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

slate run pharmaceuticals, llc - ibuprofen (unii: wk2xyi10qm) (ibuprofen - unii:wk2xyi10qm) - carefully consider the potential benefits and risks of ibuprofen tablets and other treatment options before deciding to use ibuprofen. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see warnings]. ibuprofen tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. ibuprofen tablets are indicated for relief of mild to moderate pain. ibuprofen tablets are also indicated for the treatment of primary dysmenorrhea. controlled clinical trials to establish the safety and effectiveness of ibuprofen tablets in children have not been conducted. ibuprofen tablets are contraindicated in patients with known hypersensitivity to ibuprofen. ibuprofen tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, rarely fatal, anaphylactic-like reactions to nsaids have been reported in such patients [see warnings, anaphylactoid reactions, and precautions, preexisting asthma]. ibuprofen tablets are contraindicated in the setting of coronary artery bypass graft (cabg) surgery [see warnings].

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

slate run pharmaceuticals, llc - mycophenolate sodium (unii: wx877sqi1g) (mycophenolic acid - unii:hu9dx48n0t) - mycophenolic acid delayed-release tablets are indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. mycophenolic acid delayed-release tablets are indicated for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant. mycophenolic acid delayed-release tablets are to be used in combination with cyclosporine and corticosteroids. mycophenolic acid delayed-release tablets and mycophenolate mofetil (mmf) tablets and capsules should not be used interchangeably without physician supervision because the rate of absorption following the administration of these two products is not equivalent. mycophenolic acid delayed-release tablets are contraindicated in patients with a hypersensitivity to mycophenolate sodium, mycophenolic acid (mpa), mycophenolate mofetil, or to any of its excipients. reactions like rash, pruritus, hypotension, and chest pain have been observed in clinical trials and post marketing reports [see adverse reactions ( 6)] . 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 mycophenolic acid delayed-release tablets treatment. to report a pregnancy or obtain information about the registry, visit www.mycophenolaterems.com or call 1-800-617-8191. risk summary following oral or intravenous (iv) administration, mmf is metabolized to mycophenolic acid (mpa), the active ingredient in mycophenolic acid delayed-release tablets and the active form of the drug. use of 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 (0.05 and 1.1 times exposure at the recommended clinical doses in kidney transplant patients for rats and rabbits, respectively) (see animal data) . risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient. when appropriate, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. 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, congenital malformations and pregnancy loss occurred when pregnant rats and rabbits received mycophenolate at dose multiples equivalent to and less than the recommended human dose. oral administration of mycophenolate sodium to pregnant rats from gestational day 7 to day 16 at a dose as low as 1 mg per kg resulted in malformations including anophthalmia, exencephaly, and umbilical hernia. the systemic exposure at this dose represents 0.05 times the clinical exposure at the human dose of 1,440 mg per day of mycophenolic acid delayed-release tablets. oral administration of mycophenolate to pregnant rabbits from gestational day 7 to day 19 resulted in embryofetal lethality and malformations, including ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at doses equal to or greater than 80 mg per kg per day, in the absence of maternal toxicity. this corresponds to about 1.1 times the recommended clinical dose based on 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 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 mycophenolic acid delayed-release tablets and any potential adverse effects on the breastfed infant from mycophenolic acid delayed-release tablets or from the underlying maternal condition. because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. 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 to 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 female patients taking mycophenolic acid delayed-release tablets who are considering pregnancy, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient. pregnancy testing to prevent unplanned exposure during pregnancy, females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 miu/ml immediately before starting mycophenolic acid delayed-release tablets. 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 embryo-fetal toxicity whenever possible. contraception female patients females of reproductive potential taking mycophenolic acid delayed-release tablets must receive contraceptive counseling and use acceptable contraception (see table 5 for acceptable contraception methods). patients must use acceptable birth control during entire mycophenolic acid delayed-release tablets therapy, and for 6 weeks after stopping mycophenolic acid delayed-release tablets, unless the patient chooses abstinence (she chooses to avoid heterosexual intercourse completely). patients should be aware that mycophenolic acid delayed-release tablets reduce blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness [see patient counseling information ( 17), drug interactions ( 7.8)] . or or   choose one barrier method   from each column (must   choose two methods) male patients genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 2.5 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 mycophenolic acid delayed-release tablets and for at least 90 days after cessation of treatment [see use in specific populations ( 8.1), nonclinical toxicology ( 13.1), patient counseling information ( 17)] . the safety and effectiveness of mycophenolic acid delayed-release tablets have been established in pediatric kidney transplant patients 5 to 16 years of age who were initiated on mycophenolic acid delayed-release tablets at least 6 months post-transplant. use of mycophenolic acid delayed-release tablets in this age group is supported by evidence from adequate and well-controlled studies of mycophenolic acid delayed-release tablets in a similar population of adult kidney transplant patients with additional pharmacokinetic data in pediatric kidney transplant patients [see dosage and administration ( 2.2, 2.3), clinical pharmacology ( 12.3)] . pediatric doses for patients with bsa<1.19 m 2 cannot be accurately administered using currently available formulations of mycophenolic acid delayed-release tablets. the safety and effectiveness of mycophenolic acid delayed-release tablets in de novo pediatric kidney transplant patients and in pediatric kidney transplant patients below the age of 5 years have not been established. clinical studies of mycophenolic acid delayed-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. of the 372 patients treated with mycophenolic acid delayed-release tablets in the clinical trials, 6% (n=21) were 65 years of age and older and 0.3% (n=1) were 75 years of age and older. 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, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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

