Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine 300 mg in 5 ml - oxcarbazepine oral suspension is indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. oxcarbazepine is contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [see warnings and precautions (5.2, 5.3)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as oxcarbazepine, during pregnancy. encourage women who are taking oxcarbazepine during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/ . risk summary there are no adequate data on the developmental risks associated with the use of ox

Vereinigtes Königreich - Englisch - MHRA (Medicines & Healthcare Products Regulatory Agency)

reckitt benckiser healthcare (uk) ltd - calcium carbonate; sodium bicarbonate; sodium alginate - oral suspension - 32.5mg/1ml ; 21.3mg/1ml ; 50mg/1ml

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

avpak - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine oral suspension is indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. oxcarbazepine oral suspension is contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [see warnings and precautions (5.2, 5.3)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as oxcarbazepine, during pregnancy. encourage women who are taking oxcarbazepine during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

aurobindo pharma limited - clobazam (unii: 2mro291b4u) (clobazam - unii:2mro291b4u) - clobazam oral suspension is indicated for the adjunctive treatment of seizures associated with lennox-gastaut syndrome (lgs) in patients 2 years of age or older. clobazam oral suspension is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. hypersensitivity reactions have included serious dermatological reactions [see warnings and precautions (5.6, 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 cmax ) 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 oral suspension 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. clobazam (kloe′ ba zam) oral suspension, civ   read this instructions for use before using clobazam oral suspension and each time you get a refill. there may be new information. this leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment. prepare clobazam oral suspension dose you will need the following supplies: see figure a - clobazam oral suspension bottle - bottle adapter - oral dosing syringe (2 dosing syringes are included in the clobazam oral suspension box). - use only 1 syringe to take your dose of clobazam oral suspension. if you lose or damage the syringe, or cannot read the markings, use the other syringe. figure a step 1. remove the clobazam oral suspension bottle, bottle adapter, and 1 syringe from the box. step 2. shake the bottle well before each use. see figure b figure b step 3. uncap the bottle and firmly insert the bottle adapter into the bottle until the adapter top is even with the bottle top. see figure c figure c once the bottle adapter is in place, it should not be removed. step 4. check your dose in milliliters (ml) as prescribed by your healthcare provider. find this number on the syringe. do not take more than the prescribed total dose in 1 day. see figure d figure d step 5. push the plunger all the way down and then insert the syringe into the upright bottle through the opening in the bottle adapter. see figure e figure e step 6. with the syringe in place, turn the bottle upside down. pull the plunger to the number of mls needed (the amount of liquid medicine in step 4). see figure f figure f measure the mls of medicine using the edge of the violet plunger. see figure g figure g step 7. remove the syringe from the bottle adapter. slowly squirt clobazam oral suspension directly into the corner of your mouth or your child’s mouth until all of the liquid medicine in the syringe is given. see figure h figure h step 8. cap the bottle tightly with the adapter in place. if the cap does not fit securely, check to see if the adapter is fully inserted. see figure i - store and dispense clobazam oral suspension in its original bottle in an upright position at 68°f to 77°f (20°c to 25°c). - use clobazam oral suspension within 90 days of first opening bottle. - after 90 days safely throw away any clobazam oral suspension that has not been used. figure i step 9. wash the oral syringe after each use. - to clean the oral syringe, take apart by removing the plunger completely. pull plunger straight out of the barrel. - the barrel and plunger can be washed with soap and water, rinsed, and allowed to dry. - do not wash the oral syringe in the dishwasher. this instruction for use has been approved by the u.s. food and drug administration. distributed by: aurobindo pharma usa, inc. 279 princeton-hightstown road east windsor, nj 08520 manufactured by: aurobindo pharma limited hyderabad-500 032, india revised: 04/2024

