Stany Zjednoczone - angielski - NLM (National Library of Medicine)

cipla usa inc. - abacavir sulfate (unii: j220t4j9q2) (abacavir - unii:wr2tip26vs) - abacavir 300 mg - abacavir tablets usp 300 mg, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (hiv-1) infection. abacavir tablet is contraindicated in patients: - who have the hla-b*5701 allele [see warnings and precautions (5.1)] . - with prior hypersensitivity reaction to abacavir [see warnings and precautions (5.1)] . - with moderate or severe hepatic impairment [see use in specific populations (8.6)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir sulfate 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 overall risk of birth defects for abacavir compared with the background rate for birth defects of 2.7% in the metropolitan atlanta congenital defects program (macdp) reference population (see dat

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

teva pharmaceuticals usa, inc. - abacavir sulfate (unii: j220t4j9q2) (abacavir - unii:wr2tip26vs), lamivudine (unii: 2t8q726o95) (lamivudine - unii:2t8q726o95) - abacavir 600 mg - abacavir and lamivudine tablets, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus type 1 (hiv-1) infection. abacavir and lamivudine tablets are contraindicated in patients: - who have the hla-b*5701 allele [see warnings and precautions (5.1)]. - with prior hypersensitivity reaction to abacavir [see warnings and precautions (5.1)] or lamivudine. - with moderate or severe hepatic impairment [see use in specific populations (8.7)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir and lamivudine tablets 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 overall risk of birth defects for abacavir or lamivudine compared with the background rate for birth defects of 2.7% in the metropolitan atlanta congenital de

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

lupin pharmaceuticals, inc. - abacavir sulfate (unii: j220t4j9q2) (abacavir - unii:wr2tip26vs), lamivudine (unii: 2t8q726o95) (lamivudine - unii:2t8q726o95) - abacavir 600 mg - abacavir and lamivudine tablets, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus type 1 (hiv-1) infection. abacavir and lamivudine tablets are contraindicated in patients: -   who have the hla-b*5701 allele [see warnings and precautions (5.1)]. -   with prior hypersensitivity reaction to abacavir [see warnings and precautions (5.1)] or lamivudine. -   with moderate or severe hepatic impairment [see use in specific populations (8.7)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir and lamivudine tablets during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. available data from the (apr) show no difference in the overall risk of birth defects for abacavir or lamivudine compared with the background rate for birth defects of 2.7% in the metropolitan atlanta congenital defe

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

lupin limited - lamivudine (unii: 2t8q726o95) (lamivudine - unii:2t8q726o95), zidovudine (unii: 4b9xt59t7s) (zidovudine - unii:4b9xt59t7s), abacavir sulfate (unii: j220t4j9q2) (abacavir - unii:wr2tip26vs) - lamivudine 150 mg - abacavir, lamivudine and zidovudine tablet is indicated in combination with other antiretrovirals or alone for the treatment of human immunodeficiency virus type 1 (hiv-1) infection. limitations of use: - limited data exist on the use of abacavir, lamivudine and zidovudine tablets alone in patients with higher baseline viral load levels (greater than 100,000 copies per ml) [see clinical studies (14)] . abacavir, lamivudine and zidovudine tablets are contraindicated in patients: - who have the hla-b*5701 allele [see warnings and precautions (5.1)]. - with prior hypersensitivity reaction to abacavir [see warnings and precautions (5.1)], lamivudine, or zidovudine. - with moderate or severe hepatic impairment [see use in specific populations (8.7)] . teratogenic effects pregnancy category c: there are no adequate and well-controlled studies of abacavir, lamivudine and zidovudine tablets in pregnant women. reproduction studies with abacavir, lamivudine, and zidovudine have been p