slate run pharmaceuticals, llc - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - 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 (xl) 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 (xl) 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)

slate run pharmaceuticals, llc - desvenlafaxine succinate (unii: zb22enf0xr) (desvenlafaxine - unii:ng99554anw) - desvenlafaxine is indicated for the treatment of adults with major depressive disorder (mdd) [see clinical studies ( 14)] . - hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine formulation. angioedema has been reported in patients treated with desvenlafaxine [see adverse reactions ( 6.1)] . - the use of maois intended to treat psychiatric disorders with desvenlafaxine or within 7 days of stopping treatment with desvenlafaxine is contraindicated because of an increased risk of serotonin syndrome. the use of desvenlafaxine within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration ( 2.7) and warnings and precautions ( 5.2)] . - starting desvenlafaxine 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 ( 2.8) and warnings and precautions ( 5.2)] . 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. risk summary based on data from published observational studies, exposure to snris, 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 ( 5.4) and clinical considerations ] . there are no published studies on desvenlafaxine in pregnant women; however published epidemiologic studies of pregnant women exposed to venlafaxine, the parent compound, have not reported a clear association with adverse developmental outcomes (see data) . there are risks associated with untreated depression in pregnancy and with exposure to snris and ssris, including desvenlafaxine, during pregnancy ( see clinical considerations) . in reproductive developmental studies in rats and rabbits treated with desvenlafaxine succinate, there was no evidence of teratogenicity at a plasma exposure (auc) that is up to 19-times (rats) and 0.5-times (rabbits) the exposure at an adult human dose of 100 mg per day. however, fetotoxicity and pup deaths were observed in rats at 4.5-times the auc exposure observed with an adult human dose of 100 mg per day. 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 a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, showed that women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication. maternal adverse reactions exposure to desvenlafaxine in mid to late pregnancy may increase the risk for preeclampsia, and exposure to desvenlafaxine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [ see warnings and precautions ( 5.4) ] . fetal/neonatal adverse reactions exposure to snris or ssris in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding. monitor neonates who were exposed to desvenlafaxine in the third trimester of pregnancy for drug discontinuation syndrome (see data). data human data published epidemiological studies of pregnant women exposed to the parent compound venlafaxine have not reported a clear association with major birth defects or miscarriage. methodological limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders, and confirmatory studies; therefore, these studies cannot establish or exclude any drug-associated risk during pregnancy. retrospective cohort studies based on claims data have shown an association between venlafaxine use and preeclampsia, compared to depressed women who did not take an antidepressant during pregnancy. one study that assessed venlafaxine exposure in the second trimester or first half of the third trimester and preeclampsia showed an increased risk compared to unexposed depressed women [adjusted (adj) rr 1.57, 95% ci 1.29 to 1.91]. preeclampsia was observed at venlafaxine doses equal to or greater than 75 mg/day and a duration of treatment >30 days. another study that assessed venlafaxine exposure in gestational weeks 10 to 20 and preeclampsia showed an increased risk at doses equal to or greater than 150 mg/day. available data are limited by possible outcome misclassification and possible confounding due to depression severity and other confounders. retrospective cohort studies based on claims data have suggested an association between venlafaxine use near the time of delivery or through delivery and postpartum hemorrhage. one study showed an increased risk for postpartum hemorrhage when venlafaxine exposure occurred through delivery, compared to unexposed depressed women [adj rr 2.24 (95% ci 1.69 to 2.97)]. there was no increased risk in women who were exposed to venlafaxine earlier in pregnancy. limitations of this study include possible confounding due to depression severity and other confounders. another study showed an increased risk for postpartum hemorrhage when snri exposure occurred for at least 15 days in the last month of pregnancy or through delivery, compared to unexposed women (adj rr 1.64 to 1.76). the results of this study may be confounded by the effects of depression. neonates exposed to snris or ssris, 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)] . animal data when desvenlafaxine succinate was administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 300 mg/kg/day and 75 mg/kg/day, respectively, no teratogenic effects were observed. these doses were associated with a plasma exposure (auc) 19 times (rats) and 0.5 times (rabbits) the auc exposure at an adult human dose of 100 mg per day. however, fetal weights were decreased and skeletal ossification was delayed in rats in association with maternal toxicity at the