United States - English - 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 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 tablet 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 tablet 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. for additional information, consult the prescribing information for emtriva and viread. emtricitabine and tenofovir disoproxil fumarate tablet 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 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 is 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)] .

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

amneal pharmaceuticals ny llc - isotretinoin (unii: eh28up18if) (isotretinoin - unii:eh28up18if) - isotretinoin 10 mg - severe recalcitrant nodular acne isotretinoin capsules are indicated for the treatment of severe recalcitrant nodular acne. nodules are inflammatory lesions with a diameter of 5 mm or greater. the nodules may become suppurative or hemorrhagic. “severe,” by definition,2 means “many” as opposed to “few or several” nodules. because of significant adverse effects associated with its use, isotretinoin capsules should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics . in addition, isotretinoin capsulesare indicated only for those patients who are not pregnant, because isotretinoin capsules can cause life-threatening birth defects (see boxed contraindications and warnings ). a single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients.1,3,4 if a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off isotretinoin capsules. the optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see warnings, skeletal, bone mineral density, hyperostosis, premature epiphyseal closure ). pregnancy: category x. see boxed contraindications and warnings . allergic reactions isotretinoin capsules are contraindicated in patients who are hypersensitive to this medication or to any of its components (see precautions, hypersensitivity ).

United States - English - 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 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 tablet 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 tablet 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. for additional information, consult the prescribing information for emtriva and viread. emtricitabine and tenofovir disoproxil fumarate tablet 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 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 is 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)] .

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

amneal pharmaceuticals ny llc - ipratropium bromide (unii: j697uz2a9j) (ipratropium - unii:gr88g0i6ul) - ipratropium bromide nasal solution 0.03% is indicated for the symptomatic relief of rhinorrhea associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. ipratropium bromide nasal solution 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis. ipratropium bromide nasal solution 0.03% is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients. ipratropium bromide nasal solution 0.03%, nasal spray, 21 mcg/spray read complete instructions carefully before using. in order to ensure proper dosing, do not attempt to change the size of the spray opening. ipratropium bromide nasal solution 0.03% is indicated for the symptomatic relief of rhinorrhea (runny nose) associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. ipratropium bromide nasal solution 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis. read complete instructions carefully and use only as directed. to use: 1. remove the clear plastic dust cap and the green safety clip from the nasal spray pump (figure 1). the safety clip prevents the accidental discharge of the spray in your pocket or purse. 2. the nasal spray pump must be primed before ipratropium bromide nasal solution 0.03% is used for the first time. to prime the pump, hold the bottle with your thumb at the base and your index and middle fingers on the white shoulder area. make sure the bottle points upright and away from your eyes. press your thumb firmly and quickly against the bottle seven times (figure 2). the pump is now primed and can be used. your pump should not have to be reprimed unless you have not used the medication for more than 24 hours; repriming the pump will only require two sprays. if you have not used your nasal spray for more than seven days, repriming the pump will require seven sprays. 3. before using ipratropium bromide nasal solution 0.03%, blow your nose gently to clear your nostrils if necessary. 4. close one nostril by gently placing your finger against the side of your nose, tilt your head slightly forward and, keeping the bottle upright, insert the nasal tip into the other nostril (figure 3). point the tip toward the back  and outer  side of the nose. 5. press firmly and quickly upwards with the thumb at the base while holding the white shoulder portion of the pump between your index and middle fingers. following each spray, sniff deeply and breathe out through your mouth. 6. after spraying the nostril and removing the unit, tilt your head backwards for a few seconds to let the spray spread over the back of the nose. 7. repeat steps 4 through 6 in the same nostril. 8. repeat steps 4 through 7 in the other nostril (i.e., two sprays per nostril). 9. replace the clear plastic dust cap and safety clip. 10. at some time before the medication is completely used up, you should consult your physician or pharmacist to determine whether a refill is needed. you should not take extra doses or stop using ipratropium bromide nasal solution 0.03% without consulting your physician. to clean: if the nasal tip becomes clogged, remove the clear plastic dust cap and safety clip. hold the nasal tip under running, warm tap water (figure 4) for about a minute. dry the nasal tip, reprime the nasal spray pump (step 2 above), and replace the plastic dust cap and safety clip. caution: ipratropium bromide nasal solution 0.03% is intended to relieve your rhinorrhea (runny nose) with regular use. it is therefore important that you use ipratropium bromide nasal solution 0.03% as prescribed by your physician. for most patients, some improvement in runny nose is usually apparent during the first full day of treatment with ipratropium bromide nasal solution 0.03%. some patients may require up to two weeks of treatment to obtain maximum benefit. do not spray ipratropium bromide nasal solution 0.03% in your eyes. should this occur, immediately flush your eye with cool tap water for several minutes. if you accidentally spray ipratropium bromide nasal solution 0.03% in your eyes, you may experience a temporary blurring of vision, visual halos or colored images in association with red eyes from conjunctival and corneal congestion, development or worsening of narrow-angle glaucoma, pupil dilation, or acute eye pain/discomfort, and increased sensitivity to light, which may last a few hours. should acute eye pain or blurred vision occur, contact your doctor. should you experience excessive nasal dryness or episodes of nasal bleeding contact your doctor. if you have glaucoma or difficulty urinating due to an enlargement of the prostate, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.03%. if you are pregnant or you are breast feeding your baby, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.03%. address medical inquiries to: www.amneal.com or 1-877-835-5472. store tightly closed at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. avoid freezing. keep out of reach of children. distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 04-2022-01

