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lupin pharmaceuticals, inc. - eszopiclone (unii: uzx80k71oe) (eszopiclone - unii:uzx80k71oe) - eszopiclone 1 mg - eszopiclone tablet is indicated for the treatment of insomnia. in controlled outpatient and sleep laboratory studies, eszopiclone tablets administered at bedtime decreased sleep latency and improved sleep maintenance. the clinical trials performed in support of efficacy were up to 6 months in duration. the final formal assessments of sleep latency and maintenance were performed at 4 weeks in the 6-week study (adults only), at the end of both 2-week studies (elderly only) and at the end of the 6-month study (adults only). - eszopiclone is contraindicated in patients who have experienced complex sleep behaviors after taking eszopiclone [see warnings and precautions (5.1)]. - eszopiclone is contraindicated in patients with known hypersensitivity to eszopiclone. hypersensitivity reactions include anaphylaxis and angioedema [see warnings and precautions (5.3)] . risk summary available pharmacovigilance data with eszopiclone use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies conducted in pregnant rats and rabbits throughout organogenesis, there was no evidence of teratogenicity. administration of eszopiclone to rats throughout pregnancy and lactation resulted in offspring toxicities at all doses tested; the lowest dose was approximately 200 times the maximum recommended human dose (mrhd) of 3 mg/day based on mg/m2 body surface area (see data). 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 and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data: oral administration of eszopiclone to pregnant rats (62.5, 125, or 250 mg/kg/day) and rabbits (4, 8, or 16 mg/kg/day) throughout organogenesis showed no evidence of teratogenicity up to the highest doses tested. in rats, reduced fetal weight and increased incidences of skeletal variations and/or delayed ossification were observed at the mid and high doses. the no-observed-effect dose for adverse effects on embryofetal development is 200 times the mrhd of 3 mg/day on a mg/m2 basis. no effects on embryofetal development were observed in rabbits; the highest dose tested is approximately 100 times the mrhd on a mg/m2 basis. oral administration of eszopiclone (60, 120, or 180 mg/kg/day) to pregnant rats throughout the pregnancy and lactation resulted in increased post-implantation loss, decreased postnatal pup weights and survival, and increased pup startle response at all doses. the lowest dose tested is approximately 200 times the mrhd on a mg/m2 basis. eszopiclone had no effects on other developmental measures or reproductive function in the offspring. risk summary there are no data on the presence of eszopiclone in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for eszopiclone and any potential adverse effects on the breastfed infant from eszopiclone or from the underlying maternal condition. safety and effectiveness of eszopiclone have not been established in pediatric patients. eszopiclone failed to demonstrate efficacy in controlled clinical studies of pediatric patients with attention-deficit/hyperactivity (adhd) associated insomnia. in a 12-week controlled study, 483 pediatric patients (aged 6 to 17 years) with insomnia associated with adhd (with 65% of the patients using concomitant adhd treatments) were treated with oral tablets of eszopiclone (1, 2 or 3 mg tablets, n=323), or placebo (n=160). eszopiclone did not significantly decrease latency to persistent sleep, compared to placebo, as measured by polysomnography after 12 weeks of treatment. psychiatric and nervous system disorders comprised the most frequent treatment-emergent adverse reactions observed with eszopiclone versus placebo and included dysgeusia (9% vs. 1%), dizziness (6% vs. 2%), hallucinations (2% vs. 0%) and suicidal ideation (0.3% vs. 0%). nine patients on eszopiclone (3%) discontinued treatment due to an adverse reaction compared to 3 patients on placebo (2%). in studies in which eszopiclone (2 to 300 mg/kg/day) was orally administered to young rats from weaning through sexual maturity, neurobehavioral impairment (altered auditory startle response) and reproductive toxicity (adverse effects on male reproductive organ weights and histopathology) were observed at doses ≥ 5 mg/kg/day. delayed sexual maturation was noted in males and females at ≥10 mg/kg/day. the no-effect dose (2 mg/kg) was associated with plasma exposures (auc) for eszopiclone and metabolite (s)-desmethylzopiclone [(s)-dmz] approximately 2 times plasma exposures in humans at the mrhd in adults (3 mg/day). when eszopiclone (doses from 1 to 50 mg/kg/day) was orally administered to young dogs from weaning through sexual maturity, neurotoxicity (convulsions) was observed at doses ≥ 5 mg/kg/day. hepatotoxicity (elevated liver enzymes and hepatocellular vacuolation and degeneration) and reproductive toxicity (adverse effects on male reproductive organ weights and histopathology) were noted at doses ≥10 mg/kg/day. the no-effect dose (1 mg/kg) was associated with plasma exposures (auc) to eszopiclone and (s)-dmz approximately 3 and 2 times, respectively, plasma exposures in humans at the mrhd in adults. a total of 287 subjects in double-blind, parallel-group, placebo-controlled clinical trials who received eszopiclone were 65 to 86 years of age. the overall pattern of adverse events for elderly subjects (median age = 71 years) in 2-week studies with nighttime dosing of 2 mg eszopiclone was not different from that seen in younger adults [see adverse reactions (6)] . eszopiclone 2 mg exhibited significant reduction in sleep latency and improvement in sleep maintenance in the elderly population. compared with nonelderly adults, subjects 65 years and older had longer elimination and higher total exposure to eszopiclone. therefore, dose reduction is recommended in elderly patients [see dosage and administration (2.2), clinical pharmacology (12.3)] . no dose adjustment is necessary for patients with mild-to-moderate hepatic impairment. exposure was increased in severely impaired patients compared with healthy volunteers. the dose of eszopiclone should not exceed 2 mg in patients with severe hepatic impairment. eszopiclone should be used with caution in patients with hepatic impairment [see dosage and administration (2.3), clinical pharmacology (12.3)] . eszopiclone is a schedule iv controlled substance under the controlled substances act. other substances under the same classification are benzodiazepines and the nonbenzodiazepine hypnotics zaleplon and zolpidem. while eszopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, it shares some of the pharmacologic properties of the benzodiazepines. abuse and addiction are separate and distinct from physical dependence and tolerance. abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist. tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time. tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects. addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. it is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common. in a study of abuse liability conducted in individuals with known histories of benzodiazepine abuse, eszopiclone at doses of 6 and 12 mg produced euphoric effects similar to those of diazepam 20 mg. in this study, at doses 2-fold or greater than the maximum recommended doses, a dose-related increase in reports of amnesia and hallucinations was observed for both eszopiclone and diazepam. the clinical trial experience with eszopiclone revealed no evidence of a serious withdrawal syndrome. nevertheless, the following adverse events included in dsm-iv criteria for uncomplicated sedative/hypnotic withdrawal were reported during clinical trials following placebo substitution occurring within 48 hours following the last eszopiclone treatment: anxiety, abnormal dreams, nausea, and upset stomach. these reported adverse events occurred at an incidence of 2% or less. use of benzodiazepines and similar agents may lead to physical and psychological dependence. the risk of abuse and dependence increases with the dose and duration of treatment and concomitant use of other psychoactive drugs. the risk is also greater for patients who have a history of alcohol or drug abuse or history of psychiatric disorders. these patients should be under careful surveillance when receiving eszopiclone or any other hypnotic. some loss of efficacy to the hypnotic effect of benzodiazepines and benzodiazepine-like agents may develop after repeated use of these drugs for a few weeks. no development of tolerance to any parameter of sleep measurement was observed over six months. tolerance to the efficacy of eszopiclone 3 mg was assessed by 4-week objective and 6-week subjective measurements of time to sleep onset and sleep maintenance for eszopiclone in a placebo-controlled 44-day study, and by subjective assessments of time to sleep onset and wake time after sleep onset (waso) in a placebo-controlled study for 6 months.

