Philippines - English - FDA (Food And Drug Administration)

cadila pharamceuticals limited - drug - montelukast (as sodium) - aerokids

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

cadila pharmaceuticals limited - ofloxacin (unii: a4p49jaz9h) (ofloxacin - unii:a4p49jaz9h) - ofloxacin 200 mg - to reduce the development of drug-resistant bacteria and maintain the effectiveness of ofloxacin tablets, usp and other antibacterial drugs, ofloxacin tablets, usp should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. ofloxacin tablets, usp are indicated for the treatment of adults with mild to moderate infections (unless otherwise indicated) caused by susceptible strains of the designated microorganisms in the infections listed below. please see dosage and administration   for specific recommendations. acute bacterial exacerbations of chronic bronchitis (abecb) due to haemophilus influenzae or streptococcus pneumonia . because fluoroquinolones, including ofloxacin, ha

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

cadila healthcare limited - metronidazole (unii: 140qmo216e) (metronidazole - unii:140qmo216e) - metronidazole 250 mg - symptomatic  trichomoniasis. metronidazole tablets, usp are indicated for the treatment of t.  vaginalis infection in females and males when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures). asymptomatic  trichomoniasis. metronidazole tablets, usp are indicated in the treatment of asymptomatic t.  vaginalis infection in females when the organism is associated with endocervicitis, cervicitis, or cervical erosion. since there is evidence that presence of the trichomonad can interfere with accurate assessment of abnormal cytological smears, additional smears should be performed after eradication of the parasite. treatment  of  asymptomatic  sexual  partners.  t.  vaginalis infection is a venereal disease. therefore, asymptomatic sexual partners of treated patients should be treated simultaneously if the organism has been found to be present, in order to prevent reinfection of the partner. the decision as to whether to treat an asymptomatic

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

cadila healthcare limited - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole orally disintegrating tablets are indicated for the treatment of: -   schizophrenia [see clinical studies (14.1)] additional pediatric use information is approved for otsuka america pharmaceutical, inc.'s abilify® (aripiprazole) product. however, due to otsuka america pharmaceutical, inc.'s marketing exclusivity rights, this drug product is not labeled with that information. aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)]. pregnancy exposure registry   there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/. risk

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

cadila pharmaceuticals limited - venlafaxine hydrochloride (unii: 7d7rx5a8mo) (venlafaxine - unii:grz5rcb1qg) - venlafaxine tablets are indicated for the treatment of major depressive disorder. the efficacy of venlafaxine tablets in the treatment of major depressive disorder was established in 6 week controlled trials of adult outpatients whose diagnoses corresponded most closely to the dsm-iii or dsm-iii-r category of major depression and in a 4 week controlled trial of inpatients meeting diagnostic criteria for major depression with melancholia (see clinical trials ). a major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation. the efficacy of venlafaxine hydrochloride extended-release capsules in maintaining an antidepressant response for up to 26 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial. the efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then followed for a period of up to 52 weeks was demonstrated in a second placebo-controlled trial (seeclinical trials ). nevertheless, the physician who elects to use venlafaxine tablets/venlafaxine hydrochloride extended-release capsules for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. hypersensitivity to venlafaxine hydrochloride or to any excipients in the formulation the use of maois intended to treat psychiatric disorders with venlafaxine hydrochloride or within 7 days of stopping treatment with venlafaxine hydrochloride is contraindicated because of an increased risk of serotonin syndrome. the use of venlafaxine hydrochloride within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated (see warnings and dosage and administration ). starting venlafaxine hydrochloride 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 warnings and dosage and administration ). venlafaxine hydrochloride is not a controlled substance. in vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine, phencyclidine (pcp), or n-methyl-d- aspartic acid (nmda) receptors. venlafaxine was not found to have any significant cns stimulant activity in rodents. in primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability. discontinuation effects have been reported in patients receiving venlafaxine (seedosage and administration ). while venlafaxine hydrochloride has not been systematically studied in clinical trials for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. however, it is not possible to predict on the basis of premarketing 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 venlafaxine hydrochloride (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