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

amneal pharmaceuticals ny llc - ipratropium bromide (unii: j697uz2a9j) (ipratropium - unii:gr88g0i6ul) - ipratropium bromide nasal solution 0.06% is indicated for the symptomatic relief of rhinorrhea associated with the common cold or seasonal allergic rhinitis for adults and children age 5 years and older. ipratropium bromide nasal solution 0.06% does not relieve nasal congestion or sneezing associated with the common cold or seasonal allergic rhinitis. the safety and effectiveness of the use of ipratropium bromide nasal solution 0.06% beyond four days in patients with the common cold or beyond three weeks in patients with seasonal allergic rhinitis has not been established. ipratropium bromide nasal solution 0.06% is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients. ipratropium bromide nasal solution 0.06%  nasal spray 42 mcg/spray   read complete instructions carefully before using.   in order to ensure proper dosing, do not attempt to change the size of the spray opening. ipratropium bromide nasal solution 0.06% is indicated for the symptomatic relief of rhinorrhea (runny nose) associated with the common cold or seasonal allergic rhinitis for adults and children age 5 years and older. ipratropium bromide nasal solution 0.06% does not relieve nasal congestion or sneezing associated with the common cold or seasonal allergic rhinitis. do not use ipratropium bromide nasal solution 0.06% for longer than four days for a common cold or three weeks for seasonal allergic rhinitis unless instructed by your physician. read complete instructions carefully and use only as directed. to use: 1. remove the clear plastic dust cap and the green safety clip from the nasal spray pump (figure 1). the safety clip prevents the accidental discharge of the spray in your pocket or purse. 2. the nasal spray pump must be primed before ipratropium bromide nasal solution 0.06% is used for the first time. to prime the pump, hold the bottle with your thumb at the base and your index and middle fingers on the white shoulder area. make sure the bottle points upright and away from your eyes. press your thumb firmly and quickly against the bottle seven times (figure 2). the pump is now primed and can be used. your pump should not have to be reprimed unless you have not used the medication for more than 24 hours; repriming the pump will only require two sprays. if you have not used your nasal spray for more than seven days, repriming the pump will require seven sprays. 3. before using ipratropium bromide nasal solution 0.06%, blow your nose gently to clear your nostrils if necessary. 4. close one nostril by gently placing your finger against the side of your nose, tilt your head slightly forward and, keeping the bottle upright, insert the nasal tip into the other nostril (figure 3). point the tip toward the back  and outer  side of the nose. 5. press firmly and quickly upwards with the thumb at the base while holding the white shoulder portion of the pump between your index and middle fingers. following each spray, sniff deeply and breathe out through your mouth. 6. after spraying the nostril and removing the unit, tilt your head backwards for a few seconds to let the spray spread over the back of the nose. 7. repeat steps 4 through 6 in the same nostril. 8. repeat steps 4 through 7 in the other nostril (i.e., two sprays per nostril). 9. replace the clear plastic dust cap and safety clip. 10. at some time before the medication is completely used up, you should consult your physician or pharmacist to determine whether a refill is needed. you should not take extra doses or stop using ipratropium bromide nasal solution 0.06% without consulting your physician. to clean: if the nasal tip becomes clogged, remove the clear plastic dust cap and safety clip. hold the nasal tip under running, warm tap water (figure 4) for about a minute. dry the nasal tip, reprime the nasal spray pump (step 2 above), and replace the plastic dust cap and safety clip. caution: ipratropium bromide nasal spray 0.06% is intended to relieve your rhinorrhea (runny nose) with regular use. it is therefore important that you use ipratropium bromide nasal solution 0.06% as prescribed by your physician. for most patients, some improvement in runny nose is apparent following the first dose of treatment with ipratropium bromide nasal solution 0.06%. do not use ipratropium bromide nasal solution 0.06% for longer than four days for your cold or three weeks for seasonal allergic rhinitis unless instructed by your physician. do not spray ipratropium bromide nasal solution 0.06% in your eyes.  should this occur, immediately flush your eye with cool tap water for several minutes. if you accidentally spray ipratropium bromide nasal solution 0.06% in your eyes, you may experience a temporary blurring of vision, visual halos or colored images in association with red eyes from conjunctival and corneal congestion, development or worsening of narrow-angle glaucoma, pupil dilation , or acute eye pain/discomfort, and increased sensitivity to light, which may last a few hours. should acute eye pain or blurred vision occur, contact your doctor. should you experience excessive nasal dryness or episodes of nasal bleeding contact your doctor. if you have glaucoma or difficulty urinating due to an enlargement of the prostate, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.06%. if you are pregnant or you are breast feeding your baby, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.06%. address medical inquiries to: www.amneal.com or 1-877- 835-5472. storage: store tightly closed at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. avoid freezing. keep out of reach of children. distributed by: amneal pharmaceuticals llc  bridgewater, nj 08807 rev. 04-2021-00

