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avkare, inc. - pantoprazole sodium (unii: 6871619q5x) (pantoprazole - unii:d8tst4o562) - pantoprazole 20 mg - pantoprazole sodium delayed-release tablets are indicated for: pantoprazole sodium delayed-release tablets are indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (ee). for those adult patients who have not healed after 8 weeks of treatment, an additional 8 week course of pantoprazole sodium delayed-release tablets may be considered. safety of treatment beyond 8 weeks in pediatric patients has not been established. pantoprazole sodium delayed-release tablets are indicated for maintenance of healing of ee and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gerd. controlled studies did not extend beyond 12 months. pantoprazole sodium delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison (ze) syndrome. - pantoprazole sodium delayed-release tablets are contraindic

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avkare - benazepril hydrochloride (unii: n1sn99t69t) (benazeprilat - unii:jrm708l703) - benazepril hydrochloride 5 mg - benazepril hcl tablets, usp 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. 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 d

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avkare - fluoxetine hydrochloride (unii: i9w7n6b1kj) (fluoxetine - unii:01k63sup8d) - fluoxetine 10 mg - fluoxetine capsules are indicated for the treatment of: - acute and maintenance treatment of major depressive disorder [see clinical studies ( 14.1)] . - acute and maintenance treatment of obsessions and compulsions in patients with obsessive compulsive disorder (ocd) [see clinical studies ( 14.2)]. - acute and maintenance treatment of binge-eating and vomiting behaviors in patients with moderate to severe bulimia nervosa [see clinical studies ( 14.3)] . - acute treatment of panic disorder, with or without agoraphobia [see clinical studies ( 14.4)]. fluoxetine capsules and olanzapine in combination are indicated for the treatment of: - acute treatment of depressive episodes associated with bipolar i disorder. fluoxetine capsules monotherapy is not indicated for the treatment of depressive episodes associated with bipolar i disorder. when using fluoxetine capsules and olanzapine in combination, also refer to the clinical studies section of the package insert for symbyax ® . when using fluoxetine and olanzapine in combination, also refer to the contraindications section of the package insert for symbyax. the use of maois intended to treat psychiatric disorders with fluoxetine or within 5 weeks of stopping treatment with fluoxetine is contraindicated because of an increased risk of serotonin syndrome. the use of fluoxetine within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [ see dosage and administration ( 2.9 ) and warnings and precautions ( 5.2 )]. starting fluoxetine in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [ see dosage and administration ( 2.10) and warnings and precautions ( 5.2 )]. the use of fluoxetine is contraindicated with the following: - pimozide [ see warnings and precautions ( 5.11) and drug interactions ( 7.7 , 7.8 )] - thioridazine [ see warnings and precautions ( 5.11) and drug interactions ( 7.7 , 7.8) ] pimozide and thioridazine prolong the qt interval. fluoxetine can increase the levels of pimozide and thioridazine through inhibition of cyp2d6. fluoxetine can also prolong the qt interval. when using fluoxetine and olanzapine in combination, also refer to the use in specific populations section of the package insert for symbyax. pregnancy category c — fluoxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. all pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. treatment of pregnant women during the first trimester — there are no adequate and well-controlled clinical studies on the use of fluoxetine in pregnant women. results of a number of published epidemiological studies assessing the risk of fluoxetine exposure during the first trimester of pregnancy have demonstrated inconsistent results. more than 10 cohort studies and case-control studies failed to demonstrate an increased risk for congenital malformations overall. however, one prospective cohort study conducted by the european network of teratology information services reported an increased risk of cardiovascular malformations in infants born to women (n = 253) exposed to fluoxetine during the first trimester of pregnancy compared to infants of women (n = 1359) who were not exposed to fluoxetine. there was no specific pattern of cardiovascular malformations. overall, however, a causal relationship has not been established. nonteratogenic effects — neonates exposed to fluoxetine and other ssris or serotonin and norepinephrine reuptake inhibitors (snris), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [ see warnings and precautions ( 5.2 )]. infants exposed to ssris in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. several recent epidemiological studies suggest a positive statistical association between ssri use (including fluoxetine) in pregnancy and pphn. other studies do not show a significant statistical association. physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission. women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy. when treating a pregnant woman with fluoxetine, the physician should carefully consider both the potential risks of taking an ssri, along with the established benefits of treating depression with an antidepressant. the decision can only be made on a case by case basis [see dosage and administration ( 2.7)]. animal data — in embryo-fetal development studies in rats and rabbits, there was no evidence of teratogenicity following administration of fluoxetine at doses up to 12.5 and 15 mg/kg/day, respectively (1.5 and 3.6 times, respectively, the maximum recommended human dose (mrhd) of 80 mg on a mg/m 2 basis) throughout organogenesis. however, in rat reproduction studies, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths during the first 7 days postpartum occurred following maternal exposure to 12 mg/kg/day (1.5 times the mrhd on a mg/m 2 basis) during gestation or 7.5 mg/kg/day (0.9 times the mrhd on a mg/m 2 basis) during gestation and lactation. there was no evidence of developmental neurotoxicity in the surviving offspring of rats treated with 12 mg/kg/day during gestation. the no-effect dose for rat pup mortality was 5 mg/kg/day (0.6 times the mrhd on a mg/m 2 basis). the effect of fluoxetine on labor and delivery in humans is unknown. however, because fluoxetine crosses the placenta and because of the possibility that fluoxetine may have adverse effects on the newborn, fluoxetine should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus. because fluoxetine is excreted in human milk, nursing while on fluoxetine is not recommended. in one breast-milk sample, the concentration of fluoxetine plus norfluoxetine was 70.4 ng/ml. the concentration in the mother’s plasma was 295.0 ng/ml. no adverse effects on the infant were reported. in another case, an infant nursed by a mother on fluoxetine developed crying, sleep disturbance, vomiting, and watery stools. the infant’s plasma drug levels