Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp. - carbamazepine (unii: 33cm23913m) (carbamazepine - unii:33cm23913m) - carbamazepine 100 mg - carbamazepine extended-release capsules are indicated for use as an anticonvulsant drug. evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: - partial seizures with complex symptomatology (psychomotor, temporal lobe). patients with these seizures appear to show greater improvements than those with other types. - generalized tonic-clonic seizures (grand mal). - mixed seizure patterns which include the above, or other partial or generalized seizures. absence seizures (petit mal) do not appear to be controlled by carbamazepine (see precautions, general ). carbamazepine extended-release capsules are indicated in the treatment of the pain associated with true trigeminal neuralgia. beneficial results have also been reported in glossopharyngeal neuralgia. this drug is not a simple analgesic and should not be used for the relief of trivial aches or pains. carbamazepine should not be used in patient

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp - quinapril hydrochloride (unii: 33067b3n2m) (quinaprilat - unii:34ssx5lde5), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - quinapril 10 mg - hypertension quinapril hydrochloride and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with quinapril hydrochloride and hydrochlorothiazide. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education progr

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp. - cyclosporine (unii: 83hn0gtj6d) (cyclosporine - unii:83hn0gtj6d) - cyclosporine 25 mg - cyclosporine capsules, (non-modified) are indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. it is always to be used with adrenal corticosteroids. the drug may also be used in the treatment of chronic rejection in patients previously treated with other immunosuppressive agents.    cyclosporine capsules are contraindicated in patients with a hypersensitivity to cyclosporine or to any of the ingredients of the formulation.

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp. - selegiline hydrochloride (unii: 6w731x367q) (selegiline - unii:2k1v7gp655) - selegiline hydrochloride tablets usp are indicated as an adjunct in the management of parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. there is no evidence from controlled studies that selegiline has any beneficial effect in the absence of concurrent levodopa therapy. evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added selegiline or placebo in patients receiving levodopa/carbidopa. selegiline was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state). selegiline hydrochloride is contraindicated in patients with a known hypersensitivity to this drug. selegiline is contraindicated for use with meperidine. this contraindication is often extended to other opioids. (see drug interactions .)

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp - abacavir sulfate (unii: j220t4j9q2) (abacavir - unii:wr2tip26vs) - abacavir 300 mg - abacavir tablets, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (hiv-1) infection. abacavir tablets are contraindicated in patients: - who have the hla-b*5701 allele [see warnings and precautions (5.1)]. - with prior hypersensitivity reaction to abacavir [see warnings and precautions (5.1)].  - with moderate or severe hepatic impairment [see use in specific populations (8.6)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary available data from the apr show no difference in the overall risk of birth defects for abacavir compared with the background rate for birth defects of 2.7% in the metropolitan atlanta congenital defects program (macdp) reference population (see data). the apr uses the macdp a

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp - teriflunomide (unii: 1c058ikg3b) (teriflunomide - unii:1c058ikg3b) - teriflunomide tablets are indicated for the treatment of relapsing forms of multiple sclerosis (ms), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. teriflunomide tablets are contraindicated in/with: - patients with severe hepatic impairment [see warnings and precautions (5.1)] . - pregnant women and females of reproductive potential not using effective contraception. teriflunomide tablets may cause fetal harm [see warnings and precautions (5.2, 5.3) and use in specific populations (8.1)] . - patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in teriflunomide tablets. reactions have included anaphylaxis, angioedema, and serious skin reactions [see warnings and precautions (5.5)]. - coadministration with leflunomide [see clinical pharmacology (12.3)]. risk summary teriflunomide tablets are contraindicated for use in pregnant women and females of reproduct

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp. - levetiracetam (unii: 44yrr34555) (levetiracetam - unii:44yrr34555) - levetiracetam 500 mg - levetiracetam extended-release tablets are indicated for the treatment of partial-onset seizures in patients 12 years of age and older. levetiracetam extended-release tablets are contraindicated in patients with a hypersensitivity to levetiracetam. reactions have included anaphylaxis and angioedema [see warnings and precautions (5.4)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), including levetiracetam extended-release tablets, during pregnancy. encourage women who are taking levetiracetam extended-release tablets during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary prolonged experience with levetiracetam tablets in pregnant women has not identified a drug-associated risk of major birth defects or miscarriage, based on published literature, which includes data from pregnancy re