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

amneal pharmaceuticals ny llc - oseltamivir phosphate (unii: 4a3o49ngez) (oseltamivir acid - unii:k6106lv5q8) - oseltamivir phosphate capsules are indicated for the treatment of acute, uncomplicated illness due to influenza a and b infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. oseltamivir phosphate capsules are indicated for the prophylaxis of influenza a and b in patients 1 year and older. - oseltamivir phosphate capsules are not a substitute for early influenza vaccination on an annual basis as recommended by the centers for disease control and prevention advisory committee on immunization practices. - influenza viruses change over time. emergence of resistance substitutions could decrease drug effectiveness. other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate capsules [see microbiology (12.4)] . - oseltamivir phosphate capsules are not recommended for patients with end-stage renal disease not undergoing dialysis [see dosage and administration (2.4) and use in specific populations (8.6)] . oseltamivir phosphate capsules are contraindicated in patients with known serious hypersensitivity to oseltamivir or any component of the product. severe allergic reactions have included anaphylaxis and serious skin reactions including toxic epidermal necrolysis, stevens-johnson syndrome, and erythema multiforme [see warnings and precautions (5.1)] . risk summary there are no adequate and well-controlled studies with oseltamivir phosphate in pregnant women to inform a drug‐associated risk of adverse developmental outcomes. available published epidemiological data suggest that oseltamivir phosphate, taken in any trimester, is not associated with an increased risk of birth defects. however, these studies individually are limited by small sample sizes, use of different comparison groups, and some lacked information on dose, which preclude a definitive assessment of the risk [see data and clinical pharmacology (12.3)] . in animal reproduction studies with oseltamivir, no adverse developmental effects were observed at clinically relevant exposures (see data) . the background risk of major birth defects and miscarriage for the indicated populations 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 is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birth weight and small for gestational age. data human data published prospective and retrospective observational studies of more than 5,000 women exposed to oseltamivir phosphate during pregnancy, including more than 1,000 women exposed in the first trimester, suggest that the observed rate of congenital malformations was not increased above the rate in the general comparison population, regardless of when therapy was administered during the gestational period. however, individually, none of these studies had adequate sample sizes and some lacked information on dose, which preclude a definitive assessment of the risk. animal data oseltamivir was administered orally during organogenesis to pregnant rats (at 50, 250, or 1,500 mg/kg/day on gestation days 6 to 17) and rabbits (at 50, 150, or 500 mg/kg/day on gestation days 6 to 18). in rats, embryo‐fetal effects consisting of an increased incidence of minor skeletal malformations were observed at a maternally toxic dose (1,500 mg/kg/day), resulting in systemic drug exposures (based on auc for oseltamivir carboxylate) 190 times human exposures at the maximum recommended human dose (mrhd) of oseltamivir phosphate (75 mg twice a day). in the rabbit study, embryo‐fetal effects consisting of an increased incidence of minor skeletal abnormalities and variants were observed at maternally toxic doses (> 150 mg/kg/day)  resulting in systemic exposures (based on auc for oseltamivir carboxylate) ≥ 8 times human exposures at the mrhd of oseltamivir phosphate. in prenatal and postnatal development studies in rats, oseltamivir was administered orally (at 50, 250, 500, or 1,500 mg/kg/day) from organogenesis through late gestation, delivery, and lactation (gestation day 6 to postpartum/lactation day 20). prolonged parturition duration and reduced offspring viability were observed at a maternally toxic dose (1,500 mg/kg/day). no adverse maternal or offspring effects were observed at doses ≤ 500 mg/kg/day, resulting in systemic drug exposures (based on auc for oseltamivir carboxylate) 44 times human exposures at the mrhd of oseltamivir phosphate. risk summary based on limited published data, oseltamivir and oseltamivir carboxylate have been shown to be present in human milk at low levels considered unlikely to lead to toxicity in the breastfed infant. post-marketing experience has not reported any information to suggest serious adverse effects of oseltamivir exposure via breast milk in infants. it is not known if oseltamivir affects human milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oseltamivir phosphate and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. treatment of influenza the safety and efficacy of oseltamivir phosphate for the treatment of influenza in pediatric patients 2 weeks old to 17 years of age has been established [see dosage and administration (2.2), clinical pharmacology (12.3), and clinical studies (14.1)] and is based on: - 13 to 17 years of age: safety and efficacy in adolescent patients 13 to 17 years of age was supported by adequate and well-controlled trials in adults and adolescents and younger pediatric patients and safety data in adolescents treated with oseltamivir phosphate in a study of treatment and prophylaxis. - 1 year to 12 years of age: safety and efficacy in pediatric patients 1 year to 12 years of age was supported by results of one double-blind, placebo-controlled trial in 452 pediatric patients with influenza in whom oseltamivir phosphate 2 mg per kg twice daily or placebo was administered within 48 hours of symptom onset [see clinical studies (14.1)] . additional safety information was