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

remedyrepack inc. - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine oral suspension is indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. oxcarbazepine oral suspension is contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [see warnings and precautions (5.2, 5.3)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as oxcarbazepine, during pregnancy. encourage women who are taking oxcarbazepine during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

avpak - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine oral suspension is indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. oxcarbazepine oral suspension is contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [see warnings and precautions (5.2, 5.3)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as oxcarbazepine, during pregnancy. encourage women who are taking oxcarbazepine during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

taro pharmaceuticals u.s.a., inc. - clobazam (unii: 2mro291b4u) (clobazam - unii:2mro291b4u) - clobazam oral suspension is indicated for the adjunctive treatment of seizures associated with lennox-gastaut syndrome (lgs) in patients 2 years of age or older. clobazam oral suspension is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. hypersensitivity reactions have included serious dermatological reactions [see warnings and precautions (5.5)]. pregnancy registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as clobazam, during pregnancy. physicians are advised to recommend that pregnant patients taking clobazam oral suspension enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll-free number 1-888-233-2334, and must be done by patients themselves. information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. risk summary there are no adequate and well-controlled studies of clobazam in pregnant women. availabl

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

novitium pharma llc - felbamate (unii: x72rbb02n8) (felbamate - unii:x72rbb02n8) - felbamate oral suspension is not indicated as a first line antiepileptic treatment (see warnings ). felbamate oral suspension is recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. if these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgement, felbamate oral suspension can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with lennox-gastaut syndrome in children. felbamate oral suspension is contraindicated in patients with known hypersensitivity to felbamate, its ingredients, or known sensitivity to other carbamates. it should not be used in patients with a hi

Singapur - Englisch - HSA (Health Sciences Authority)

opella healthcare singapore pte. ltd. - fexofenadine 28 mg/5 ml eqv fexofenadine hydrochloride - suspension - 30.00 mg/5 ml - fexofenadine 28 mg/5 ml eqv fexofenadine hydrochloride 30.00 mg/5 ml

Vereinigte Staaten - Englisch - NLM (National Library of Medicine)