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

cadila healthcare limited - nortriptyline hydrochloride (unii: 00fn6ih15d) (nortriptyline - unii:bl03sy4lxb) - nortriptyline hydrochloride capsules are indicated for the relief of symptoms of depression. endogenous depressions are more likely to be alleviated than are other depressive states. the use of maois intended to treat psychiatric disorders with nortriptyline hydrochloride or within 14 days of stopping treatment with nortriptyline hydrochloride is contraindicated because of an increased risk of serotonin syndrome. the use of nortriptyline hydrochloride within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated (see warnings and dosage and administration ). starting nortriptyline hydrochloride 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 warnings and dosage and administration ). cross-sensitivity between nortriptyline hydrochloride and other dibenzazepines is a possibility. nortriptyline hydrochloride is contraindicated during the acute rec

Tanzania - English - Tanzania Medicinces & Medical Devices Authority

cadila healthcare limited, india - teneligliptin - tablet, film-coated - 20

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

cadila pharmaceuticals limited - fluoxetine hydrochloride (unii: i9w7n6b1kj) (fluoxetine - unii:01k63sup8d) - 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 is indicated for the treatment of: • acute treatment of depressive episodes associated with bipolar i disorder. • treatment resistant depression (major depressive disorder in patient, who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode). fluoxetine capsules monotherapy is not indicated for the treatment of depressive episodes associated with bipolar i disorder or the treatment of treatment resistant depression. 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 capsules or within 5 weeks of stopping treatment with fluoxetine capsules is contraindicated because of an increased risk of serotonin syndrome. the use of fluoxetine capsules 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 capsules 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 capsules 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 capsules can increase the levels of pimozide and thioridazine through inhibition of cyp2d6. fluoxetine capsules 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 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-researchprograms/pregnancyregistry/antidepressants/. risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.7) and clinical considerations]. available data from published epidemiologic studies and postmarketing reports over several decades have not established an increased risk of major birth defects or miscarriage. some studies have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship (see data ). there are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (pphn) (see data ) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (ssris), including fluoxetine, during pregnancy (see clinical considerations ). in rats and rabbits treated with fluoxetine during the period of organogenesis, there was no evidence of developmental effects at doses up to 1.6 and 3.9 times, respectively, the maximum recommended human dose (mrhd) of 60 mg/day given to adolescents on a mg/m2 basis. however, in other reproductive studies in rats, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths early after birth occurred at doses that are 1.5 times (during gestation) and 0.97 time (during gestation and lactation) the mrhd given to adolescents on a mg/m2 basis. 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 us 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 women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions  use of fluoxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.7)]. fetal/neonatal adverse reactions neonates exposed to fluoxetine and other ssri or 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, tremors, jitteriness, irritability, and constant crying. these findings 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) ]. data human data — it has been shown that ssris (including fluoxetine) can cross the placenta. published epidemiological studies of pregnant women exposed to fluoxetine have not established an increased risk of major birth defects, miscarriage, and other adverse developmental outcomes. several publications reported an increased incidence of cardiovascular malformations in children with in utero exposure to fluoxetine. however, these studies results do not establish a causal relationship. methodologic limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders and confirmatory studies. however, these studies cannot definitely establish or exclude any drug-associated risk during pregnancy. exposure to ssris, particularly later in pregnancy, may have an increased risk for 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.   animal data — in embryofetal development studies in rats and rabbits, there was no evidence of malformations or developmental variations following administration of fluoxetine at doses up to 12.5 and 15 mg/kg/day, respectively (1.6 and 3.9 times, respectively, the mrhd of 60 mg given to adolescents on a mg/m2 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 given to adolescents on a mg/m2 basis) during gestation or 7.5 mg/kg/day (0.97 time the mrhd given to adolescents on a mg/m2 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 (0.65 time the mrhd given to adolescents on a mg/m2 basis). risk summary data from published literature report the presence of fluoxetine and norfluoxetine in human milk (see data ). there are reports of agitation, irritability, poor feeding, and poor weight gain in infants exposed to fluoxetine through breast milk (see clinical considerations ). there are no data on the effect of fluoxetine or its metabolites on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for fluoxetine and any potential adverse effects on the breastfed child from fluoxetine or the underlying maternal condition clinical considerations infants exposed to fluoxetine should be monitored for agitation, irritability, poor feeding, and poor weight gain. data a study of 19 nursing mothers on fluoxetine with daily doses of 10 to 60 mg showed that fluoxetine was detectable in 30% of nursing infant sera (range: 1 to 84 ng/ml) whereas norfluoxetine was found in 85% (range: <1 to 265 ng/ml). 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/m2 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. us 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, healthcare providers 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).