provided in a double-blind, placebo-controlled trial in pediatric patients 6 to 12 years of age with known asthma. efficacy could not be established in pediatric patients with asthma. - 2 weeks to less than 1 year of age: safety and efficacy in pediatric patients 2 weeks to less than 1 year of age is supported by adequate and well-controlled trials in adults and older pediatric patients and two open-label trials of oseltamivir phosphate (2 to 3.5 mg per kg twice daily for 5 days) in 136 pediatric subjects 2 weeks to less than 1 year of age. in these two trials, the oseltamivir plasma concentrations in these subjects were similar to or higher than the oseltamivir plasma concentrations observed in older pediatric subjects and adults [see clinical pharmacology (12.3) and clinical studies (14.1)] . the safety and efficacy of oseltamivir phosphate for treatment of influenza in pediatric patients less than 2 weeks of age have not been established. prophylaxis of influenza the safety and efficacy of oseltamivir phosphate for the prophylaxis of influenza in pediatric patients 1 year to 17 years old has been established [see dosage and administration (2.3), clinical pharmacology (12.3), and clinical studies (14.2)] and is based on: - 13 to 17 years of age: prophylaxis in adolescent patients 13 to 17 years of age is supported by one randomized, placebo-controlled post-exposure household prophylaxis trial of oseltamivir phosphate 75 mg taken orally once daily for 7 days in household contacts including 207 adolescents [see clinical studies (14.2)] . - 1 year to 12 years of age: oseltamivir phosphate for prophylaxis in pediatric patients 1 year to 12 years of age is supported by one randomized, open-label, post-exposure household prophylaxis trial including pediatric subjects 1 year to 12 years of age who received 30 to 60 mg of oseltamivir phosphate for oral suspension (supplied as powder) taken orally once daily for 10 days [see clinical studies (14.2)] . additional safety information was provided in a 6-week seasonal prophylaxis (community outbreak) safety study in 49 patients 1 year to 12 years of age. the safety and efficacy of oseltamivir phosphate for prophylaxis of influenza have not been established for pediatric patients less than 1 year of age. treatment of influenza of the 4,765 adults in clinical trials of oseltamivir phosphate for the treatment of influenza, 948 (20%) were 65 years and older, while 329 (7%) were 75 years and older. in three double-blind, placebo-controlled trials in the treatment of influenza in patients at least 65 years old, that enrolled 741 subjects (374 received placebo and 362 received oseltamivir phosphate), 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 subjects [see clinical studies (14.1)] . prophylaxis of influenza of the 4,603 adults in clinical trials of oseltamivir phosphate for the prophylaxis of influenza, 1,046 (23%) were 65 years and older, while 719 (16%) were 75 years and older. in a randomized, placebo-controlled trial in elderly residents of nursing homes who took oseltamivir phosphate for up to 42 days for the prophylaxis of influenza (oseltamivir phosphate n=276, placebo n=272), 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 subjects [see clinical studies (14.2)] . patients with renal impairment had higher blood levels of oseltamivir carboxylate compared to patients with normal renal function which may increase the risk of  oseltamivir phosphate-associated adverse reactions. therefore, dosage adjustment is recommended for patients with a serum creatinine clearance between 10 and 60 ml/minute and for patients with end-stage renal disease (esrd) undergoing routine hemodialysis or continuous peritoneal dialysis treatment [see dosage and administration (2.4)] . oseltamivir phosphate is not recommended for patients with esrd not undergoing dialysis [see indications and usage (1.3) and clinical pharmacology (12.3)] . no dosage adjustment is required in patients with mild to moderate hepatic impairment. the safety and pharmacokinetics in patients with severe hepatic impairment have not been evaluated [see clinical pharmacology (12.3)] . efficacy of oseltamivir phosphate in the treatment of influenza in patients with chronic cardiac disease and/or respiratory disease was evaluated in one randomized, placebo-controlled clinical trial. efficacy in this population, as measured by time to alleviation of all symptoms, was not established, but no new safety signals were identified [see clinical studies (14.1)] . no clinical trial data are available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization. efficacy of oseltamivir phosphate for the treatment or prophylaxis of influenza has not been established in immunocompromised patients [see clinical studies (14.2)] . safety of oseltamivir phosphate has been demonstrated for up to 12 weeks for prophylaxis of influenza in immunocompromised patients [see adverse reactions (6.1)] . oseltamivir phosphate ( oh” sel tam’ i vir fos’ fate) capsules, usp, for oral use how do i mix the contents of oseltamivir phosphate capsules with sweetened liquids, if directed by my healthcare provider or pharmacist? you will need: - the prescribed dose of oseltamivir phosphate capsules. - a small bowl. - sweetened liquid, such as chocolate syrup (regular or sugar-free), corn syrup, caramel topping, or light brown sugar (dissolved in water). step 1. open the contents of the prescribed dose of oseltamivir phosphate capsules into a small bowl. step 2. add a small amount of the sweetened liquid to the capsule contents. step 3. stir the mixture and give the entire dose of oseltamivir phosphate capsules. manufactured by: amneal pharmaceuticals pvt. ltd. ahmedabad 382220, india or amneal pharmaceuticals pvt. ltd. oral solid dosage unit ahmedabad 382213, india distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 09-2022-00 this instructions for use has been approved by the u.s. food and drug administration. 