were 340 ng/ml of fluoxetine and 208 ng/ml of norfluoxetine on the second day of feeding. use of fluoxetine in children — the efficacy of fluoxetine for the treatment of major depressive disorder was demonstrated in two 8- to 9-week placebo-controlled clinical trials with 315 pediatric outpatients ages 8 to ≤18 [ see clinical studies ( 14.1) ] . the efficacy of fluoxetine for the treatment of ocd was demonstrated in one 13-week placebo-controlled clinical trial with 103 pediatric outpatients ages 7 to <18 [ see clinical studies ( 14.2) ] . the safety and effectiveness in pediatric patients <8 years of age in major depressive disorder and <7 years of age in ocd have not been established. fluoxetine pharmacokinetics were evaluated in 21 pediatric patients (ages 6 to ≤18) with major depressive disorder or ocd [ see clinical pharmacology ( 12.3) ] . the acute adverse reaction profiles observed in the 3 studies (n=418 randomized; 228 fluoxetine-treated, 190 placebo-treated) were generally similar to that observed in adult studies with fluoxetine. the longer-term adverse reaction profile observed in the 19-week major depressive disorder study (n=219 randomized; 109 fluoxetine-treated, 110 placebo-treated) was also similar to that observed in adult trials with fluoxetine [ see adverse reactions ( 6.1) ] . manic reaction, including mania and hypomania, was reported in 6 (1 mania, 5 hypomania) out of 228 (2.6%) fluoxetine-treated patients and in 0 out of 190 (0%) placebo-treated patients. mania/hypomania led to the discontinuation of 4 (1.8%) fluoxetine-treated patients from the acute phases of the 3 studies combined. consequently, regular monitoring for the occurrence of mania/hypomania is recommended. as with other ssris, decreased weight gain has been observed in association with the use of fluoxetine in children and adolescent patients. after 19 weeks of treatment in a clinical trial, pediatric subjects treated with fluoxetine gained an average of 1.1 cm less in height and 1.1 kg less in weight than subjects treated with placebo. in addition, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels. the safety of fluoxetine treatment for pediatric patients has not been systematically assessed for chronic treatment longer than several months in duration. in particular, there are no studies that directly evaluate the longer-term effects of fluoxetine on the growth, development and maturation of children and adolescent patients. therefore, height and weight should be monitored periodically in pediatric patients receiving fluoxetine [ see warnings and precautions ( 5.6) ]. fluoxetine is approved for use in pediatric patients with mdd and ocd [ see box warning and warnings and precautions ( 5.1) ] . anyone considering the use of fluoxetine in a child or adolescent must balance the potential risks with the clinical need. animal data - significant toxicity on muscle tissue, neurobehavior, reproductive organs, and bone development has been observed following exposure of juvenile rats to fluoxetine from weaning through maturity. oral administration of fluoxetine to rats from weaning postnatal day 21 through adulthood day 90 at 3, 10, or 30 mg/kg/day was associated with testicular degeneration and necrosis, epididymal vacuolation and hypospermia (at 30 mg/kg/day corresponding to plasma exposures [auc] approximately 5 to 10 times the average auc in pediatric patients at the mrhd of 20 mg/day), increased serum levels of creatine kinase (at auc as low as 1 to 2 times the average auc in pediatric patients at the mrhd of 20 mg/day), skeletal muscle degeneration and necrosis, decreased femur length/growth and body weight gain (at auc 5 to 10 times the average auc in pediatric patients at the mrhd of 20 mg/day). the high dose of 30 mg/kg/day exceeded a maximum tolerated dose. when animals were evaluated after a drug-free period (up to 11 weeks after cessation of dosing), fluoxetine was associated with neurobehavioral abnormalities (decreased reactivity at auc as low as approximately 0.1 to 0.2 times the average auc in pediatric patients at the mrhd and learning deficit at the high dose), and reproductive functional impairment (decreased mating at all doses and impaired fertility at the high dose). in addition, the testicular and epididymal microscopic lesions and decreased sperm concentrations found in high dose group were also observed, indicating that the drug effects on reproductive organs are irreversible. the reversibility of fluoxetine-induced muscle damage was not assessed. these fluoxetine toxicities in juvenile rats have not been observed in adult animals. plasma exposures (auc) to fluoxetine in juvenile rats receiving 3, 10, or 30 mg/kg/day doses in this study are approximately 0.1 to 0.2, 1 to 2, and 5 to 10 times, respectively, the average exposure in pediatric patients receiving the mrhd of 20 mg/day. rat exposures to the major metabolite, norfluoxetine, are approximately 0.3 to 0.8, 1 to 8, and 3 to 20 times, respectively, the pediatric exposure at the mrhd. a specific effect on bone development was reported in juvenile mice administered fluoxetine by the intraperitoneal route to 4 week old mice for 4 weeks at doses 0.5 and 2 times the oral mrhd of 20 mg/day on mg/m 2 basis. there was a decrease in bone mineralization and density at both doses, but the overall growth (body weight gain or femur length) was not affected. use of fluoxetine in combination with olanzapine in children and adolescents: safety and efficacy of fluoxetine and olanzapine in combination in patients 10 to 17 years of age have been established for the acute treatment of depressive episodes associated with bipolar i disorder. safety and effectiveness of fluoxetine and olanzapine in combination in patients less than 10 years of age have not been established. u.s. fluoxetine clinical trials included 687 patients ≥65 years of age and 93 patients ≥75 years of age. the efficacy in geriatric patients has been established [ see clinical studies ( 14.1) ] . for pharmacokinetic information in geriatric patients, [ see clinical pharmacology ( 12.4) ] . no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. snris and ssris, including fluoxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [ see warnings and precautions ( 5.9) ] . clinical studies of olanzapine and fluoxetine in combination did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients. in subjects with cirrhosis of the liver, the clearances of fluoxetine and its active metabolite, norfluoxetine, were decreased, thus increasing the elimination half-lives of these substances. a lower or less frequent dose of fluoxetine should be used in patients with cirrhosis. caution is advised when using fluoxetine in patients with diseases or conditions that could affect its metabolism [ see dosage and administration ( 2.7) and clinical pharmacology ( 12.4) ] . fluoxetine has not been systematically studied, in animals or humans, for its potential for abuse, tolerance, or physical dependence. while the premarketing clinical experience with fluoxetine did not reveal any tendency for a withdrawal syndrome or any drug seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of fluoxetine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