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp. - tetrabenazine (unii: z9o08yrn8o) (tetrabenazine - unii:z9o08yrn8o) - tetrabenazine tablets are indicated for the treatment of chorea associated with huntington's disease. tetrabenazine tablets are contraindicated in patients: - who are actively suicidal, or in patients with untreated or inadequately treated depression [see warnings and precautions (5.1)] . who are actively suicidal, or in patients with untreated or inadequately treated depression [see warnings and precautions (5.1)] . - with hepatic impairment [see use in specific populations (8.6), clinical pharmacology (12.3)] . with hepatic impairment [see use in specific populations (8.6), clinical pharmacology (12.3)] . - taking monoamine oxidase inhibitors (maois). tetrabenazine tablets should not be used in combination with an maoi, or within a minimum of 14 days of discontinuing therapy with an maoi [see drug interactions (7.3)] . taking monoamine oxidase inhibitors (maois). tetrabenazine tablets should not be used in combination with an maoi, or within a minimum of 14 days of discontinuing therapy with an maoi [see drug interactions (7.3)] . - taking reserpine. at least 20 days should elapse after stopping reserpine before starting tetrabenazine tablets [see drug interactions (7.2)] . taking reserpine. at least 20 days should elapse after stopping reserpine before starting tetrabenazine tablets [see drug interactions (7.2)] . - taking deutetrabenazine or valbenazine [see drug interactions (7.7)] . taking deutetrabenazine or valbenazine [see drug interactions (7.7)] . risk summary there are no adequate data on the developmental risk associated with the use of tetrabenazine in pregnant women. administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality. administration of a major human metabolite of tetrabenazine to rats during pregnancy or during pregnancy and lactation produced adverse effects on the developing fetus and offspring (increased mortality, decreased growth, and neurobehavioral and reproductive impairment). the adverse developmental effects of tetrabenazine and a major human metabolite of tetrabenazine in rats occurred at clinically relevant doses [see data] .   in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. the background risk of major birth defects and miscarriage for the indicated population is unknown.   data   animal data tetrabenazine had no clear effects on embryofetal development when administered to pregnant rats throughout the period of organogenesis at oral doses up to 30 mg/kg/day (or 3 times the maximum recommended human dose [mrhd] of 100 mg/day on a mg/m2 basis). tetrabenazine had no effects on embryofetal development when administered to pregnant rabbits during the period of organogenesis at oral doses up to 60 mg/kg/day (or 12 times the mrhd on a mg/m2 basis).   when tetrabenazine (5, 15, and 30 mg/kg/day) was orally administered to pregnant rats from the beginning of organogenesis through the lactation period, an increase in stillbirths and offspring postnatal mortality was observed at 15 and 30 mg/kg/day and delayed pup maturation was observed at all doses. a no-effect dose for pre- and postnatal developmental toxicity in rats was not identified. the lowest dose tested (5 mg/kg/day) was less than the mrhd on a mg/m2 basis.   