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lupin pharmaceuticals, inc. - drospirenone (unii: n295j34a25) (drospirenone - unii:n295j34a25), ethinyl estradiol (unii: 423d2t571u) (ethinyl estradiol - unii:423d2t571u), levomefolate calcium (unii: a9r10k3f2f) (levomefolic acid - unii:8s95dh25xc) - drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets are indicated for use by women to prevent pregnancy. drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets are also indicated for the treatment of symptoms of premenstrual dysphoric disorder (pmdd) in women who choose to use an oral contraceptive as their method of contraception. the effectiveness of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets for pmdd when used for more than three menstrual cycles has not been evaluated. the essential features of pmdd according to the diagnostic and statistical manual-4th edition (dsm-iv) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. physical symptoms associat

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lupin pharmaceuticals, inc. - clobazam (unii: 2mro291b4u) (clobazam - unii:2mro291b4u) - clobazam tablets are indicated for the adjunctive treatment of seizures associated with lennox-gastaut syndrome (lgs) in patients 2 years of age or older. clobazam is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. hypersensitivity reactions have included serious dermatological reactions [see warnings and precautions (5.6)]. pregnancy registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as clobazam, during pregnancy. healthcare providers are encouraged to recommend that pregnant women taking clobazam enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or online at http://www.aedpregnancyregistry.org/. risk summary neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see warnings and precaution (5.8) and clinical  considerations] . available data from published obse

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lupin pharmaceuticals, inc. - phenytoin sodium (unii: 4182431bjh) (phenytoin - unii:6158tkw0c5) - extended phenytoin sodium capsules are indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. extended phenytoin sodium capsules are contraindicated in patients with: - a history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see warnings and precautions (4,5.5)]. reactions have included angioedema. - a history of prior acute hepatotoxicity attributable to phenytoin [see warnings and precautions (4, 5.8)]. - coadministration with delavirdine because of the potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), such as extended phenytoin sodium capsules, during pregnancy. physicians are advised to recommend that p

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lupin pharmaceuticals, inc. - drospirenone (unii: n295j34a25) (drospirenone - unii:n295j34a25), ethinyl estradiol (unii: 423d2t571u) (ethinyl estradiol - unii:423d2t571u), levomefolate calcium (unii: a9r10k3f2f) (levomefolic acid - unii:8s95dh25xc) - drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets are indicated for use by women to prevent pregnancy. drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets are also indicated for the treatment of symptoms of premenstrual dysphoric disorder (pmdd) in women who choose to use an oral contraceptive as their method of contraception. the effectiveness of drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets for pmdd when used for more than three menstrual cycles has not been evaluated. the essential features of pmdd according to the diagnostic and statistical manual-4th edition (dsm-iv) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. physical symptoms associat

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lupin pharmaceuticals, inc. - lurasidone hydrochloride (unii: o0p4i5851i) (lurasidone - unii:22ic88528t) - lurasidone hydrochloride tablets are indicated for: - treatment of adult and adolescent patients (13 to 17 years) with schizophrenia [see clinical studies (14.1)] . - monotherapy treatment of adult and pediatric patients (10 to 17 years) with major depressive episode associated with bipolar i disorder (bipolar depression) [see clinical studies (14.2)] . - adjunctive treatment with lithium or valproate in adult patients with major depressive episode associated with bipolar i disorder (bipolar depression) [see clinical studies (14.2)] . - known hypersensitivity to lurasidone hcl or any components in the formulation. angioedema has been observed with lurasidone [see adverse reactions (6.1)] . - strong cyp3a4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see drug interactions (7.1)]. - strong cyp3a4 inducers (e.g., rifampin, avasimibe, st. john's wort, phenytoin, carbamazepine, etc.) [see drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lurasidone hydrochloride during pregnancy. for more information, contact