highest dose, with an auc exposure at the no-effect dose that is 4.5-times the auc exposure at an adult human dose of 100 mg per day. when desvenlafaxine succinate was administered orally to pregnant rats throughout gestation and lactation, there was a decrease in pup weights and an increase in pup deaths during the first four days of lactation at the highest dose of 300 mg/kg/day. the cause of these deaths is not known. the auc exposure at the no-effect dose for rat pup mortality was 4.5-times the auc exposure at an adult human dose of 100 mg per day. post-weaning growth and reproductive performance of the progeny were not affected by maternal treatment with desvenlafaxine succinate at exposures 19 times the auc exposure at an adult human dose of 100 mg per day. risk summary available limited data from published literature show low levels of desvenlafaxine in human milk, and have not shown adverse reactions in breastfed infants (see data) . there are no data on the effects of desvenlafaxine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for desvenlafaxine and any potential adverse effects on the breastfed child from desvenlafaxine or from the underlying maternal condition. data a lactation study was conducted in 10 breastfeeding women (at a mean of 4.3 months post-partum) who were being treated with a 50 to 150 mg daily dose of desvenlafaxine for postpartum depression. sampling was performed at steady state (up to 8 samples) over a 24 hour dosing period, and included foremilk and hindmilk. the mean relative infant dose was calculated to be 6.8% (range of 5.5 to 8.1%). no adverse reactions were seen in the infants. the safety and effectiveness of desvenlafaxine have not been established in pediatric patients for the treatment of mdd. efficacy was not demonstrated in two adequate and well controlled, 8-week, randomized, double-blind, placebo-controlled, parallel group studies conducted in 587 patients (7 to 17 years of age) for the treatment of mdd. antidepressants, such as desvenlafaxine, increase the risk of suicidal thoughts and behaviors in pediatric patients [see the boxed warning and warnings and precautions ( 5.1)] . desvenlafaxine was associated with a decrease in body weight in placebo-controlled trials in pediatric patients with mdd. the incidence of weight loss (≥3.5% of baseline weight) was 22%, 14%, and 7% for patients treated with low dose desvenlafaxine, high dose desvenlafaxine, and placebo, respectively. the risks associated with longer term desvenlafaxine use were assessed in 6-month, open-label extension studies in pediatric patients (7 to 17 years of age) with mdd. pediatric patients (7 to 17 years of age) had mean changes in weight that approximated expected changes, based on data from age- and sex-matched peers. in clinical trials, when compared to adult patients receiving the same dose of desvenlafaxine, exposure to desvenlafaxine was similar in adolescent patients 12 to 17 years of age, and was about 30% higher in pediatric patients 7 to 11 years of age. juvenile animal studies in a juvenile animal study, male and female rats were treated with desvenlafaxine (75, 225 and 675 mg/kg/day) starting on postnatal day (pnd) 22 through 112. behavioral deficits (longer time immobile in a motor activity test, longer time swimming in a straight channel test, and lack of habituation in an acoustic startle test) were observed in males and females but were reversed after a recovery period. a no adverse effect level (noael) was not identified for these deficits. the low adverse effect level (loael) was 75 mg/kg/day which was associated with plasma exposure (auc) twice the levels measured with a pediatric dose of 100 mg/day. in a second juvenile animal study, male and female rats were administered desvenlafaxine (75, 225 or 675 mg/kg/day) for 8 to 9 weeks starting on pnd 22 and were mated with naïve counterparts. delays in sexual maturation and decreased fertility, number of implantation sites and total live embryos were observed in treated females at all doses. the loael for these findings is 75 mg/kg/day which was associated with an auc twice the levels measured with a pediatric dose of 100 mg/day. these findings were reversed at the end of a 4-week recovery period. the relevance of these findings to humans is not known. of the 4,158 patients in pre-marketing clinical studies with desvenlafaxine, 6% were 65 years of age or older. no overall differences in safety or efficacy were observed between these patients and younger patients; however, in the short-term placebo-controlled studies, there was a higher incidence of systolic orthostatic hypotension in patients ≥65 years of age compared to patients <65 years of age treated with desvenlafaxine [see adverse reactions ( 6.1)] . for elderly patients, possible reduced renal clearance of desvenlafaxine should be considered when determining dose [see dosage and administration ( 2.2) and clinical pharmacology ( 12.3)] . ssris and snris, including desvenlafaxine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see warnings and precautions ( 5.9)] . adjust the maximum recommended dosage in patients with moderate or severe renal impairment (cl cr  15 to 50 ml/min, c-g), or end-stage renal disease (cl cr  <15 ml/min, c-g) [see dosage and administration ( 2.2) and clinical pharmacology ( 12.3)] . adjust the maximum recommended dosage in patients with moderate to severe hepatic impairment (child-pugh score 7 to 15) [see dosage and administration ( 2.3) and clinical pharmacology ( 12.3)] . desvenlafaxine is not a controlled substance.

