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micro labs limited - clobazam (unii: 2mro291b4u) (clobazam - unii:2mro291b4u) - clobazam tablet is indicated for the adjunctive treatment of seizures associated with lennox-gastaut syndrome (lgs) in patients 2 years of age or older. clobazam tablets are contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. hypersensitivity reactions have included serious dermatological reactions [see warnings and precautions (5.6 , 5.7 ) ]. pregnancy registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as clobazam, during pregnancy. healthcare providers are encouraged to recommend that pregnant women taking clobazam enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or online at http://www.aedpregnancyregistry.org/.  risk summary neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [ see warnings and precautions (5.9) and clinical considerations ]. available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects ( see data ). administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, n-desmethylclobazam, below those expected at therapeutic doses in patients [see animal data] . data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. clobazam should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. advise a pregnant woman and women of childbearing age of the potential risk to a fetus. the 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 of miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions    benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. monitor neonates exposed to clobazam during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. monitor neonates exposed to clobazam during pregnancy for signs of withdrawal. manage these neonates accordingly [ see warnings and precautions (5.9) ]. data human data   published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. in addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings. animal data   in a study in which clobazam (0, 150, 450, or 750 mg/kg/day) was orally administered to pregnant rats throughout the period of organogenesis, embryofetal mortality and incidences of fetal skeletal variations were increased at all doses. the low-effect dose for embryofetal developmental toxicity in rats (150 mg/kg/day) was associated with plasma exposures (auc) for clobazam and its major active metabolite, n-desmethylclobazam, lower than those in humans at the maximum recommended human dose (mrhd) of 40 mg/day. oral administration of clobazam (0, 10, 30, or 75 mg/kg/day) to pregnant rabbits throughout the period of organogenesis resulted in decreased fetal body weights, and increased incidences of fetal malformations (visceral and skeletal) at the mid and high doses, and an increase in embryofetal mortality at the high dose. incidences of fetal variations were increased at all doses. the highest dose tested was associated with maternal toxicity (ataxia and decreased activity). the low-effect dose for embryofetal developmental toxicity in rabbits (10 mg/kg/day) was associated with plasma exposures for clobazam and n-desmethylclobazam lower than those in humans at the mrhd. oral administration of clobazam (0, 50, 350, or 750 mg/kg/day) to rats throughout pregnancy and lactation resulted in increased embryofetal mortality at the high dose, decreased pup survival at the mid and high doses and alterations in offspring behavior (locomotor activity) at all doses. the low-effect dose for adverse effects on pre- and postnatal development in rats (50 mg/kg/day) was associated with plasma exposures for clobazam and n-desmethylclobazam lower than those in humans at the mrhd. risk summary clobazam is excreted in human milk ( see data ).  there are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. there are no data on the effects of clobazam on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clobazam and any potential adverse effects on the breastfed infant from clobazam or from the underlying maternal condition. clinical considerations adverse reactions such as somnolence and difficulty feeding have been reported in infants during breastfeeding in postmarketing experience with clobazam. infants exposed to clobazam through breast milk should be monitored for sedation, poor feeding and poor weight gain. data scientific literature on clobazam use during lactation is limited. after short-term administration, clobazam and n-desmethylclobazam are transferred into breast milk. administration of clobazam to rats prior to and during mating and early gestation resulted in adverse effects on fertility and early embryonic development at plasma exposures for clobazam and its major active metabolite, n-desmethylclobazam, below those in humans at the mrhd [see nonclinical toxicology (13.1)] . safety and effectiveness in patients less than 2 years of age have not been established. in a study in which clobazam (0, 4, 36, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose. the effect on bone density, but not on behavior, was reversible when drug was discontinued. the no-effect level for juvenile toxicity (36 mg/kg/day) was associated with plasma exposures (auc) to clobazam and its major active metabolite, n-desmethylclobazam, less than those expected at therapeutic doses in pediatric patients. clinical studies of