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

mylan pharmaceuticals inc. - nevirapine (unii: 99dk7fvk1h) (nevirapine - unii:99dk7fvk1h) - nevirapine 100 mg - nevirapine extended-release tablets are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv-1) infection in adults and pediatric patients 6 years of age or older with a body surface area (bsa) of 1.17 m2 or greater [see clinical studies (14.1, 14.2)] . limitations of use: based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine extended-release tablets are not recommended to be initiated, unless the benefit outweighs the risk, in: nevirapine extended-release tablets are contraindicated: 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. 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 a 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 15-20%. 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. there is a risk for severe hepatic events in pregnant women exposed to nevirapine extended-release tablets [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] . 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)] . 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. nevirapine was administered orally to pregnant rats (at 0, 12.5, 25, and 50 mg/kg/day), and rabbits (at 0, 30, 100, and 300 mg/kg/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. 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 immediate-release nevirapine is present in human milk. 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 extended-release tablets. limited human data are insufficient to determine the risk of infertility in humans. based on results from animal fertility studies conducted in rats, nevirapine extended-release tablets may reduce fertility in females of reproductive potential. it is not known if these effects on fertility are reversible [see nonclinical toxicology (13.1)] . nevirapine extended-release tablets are indicated for use in combination with other antiretroviral agents for the treatment of hiv-1 infection in children 6 years of age or older with a bsa of 1.17 m2 or greater [see indications and usage (1) and dosage and administration (2.3)]. the use of nevirapine extended-release tablets for the treatment of hiv-1 infection in pediatric patients 6 to less than 18 years of age is based on pharmacokinetic, safety, and antiviral activity data from an open-label trial with nevirapine extended-release tablets. the results of this trial were supported by previous demonstration of efficacy in adult patients [see adverse reactions (6.1) , clinical pharmacology (12.3), and clinical studies (14.2)]. nevirapine extended-release tablets are not recommended for children less than 6 years of age. trial 1100.1518 did not provide sufficient pharmacokinetic data for children 3 to less than 6 years of age to support the use of nevirapine extended-release tablets in this age group. furthermore, nevirapine extended-release tablets are not recommended for children less than 3 years of age because they are not able to swallow tablets. clinical studies of nevirapine extended-release tablets 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 dose of immediate-release nevirapine (200 mg) following each dialysis treatment is indicated [see dosage and administration (2.5) and clinical pharmacology (12.3)]. nevirapine extended-release tablets have not been studied in patients with renal dysfunction. 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)]. nevirapine extended-release tablets have not been evaluated in subjects with hepatic impairment.