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avkare - norgestimate (unii: c291hfx4dy) (norgestimate - unii:c291hfx4dy), ethinyl estradiol (unii: 423d2t571u) (ethinyl estradiol - unii:423d2t571u) - norgestimate and ethinyl estradiol tablets, usp are indicated for use by females of reproductive potential to prevent pregnancy [see clinical studies (14)]. estarylla™ is contraindicated in females who are known to have or develop the following conditions: - a high risk of arterial or venous thrombotic diseases. examples include women who are known to: - smoke, if over age 35 [see boxed warning and warnings and precautions (5.1) ] - have deep vein thrombosis or pulmonary embolism, now or in the past [see warnings and precautions (5.1)] - have inherited or acquired hypercoagulopathies [see warnings and precautions (5.1)] - have cerebrovascular disease [see warnings and precautions (5.1)] - have coronary artery disease [see warnings and precautions (5.1)] - have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see warnings and precautions (5.1)] - have uncontrolled hypertension [see warnings and precautions (5.4) ] - have diabetes mellitus with vascular disease [see warnings and precautions (5.6) ] - have headaches with focal neurological symptoms or migraine headaches with aura [see warnings and precautions (5.7) ] women over age 35 with any migraine headaches [see warnings and precautions (5.7) ] - women over age 35 with any migraine headaches [see warnings and precautions (5.7) ] - liver tumors, benign or malignant, or liver disease [see warnings and precautions (5.2)] - undiagnosed abnormal uterine bleeding [see warnings and precautions (5.8) ] - pregnancy, because there is no reason to use cocs during pregnancy [see warnings and precautions (5.9) and use in specific populations (8.1)] - current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see warnings and precautions (5.11) ] - use of hepatitis c drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alt elevations [see warnings and precautions (5.3)] there is little or no increased risk of birth defects in women who inadvertently use cocs during early pregnancy. epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose cocs prior to conception or during early pregnancy. do not administer cocs to induce withdrawal bleeding as a test for pregnancy. do not use cocs during pregnancy to treat threatened or habitual abortion. advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. cocs can reduce milk production in breastfeeding mothers. this is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. small amounts of oral contraceptive steroids and/or metabolites are present in breast milk. safety and efficacy of norgestimate and ethinyl estradiol have been established in women of reproductive age. efficacy is expected to be the same for post-pubertal adolescents under the age of 18 and for users 18 years and older. use of this product before menarche is not indicated. norgestimate and ethinyl estradiol has not been studied in postmenopausal women and is not indicated in this population. the pharmacokinetics of norgestimate and ethinyl estradiol has not been studied in subjects with hepatic impairment. however, steroid hormones may be poorly metabolized in patients with hepatic impairment. acute or chronic disturbances of liver function may necessitate the discontinuation of coc use until markers of liver function return to normal and coc causation has been excluded. [see contraindications (4) and warnings and precautions (5.2). ] the pharmacokinetics of norgestimate and ethinyl estradiol has not been studied in women with renal impairment.