clobazam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. however, elderly subjects appear to eliminate clobazam more slowly than younger subjects based on population pharmacokinetic analysis. for these reasons, the initial dose in elderly patients should be 5 mg/day. patients should be titrated initially to 10 to 20 mg/day. patients may be titrated further to a maximum daily dose of 40 mg if tolerated [see dosage and administration (2.4) , clinical pharmacology (12.3) ] . concentrations of clobazam’s active metabolite, n-desmethylclobazam, are higher in cyp2c19 poor metabolizers than in extensive metabolizers. for this reason, dosage modification is recommended [see dosage and administration (2.5),clinical pharmacology (12.3)] . the pharmacokinetics of clobazam were evaluated in patients with mild and moderate renal impairment. there were no significant differences in systemic exposure (auc and c max ) between patients with mild or moderate renal impairment and healthy subjects. no dose adjustment is required for patients with mild and moderate renal impairment. there is essentially no experience with clobazam in patients with severe renal impairment or esrd. it is not known if clobazam or its active metabolite, n-desmethylclobazam, is dialyzable [see dosage and administration (2.6) , clinical pharmacology (12.3)] . clobazam is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of clobazam. for this reason, dosage adjustment is recommended in patients with mild to moderate hepatic impairment (child-pugh score 5 to 9). there is inadequate information about metabolism of clobazam in patients with severe hepatic impairment [see dosage and administration (2.7) , clinical pharmacology (12.3)] . clobazam tablet contains clobazam, a schedule iv controlled substance. clobazam is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see warnings and precautions (5.2)]. the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). the world health organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with clobazam. physical dependence clobazam may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see warnings and precautions (5.3)]. in clinical trials, cases of dependency were reported following abrupt discontinuation of clobazam. to reduce the risk of withdrawal reactions, use a gradual taper to discontinue clobazam or reduce the dosage [see  dosage and administration (2.2)and warnings and precautions (5.3)]. acute withdrawal signs and symptoms acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. protracted withdrawal syndrome protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance tolerance to clobazam may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of clobazam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

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aurobindo pharma limited - glipizide (unii: x7wdt95n5c) (glipizide - unii:x7wdt95n5c) - glipizide 2.5 mg - glipizide extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. glipizide extended-release tablets are not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. glipizide is contraindicated in patients with: • known hypersensitivity to glipizide or any of the product’s ingredients. • hypersensitivity to sulfonamide derivatives. risk summary available data from a small number of published studies and postmarketing experience with glipizide extended-release tablets use in pregnancy over decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal outcomes. however, sulfonylureas (including glipizide) cross the placenta and have been associated with neonatal adverse reactions such as hypoglycemia. therefore, glipizide extended-release tablets should be discontinued at least two weeks before expected delivery (see clinical considerations). poo

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dr. reddy's laboratories limited - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - tablet - 7.5 mg - carefully consider the potential benefits and risks of meloxicam tablets and other treatment options before deciding to use meloxicam tablets. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). meloxicam tablets are indicated for relief of the signs and symptoms of osteoarthritis. meloxicam tablets are contraindicated in patients with known hypersensitivity to meloxicam. meloxicam tablet 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, pre-existing asthma ). meloxicam tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (cabg) surgery (see warnings ).

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aurobindo pharma limited - metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - metformin hydrochloride 500 mg - 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 m2 ) [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 clinical considerations]. no adverse developmental effects were ob