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

remedyrepack inc. - abacavir sulfate (unii: j220t4j9q2) (abacavir - unii:wr2tip26vs) - abacavir tablets usp 300 mg, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (hiv-1) infection. abacavir tablet is contraindicated in patients: - who have the hla-b*5701 allele [see warnings and precautions ( 5.1)] . - with prior hypersensitivity reaction to abacavir [see warnings and precautions ( 5.1)] . - with moderate or severe hepatic impairment [see use in specific populations ( 8.6)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir sulfate 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 overall risk of birth defects for abacavir compared with the background rate for birth defects of 2.7% in the metropolitan atlanta congenital defects program (macdp) reference population (see data) . the apr uses the macdp as the u.s. reference population for birth defects in the general population. the macdp evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks' gestation. 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 for major birth defects and miscarriage for the indicated population is unknown. in animal reproduction studies, oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (auc) at the recommended clinical daily dose. however, no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis, at exposures approximately 9 times the human exposure (auc) at the recommended clinical dose (see data) . data human data: based on prospective reports to the apr of exposures to abacavir during pregnancy resulting in live births (including over 1,300 exposed in the first trimester and over 1,300 exposed in second/third trimester), there was no difference between the overall risk of birth defects for abacavir compared with the background birth defect rate of 2.7% in the u.s. reference population of the macdp. the prevalence of defects in live births was 3.2% (95% ci: 2.3% to 4.3%) following first trimester exposure to abacavir-containing regimens and 2.9% (95% ci: 2.1% to 4.0%) following second/third trimester exposure to abacavir-containing regimens. abacavir has been shown to cross the placenta and concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery [see clinical pharmacology ( 12.3)] . animal data: abacavir was administered orally to pregnant rats (at 100, 300, and 1,000 mg per kg per day) and rabbits (at 125, 350, or 700 mg per kg per day) during organogenesis (on gestation days 6 through 17 and 6 through 20, respectively). fetal malformations (increased incidences of fetal anasarca and skeletal malformations) or developmental toxicity (decreased fetal body weight and crown-rump length) were observed in rats at doses up to 1,000 mg per kg per day, resulting in exposures approximately 35 times the human exposure (auc) at the recommended daily dose. no developmental effects were observed in rats at 100 mg per kg per day, resulting in exposures (auc) 3.5 times the human exposure at the recommended daily dose. in a fertility and early embryo-fetal development study conducted in rats (at 60, 160, or 500 mg per kg per day), embryonic and fetal toxicities (increased resorptions, decreased fetal body weights) or toxicities to the offspring (increased incidence of stillbirth and lower body weights) occurred at doses up to 500 mg per kg per day. no developmental effects were observed in rats at 60 mg per kg per day, resulting in exposures (auc) approximately 4 times the human exposure at the recommended daily dose. studies in pregnant rats showed that abacavir is transferred to the fetus through the placenta. in pregnant rabbits, no developmental toxicities and no increases in fetal malformations occurred at up to the highest dose evaluated, resulting in exposures (auc) approximately 9 times the human exposure at the recommended dose. risk summary the centers for disease control and prevention recommends that hiv-1-infected mothers in the united states not breastfeed their infants to avoid risking postnatal transmission of hiv-1 infection. abacavir is present in human milk. there is no information on the effects of abacavir on the breastfed infant or the effects of the drug 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) adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving abacavir tablets. the safety and effectiveness of abacavir sulfate have been established in pediatric patients aged 3 months and older. use of abacavir sulfate is supported by pharmacokinetic trials and evidence from adequate and well-controlled trials of abacavir sulfate in adults and pediatric subjects [see dosage and administration ( 2.3), adverse reactions ( 6.2), clinical pharmacology ( 12.3), clinical studies ( 14.2)] . clinical trials of abacavir sulfate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. in general, caution should be exercised in the administration of abacavir sulfate in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. a dose reduction is required for patients with mild hepatic impairment (child-pugh class a) [see dosage and administration ( 2.4)] . the safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate or severe hepatic impairment; therefore, abacavir sulfate is contraindicated in these patients [see contraindications ( 4), clinical pharmacology ( 12.3)] .

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

zydus pharmaceuticals (usa) inc. - carbamazepine (unii: 33cm23913m) (carbamazepine - unii:33cm23913m) - carbamazepine extended-release tablets are indicated for use as an anticonvulsant drug. evidence supporting efficacy of carbamazepine extended-release tablets as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: - partial seizures with complex symptomatology (psychomotor, temporal lobe). patients with these seizures appear to show greater improvement than those with other types. - generalized tonic-clonic seizures (grand mal). - mixed seizure patterns which include the above, or other partial or generalized seizures. absence seizures (petit mal) do not appear to be controlled by carbamazepine extended-release tablets (see precautions, general). carbamazepine extended-release tablets are indicated in the treatment of the pain associated with true trigeminal neuralgia. beneficial results have also been reported in glossopharyngeal neuralgia. this drug is not a simple analgesic and should not be used for the relief of trivial aches or pains. carbamazepine should not be used in patients with a history of previous bone marrow depression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc. likewise, on theoretical grounds its use with monoamine oxidase (mao) inhibitors is not recommended. before administration of carbamazepine, mao inhibitors should be discontinued for a minimum of 14 days, or longer if the clinical situation permits. coadministration of carbamazepine and nefazodone may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. coadministration of carbamazepine with nefazodone is contraindicated. no evidence of abuse potential has been associated with carbamazepine, nor is there evidence of psychological or physical dependence in humans.