because  rats dosed orally with tetrabenazine do not produce 9-desmethyl-β-dhtbz, a major human metabolite of tetrabenazine, the metabolite was directly administered to pregnant and lactating rats. oral administration of 9-desmethyl-β-dhtbz (8, 15, and 40 mg/kg/day) throughout the period of organogenesis produced increases in embryofetal mortality at 15 and 40 mg/kg/day and reductions in fetal body weights at 40 mg/kg/day, which was also maternally toxic. when 9-desmethyl-β-dhtbz (8, 15, and 40 mg/kg/day) was orally administered to pregnant rats from the beginning of organogenesis through the lactation period, increases in gestation duration, stillbirths, and offspring postnatal mortality (40 mg/kg/day); decreases in pup weights (40 mg/kg/day); and neurobehavioral (increased activity, learning and memory deficits) and reproductive (decreased litter size) impairment (15 and 40 mg/kg/day) were observed. maternal toxicity was seen at the highest dose. the no-effect dose for developmental toxicity in rats (8 mg/kg/day) was associated with plasma exposures (auc) of 9-desmethyl-β-dhtbz in pregnant rats lower than that in humans at the mrhd. risk summary there are no data on the presence of tetrabenazine or its metabolites in human milk, the effects on the breastfed infant, or the effects of the drug on milk production.   the  developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tetrabenazine and any potential adverse effects on the breastfed infant from tetrabenazine or from the underlying maternal condition.   safety and effectiveness in pediatric patients have not been established. the pharmacokinetics of tetrabenazine and its primary metabolites have not been formally studied in geriatric subjects. because the safety and efficacy of the increased exposure to tetrabenazine and other circulating metabolites are unknown, it is not possible to adjust the dosage of tetrabenazine in hepatic impairment to ensure safe use. the use of tetrabenazine in patients with hepatic impairment is contraindicated [see contraindications (4), clinical pharmacology (12.3)] . patients who require doses of tetrabenazine tablets greater than 50 mg per day, should be first tested and genotyped to determine if they are poor (pms) or extensive metabolizers (ems) by their ability to express the drug metabolizing enzyme, cyp2d6. the dose of tetrabenazine should then be individualized accordingly to their status as either poor (pms) or extensive metabolizers (ems) [see dosage and administration (2.2), warnings and precautions (5.3), clinical pharmacology (12.3)] .   poor metabolizers   poor cyp2d6 metabolizers (pms) will have substantially higher levels of exposure to the primary metabolites (about 3-fold for α-htbz and 9-fold for β-htbz) compared to ems. the dosage should, therefore, be adjusted according to a patient’s cyp2d6 metabolizer status by limiting a single dose to a maximum of 25 mg and the recommended daily dose to not exceed a maximum of 50 mg/day in patients who are cyp2d6 pms [see dosage and administration (2.2), warnings and precautions (5.3), clinical pharmacology (12.3)] .   extensive/intermediate metabolizers   in extensive (ems) or intermediate metabolizers (ims), the dosage of tetrabenazine can be titrated to a maximum single dose of 37.5 mg and a recommended maximum daily dose of 100 mg [see dosage and administration (2.2), drug interactions (7.1), clinical pharmacology (12.3)]. tetrabenazine is not a controlled substance. clinical trials did not reveal patients developed drug seeking behaviors, though these observations were not systematic. abuse has not been reported from the postmarketing experience in countries where tetrabenazine has been marketed. as with any cns-active drug, prescribers should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of tetrabenazine misuse or abuse (such as development of tolerance, increasing dose requirements, drug-seeking behavior). abrupt discontinuation of tetrabenazine from patients did not produce symptoms of withdrawal or a discontinuation syndrome; only symptoms of the original disease were observed to re-emerge [see dosage and administration (2.4)].