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dr.reddy's laboratories limited - omeprazole (unii: kg60484qx9) (omeprazole - unii:kg60484qx9), sodium bicarbonate (unii: 8mdf5v39qo) (bicarbonate ion - unii:hn1zra3q20) - omeprazole 20 mg - omeprazole and sodium bicarbonate capsules are indicated in adults for the: - short-term treatment of active duodenal ulcer. most patients heal within four weeks. some patients may require an additional four weeks of therapy. - short-term treatment (4 to 8 weeks) of active benign gastric ulcer. - treatment of heartburn and other symptoms associated with gerd for up to 4 weeks. - short-term treatment (4 to 8 weeks) of ee due to acid-mediated gerd which has been diagnosed by endoscopy in adults. the efficacy of omeprazole and sodium bicarbonate capsules used for longer than 8 weeks in patients with ee has not been established. if a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. if there is recurrence of ee or gerd symptoms (e.g., heartburn), additional 4 to 8 week courses of omeprazole and sodium bicarbonate capsules may be considered. - the efficacy of omeprazole and sodium bicarbonate capsules used for longer than 8 weeks in patients with ee has not been e

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aurobindo pharma limited - eszopiclone (unii: uzx80k71oe) (eszopiclone - unii:uzx80k71oe) - eszopiclone 1 mg - eszopiclone tablets are indicated for the treatment of insomnia. in controlled outpatient and sleep laboratory studies, eszopiclone tablets administered at bedtime decreased sleep latency and improved sleep maintenance. the clinical trials performed in support of efficacy were up to 6 months in duration.  the final formal assessments of sleep latency and maintenance were performed at 4 weeks in the 6-week study (adults only), at the end of both 2-week studies (elderly only) and at the end of the 6-month study (adults only). - eszopiclone tablets are contraindicated in patients who have experienced complex sleep behaviors after taking eszopiclone tablets [see warnings and precautions (5.1)]. - eszopiclone tablets are contraindicated in patients with known hypersensitivity to eszopiclone. hypersensitivity reactions include anaphylaxis and angioedema [see warnings and precautions (5.3)] . risk summary available pharmacovigilance data with eszopiclone use in pregnant women are insufficient to identify a drug-asso

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aurobindo pharma limited - moxifloxacin hydrochloride (unii: c53598599t) (moxifloxacin - unii:u188xyd42p) - moxifloxacin 400 mg - moxifloxacin tablets are indicated in adult patients for the treatment of community acquired pneumonia caused by susceptible isolates of streptococcus pneumoniae (including multi-drug resistant streptococcus pneumoniae [mdrsp]), haemophilus influenzae, moraxella catarrhalis, methicillin-susceptible staphylococcus aureus, klebsiella pneumoniae, mycoplasma pneumoniae, or chlamydophila pneumoniae [see clinical studies (14.3)] . mdrsp isolates are isolates resistant to two or more of the following antibacterial drugs: penicillin (minimum inhibitory concentrations [mic] ≥ 2 mcg/ml), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. moxifloxacin tablets are indicated in adult patients for the treatment of uncomplicated skin and skin structure infections caused by susceptible isolates of methicillin-susceptible staphylococcus aureus or streptococcus pyogenes [see clinical studies (14.4)]. moxifloxacin tablets are indicated in adult patients for the treatment of complicated skin and skin structure infections caused by susceptible isolates of methicillin-susceptible staphylococcus aureus, escherichia coli, klebsiella pneumoniae, or enterobacter cloacae [see clinical studies (14.5)]. moxifloxacin tablets are indicated in adult patients for the treatment of complicated intra-abdominal infections (ciai) including polymicrobial infections such as abscess caused by susceptible isolates of escherichia coli, bacteroides fragilis, streptococcus anginosus, streptococcus constellatus, enterococcus faecalis, proteus mirabilis, clostridium perfringens, bacteroides thetaiotaomicron, or peptostreptococcus species [see clinical studies (14.6)] . moxifloxacin tablets are indicated in adult patients for the treatment of plague, including pneumonic and septicemic plague, due to susceptible isolates of yersinia pestis and prophylaxis of plague in adult patients. efficacy studies of moxifloxacin could not be conducted in humans with plague for feasibility reasons. therefore, this indication is based on an efficacy study conducted in animals only [see clinical studies (14.7)] . moxifloxacin tablets are indicated in adult patients for the treatment of acute bacterial sinusitis (abs) caused by susceptible isolates of streptococcus pneumoniae, haemophilus influenzae , or moraxella catarrhalis [see clinical studies (14.1)] . because fluoroquinolones, including moxifloxacin tablets, have been associated with serious adverse reactions [see  warnings and precautions (5.1 to 5.14)] and for some patients abs is self-limiting, reserve moxifloxacin tablets for treatment of abs in patients who have no alternative treatment options. moxifloxacin tablets are indicated in adult patients for the treatment of acute bacterial exacerbation of chronic bronchitis (abecb) caused by susceptible isolates of streptococcus pneumoniae, haemophilus influenzae, haemophilus parainfluenzae, klebsiella pneumoniae, methicillin-susceptible staphylococcus aureus, or moraxella catarrhalis [see clinical studies (14.2)]. because fluoroquinolones, including moxifloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions (5.1 to 5.14)] and for some patients abecb is self-limiting, reserve moxifloxacin tablets for treatment of abecb in patients who have no