aurobindo pharma limited - nevirapine hemihydrate (unii: b7xf2td73c) (nevirapine - unii:99dk7fvk1h) - nevirapine 50 mg in 5 ml - nevirapine oral suspension is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv-1) infection in adults and pediatric patients 15 days and older [see clinical studies (14.1, 14.2)] . limitations of use: based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine oral suspension is not recommended to be initiated, unless the benefit outweighs the risk, in: - adult females with cd4+ cell counts greater than 250 cells/mm3 or - adult males with cd4+ cell counts greater than 400 cells/mm3 [see warnings and precautions (5.1)]. nevirapine oral suspension is contraindicated: - in patients with moderate or severe (child-pugh class b or c, respectively) hepatic impairment [see warnings and precautions (5.1)  and use in specific populations (8.7) ]. - for use as part of occupational and non-occupational post-exposure prophylaxis (pep) regimens [see warnings and precautions (5.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to nevirapine during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary available data from the apr show no difference in the risk of overall major birth defects for nevirapine compared with the background rate for major birth defects of 2.7% in the u.s. reference population of the metropolitan atlanta congenital defects program (macdp) [see data] . the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15 to 20%. the background risk of birth defects and miscarriage for the indicated population is unknown. methodological limitations of the apr include the use of macdp as the external comparator group. the macdp population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation. in literature reports, immediate-release nevirapine exposure (cmin ) can be up to 29% lower during pregnancy. however, as this reduction was not found to be clinically meaningful, dose adjustment is not necessary [see data] . there is a risk for severe hepatic events in pregnant women exposed to nevirapine [see clinical considerations] . in animal reproduction studies, no evidence of adverse developmental outcomes was observed following oral administration of nevirapine during organogenesis in the rat and rabbit, at systemic exposures (auc) to nevirapine approximately equal (rats) and 50% higher (rabbits) than the exposure in humans at the recommended 400 mg daily dose [see data] . clinical considerations maternal adverse reactions severe hepatic events, including fatalities, have been reported in pregnant women receiving chronic nevirapine therapy as part of combination treatment of hiv-1 infection. regardless of pregnancy status, women with cd4+ cell counts greater than 250 cells/mm3 should not initiate nevirapine unless the benefit outweighs the risk. it is unclear if pregnancy augments the risk observed in non-pregnant women [see warnings and precautions (5.1)] . data human data based on prospective reports to the apr of exposures to nevirapine during pregnancy resulting in live births (including over 1100 exposed in the first trimester and over 1500 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.0% (95% ci: 2.1%, 4.1%) and 3.3% (95% ci: 2.4%, 4.3%) following first and second/third trimester exposure, respectively, to nevirapine-containing regimens, compared with the background birth defect rate of 2.7% in a u.s. reference population of the macdp. there are several literature reports of chronic administration of immediate-release nevirapine during pregnancy, in which nevirapine pharmacokinetics were compared between pregnancy and postpartum. in these studies, the mean difference in nevirapine cmin during pregnancy as compared to postpartum ranged from no difference to approximately 29% lower. animal data nevirapine was administered orally to pregnant rats (at 0, 12.5, 25, and 50 mg per kg per day) and rabbits (at 0, 30, 100, and 300 mg per kg per day) through organogenesis (on gestation days 7 through 16, and 6 through 18, respectively). no adverse developmental effects were observed at doses producing systemic exposures (auc) approximately equivalent to (rats) or approximately 50% higher (rabbits) than human exposure at the recommended daily dose. in rats, decreased fetal body weights were observed at a maternally toxic dose at an exposure approximately 50% higher than the recommended daily dose. risk summary the centers for disease control and prevention recommend that hiv-1 infected mothers in the united states not breastfeed their infants to avoid risking postnatal transmission of hiv-1 infection. published data report that nevirapine is present in human milk [see data] . there are limited data on the effects of nevirapine on the breastfed infant. there is no information on the effects of nevirapine on milk production. because of the potential for (1) hiv-1 transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants), and (3) serious adverse reactions in nursing infants, mothers should not breastfeed if they are receiving nevirapine. data based on five publications, immediate-release nevirapine was excreted in breast milk at median concentrations ranging from 4080 to 6795 ng/ml, and the median maternal breast milk to maternal plasma concentration ratio range was 59 to 88%. reported infant nevirapine median plasma concentrations were low, ranging from 734 to 1140 ng/ml. the estimated nevirapine dose of 704 to 682 mcg/kg/day for infants fed exclusively with breast milk was lower than the daily recommended nevirapine dose for infants. published literature indicates that rash and hyperbilirubinemia have been seen in infants exposed to nevirapine through breastmilk. infertility limited human data are insufficient to determine the risk of infertility in humans. based on results from animal fertility studies conducted in rats, nevirapine may reduce fertility in females of reproductive potential. it is not known if these effects on fertility are reversible [see nonclinical toxicology (13.1)] . the safety, pharmacokinetic profile, and virologic and immunologic responses of nevirapine have been evaluated in hiv-1 infected pediatric subjects aged 3 months to 18 years [see adverse reactions (6.1) and clinical studies (14.2)] . the safety and pharmacokinetic profile of nevirapine has been evaluated in hiv-1 infected pediatric subjects aged 15 days to less than 3 months [see adverse reactions (6.1) and clinical studies (14.2)] . the most frequently reported adverse events related to nevirapine in pediatric subjects were similar to those observed in adults, with the exception of granulocytopenia, which was more commonly observed in children receiving both zidovudine and nevirapine [see adverse reactions (6.1)  and clinical studies (14.2) ]. clinical trials of nevirapine did not include sufficient numbers of subjects aged 65 and older to determine whether elderly subjects respond differently from younger subjects. 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. in subjects with renal impairment (mild, moderate or severe), there were no significant changes in the pharmacokinetics of nevirapine. nevirapine is extensively metabolized by the liver and nevirapine metabolites are extensively eliminated by the kidney. nevirapine metabolites may accumulate in patients receiving dialysis; however, the clinical significance of this accumulation is not known. no adjustment in nevirapine dosing is required in patients with crcl greater than or equal to 20 ml per min. the pharmacokinetics of nevirapine have not been evaluated in patients with crcl less than 20 ml per min. in patients undergoing chronic hemodialysis, an additional 200 mg dose following each dialysis treatment is indicated [see dosage and administration (2.4) and clinical pharmacology (12.3) ] . because increased nevirapine levels and nevirapine accumulation may be observed in patients with serious liver disease, do not administer nevirapine to patients with moderate or severe (child-pugh class b or c, respectively) hepatic impairment [see contraindications (4), warnings and precautions (5.1), and clinical pharmacology (12.3)] .