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp. - pazopanib (unii: 7rn5dr86ck) (pazopanib - unii:7rn5dr86ck) - pazopanib tablets are indicated for the treatment of adults with advanced renal cell carcinoma (rcc). pazopanib tablets are indicated for the treatment of adults with advanced soft tissue sarcoma (sts) who have received prior chemotherapy. limitations of use : the efficacy of pazopanib tablets for the treatment of patients with adipocytic sts or gastrointestinal stromal tumors has not been demonstrated. none. risk summary based on animal reproduction studies and its mechanism of action [see clinical pharmacology (12.1)], pazopanib tablets can cause fetal harm when administered to a pregnant woman. there are no available data on pazopanib tablets use in pregnant women to evaluate for a drug-associated risk. in animal developmental and reproductive toxicology studies, oral administration of pazopanib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity, and abortion at systemic exposures lower than that observed at the mrhd of 800 mg/day (based on auc) (see data). advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects in clinically recognized pregnancies and miscarriage is 2% to 4% and 15% to 20%, respectively. data animal data in a female fertility and early embryonic development study, female rats were administered oral pazopanib at least 15 days prior to mating and for 6 days after mating, which resulted in increased pre-implantation loss and early resorptions at dosages greater than or equal to 30 mg/kg/day (approximately 0.4-fold the auc at the mrhd of 800 mg/day). total litter resorption was seen at 300 mg/kg/day (approximately 0.8-fold the auc at the mrhd of 800 mg/day). postimplantation loss, embryolethality, and decreased fetal body weights were noted in females administered doses greater than or equal to 10 mg/kg/day (approximately 0.3-fold the auc at the mrhd of 800 mg/day). in embryo-fetal developmental toxicity studies in rats and rabbits, oral pazopanib was administered to pregnant animals during organogenesis. in rats, dose levels of greater than or equal to 3 mg/kg/day (approximately 0.1-fold the auc at the mrhd of 800 mg/day) resulted in teratogenic effects, including cardiovascular malformations (retroesophageal subclavian artery, missing innominate artery, changes in the aortic arch), incomplete or absent ossification, increases in postimplantation loss, embryolethality and reduced fetal body weight. in rabbits, maternal toxicity, increased postimplantation loss and abortion were observed at doses greater than or equal to 30 mg/kg/day (approximately 0.007-fold the auc at the mrhd of 800 mg/day). in addition, severe maternal body weight loss and 100% litter loss were observed at doses greater than or equal to 100 mg/kg/day (0.02-fold the auc at the mrhd of 800 mg/day), while fetal weight was reduced at doses greater than or equal to 3 mg/kg/day (auc not calculated). risk summary there is no data on the presence of pazopanib or its metabolites in human milk or their effects on the breastfed infant or milk production. because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with pazopanib tablets and for 2 weeks after the final dose. pazopanib tablets can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)). pregnancy testing verify pregnancy status of females of reproductive potential prior to starting treatment with pazopanib tablets. contraception females advise females of reproductive potential to use effective contraception during treatment with pazopanib tablets and for at least 2 weeks after the last dose. males advise males (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment with pazopanib tablets and for at least 2 weeks after the last dose. infertility based on findings from animal studies, pazopanib tablets may impair fertility in females and males of reproductive potential while receiving treatment [see nonclinical toxicology (13.1) ]. the safety and effectiveness of pazopanib tablets in pediatric patients have not been established. pazopanib tablets are not indicated for use in pediatric patients [see warnings and precautions (5.18)] . based on its mechanism of action, pazopanib may have severe effects on organ growth and maturation during early postnatal development. administration of pazopanib to juvenile rats < 21 days old resulted in toxicity to the lungs, liver, heart, and kidney and in death at doses significantly lower than the clinically recommended dose or doses tolerated in older animals (see juvenile animal toxicity data). the safety and efficacy of pazopanib tablets or an unapproved pazopanib formulation were investigated but not established in two open-label studies: a study in 37 pediatric patients 2 to < 17 years with recurrent or refractory solid tumors [nct00929903] and a study in 46 pediatric patients 1 year to < 17 years with refractory solid tumors, including sarcoma [nct01956669]. meaningful anti-tumor activity was not observed in these studies. juvenile animal toxicity data in rats, weaning occurs at day 21 postpartum which approximately equates to a human pediatric age of 2 years. in a juvenile