alternative treatment options. to reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin tablets and other antibacterial drugs, moxifloxacin tablets 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. moxifloxacin tablets are contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antibacterials [see warnings and precautions (5.8)] . risk summary there are no available human data establishing a drug associated risk with the use of moxifloxacin. based on animal studies with moxifloxacin, moxifloxacin hydrochloride may cause fetal harm. moxifloxacin did not cause fetal malformations when administered to pregnant rats (iv and oral), rabbits (iv), and monkeys (oral) at exposures that were 0.24 to 2.5 times of those at the human clinical dose (400 mg/day moxifloxacin hydrochloride). however, when moxifloxacin was administered to rats and rabbits during pregnancy and throughout lactation (rats only) at doses associated with maternal toxicity, decreased neonatal body weights, increased incidence of skeletal variations (rib and vertebra combined), and increased fetal loss were observed (see data). advise pregnant women of the potential risk to the fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.   data animal data animal reproductive and development studies were done in rats, rabbits and cynomolgus macaques. moxifloxacin did not cause fetal malformations when administered to pregnant rats during organogenesis (gestation days 6 to 17) at oral doses as high as 500 mg/kg/day or 0.24 times the maximum recommended human dose based on systemic exposure (auc), but decreased fetal body weights and slightly delayed fetal skeletal development were observed. intravenous administration of 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta (gestation days 6 to 17). fetal malformations were not observed at intravenous doses as high as 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) in litters of pregnant rats that received moxifloxacin during organogenesis (gestation days 6 to 17). intravenous administration of 20 mg/kg/day (approximately equal to the maximum recommended human oral dose based upon systemic exposure) to pregnant rabbits during organogenesis (gestation days 6 to 20) resulted in decreased fetal body weights and delayed fetal skeletal ossification. when rib and vertebral malformations were combined, there was an increased fetal and litter incidence of these effects in rabbits. signs of maternal toxicity in rabbits at this dose included mortality, abortions, marked reduction of food consumption, decreased water intake, body weight loss and hypoactivity. fetal malformations were not observed when pregnant cynomolgus macaques were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure) during organogenesis (gestation days 20 to 50). an increased incidence of smaller fetuses was observed at 100 mg/kg/day in macaques. in a pre- and postnatal development study conducted in rats given oral doses from gestation day 6, throughout gestation and rearing to postpartum day 21, effects observed at 500 mg/kg/day (0.24 times the maximum recommended human dose based on systemic exposure (auc)) included slight increases in duration of pregnancy and prenatal loss, reduced pup birth weight and decreased neonatal survival. treatment-related maternal mortality occurred during gestation at 500 mg/kg/day in this study. risk summary it is not known if moxifloxacin is present in human milk. based on animal studies in rats, moxifloxacin may be excreted in human milk (see data). when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for moxifloxacin hydrochloride and any potential adverse effects on the breastfed child from moxifloxacin hydrochloride or from the underlying maternal condition. data in lactating rats given a single oral dose of 4.59 mg/kg moxifloxacin (approximately 9 times less than the recommended human dose based on body surface area) 8 days postpartum, there was very low excretion of substance-related radioactivity into the milk, amounting to approximately 0.03% of the dose. effectiveness in pediatric patients and adolescents less than 18 years of age has not been established. moxifloxacin hydrochloride causes arthropathy in juvenile animals. limited information on the safety of moxifloxacin hydrochloride in 301 pediatric patients is available from the ciai trial [see boxed warning, warnings and precautions (5.11) and nonclinical toxicology (13.2)]. active controlled trial in complicated intra-abdominal infection (ciai) the safety and efficacy of moxifloxacin hydrochloride in pediatric patients for the treatment of ciai has not been demonstrated. pediatric patients 3 months to <18 years of age (mean age of 12 ± 4 years) were enrolled in a single randomized, double-blind, active controlled trial in ciai including appendicitis with perforation, abscesses and peritonitis. pediatric patients were randomized (2:1) to receive either moxifloxacin hydrochloride or comparator. this study enrolled 451 patients who received study medication, 301 treated with moxifloxacin, and 150 with comparator. of the 301 pediatric patients treated with moxifloxacin hydrochloride, 15 were below the age of 6 years and 286 were between the ages of 6 to <18 years. patients received sequential intravenous/oral moxifloxacin hydrochloride or comparator (intravenous ertapenem