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

zydus lifesciences limited - carbamazepine (unii: 33cm23913m) (carbamazepine - unii:33cm23913m) - carbamazepine extended-release tablets are indicated for use as an anticonvulsant drug. evidence supporting efficacy of carbamazepine extended-release tablets as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: - partial seizures with complex symptomatology (psychomotor, temporal lobe). patients with these seizures appear to show greater improvement than those with other types. - generalized tonic-clonic seizures (grand mal). - mixed seizure patterns which include the above, or other partial or generalized seizures. absence seizures (petit mal) do not appear to be controlled by carbamazepine extended-release tablets (see precautions, general). carbamazepine extended-release tablets are indicated in the treatment of the pain associated with true trigeminal neuralgia. beneficial results have also been reported in glossopharyngeal neuralgia. this drug is not a simple analgesic and should not be used for the relief of trivial aches or pains. carbamazepine should not be used in patients with a history of previous bone marrow depression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc. likewise, on theoretical grounds its use with monoamine oxidase (mao) inhibitors is not recommended. before administration of carbamazepine, mao inhibitors should be discontinued for a minimum of 14 days, or longer if the clinical situation permits. coadministration of carbamazepine and nefazodone may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. coadministration of carbamazepine with nefazodone is contraindicated. no evidence of abuse potential has been associated with carbamazepine, nor is there evidence of psychological or physical dependence in humans.

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

amneal pharmaceuticals ny llc - emtricitabine (unii: g70b4etf4s) (emtricitabine - unii:g70b4etf4s), tenofovir disoproxil fumarate (unii: ott9j7900i) (tenofovir anhydrous - unii:w4hfe001u5) - emtricitabine and tenofovir disoproxil fumarate tablets are indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 17 kg [see clinical studies (14)] . emtricitabine and tenofovir disoproxil fumarate tablets are indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (prep) to reduce the risk of sexually acquired hiv-1 infection. individuals must have a negative hiv-1 test immediately prior to initiating emtricitabine and tenofovir disoproxil fumarate tablets for hiv-1 prep [see dosage and administration (2.2), warnings and precautions (5.2)] .  emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep is contraindicated in individuals with unknown or positive hiv-1 status [see warnings and precautions (5.2)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to emtricitabine and tenofovir disoproxil fumarate

Stany Zjednoczone - angielski - NLM (National Library of Medicine)