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slate run pharmaceuticals, llc. - montelukast sodium (unii: u1o3j18sfl) (montelukast - unii:mhm278sd3e) - montelukast 4 mg - montelukast sodium chewable tablets are indicated for the prophylaxis and chronic treatment of asthma in patients 2 to 14 years of age. montelukast sodium chewable tablets indicated for prevention of exercise-induced bronchoconstriction (eib) in patients 6 to 14 years of age. montelukast sodium chewable tablets are indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 to 14 years of age and perennial allergic rhinitis in patients 2 to 14 years of age . because the benefits of montelukast sodium chewable tablet may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see warnings and precautions ( 5.1)], reserve use for patients who have an inadequate response or intolerance to alternative therapies. montelukast sodium chewable tablets are not indicated for the treatment of an acute asthma attack. - montelukast sodium chewable tablets are contraindicated in patients with hypersensitivity to any of its components. risk summary available data from pu

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slate run pharmaceuticals, llc - metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. metformin hydrochloride extended-release tablets are contraindicated in patients with: - severe renal impairment (egfr below 30 ml/min/1.73 m 2 ) [ see warnings and precautions (5.1) ]. - hypersensitivity to metformin. - acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. risk summary limited data with metformin hydrochloride extended-release tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see data] . there are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see

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

slate run pharmaceuticals, llc - lurasidone hydrochloride (unii: o0p4i5851i) (lurasidone - unii:22ic88528t) - lurasidone hydrochloride tablets are indicated for: 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-andresearch-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 (mr

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slate run pharmaceuticals, llc - tetrabenazine (unii: z9o08yrn8o) (tetrabenazine - unii:z9o08yrn8o) - tetrabenazine tablets are indicated for the treatment of chorea associated with huntington’s disease. tetrabenazine tablets are contraindicated in patients: risk summary there are no adequate data on the developmental risk associated with the use of tetrabenazine tablets in pregnant women. administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality. administration of a major human metabolite of tetrabenazine to rats during pregnancy or during pregnancy and lactation produced adverse effects on the developing fetus and offspring (increased mortality, decreased growth, and neurobehavioral and reproductive impairment). the adverse developmental effects of tetrabenazine and a major human metabolite of tetrabenazine in rats occurred at clinically relevant doses [see data]. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 t

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

slate run pharmaceuticals, llc - venlafaxine hydrochloride (unii: 7d7rx5a8mo) (venlafaxine - unii:grz5rcb1qg) - venlafaxine hydrochloride extended-release capsules are indicated for the treatment of major depressive disorder (mdd). efficacy was established in three short-term (4, 8, and 12 weeks) and two long-term, maintenance trials. venlafaxine hydrochloride extended-release capsules are indicated for the treatment of generalized anxiety disorder (gad). efficacy was established in two 8-week and two 26-week placebo-controlled trials. venlafaxine hydrochloride extended-release capsules are indicated for the treatment of social anxiety disorder (sad), also known as social phobia. efficacy was established in four 12-week and one 26-week, placebo-controlled trials. venlafaxine hydrochloride extended-release capsules are indicated for the treatment of panic disorder (pd), with or without agoraphobia. efficacy was established in two 12-week placebo-controlled trials. hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate or to any excipients in the formulation. the use of maois (intended to treat psychiatr

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

slate run pharmaceuticals llc - lactulose (unii: 9u7d5qh5ae) (lactulose - unii:9u7d5qh5ae) - for the treatment of constipation. in patients with a history of chronic constipation, lactulose solution therapy increases the number of bowel movements per day and the number of days on which bowel movements occur. since lactulose solution contains galactose (less than 1.6 g/15 ml), it is contraindicated in patients who require a low galactose diet.