followed by oral amoxicillin/clavulanate) for 5 to 14 days (mean duration was 9 days with a range of 1 to 24 days). the overall adverse reaction profile in pediatric patients was comparable to that of adult patients. the most frequently occurring adverse reactions in pediatric patients treated with moxifloxacin hydrochloride were qt prolongation 9.3% (28/301), vomiting, 6.6% (20/301), diarrhea 3.7% (11/301), arthralgia 3.0% (9/301), and phlebitis 2.7% (8/301) (see table 5). discontinuation of study drug due to an adverse reaction was reported in 5.3% (16/301) of moxifloxacin hydrochloride-treated patients versus 1.3% (2/150) of comparator-treated patients. the adverse reaction profile of moxifloxacin hydrochloride or comparator was similar across all age groups studied. musculoskeletal adverse reactions were monitored and followed up to 5 years after the end of study treatment. the rates of musculoskeletal adverse reactions were 4.3% (13/301) in the moxifloxacin hydrochloride-treated group versus 3.3% (5/150) in the comparator-treated group. the majority of musculoskeletal adverse reactions were reported between 12 and 53 weeks after start of study treatment with complete resolution at the end of the study [see warnings and precautions (5.11) and nonclinical toxicology (13.2)].  clinical response was assessed at the test-of-cure visit (28 to 42 days after end of treatment). the clinical response rates observed in the modified intent to treat population were 83.9% (208/248) for moxifloxacin hydrochloride and 95.5% (127/133) for comparator; see table 6. geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as moxifloxacin hydrochloride. this risk is further increased in patients receiving concomitant corticosteroid therapy. tendinitis or tendon rupture can involve the achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. caution should be used when prescribing moxifloxacin hydrochloride to elderly patients especially those on corticosteroids. patients should be informed of this potential side effect and advised to discontinue moxifloxacin tablets and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see boxed warning, and warnings and precautions (5.2)]. epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see warnings and precautions (5.9) ]. in controlled multiple-dose clinical trials, 23% of patients receiving oral moxifloxacin hydrochloride were greater than or equal to 65 years of age and 9% were greater than or equal to 75 years of age. the clinical trial data demonstrate that there is no difference in the safety and efficacy of oral moxifloxacin hydrochloride in patients aged 65 or older compared to younger adults. in trials of intravenous use, 42% of moxifloxacin hydrochloride patients were greater than or equal to 65 years of age, and 23% were greater than or equal to 75 years of age. the clinical trial data demonstrate that the safety of intravenous moxifloxacin hydrochloride in patients aged 65 or older was similar to that of comparator-treated patients. in general, elderly patients may be more susceptible to drug-associated effects of the qt interval. therefore, moxifloxacin hydrochloride should be avoided in patients taking drugs that can result in prolongation of the qt interval (for example, class ia or class iii antiarrhythmics) or in patients with risk factors for torsade de pointes (for example, known qt prolongation, uncorrected hypokalemia) [see warnings and precautions (5.6) , drug interactions (7.5) , and clinical pharmacology (12.3) ]. the pharmacokinetic parameters of moxifloxacin are not significantly altered in mild, moderate, severe, or end-stage renal disease. no dosage adjustment is necessary in patients with renal impairment, including those patients requiring hemodialysis (hd) or continuous ambulatory peritoneal dialysis (capd) [see dosage and administration (2), and clinical pharmacology (12.3)]. no dosage adjustment is recommended for mild, moderate, or severe hepatic insufficiency (child-pugh classes a, b, or c). however, due to metabolic disturbances associated with hepatic insufficiency, which may lead to qt prolongation, moxifloxacin hydrochloride should be used with caution in these patients [see warnings and precautions (5.6) and clinical pharmacology (12.3)] .

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aurobindo pharma limited - 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. - treatment resistant depression (major depressive disorder in patients, 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 capsules 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 1000 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 10-60 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. 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, 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)

dr. reddy's laboratories limited - primidone (unii: 13afd7670q) (primidone - unii:13afd7670q) - primidone 50 mg - primidone tablets, used alone or concomitantly with other anticonvulsants, are indicated in the control of grand mal, psychomotor, and focal epileptic seizures. it may control grand mal seizures refractory to other anticonvulsant therapy. primidone tablet is contraindicated in:  1) patients with porphyria and  2) patients who are hypersensitive to phenobarbital (see clinicalpharmacology ).

