to a lesser extent in urine (10%).1 3 4

Half-life

Approximately 2.4 hours.1 a

Stability Storage Oral Tablets

25°C (may be exposed to 15–30°C).1

ActionsActions

Structurally and pharmacologically related to tolcapone;1 3 7 however, unlike tolcapone, not associated with hepatotoxicity (e.g., drug-induced hepatitis, fatal liver failure).1 3 4 7

Inhibits catechol-O-methyltransferase (COMT) enzyme in peripheral tissues;1 3 4 effects on central COMT activity in humans not studied.1

Concomitant administration with levodopa and a decarboxylase inhibitor (e.g., carbidopa) results in increased and more sustained plasma levodopa concentrations compared with administration of levodopa and a decarboxylase inhibitor.1 3 4

Lacks antiparkinsonian activity when administered alone.1

Advice to Patients

Importance of taking entacapone as prescribed and not discontinuing abruptly.1

Necessity of exercising caution when driving or operating machinery when entacapone is initiated.1 Caution when taking other CNS depressants.1

Advise that entacapone may cause brownish orange discoloration of urine; not clinically important.1

Advise that hallucinations, nausea, and increased dyskinesia can occur.1

Advise patients not to rise rapidly after prolonged sitting or lying down, especially during first few weeks of therapy.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

Importance of asking patients whether they have developed any new or increased gambling urges, sexual urges, or other urges while receiving entacapone and of advising them of the importance of reporting such urges.1 8

Importance of frequent monitoring for melanoma and periodic dermatologic examinations by a dermatologist.1 8

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

Importance of informing 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.

Entacapone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

200 mg

Comtan

Novartis

Entacapone Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

200 mg with Carbidopa 12.5 mg (of anhydrous carbidopa) and Levodopa 50 mg

Stalevo

Novartis

200 mg with Carbidopa 18.75 mg (of anhydrous carbidopa) and Levodopa 75 mg

Stalevo

Novartis

200 mg with Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 100 mg

Stalevo

Novartis

200 mg with Carbidopa 31.25 mg (of anhydrous carbidopa) and Levodopa 125 mg

Stalevo

Novartis

200 mg with Carbidopa 37.5 mg (of anhydrous carbidopa) and Levodopa 150 mg

Stalevo

Novartis

200 mg with Carbidopa 50 mg (of anhydrous carbidopa) and Levodopa 200 mg

Stalevo

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Comtan 200MG Tablets (NOVARTIS): 30/$112.99 or 90/$310.97

Stalevo 100 25-100-200MG Tablets (NOVARTIS): 90/$318 or 270/$898.92

Stalevo 150 37.5-150-200MG Tablets (NOVARTIS): 30/$113.99 or 90/$334.97

Stalevo 200 50-200-200MG Tablets (NOVARTIS): 100/$363.99 or 300/$1043.97

Stalevo 50 12.5-50-200MG Tablets (NOVARTIS): 30/$110.98 or 90/$317.97

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 February 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Novartis Pharmaceuticals Corporation. Comtan (entacapone) tablets prescribing information. East Hanover, NJ; 2009 Mar.

2. LeWitt PA. New drugs for the treatment of Parkinson’s disease. Pharmacotherapy. 2000; 20:26S-32S.

3. Holm KJ, Spencer CM. Entacapone: a review of its use in Parkinson’s disease. Drugs. 1999; 58:159-77.

4. Anon. Entacapone for Parkinson’s disease. Med Lett Drugs Ther. 2000; 42:7-8.

5. Rinne UK, Larsen JP, Siden A et al. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology. 1998; 51:1309-14.

6. Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol. 1997; 42:747-55.

7. Novartis, East Hanover, NJ: Personal communication.

8. Novartis. Stalevo 50, Stalevo 75, Stalevo 100, Stalevo 125, Stalevo 150, Stalevo 200 (carbidopa, levodopa, and entacapone) tablets prescribing information. East Hanover, NJ; 2009 Mar.

9. Mylan Bertek Pharmaceuticals Inc. Apokyn (apomorphine hydrochloride) injection prescribing information. Research Triangle Park, NC; 2004 Apr.

10. van der Geest R, van Laar T, Kruger PP et al. Pharmacokinetics, enantiomer interconversion, and metabolism of R-apomorphine in patients with idiopathic Parkinson’s disease. Clin Neuropharmacol. 1998; 21:159-68. [PubMed 9617507]

11. Food and Drug Administration. FDA drug safety communication: ongoing safety review of Stalevo (entacapone/carbidopa/levodopa) and possible development of prostate cancer. Rockville, MD; 2010 Mar 31. From FDA website ().

12. Food and Drug Administration. FDA drug safety communication: ongoing safety review of Stalevo and possible increased cardiovascular risk. Rockville, MD; 2010 Aug 20. From FDA website ().