laurus labs limited - emtricitabine (unii: g70b4etf4s) (emtricitabine - unii:g70b4etf4s), tenofovir disoproxil fumarate (unii: ott9j7900i) (tenofovir anhydrous - unii:w4hfe001u5) - emtricitabine and tenofovir disoproxil fumarate tablets are indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 17 kg [see clinical studies (14)] . emtricitabine and tenofovir disoproxil fumarate tablets are indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (prep) to reduce the risk of sexually acquired hiv-1 infection. individuals must have a negative hiv-1 test immediately prior to initiating emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep [see dosage and administration (2.2), warnings and precautions (5.2 )]. emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep is contraindicated in individuals with unknown or positive hiv-1 status [see warnings and precautions (5.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to emtricitabine and tenofovir disoproxil fumarate tablets during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary data on the use of emtricitabine and tenofovir disoproxil fumarate during pregnancy from observational studies have shown no increased risk of major birth defects. available data from the apr show no significant difference in the overall risk of major birth defects with first trimester exposure for emtricitabine (ftc) (2.3%) or tenofovir disoproxil fumarate (tdf) (2.1%) compared with the background rate for major birth defects of 2.7% in a u.s. reference population of the metropolitan atlanta congenital defects program (macdp) (see data) . the rate of miscarriage for individual drugs is not reported in the apr. in the u.s. general population, the estimated background risk of miscarriage in clinically recognized pregnancies is 15 to 20%. in animal reproduction studies, no adverse developmental effects were observed when the components of emtricitabine and tenofovir disoproxil fumarate tablets were administered separately at doses/exposures ≥60 (ftc), ≥14 (tdf) and 2.7 (tenofovir) times those of the recommended daily dose of emtricitabine and tenofovir disoproxil fumarate (see data) . clinical considerations disease-associated maternal and/or embryo/fetal risk hiv-1 prep : published studies indicate an increased risk of hiv-1 infection during pregnancy and an increased risk of mother to child transmission during acute hiv-1 infection. in women at risk of acquiring hiv-1, consideration should be given to methods to prevent acquisition of hiv, including continuing or initiating emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep, during pregnancy. data human data emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep : in an observational study based on prospective reports to the apr, 78 hiv-seronegative women exposed to emtricitabine and tenofovir disoproxil fumarate during pregnancy delivered live-born infants with no major malformations. all but one were first trimester exposures, and the median duration of exposure was 10.5 weeks. there were no new safety findings in the women receiving emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep compared with hiv-1 infected women treated with other antiretroviral medications. emtricitabine : based on prospective reports to the apr of exposures to ftc-containing regimens during pregnancy resulting in live births (including over 3,300 exposed in the first trimester and over 1,300 exposed in the second/third trimester), the prevalence of major birth defects in live births was 2.6% (95% ci: 2.1% to 3.2%) and 2.3% (95% ci: 1.6% to 3.3%) following first and second/third trimester exposure, respectively, to ftc-containing regimens. tenofovir disoproxil fumarate : based on prospective reports to the apr of exposures to tdf-containing regimens during pregnancy resulting in live births (including over 4,000 exposed in the first trimester and over 1,700 exposed in the second/third trimester), the prevalence of major birth defects in live births was 2.4% (95% ci: 2.0% to 2.9%) and 2.4% (95% ci: 1.7% to 3.2%) following first and second/third trimester exposure, respectively, to tdf-containing regimens. methodologic 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. additionally, published observational studies on emtricitabine and tenofovir exposure in pregnancy have not shown an increased risk for major malformations. animal data emtricitabine : ftc was administered orally to pregnant mice (at 0, 250, 500, or 1,000 mg/kg/day), and rabbits (at 0, 100, 300, or 1,000 mg/kg/day) through organogenesis (on gestation days 6 through 15, and 7 through 19, respectively). no significant toxicological effects were observed in embryo-fetal toxicity studies performed with ftc in mice at exposures (auc) approximately 60 times higher and in rabbits at approximately 120 times higher than human exposures at the recommended daily dose. in a pre/postnatal development study in mice, ftc was administered orally at doses up to 1,000 mg/kg/day; no significant adverse effects directly related to drug were observed in the offspring exposed daily from before birth (in utero ) through sexual maturity at daily exposures (auc) of approximately 60 times higher than human exposures at the recommended daily dose. tenofovir disoproxil fumarate : tdf was administered orally to pregnant rats (at 0, 50, 150, or 450 mg/kg/day) and rabbits (at 0, 30, 100, or 300 mg/kg/day) through organogenesis (on gestation days 7 through 17, and 6 through 18, respectively). no significant toxicological effects were observed in embryo-fetal toxicity studies performed with tdf in rats at doses up to 14 times the human dose based on body surface area comparisons and in rabbits at doses up to 19 times the human dose based on body surface area comparisons. in a pre/postnatal development study in rats, tdf was administered orally through lactation at doses up to 600 mg/kg/day; no adverse effects were observed in the offspring at tenofovir exposures of approximately 2.7 times