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

aurobindo pharma limited - raloxifene hydrochloride (unii: 4f86w47br6) (raloxifene - unii:yx9162eo3i) - raloxifene hydrochloride 60 mg - raloxifene hydrochloride tablets are indicated for the treatment and prevention of osteoporosis in postmenopausal women [see clinical studies (14.1, 14.2)] . raloxifene hydrochloride tablets are indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis [see clinical studies (14.3)] . raloxifene hydrochloride tablets are indicated for the reduction in risk of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer [see clinical studies (14.4)] . the effect in the reduction in the incidence of breast cancer was shown in a study of postmenopausal women at high risk for breast cancer with a 5-year planned duration with a median follow-up of 4.3 years [see clinical studies (14.4)] . twenty-seven percent of the participants received drug for 5 years. the long-term effects and the recommended length of treatment are not known. high risk of breast cancer is defined as at least one breast biopsy showing lobular carcinoma in situ (lcis) or atypical hyperplasia, one or more first-degree relatives with breast cancer, or a 5-year predicted risk of breast cancer ≥ 1.66% (based on the modified gail model). among the factors included in the modified gail model are the following: current age, number of first-degree relatives with breast cancer, number of breast biopsies, age at menarche, nulliparity or age of first live birth. healthcare professionals can obtain a gail model risk assessment tool by dialing 1-800-545-5979. currently, no single clinical finding or test result can quantify risk of breast cancer with certainty. after an assessment of the risk of developing breast cancer, the decision regarding therapy with raloxifene hydrochloride tablets should be based upon an individual assessment of the benefits and risks. raloxifene hydrochloride tablets does not eliminate the risk of breast cancer. patients should have breast exams and mammograms before starting raloxifene hydrochloride tablets and should continue regular breast exams and mammograms in keeping with good medical practice after beginning treatment with raloxifene hydrochloride tablets. important limitations of use for breast cancer risk reduction - there are no data available regarding the effect of raloxifene hydrochloride tablets on invasive breast cancer incidence in women with inherited mutations (brca1, brca2) to be able to make specific recommendations on the effectiveness of raloxifene hydrochloride tablets. - raloxifene hydrochloride tablets are not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence. - raloxifene hydrochloride tablets are not indicated for the reduction in the risk of noninvasive breast cancer. raloxifene hydrochloride tablets are contraindicated in women with active or past history of venous thromboembolism (vte), including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis [see warnings and precautions (5.1)] . raloxifene hydrochloride is contraindicated for use in pregnancy, as it may cause fetal harm [see use in specific populations (8.1)] . risk summary raloxifene hydrochloride is contraindicated for use in pregnant women, and is not indicated for use in females of reproductive potential. based on mechanism of action, raloxifene hydrochloride may block the important functions that estrogen has during all stages of pregnancy [see clinical pharmacology (12.1)] . limited data with raloxifene hydrochloride use in pregnant women are insufficient to inform any drug associated risks for births defects or miscarriage. in rabbits and rats dosed during organogenesis or during gestation and lactation, raloxifene hydrochloride produced multiple adverse reproductive and developmental effects, including abortion; fetal anomalies; and delayed or disrupted parturition leading to maternal and neonatal mortality, at doses less than or similar to the maximum recommended human dose (based on human body surface area comparison). data animal data in the developmental and reproductive toxicity studies conducted with raloxifene hydrochloride, numerous adverse effects were observed in multiple animal species. in rabbits dosed during organogenesis, abortion and a low rate of fetal heart anomalies (ventricular septal defects) occurred at doses ≥0.1 mg/kg (≥0.04 times the human dose based on surface area, mg/m2 ). in rats dosed during organogenesis, retardation of fetal growth and developmental abnormalities (wavy ribs, kidney cavitation) occurred at doses ≥1 mg/kg (≥0.2 times the human dose based on surface area, mg/m2 ). treatment of rats during gestation and lactation with doses of 0.1 to 10 mg/kg (0.02 to 1.6 times the human dose based on surface area, mg/m2 ) produced effects that included delayed and disrupted parturition, decreased neonatal survival and altered physical development, sex- and age-specific reductions in growth and changes in pituitary hormone content, and decreased lymphoid compartment size in offspring. at 10 mg/kg, the disruption of parturition resulted in maternal and progeny morbidity and death. effects in adult offspring (4 months of age) included uterine hypoplasia and reduced fertility; however, no ovarian or vaginal pathology was observed. risk summary raloxifene hydrochloride is not indicated for use in females of reproductive potential. there is no information on the presence of raloxifene in human milk, the effects on the breastfed child, or the effects on milk production. however, based on mechanism of action, raloxifene hydrochloride may block the important functions that estrogen has in mammary tissue during lactation [see clinical pharmacology (12.1)] . safety and effectiveness in pediatric patients have not been established. of the total number of patients in placebo-controlled clinical studies of raloxifene hydrochloride, 61% were 65 and over, while 15.5% were 75 and over. 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. based on clinical trials, there is no need for dose adjustment for geriatric patients [see clinical pharmacology (12.3)] . raloxifene hydrochloride should be used with caution in patients with moderate or severe renal impairment [see warnings and precautions (5.8) and clinical pharmacology (12.3)] . raloxifene hydrochloride should be used with caution in patients with hepatic impairment [see warnings and precautions (5.5) and clinical pharmacology (12.3)] .