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

amneal pharmaceuticals ny llc - norethindrone (unii: t18f433x4s) (norethindrone - unii:t18f433x4s) - norethindrone 0.35 mg - 1.   indications. progestin-only oral contraceptives are indicated for the prevention of pregnancy.   2.   efficacy. if used perfectly, the first-year failure rate for progestin-only oral contraceptives is 0.5%. however, the typical failure rate is estimated to be closer to 5%, due to late or omitted pills. the following table lists the pregnancy rates for users of all major methods of contraception. table 2: percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception and the percentage continuing use at the end of the first year. united states. % of women experiencing an unintended pregnancy within the first year of use % of women continuing use at one year3 method (1) typical use1 (2) perfect use2 (3) (4) chance4 85 85 spermicides5 26 6 40 periodic abstinence 25 63 calendar 9 ovulation method 3 sympto-thermal6 2 post-ovulation 1 cap7 parous women 40 26 42 nulliparous women 20 9 56 sponge parous women 40 20 42 nulliparous women 20 9 56 diaphragm7 20 6 56 withdrawal 19 4 condom8 female (reality) 21 5 56 male 14 3 61 pill 5 71 progestin only 0.5 combined 0.1 iuds progesterone t 2 1.5 81 copper t380a 0.8 0.6 78 lng 20 0.1 0.1 81 depo-provera® 0.3 0.3 70 levonorgestrel implants (norplant® ) 0.05 0.05 88 female sterilization 0.5 0.5 100 male sterilization 0.15 0.10 100 emergency contraceptive pills: treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.9 lactational amenorrhea method: lam is a highly effective, temporary method of contraception.10 source: trussell, j, contraceptive efficacy. in: hatcher ra, trussell j, stewart f, cates w, stewart gk, kowal d, guest f, contraceptive technology: seventeenth revised edition. new york ny: irvington publishers, 1998. 1.   among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any reason. 2.   among couples who initiate use of a method (not necessarily for the first time), and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. 3.   among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. 4.   the percentage of women becoming pregnant noted in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. among such populations, about 89% become pregnant within one year. this estimate was lowered slightly (to 85%) to represent the percentage that would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5.   foams, creams, gels, vaginal suppositories, and vaginal film. 6.   cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. 7.   with spermicidal cream or jelly. 8.   without spermicides. 9.   the treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. the food and drug administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: ovral® (1 dose is 2 white pills), alesse® (1 dose is 5 pink pills), nordette® or levlen® (1 dose is 4 yellow pills). 10. however, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age. progestin-only oral contraceptives (pops) should not be used by women who currently have the following conditions: - known or suspected pregnancy - known or suspected carcinoma of the breast - undiagnosed abnormal genital bleeding - hypersensitivity to any component of this product - benign or malignant liver tumors - acute liver disease