the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery [see clinical considerations] . there are no studies of lurasidone hydrochloride use in pregnant women. the limited available data are not sufficient to inform a drug-associated risk of birth defects or miscarriage. in animal reproduction studies, no teratogenic effects were seen in pregnant rats and rabbits given lurasidone during the period of organogenesis at doses approximately 1.5- and 6-times, the maximum recommended human dose (mrhd) of 160 mg/day, respectively based on mg/m2 body surface area [ s e e data] . the estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to20%, respectively. clinical considerations fetal/neonatal adverse reactions: extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. these symptoms have varied in severity. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. data animal data: pregnant rats were treated with oral lurasidone at doses of 3, 10, and 25 mg/kg/day during the period of organogenesis. these doses are 0.2, 0.6, and 1.5 times the mrhd of 160 mg/day based on mg/m2 body surface area. no teratogenic or embryo-fetal effects were observed up to 1.5 times the mrhd of 160 mg/day, based on mg/m2 . pregnant rabbits were treated with oral lurasidone at doses of 2, 10, and 50 mg/kg/day during the period of organogenesis. these doses are 0.2, 1.2 and 6 times the mrhd of 160 mg/day based on mg/m2 . no teratogenic or embryo-fetal effects were observed up to 6 times the mrhd of 160 mg/day based on mg/m2 . pregnant rats were treated with oral lurasidone at doses of 0.4, 2, and 10 mg/kg/day during the periods of organogenesis and lactation. these doses are 0.02, 0.1 and 0.6 times the mrhd of 160 mg/day based on mg/m2 . no pre- and postnatal developmental effects were observed up to 0.6 times the mrhd of 160 mg/day, based on mg/m2 . risk summary lactation studies have not been conducted to assess the presence of lurasidone in human milk, the effects on the breastfed infant, or the effects on milk production. lurasidone is present in rat milk. the development and health benefits of breastfeeding should be considered along with the mother's clinical need for lurasidone hydrochloride and any potential adverse effects on the breastfed infant from lurasidone hydrochloride or from the underlying maternal condition. schizophrenia the safety and effectiveness of lurasidone hydrochloride 40-mg/day and 80-mg/day for the treatment of schizophrenia in adolescents (13 to 17 years) was established in a 6-week, placebocontrolled clinical study in 326 adolescent patients [see dosage and administration ( 2.1 ), adverse reactions ( 6.1 ), and clinical studies ( 14.1 )]. the safety and effectiveness of lurasidone hydrochloride has not been established in pediatric patients less than 13 years of age with schizophrenia. bipolar depression the safety and effectiveness of lurasidone hydrochloride 20 to 80 mg/day for the treatment of bipolar depression in pediatric patients (10 to 17 years) was established in a 6-week, placebocontrolled clinical study in 347 pediatric patients [see dosage and administration ( 2.2 ), adverse reactions ( 6.1 ), and clinical studies (14.2)]. the safety and effectiveness of lurasidone hydrochloride has not been established in pediatric patients less than 10 years of age with bipolar depression. irritability associated with autistic disorder the effectiveness of lurasidone hydrochloride in pediatric patients for the treatment of irritability associated with autistic disorder has not been established. efficacy was not demonstrated in a 6-week study evaluating lurasidone hydrochloride 20 mg/day and 60 mg/day for the treatment of pediatric patients 6 to 17 years of age with irritability associated with autistic disorder diagnosed by diagnostic and statistical manual of mental disorders, 4th ed., text revision [dsm-iv-tr] criteria. the primary objective of the study as measured by improvement from baseline in the irritability subscale of the aberrant behavior checklist (abc) at endpoint (week 6) was not met. a total of 149 patients were randomized to lurasidone hydrochloride or placebo. vomiting occurred at a higher rate than reported in other lurasidone hydrochloride studies (4/49 or 8% for 20mg, 14/51 or 27% for 60mg, and 2/49 or 4% for placebo), particularly in children ages 6 to 12 (13 out of 18 patients on lurasidone hydrochloride with vomiting). in a long-term, open-label study that enrolled pediatric patients (age 6 to 17 years) with schizophrenia, bipolar depression, or autistic disorder from three short-term, placebo-controlled trials, 54% (378/701) received lurasidone for 104 weeks. there was one adverse event in this trial that was considered possibly drug-related and has not been reported in adults receiving lurasidone: a 10 year old male experienced a prolonged, painful erection, consistent with priapism, that led to treatment discontinuation. in