higher than human exposures at the recommended daily dose of emtricitabine and tenofovir disoproxil fumarate. risk summary based on published data, ftc and tenofovir have been shown to be present in human breast milk (see data) . it is not known if the components of emtricitabine and tenofovir disoproxil fumarate tablets affect milk production or have effects on the breastfed child. treatment of hiv-1 infection: the centers for disease control and prevention recommend that hiv-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv-1. because of the potential for: (1) hiv transmission (in hiv-negative infants); (2) developing viral resistance (in hiv-positive infants); and (3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are taking emtricitabine and tenofovir disoproxil fumarate for the treatment of hiv-1. hiv-1 prep: in hiv-uninfected women, the developmental and health benefits of breastfeeding and the mother’s clinical need for emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep should be considered along with any potential adverse effects on the breastfed child from emtricitabine and tenofovir disoproxil fumarate and the risk of hiv-1 acquisition due to nonadherence and subsequent mother to child transmission. women should not breastfeed if acute hiv-1 infection is suspected because of the risk of hiv-1 transmission to the infant. data hiv-1 prep : in a study of 50 breastfeeding women who received emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep between 1 and 24 weeks postpartum (median 13 weeks), after 7 days of treatment, tenofovir was undetectable but ftc was detectable in the plasma of most infants. in these infants, the average ftc plasma concentration was less than 1% of the ftc cmax observed in hiv-infected infants (up to 3 months of age) receiving the therapeutic dose of ftc (3 mg/kg/day). there were no serious adverse events. two infants (4%) had an adverse event of mild diarrhea which resolved. treatment of hiv-1 infection no pediatric clinical trial was conducted to evaluate the safety and efficacy of emtricitabine and tenofovir disoproxil fumarate in patients with hiv-1 infection. data from previously conducted trials with the individual drug products, ftc and tdf, were relied upon to support dosage recommendations for emtricitabine and tenofovir disoproxil fumarate tablets. for additional information, consult the prescribing information for emtriva and viread. emtricitabine and tenofovir disoproxil fumarate should only be administered to hiv-1 infected pediatric patients with body weight greater than or equal to 17 kg and who are able to swallow a tablet. because it is a fixed-dose combination tablet, emtricitabine and tenofovir disoproxil fumarate tablet cannot be adjusted for patients of lower weight [see warnings and precautions (5.5) , adverse reactions (6.1) and clinical pharmacology (12.3)] . emtricitabine and tenofovir disoproxil fumarate tablets are not approved for use in pediatric patients weighing less than 17 kg. hiv-1 prep the safety and effectiveness of emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep in at-risk adolescents weighing at least 35 kg is supported by data from adequate and well-controlled studies of emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep in adults with additional data from safety and pharmacokinetic studies in previously conducted trials with the individual drug products, ftc and tdf, in hiv-1 infected adults and pediatric subjects [see dosage and administration (2.5), adverse reactions (6.1), clinical pharmacology (12.3 and 12.4), and clinical studies (14.3 and 14.4)] . safety, adherence, and resistance were evaluated in a single-arm, open-label clinical trial (atn113) in which 67 hiv-1 uninfected at-risk adolescent men who have sex with men received emtricitabine and tenofovir disoproxil fumarate once daily for hiv-1 prep. the mean age of subjects was 17 years (range 15 to 18 years); 46% were hispanic, 52% black, and 37% white. the safety profile of emtricitabine and tenofovir disoproxil fumarate in atn113 was similar to that observed in the adult hiv-1 prep trials [see adverse reactions (6.1)] . in the atn113 trial, hiv-1 seroconversion occurred in 3 subjects. tenofovir diphosphate levels in dried blood spot assays indicate that these subjects had poor adherence. no tenofovir- or ftc-associated hiv-1 resistance substitutions were detected in virus isolated from the 3 subjects who seroconverted [see microbiology (12.4)]. adherence to study drug, as demonstrated by tenofovir diphosphate levels in dried blood spot assays, declined markedly after week 12 once subjects switched from monthly to quarterly visits, suggesting that adolescents may benefit from more frequent visits and counseling [see warnings and precautions (5.2)] . safety and effectiveness of emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep in pediatric patients weighing less than 35 kg have not been established. clinical trials of ftc, tdf, or emtricitabine and tenofovir disoproxil fumarate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. treatment of hiv-1 infection the dosing interval for emtricitabine and tenofovir disoproxil fumarate should be modified in hiv-infected adult individuals with estimated creatinine clearance of 30 to 49 ml/min. emtricitabine and tenofovir disoproxil fumarate is not recommended in individuals with estimated creatinine clearance below 30 ml/min and in individuals with end-stage renal disease requiring dialysis [see dosage and administration (2.6)] . hiv-1 prep emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep is not recommended in hiv-1 uninfected individuals with estimated creatinine clearance below 60 ml/min. if a decrease in estimated creatinine clearance is observed in uninfected individuals while using emtricitabine and tenofovir disoproxil fumarate for hiv-1 prep, evaluate potential causes and re-assess potential risks and benefits of continued use [see dosage and administration (2.6)] .