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

amneal pharmaceuticals ny llc - oseltamivir phosphate (unii: 4a3o49ngez) (oseltamivir acid - unii:k6106lv5q8) - oseltamivir acid 30 mg - oseltamivir phosphate capsules are indicated for the treatment of acute, uncomplicated illness due to influenza a and b infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. oseltamivir phosphate capsules are indicated for the prophylaxis of influenza a and b in patients 1 year and older. - oseltamivir phosphate capsules are not a substitute for early influenza vaccination on an annual basis as recommended by the centers for disease control and prevention advisory committee on immunization practices. - influenza viruses change over time. emergence of resistance substitutions could decrease drug effectiveness. other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate capsules [see microbiology (12.4)] . - oseltamivir phosphate capsules are not recommended for patients with end-stage renal disease not undergoing dialysis [see dosage and administration (2.4) and use in specific populations (8.6)] . oseltamivir phosphate capsules are contraindicated in patients with known serious hypersensitivity to oseltamivir or any component of the product. severe allergic reactions have included anaphylaxis and serious skin reactions including toxic epidermal necrolysis, stevens-johnson syndrome, and erythema multiforme [see warnings and precautions (5.1)] . risk summary there are no adequate and well-controlled studies with oseltamivir phosphate in pregnant women to inform a drug‐associated risk of adverse developmental outcomes. available published epidemiological data suggest that oseltamivir phosphate, taken in any trimester, is not associated with an increased risk of birth defects. however, these studies individually are limited by small sample sizes, use of different comparison groups, and some lacked information on dose, which preclude a definitive assessment of the risk [see data and clinical pharmacology (12.3)] . in animal reproduction studies with oseltamivir, no adverse developmental effects were observed at clinically relevant exposures (see data) . the background risk of major birth defects and miscarriage for the indicated populations 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 is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birth weight and small for gestational age. data human data published prospective and retrospective observational studies of more than 5,000 women exposed to oseltamivir phosphate during pregnancy, including more than 1,000 women exposed in the first trimester, suggest that the observed rate of congenital malformations was not increased above the rate in the general comparison population, regardless of when therapy was administered during the gestational period. however, individually, none of these studies had adequate sample sizes and some lacked information on dose, which preclude a definitive assessment of the risk. animal data oseltamivir was administered orally during organogenesis to pregnant rats (at 50, 250, or 1,500 mg/kg/day on gestation days 6 to 17) and rabbits (at 50, 150, or 500 mg/kg/day on gestation days 6 to 18). in rats, embryo‐fetal effects consisting of an increased incidence of minor skeletal malformations were observed at a maternally toxic dose (1,500 mg/kg/day), resulting in systemic drug exposures (based on auc for oseltamivir carboxylate) 190 times human exposures at the maximum recommended human dose (mrhd) of oseltamivir phosphate (75 mg twice a day). in the rabbit study, embryo‐fetal effects consisting of an increased incidence of minor skeletal abnormalities and variants were observed at maternally toxic doses (> 150 mg/kg/day)  resulting in systemic exposures (based on auc for oseltamivir carboxylate) ≥ 8 times human exposures at the mrhd of oseltamivir phosphate. in prenatal and postnatal development studies in rats, oseltamivir was administered orally (at 50, 250, 500, or 1500 mg/kg/day) from organogenesis through late gestation, delivery, and lactation (gestation day 6 to postpartum/lactation day 20). prolonged parturition duration and reduced offspring viability were observed at a maternally toxic dose (1,500 mg/kg/day). no adverse maternal or offspring effects were observed at doses ≤ 500 mg/kg/day, resulting in systemic drug exposures (based on auc for oseltamivir carboxylate) 44 times human exposures at the mrhd of oseltamivir phosphate. risk summary based on limited published data, oseltamivir and oseltamivir carboxylate have been shown to be present in human milk at low levels considered unlikely to lead to toxicity in the breastfed infant. postmarketing experience has not reported any information to suggest serious adverse effects of oseltamivir exposure via breast milk in infants. it is not known if oseltamivir affects human milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oseltamivir phosphate and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. treatment of influenza the safety and efficacy of oseltamivir phosphate for the treatment of influenza in pediatric patients 2 weeks old to 17 years of age has been established [see dosage and administration (2.2), clinical pharmacology (12.3), and clinical studies (14.1)] and is based on: - 13 to 17 years of age: safety and efficacy in adolescent patients 13 to 17 years of age was supported by adequate and well-controlled trials in adults and adolescents and younger pediatric patients and safety data in adolescents treated with oseltamivir phosphate in a study of treatment and prophylaxis. - 1 year to 12 years of age: safety and efficacy in pediatric patients 1 year to 12 years of age was supported by results of one double-blind, placebo-controlled trial in 452 pediatric patients with influenza in whom oseltamivir phosphate 2 mg per kg twice