animal toxicology study performed in rats, when animals were dosed from day 9 through day 14 postpartum (pre-weaning), pazopanib caused abnormal organ growth/maturation in the kidney, lung, liver, and heart at approximately 0.1-fold the auc in adults at the mrhd of 800 mg/day of pazopanib. at approximately 0.4-fold the auc in adults at the mrhd of 800 mg/day, pazopanib administration resulted in mortality. in repeat-dose toxicology studies in rats, including 4-week, 13-week, and 26-week administration, toxicities in bone, teeth, and nail beds were observed at doses greater than or equal to 3 mg/kg/day (approximately 0.07-fold the auc at the mrhd of 800 mg/day). doses of 300 mg/kg/day (approximately 0.8-fold the auc at the mrhd of 800 mg/day) were not tolerated in 13- and 26-week studies and animals required dose reductions due to body weight loss and morbidity. hypertrophy of epiphyseal growth plates, nail abnormalities (including broken, overgrown, or absent nails) and tooth abnormalities in growing incisor teeth (including excessively long, brittle, broken, and missing teeth, and dentine and enamel degeneration and thinning) were observed in rats at doses greater than or equal to 30 mg/kg/day (approximately 0.35-fold the auc at the mrhd of 800 mg/day) at 26 weeks, with the onset of tooth and nail bed alterations noted clinically after 4 to 6 weeks. similar findings were noted in repeat-dose studies in juvenile rats dosed with pazopanib beginning day 21 postpartum (post-weaning). in the post-weaning animals, the occurrence of changes in teeth and bones occurred earlier and with greater severity than in older animals. there was evidence of tooth degeneration and decreased bone growth at doses greater than or equal to 30 mg/kg (approximately 0.1- to 0.2-fold the auc at the mrhd of 800 mg/day). pazopanib exposure in juvenile rats was lower than that seen at the same dose levels in adult animals, based on comparative auc values. at pazopanib doses approximately 0.5- to 0.7-fold the auc at the mrhd of 800 mg/day, decreased bone growth in juvenile rats persisted even after the end of the dosing period. finally, despite lower pazopanib exposures than those reported in adult animals or adult humans, juvenile animals administered 300 mg/kg/dose pazopanib required dose reduction within 4 weeks of dosing initiation due to significant toxicity, although adult animals could tolerate this same dose for at least 3 times as long [see warnings and precautions (5.18)].  in pooled clinical trials with pazopanib tablets, 30% of 2,080 patients were aged ≥ 65 years. more patients ≥ 65 years had alt elevations > 3 x uln compared to patients < 65 years (23% versus 18%) [see warnings and precautions (5.1)]. in the rcc trials, 33% of 586 patients were aged ≥ 65 years. no overall differences in safety or effectiveness of pazopanib tablets were observed between these patients and younger patients. in the sts trials, 24% of 382 patients were aged ≥ 65 years. patients aged ≥ 65 years had a higher incidence of grade 3 or 4 fatigue (19% versus 12% for patients aged < 65 years), hypertension (10% versus 6%), decreased appetite (11% versus 2%), alt elevations (3% versus 2%) and ast elevations (4% versus 1%). in the randomized sts trial (veg110727), no overall differences in effectiveness of pazopanib tablets were observed between patients aged ≥ 65 years and younger patients. no dose adjustment is recommended for patients with renal impairment. pazopanib tablets have not been studied in patients with severe renal impairment or in patients undergoing peritoneal dialysis or hemodialysis. no dose adjustment is required in patients with mild hepatic impairment (either total bilirubin ≤ uln and alt > uln or bilirubin > 1 to 1.5 x uln and any alt value). pazopanib tablets are not recommended in patients with moderate (total bilirubin > 1.5 to 3 x uln and any alt value) and severe (total bilirubin > 3 x uln and any alt value) hepatic impairment [see dosage and administration (2.3), clinical pharmacology (12.3) ].

Marekani - Kiingereza - NLM (National Library of Medicine)

apotex corp. - clopidogrel bisulfate (unii: 08i79htp27) (clopidogrel - unii:a74586sno7) - clopidogrel 75 mg - - clopidogrel tablets are indicated to reduce the rate of myocardial infarction (mi) and stroke in patients with non-st-segment elevation acs (unstable angina [ua]/non-st-elevation myocardial infarction [nstemi]), including patients who are to be managed medically and those who are to be managed with coronary revascularization. clopidogrel should be administered in conjunction with aspirin. - clopidogrel tablets are indicated to reduce the rate of myocardial infarction and stroke in patients with acute st-elevation myocardial infarction (stemi) who are to be managed medically. clopidogrel tablets should be administered in conjunction with aspirin. in patients with established peripheral arterial disease or with a history of recent myocardial infarction (mi) or recent stroke clopidogrel tablets are indicated to reduce the rate of mi and stroke. clopidogrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage. clopidogrel tablets are contrai