13. Stocchi F, Rascol O, Kieburtz K et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol. 2010; 68:18-27. [PubMed 20582993]

a. Heikkinen H, Saraheimo M, Antila S et al. Pharmacokinetics of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, in man. A study using a stable isotope technique. Eur J Clin Pharmacol. 2001; 56: 821-6. [PubMed 11294372]

More Comtan resources Comtan Side Effects (in more detail) Comtan Dosage Comtan Use in Pregnancy & Breastfeeding Drug Images Comtan Drug Interactions Comtan Support Group 2 Reviews for Comtan - Add your own review/rating Comtan Prescribing Information (FDA) Comtan MedFacts Consumer Leaflet (Wolters Kluwer) Comtan Concise Consumer Information (Cerner Multum) Comtan Advanced Consumer (Micromedex) - Includes Dosage Information Entacapone Professional Patient Advice (Wolters Kluwer) Compare Comtan with other medications Parkinson's Disease
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Soft Tissue Sarcoma Medications


Definition of Soft Tissue Sarcoma: Rhabdomyosarcoma is a malignant (cancerous), soft tissue tumor found in children. The most common sites are the structures of the head and neck, the urogenital tract, and the arms or legs.

Drugs associated with Soft Tissue Sarcoma

The following drugs and medications are in some way related to, or used in the treatment of Soft Tissue Sarcoma. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Topics under Soft Tissue Sarcoma Dermatofibrosarcoma Protuberans (1 drug) Kaposi's Sarcoma (8 drugs) Rhabdomyosarcoma (3 drugs) Learn more about Soft Tissue Sarcoma

Micromedex Care Notes:

Kaposi's Sarcoma

Harvard Health Guide:

Symptoms and treatment for Soft Tissue Sarcoma
Drug List: Adriamycin Trexall
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Dispersible Aspirin Tablets BP 75mg (Boots Company plc)


Boots Dispersible Aspirin Tablets BP 75 mg

Please read this leaflet carefully. It contains important information for you. Keep this leaflet you may need to read it again Ask your pharmacist if you need more information or advice What this medicine is for

This medicine contains Aspirin, which belongs to a group of medicines called antiplatelet agents that help prevent your blood cells sticking together and forming a blood clot.

It can be used to help prevent blood clots in people who have had a stroke, heart attack, by-pass surgery, or who have angina.

This medicine is not for pain relief.

Before you take this medicine

This medicine can be taken by adults. However, some people should not take this medicine or should seek the advice of their pharmacist or doctor first. If you are taking this medicine for the first time, talk to your doctor to make sure it is suitable for you.

Do not take: If you have a stomach ulcer, or have had one If you have haemophilia or other blood clotting disorders If you are allergic to aspirin, or any other non-steroidal anti-inflammatory drug (you may have had asthma, itchy skin or a runny nose after taking them) If you have asthma If you are pregnant or breastfeeding If you have an intolerance to some sugars, unless your doctor tells you to (this medicine contains lactose) Talk to your pharmacist or doctor: If you take other medicines – blood thinning drugs (e.g. warfarin), tablets for diabetes (e.g. glibenclamide), methotrexate (used to treat cancer, skin and rheumatic problems), medicines for gout, corticosteroids (e.g. prednisolone), ibuprofen (for pain and inflammation)

Do not drink alcohol (wine, beer, spirits) whilst taking this medicine.

Other important information

There is a possible association between aspirin and Reye's syndrome when given to children. Reye's syndrome is a very rare disease, which can be fatal. For this reason aspirin should not be given to children aged under 16 years, unless on the advice of a doctor.

How to take this medicine

Check that the bottle seal is not broken before first use. If it is, do not take the tablets.

These tablets are dispersible. This means that they break up in water. Stir the tablet in a small glass of water until dispersed and drink immediately.

Adults
Take one or two tablets
Take once a day

Do not give to children under 16 years, unless your doctor tells you to.

In some cases your doctor may advise you to take up to four tablets a day. In this case follow your doctor's instructions.

Do not take more than the amount recommended above.

If you take too many tablets: Talk to a pharmacist or doctor straight away.

Possible side effects

Most people will not have problems, but some may get some of these:

If you get any of these, stop the tablets.

See a doctor at once:

You have black tarry stools, severe stomach pain, are sick and there is blood in it Allergic reactions such as difficulty breathing, swelling of the face, lips or throat, itchy, lumpy skin, runny nose These other effects may not bother you.

If they do, talk to a pharmacist:

Feeling sick, or being sick Indigestion, mild stomach pain

If any side effect becomes severe, or if you notice any side effect not listed here, please tell your pharmacist or doctor.

How to store this medicine

Keep this medicine in a safe place out of the sight and reach of children, preferably in a locked cupboard.

Use by the date on the label edge.

What is in this medicine

Each dispersible tablet contains Aspirin 75 mg, which is the active ingredient.

As well as the active ingredient, each tablet also contains calcium carbonate, maize starch, lactose, anhydrous citric acid, sodium saccharin, sodium lauryl sulphate, povidone.

The pack contains 100 round, white tablets.

Who makes this medicine Manufactured for the Marketing Authorisation holder The Boots Company PLC Nottingham NG2 3AA

by

Hamol Limited Nottingham NG90 2DB

PL00014/5322

P

Leaflet prepared November 2008

If you would like any further information about this medicine, please contact

The Boots Company PLC Nottingham NG2 3AA

BTC8368 vC 15/12/08


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