daily or placebo was administered within 48 hours of symptom onset [see clinical studies (14.1)] . additional safety information was provided in a double-blind, placebo-controlled trial in pediatric patients 6 to 12 years of age with known asthma. efficacy could not be established in pediatric patients with asthma. - 2 weeks to less than 1 year of age: safety and efficacy in pediatric patients 2 weeks to less than 1 year of age is supported by adequate and well-controlled trials in adults and older pediatric patients and two open-label trials of oseltamivir phosphate (2 to 3.5 mg per kg twice daily for 5 days) in 136 pediatric subjects 2 weeks to less than 1 year of age. in these two trials, the oseltamivir plasma concentrations in these subjects were similar to or higher than the oseltamivir plasma concentrations observed in older pediatric subjects and adults [see clinical pharmacology (12.3) and clinical studies (14.1)] . the safety and efficacy of oseltamivir phosphate for treatment of influenza in pediatric patients less than 2 weeks of age have not been established. prophylaxis of influenza the safety and efficacy of oseltamivir phosphate for the prophylaxis of influenza in pediatric patients 1 year to 17 years old has been established [see dosage and administration (2.3), clinical pharmacology (12.3), and clinical studies (14.2)] and is based on: - 13 to 17 years of age: prophylaxis in adolescent patients 13 to 17 years of age is supported by one randomized, placebo-controlled post-exposure household prophylaxis trial of oseltamivir phosphate 75 mg taken orally once daily for 7 days in household contacts including 207 adolescents [see clinical studies (14.2)] . - 1 year to 12 years of age: oseltamivir phosphate for prophylaxis in pediatric patients 1 year to 12 years of age is supported by one randomized, open-label, post-exposure household prophylaxis trial including pediatric subjects 1 year to 12 years of age who received 30 to 60 mg of oseltamivir phosphate for oral suspension (supplied as powder) taken orally once daily for 10 days [see clinical studies (14.2)] . additional safety information was provided in a 6-week seasonal prophylaxis (community outbreak) safety study in 49 patients 1 year to 12 years of age. the safety and efficacy of oseltamivir phosphate for prophylaxis of influenza have not been established for pediatric patients less than 1 year of age. treatment of influenza of the 4,765 adults in clinical trials of oseltamivir phosphate for the treatment of influenza, 948 (20%) were 65 years and older, while 329 (7%) were 75 years and older. in three double-blind, placebo-controlled trials in the treatment of influenza in patients at least 65 years old, that enrolled 741 subjects (374 received placebo and 362 received oseltamivir phosphate), 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 subjects [see clinical studies (14.1)] . prophylaxis of influenza of the 4,603 adults in clinical trials of oseltamivir phosphate for the prophylaxis of influenza, 1,046 (23%) were 65 years and older, while 719 (16%) were 75 years and older. in a randomized, placebo-controlled trial in elderly residents of nursing homes who took oseltamivir phosphate for up to 42 days for the prophylaxis of influenza (oseltamivir phosphate n=276, placebo n=272), 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 subjects [see clinical studies (14.2)] . patients with renal impairment had higher blood levels of oseltamivir carboxylate compared to patients with normal renal function which may increase the risk of  oseltamivir phosphate-associated adverse reactions. therefore, dosage adjustment is recommended for patients with a serum creatinine clearance between 10 and 60 ml/minute and for patients with end-stage renal disease (esrd) undergoing routine hemodialysis or continuous peritoneal dialysis treatment [see dosage and administration (2.4)] . oseltamivir phosphate is not recommended for patients with esrd not undergoing dialysis [see indications and usage (1.3) and clinical pharmacology (12.3)] . no dosage adjustment is required in patients with mild to moderate hepatic impairment. the safety and pharmacokinetics in patients with severe hepatic impairment have not been evaluated [see clinical pharmacology (12.3)] . efficacy of oseltamivir phosphate in the treatment of influenza in patients with chronic cardiac disease and/or respiratory disease was evaluated in one randomized, placebo-controlled clinical trial. efficacy in this population, as measured by time to alleviation of all symptoms, was not established, but no new safety signals were identified [see clinical studies (14.1)] . no clinical trial data are available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization. efficacy of oseltamivir phosphate for the treatment or prophylaxis of influenza has not been established in immunocompromised patients [see clinical studies (14.2)] . safety of oseltamivir phosphate has been demonstrated for up to 12 weeks for prophylaxis of influenza in immunocompromised patients [see adverse reactions (6.1)] . oseltamivir phosphate ( oh” sel tam’ i vir fos’ fate) capsules, usp, for oral use how do i mix the contents of oseltamivir phosphate capsules with sweetened liquids, if directed by my healthcare provider or pharmacist? you will need: - the prescribed dose of oseltamivir phosphate capsules - a small bowl - sweetened liquid, such as chocolate syrup (regular or sugar-free), corn syrup, caramel topping, or light brown sugar (dissolved in water) step 1. open the contents of the prescribed dose of oseltamivir phosphate capsules into a small bowl. step 2. add a small amount of the sweetened liquid to the capsule contents. step 3. stir the mixture and give the entire dose of oseltamivir phosphate capsules. distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 04-2018-01