this trial, the mean increase in height from open-label baseline to week 104 was 4.94 cm. to adjust for normal growth, z-scores were derived (measured in standard deviations [sd]), which normalize for the natural growth of children and adolescents by comparisons to age- and sex-matched population standards. a z-score change <0.5 sd is considered not clinically significant. in this trial, the mean change in height z-score from open-label baseline to week 104 was +0.05 sd, indicating minimal deviation from the normal growth curve. juvenile animal studies adverse effects were seen on growth, physical and neurobehavioral development at doses as low as 0.2 times the mrhd based on mg/m2 . lurasidone was orally administered to rats from postnatal days 21 through 91 (this period corresponds to childhood, adolescence, and young adulthood in humans) at doses of 3, 30, and 150 (males) or 300 (females) mg/kg/day which are 0.2 to 10 times (males) and 20 times (females) the maximum recommended adult human dose (mrhd) of 160 mg/day based on mg/m2 . the adverse effects included dose-dependent decreases in femoral length, bone mineral content, body and brain weights at 2 times the mrhd in both sexes, and motor hyperactivity at 0.2 and 2 times the mrhd in both sexes based on mg/m2 . in females, there was a delay in attainment of sexual maturity at 2 times the mrhd, associated with decreased serum estradiol. mortality occurred in both sexes during early post- weaning period and some of the male weanlings died after only 4 treatments at doses as low as 2 times the mrhd based on mg/m2 . histopathological findings included increased colloid in the thyroids and inflammation of the prostate in males at 10 times mrhd based on mg/m2 and mammary gland hyperplasia, increased vaginal mucification, and increased ovarian atretic follicles at doses as low as 0.2 times the mrhd based on mg/m2 . some of these findings were attributed to transiently elevated serum prolactin which was seen in both sexes at all doses. however, there were no changes at any dose level in reproductive parameters (fertility, conception indices, spermatogenesis, estrous cycle, gestation length, parturition, number of pups born). the no effect dose for neurobehavioral changes in males is 0.2 times the mrhd based on mg/m2 and could not be determined in females. the no effect dose for growth and physical development in both sexes is 0.2 times the mrhd based on mg/m2 . clinical studies with lurasidone hydrochloride did not include sufficient numbers of patients aged 65 and older to determine whether or not they respond differently from younger patients. in elderly patients with psychosis (65 to 85), lurasidone hydrochloride concentrations (20 mg/day) were similar to those in young subjects. it is unknown whether dose adjustment is necessary on the basis of age alone. elderly patients with dementia-related psychosis treated with lurasidone hydrochloride are at an increased risk of death compared to placebo. lurasidone hydrochloride is not approved for the treatment of patients with dementia-related psychosis [see boxed warning, warnings and precautions (5.1, 5.3)] . reduce the maximum recommended dosage in patients with moderate or severe renal impairment (clcr <50 ml/minute). patients with impaired renal function (clcr <50 ml/minute) had higher exposure to lurasidone than patients with normal renal function [see clinical pharmacology (12.3)] . greater exposure may increase the risk of lurasidone hydrochloride-associated adverse reactions [see dosage and administration (2.4)] reduce the maximum recommended dosage in patients with moderate to severe hepatic impairment (child-pugh score ≥7). patients with moderate to severe hepatic impairment (child- pugh score ≥7) generally had higher exposure to lurasidone than patients with normal hepatic function [see clinical pharmacology (12.3)] . greater exposure may increase the risk of lurasidone hydrochloride-associated adverse reactions [see dosage and administration (2.5)]. no dosage adjustment for lurasidone hydrochloride is required on the basis of a patient's sex, race, or smoking status [see clinical pharmacology (12.3)]. lurasidone hydrochloride is not a controlled substance. lurasidone hydrochloride has not been systematically studied in humans for its potential for abuse or physical dependence or its ability to induce tolerance. while clinical studies with lurasidone hydrochloride did not reveal any tendency for drug-seeking behavior, these observations were not systematic and it is not possible to predict the extent to which a cns-active drug will be misused, diverted and/or abused once it is marketed. patients should be evaluated carefully for a history of drug abuse, and such patients should be observed carefully for signs of lurasidone hydrochloride misuse or abuse (e.g., development of tolerance, drug-seeking behavior, increases in dose).