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

avkare - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1), misoprostol (unii: 0e43v0bb57) (misoprostol - unii:0e43v0bb57) - diclofenac sodium 50 mg - diclofenac sodium and misoprostol delayed-release tablets are indicated for treatment of the signs and symptoms of osteoarthritis or rheumatoid arthritis in patients at high risk of developing nsaid-induced gastric and duodenal ulcers and their complications. for a list of factors that may increase the risk of nsaid-induced gastric and duodenal ulcers and their complications [see warnings and precautions (5.2) ]. diclofenac sodium and misoprostol is contraindicated in the following patients: ● known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac sodium/misoprostol, other prostaglandins, or any components of the drug product [see warnings and precautions ( 5.7 , 5.9 )] ● history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions ( 5.7 , 5.8 )] ● in the

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avkare - nitroglycerin (unii: g59m7s0ws3) (nitroglycerin - unii:g59m7s0ws3) - nitroglycerin 2.5 mg - nitroglycerin extended-release capsules are indicated for the prevention of angina pectoris due to coronary artery disease. the onset of action of oral nitroglycerin is not sufficiently rapid for this product to be useful in aborting an acute anginal episode. allergic reactions to organic nitrates are extremely rare, but they do occur. nitroglycerin is contraindicated in patients who are allergic to it.

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avkare - imipramine hydrochloride (unii: bke5q1j60u) (imipramine - unii:ogg85sx4e4) - imipramine hydrochloride 10 mg - depression - for the relief of symptoms of depression. endogenous depression is more likely to be alleviated than other depressive states. one to three weeks of treatment may be needed before optimal therapeutic effects are evident. childhood enuresis - may be useful as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older, after possible organic causes have been excluded by appropriate tests. in patients having daytime symptoms of frequency and urgency, examination should include voiding cystourethrography and cystoscopy, as necessary. the effectiveness of treatment may decrease with continued drug administration. the concomitant use of monoamine oxidase inhibiting compounds is contraindicated. hyperpyretic crises or severe convulsive seizures may occur in patients receiving such combinations. the potentiation of adverse effects can be serious, or even fatal. when it is desired to substitute imipramine hydrochloride tablets usp in patients receiving a monoamine oxidase inhibi