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

cadila healthcare limited - mirtazapine (unii: a051q2099q) (mirtazapine - unii:a051q2099q) - mirtazapine 15 mg - mirtazapine orally disintegrating tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies (14)] . mirtazapine orally disintegrating tablets are contraindicated in patients: - taking, or within 14 days of stopping, maois (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.3), drug interactions (7)]. - with a known hypersensitivity to mirtazapine or to any of the excipients in mirtazapine orally disintegrating tablets. severe skin reactions, including stevens-johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have been reported following the use of mirtazapine orally disintegrating tablets[see adverse reactions 6.2]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encourag

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

cadila pharmaceuticals limited - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - bupropion hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd), as defined by the diagnostic and statistical manual (dsm). the efficacy of bupropion hydrochloride tablets in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with mdd [see clinical studies (14)] .  •bupropion hydrochloride tablets are contraindicated in patients with a seizure disorder. •bupropion hydrochloride tablets 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 tablets [ see warnings and precautions (5.3) ]. •bupropion hydrochloride tablets are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see warnings and precautions (5.3) , drug interactions (7.3) ]. •the use of maois (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride tablets or within 14 days of discontinuing treatment with bupropion hydrochloride tablets are contraindicated. there is an increased risk of hypertensive reactions when bupropion hydrochloride tablets are used concomitantly with maois. the use of bupropion hydrochloride tablets within 14 days of discontinuing treatment with an maoi is also contraindicated. starting bupropion hydrochloride tablets in a patient treated with reversible maois such as linezolid or intravenous methylene blue is contraindicated [see dosage and administration (2.4 , 2.5) , warnings and precautions (5.4) , drug interactions (7.6) ] .  •bupropion hydrochloride tablets are contraindicated in patients with known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride tablets. anaphylactoid/anaphylactic reactions and stevens-johnson syndrome have been reported [see warnings and precautions (5.8)]. pregnancy exposure registry there is an independent pregnancy exposure registry that monitors pregnancy outcomes in women exposed to any 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/research/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 in pregnancy (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 is unknown for the indicated population. 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 of 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 had a limited number of exposed cases with cardiovascular malformations, and a case-control study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) of self-reported bupropion use 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 for left ventricular outflow tract obstruction (lvoto) are inconsistent and do not allow conclusions regarding a possible association. the united healthcare database lacked sufficient power to evaluate this association; the nbdps found increased risk for lvoto (n = 10; adjusted 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 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/m2 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/m2 basis) and greater. decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 2 times the mrhd on a mg/m2 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/m2 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 and any potential adverse effects on the breastfed child from bupropion or from the underlying maternal condition. data in a lactation study of 10 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 [see boxed warning, warnings and precautions (5.1)] . of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. in addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). 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 (2.3) , use in specific populations (8.6) , clinical pharmacology (12.3)] . consider a reduced dose and/or dosing frequency of bupropion hydrochloride tablets in patients with renal impairment (gfr less than 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 (2.3 ) , clinical pharmacology (12.3) ] . in patients with moderate to severe hepatic impairment (child-pugh score: 7 to 15), the maximum dose of bupropion hydrochloride tablets is 75 mg daily. 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 (2.2), clinical pharmacology (12.3) ]. bupropion is not a controlled substance. humans   controlled clinical trials conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed subjects showed some increase in motor activity and agitation/excitement, often typical of central stimulant activity. in a population of individuals experienced with drugs of abuse, a single oral dose of 400 mg of bupropion produced mild amphetamine-like activity as compared with placebo on the morphine-benzedrine subscale of the addiction research center inventories (arci) and a score greater than placebo but less than 15 mg of the schedule ii stimulant dextroamphetamine on the liking scale of the arci. these scales measure general feelings of euphoria and drug liking which are often associated with abuse potential. findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. nonetheless, evidence from single-dose trials does suggest that the recommended daily dosage of bupropion when administered orally in divided doses is not likely to be significantly reinforcing to amphetamine or cns stimulant abusers. however, higher doses (which could not be tested because of the risk of seizure) might be modestly attractive to those who abuse cns stimulant drugs. bupropion hydrochloride 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 behavior 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.