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lupin pharmaceuticals, inc. - prasugrel hydrochloride (unii: g89jq59i13) (prasugrel - unii:34k66tbt99) - prasugrel tablet  is indicated to reduce the rate of thrombotic cv events (including stent thrombosis) in patients with acute coronary syndrome (acs) who are to be managed with percutaneous coronary intervention (pci) as follows: -   patients with unstable angina (ua) or non-st-elevation myocardial infarction (nstemi). -   patients with st-elevation myocardial infarction (stemi) when managed with primary or delayed pci. prasugrel tablet has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (mi), or nonfatal stroke compared to clopidogrel. the difference between treatments was driven predominantly by mi, with no difference on strokes and little difference on cv death [see clinical studies (14)]. prasugrel is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage (ich) [see warnings and precautions (5.1) and adverse reactions (6.1)] . prasugrel is contraindicated in patients with a history of prior

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lupin pharmaceuticals, inc. - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288) - amlodipine 2.5 mg - amlodipine besylate 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 amlodipine besylate. 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 program's joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. amlodipine besylate tablets may be used alone or in combination with other antihypertensive agents. chronic stable angina amlodipine besylate tablets are indicated for the symptomatic treatment of chronic stable angina. amlodipine besylate tablets may be used alone or in combination with other antianginal agents. vasospastic angina (prinzmetal's or variant angina) amlodipine besylate tablets are indicated for the treatment of confirmed or suspected vasospastic angina. amlodipine besylate tablets may be used as monotherapy or in combination with other antianginal agents. angiographically documented cad in patients with recently documented cad by angiography and without heart failure or an ejection fraction <40%, amlodipine besylate tablets are indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure. amlodipine besylate tablets are contraindicated in patients with known sensitivity to amlodipine. risk summary the limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. there are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy [see clinical considerations] . in animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (mrhd), respectively. however for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose [see data]. 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 and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations: disease-associated maternal and/or embryo/fetal risk hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. data: animal data no evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (approximately 10 and 20 times the mrhd based on body surface area, respectively) during their respective periods of major organogenesis. however for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold)in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. risk summary limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. no adverse effects of amlodipine on the breastfed infant have been observed. there is no available information on the effects of amlodipine on milk production. amlodipine besylate (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years [see clinical studies (14.1)]. effect of amlodipine besylate on blood pressure in patients less than 6 years of age is not known. clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. elderly patients have decreased clearance of amlodipine with a resulting increase of auc of approximately 40 to 60%, and a lower initial dose may be required [see dosage and administration (2.1)] .

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lupin pharmaceuticals, inc. - ethacrynic acid (unii: m5dp350vzv) (ethacrynic acid - unii:m5dp350vzv) - ethacrynic acid tablets, usp are indicated for treatment of edema when an agent with greater diuretic potential than those commonly employed is required. - treatment of the edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. - short-term management of ascites due to malignancy, idiopathic edema, and lymphedema. - short-term management of hospitalized pediatric patients, other than infants, with congenital heart disease or the nephrotic syndrome. - intravenous ethacrynate sodium is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema, or when gastrointestinal absorption is impaired or oral medication is not practicable. all diuretics, including ethacrynic acid, are contraindicated in anuria. if increasing electrolyte imbalance, azotemia, and/or oliguria occur during treatment of severe, progressive renal disease, the diuretic should be discontinued. in a few patients this diuretic has produced severe, watery

United States - English - NLM (National Library of Medicine)