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

avkare - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - bupropion hydrochloride 150 mg - bupropion hydrochloride extended-release tablets (xl) are indicated for the treatment of major depressive disorder (mdd), as defined by the diagnostic and statistical manual (dsm). the efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with mdd. the efficacy of the sustained-release formulation of bupropion in the maintenance treatment of mdd was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8-week study of acute treatment [see clinical studies ( 14.1)]. bupropion hydrochloride extended-release tablets (xl) are indicated for the prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (sad). the efficacy of bupropion hydrochloride extended-release tablets in the prevention of seasonal major depressive episodes was established in 3 placebo-controlled trials in adult outpatients with a history of mdd with an autumn-winter seasonal pattern as defined in the dsm [see clinical studies ( 14.2)]. - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients with seizure disorder. - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with bupropion hydrochloride extended-release tablets (xl) [see warnings and precautions ( 5.3)]. - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see warnings and precautions ( 5.3) and drug interactions ( 7.3)]. - the use of maois (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride extended-release tablets (xl) or within 14 days of discontinuing treatment with bupropion hydrochloride extended-release tablets (xl) is contraindicated. there is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (xl) are used concomitantly with maois. the use of bupropion hydrochloride extended-release tablets (xl) within 14 days of discontinuing treatment with an maoi is also contraindicated. starting bupropion hydrochloride extended-release tablets (xl) in a patient treated with reversible maois such as linezolid or intravenous methylene blue is contraindicated [see dosage and administration ( 2.9), warnings and precautions ( 5.4) and drug interactions ( 7.6)]. - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients with known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release tablets (xl). anaphylactoid/anaphylactic reactions and stevens-johnson syndrome have been reported [see warnings and precautions ( 5.8)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. risk summary data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see data) . there are risks to the mother associated with untreated depression (see clinical considerations) . when bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (mrhd) of 450 mg/day. when given to pregnant rabbits during organogenesis, non-dose-related increases in incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the mrhd and greater. decreased fetal weights were seen at doses twice the mrhd and greater (see animal data) . the estimated background risk for major birth defects and miscarriage are unknown for the indicated population. all pregnancies have a background rate 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 a prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. data human data data from the international bupropion pregnancy registry (675 first trimester exposures) and a retrospective cohort study using the united healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. the registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations. no increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. the prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international pregnancy registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). data from the united healthcare database, which has a limited number of exposed cases with cardiovascular malformations, and a case-controlled study (6,853 infants with cardiovascular malformations and 5,753 with non-cardiovascular malformations) from the national birth defects prevention study (nbdps) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester. study findings on bupropion exposure during the first trimester and risk left ventricular outflow tract obstruction (lvoto) are inconsistent and do not allow conclusions regarding possible association. the united healthcare database lacked sufficient power to evaluate this association; the nbdps found increased risk for lvoto (n = 10; adjusted odds ratio (or) = 2.6; 95% ci 1.2, 5.7), and the slone epidemiology case control study did not find increased risk for lvoto. study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (vsd) are inconsistent and do not allow conclusions regarding a possible association. the slone epidemiology study found an increased risk for vsd following first trimester maternal bupropion exposure (n = 17; adjusted or = 2.5; 95% ci: 1.3, 5.0) but did not find an increased risk for any other cardiovascular malformations studied (including lvoto as above). the nbdps and united healthcare database study did not find an association between first trimester maternal bupropion exposure and vsd. for the findings of lvoto and vsd, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. animal data in studies conducted in pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 10 and 6 times the mrhd, respectively, on a mg/m 2 basis). there was no evidence of fetal malformations in rats. when given to pregnant rabbits during organogenesis, non-dose-related increases in incidence of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the mrhd on a mg/m 2 basis) and greater. decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 2 times the mrhd on a mg/m 2 basis) and greater. no maternal toxicity was evident at doses of 50 mg/kg/day or less. in a pre-and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 3 times the mrhd on a mg/m 2 basis) from embryonic implantation through lactation had no effect on pup growth or development. risk summary data from published literature report the presence of bupropion and its metabolites in human milk (see data) . there are no data on the effects of bupropion or its metabolites on milk production. limited data from postmarketing reports have not identified a clear association of adverse reactions in the breastfed infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for bupropion hydrochloride extended-release tablets (xl) and any potential adverse effects on the breastfed child from bupropion hydrochloride extended-release tablets (xl) or from the underlying maternal condition. data in a lactation study of ten women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. the average daily infant exposure (assuming 150 ml/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. postmarketing reports have described seizures in breastfed infants. the relationship of bupropion exposure and these seizures is unclear. safety and effectiveness in the pediatric population have not been established. when considering the use of bupropion hydrochloride extended-release tablets (xl) in a child or adolescent, balance the potential risks with the clinical need [see boxed warning and warnings and precautions ( 5.1)]. of the approximately 6,000 patients who participated in clinical trials with bupropion hydrochloride sustained-release tablets (depression and smoking cessation studies), 275 were ≥65 years old and 47 were ≥75 years old. in addition, several hundred patients ≥65 years of age participated in clinical trials using the immediate-release formulation of bupropion hydrochloride (depression studies). no overall differences in safety or effectiveness were observed between these subjects and younger subjects. reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. the risk of adverse reactions may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see dosage and administration ( 2.7), use in specific populations ( 8.6), and clinical pharmacology ( 12.3)] . consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (xl) in patients with renal impairment (glomerular filtration rate: <90 ml/min). bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see dosage and administration ( 2.7) and clinical pharmacology ( 12.3)]. in patients with moderate to severe hepatic impairment (child-pugh score: 7 to 15), the maximum bupropion hydrochloride extended-release tablets (xl) dose is 150 mg every other day. in patients with mild hepatic impairment (child-pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see dosage and administration ( 2.6) and clinical pharmacology ( 12.3)]. bupropion is not a controlled substance. humans controlled clinical studies of bupropion hcl immediate-release conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed patients demonstrated an increase in motor activity and agitation/excitement. in a population of individuals experienced with drugs of abuse, a single dose of 400 mg bupropion produced mild amphetamine-like activity as compared to placebo on the morphine-benzedrine subscale of the addiction research center inventories (arci), and a score intermediate between placebo and amphetamine on the liking scale of the arci. these scales measure general feelings of euphoria and drug desirability. findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or cns stimulant abusers. however, higher doses (that could not be tested because of the risk of seizure) might be modestly attractive to those who abuse cns stimulant drugs. bupropion hydrochloride extended-release tablets are intended for oral use only. the inhalation of crushed tablets or injection of dissolved bupropion has been reported. seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection. animals studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. in rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavioral response, and increase rates of responding in several schedule-controlled behavior paradigms. in primate models assessing the positive reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. in rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

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

avkare, inc. - sildenafil citrate (unii: bw9b0ze037) (sildenafil - unii:3m7ob98y7h) - sildenafil 20 mg - sildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (who group i) in adults to improve exercise ability and delay clinical worsening. the delay in clinical worsening was demonstrated when sildenafil tablets were added to background epoprostenol therapy [see   clinical studies (14) ] .  studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with new york heart association (nyha) functional class ii-iii symptoms and idiopathic etiology (71%) or associated with connective tissue disease (ctd) (25%). limitation of use adding sildenafil to bosentan therapy does not result in any beneficial effect on exercise capacity [see clinical studies (14 ) ] . sildenafil tablets are contraindicated in patients with:sildenafil tablets are contraindicated in patients with: - concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension . concomitant use of organic nitrates in a

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

avkare, inc. - flecainide acetate (unii: m8u465q1wq) (flecainide - unii:k94fts1806) - flecainide acetate 50 mg - in patients without structural heart disease, flecainide is indicated for the prevention of - paroxysmal supraventricular tachycardias (psvt), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms - paroxysmal atrial fibrillation/flutter (paf) associated with disabling symptoms flecainide is also indicated for the prevention of - documented ventricular arrhythmias, such as sustained ventricular tachycardia (sustained vt), that in the judgment of the physician, are lifethreatening. use of flecainide for the treatment of sustained vt, like other antiarrhythmics, should be initiated in the hospital. the use of flecainide is not recommended in patients with less severe ventricular arrhythmias even if the patients are symptomatic. because of the proarrhythmic effects of flecainide, its use should be reserved for patients in whom, in the opinion