lupin pharmaceuticals, inc. - mycophenolate mofetil (unii: 9242ecw6r0) (mycophenolic acid - unii:hu9dx48n0t) - mycophenolate mofetil (mmf) is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see clinical studies (14.1)] , heart [see clinical studies (14.2)] or liver transplants [see clinical studies (14.3)], in combination with other immunosuppressants. allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (mmf), mycophenolic acid (mpa) or any component of the drug product. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing mycophenolate mofetil treatment. to report a pregnancy or obtain information about the registry, visit www.mycophenolaterems.com or call 1-800-617-8191. risk summary use of mycophenolate mofetil (mmf) during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems [see human data] . oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see animal data] . consider alternative immunosuppressants with less potential for embryofetal toxicity. risks and benefits of mycophenolate mofetil should be discussed with the pregnant woman. the estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. 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. data human data a spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23 to 27% of live births in mmf exposed pregnancies, based on published data from pregnancy registries. malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45 to 49% following mmf exposure. animal data in animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. oral administration of mmf to pregnant rats from gestational day 7 to day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for bsa. oral administration of mmf to pregnant rabbits from gestational day 7 to day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for bsa. risk summary there are no data on the presence of mycophenolate in human milk, or the effects on milk production. there are limited data in the national transplantation pregnancy registry on the effects of mycophenolate on a breastfed child [see data]. studies in rats treated with mmf have shown mycophenolic acid (mpa) to be present in milk. because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mycophenolate mofetil and any potential adverse effects on the breastfed infant from mycophenolate mofetil or from the underlying maternal condition. data limited information is available from the national transplantation pregnancy registry. of seven infants reported by the national transplantation pregnancy registry to have been breastfed while the mother was taking mycophenolate, all were born at 34-40 weeks gestation, and breastfed for up to 14 months. no adverse events were reported. females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning. pregnancy planning for patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. risks and benefits of mycophenolate mofetil should be discussed with the patient. pregnancy testing to prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 miu/ml immediately before starting mycophenolate mofetil. another pregnancy test with the same sensitivity should be done 8 to 10 days later. repeat pregnancy tests should be performed during routine follow-up visits. results of all pregnancy tests should be discussed with the patient. in the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. contraception female patients females of reproductive potential taking mycophenolate mofetil must receive contraceptive counseling and use acceptable contraception (see table 9 for acceptable contraception methods). patients must use acceptable birth control during the entire mycophenolate mofetil therapy, and for 6 weeks after stopping mycophenolate mofetil, unless the patient chooses abstinence. patients should be aware that mycophenolate mofetil reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see drug interactions (7.2)] . - intrauterine devices (iuds) - tubal sterilization - patient's partner vasectomy - oral contraceptive pill - transdermal patch - vaginal ring - injection - implant - diaphragm with spermicide - cervical cap with spermicide - contraceptive sponge - male condom - female condom - diaphragm with spermicide - cervical cap with spermicide - contraceptive sponge - male condom - female condom male patients genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. thus, the risk of genotoxic effects on sperm cells cannot be excluded. based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolate mofetil and for at least 90 days after cessation of treatment [see use in special populations (8.1), nonclinical toxicology (13.1), patient counseling information (17.9)]. safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogenic kidney, heart or liver transplants. kidney transplant use of mycophenolate mofetil in this population is supported by evidence from adequate and well-controlled studies of mycophenolate mofetil in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see dosage and administration (2.2), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1)]. heart transplant and liver transplant use of mycophenolate mofetil in pediatric heart transplant and liver transplant patients is supported by adequate and well controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [see dosage and administration (2.3, 2.4), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1) ]. clinical studies of mycophenolate mofetil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the geriatric and younger patients. in general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see adverse reactions (6.1), drug interactions (7)]. patients with kidney transplant no dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively but patients should be carefully monitored [see clinical pharmacology (12.3)]. in kidney transplant patients with severe chronic impairment of the graft (gfr <25 ml/min/1.73 m2 ), no dose adjustments are necessary; however, doses greater than 1 g administered twice a day should be avoided. patients with heart and liver transplant no data are available for heart or liver transplant patients with severe chronic renal impairment. mycophenolate mofetil may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks. patients with kidney transplant no dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. however, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see clinical pharmacology (12.3)]. patients with heart transplant no data are available for heart transplant patients with severe hepatic parenchymal disease.