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

amneal pharmaceuticals ny llc - methylprednisolone acetate (unii: 43502p7f0p) (methylprednisolone - unii:x4w7zr7023) - a. for intramuscular administration when oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, the intramuscular use of methylprednisolone acetate injectable suspension is indicated as follows: allergic states : control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, serum sickness, transfusion reactions. dermatologic diseases : bullous dermatitis herpetiformis, exfoliative dermatitis, mycosis fungoides, pemphigus, severe erythema multiforme (stevens-johnson syndrome). endocrine disorders : primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance), congenital adrenal hyperplasia, hypercalcemia associated with cancer, nonsupportive thyroiditis. gastrointestinal diseases : to tide the patient over a critical period of the disease in regional enteritis (systemic therapy) and ulcerative colitis. hematologic disorders : acquired (autoimmune) hemolytic anemia, congenital (erythroid) hypoplastic anemia (diamond blackfan anemia), pure red cell aplasia, select cases of secondary thrombocytopenia. miscellaneous : trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy. neoplastic diseases : for palliative management of: leukemias and lymphomas. nervous system : cerebral edema associated with primary or metastatic brain tumor or craniotomy. ophthalmic diseases : sympathetic ophthalmia, temporal arteritis, uveitis, ocular inflammatory conditions unresponsive to topical corticosteroids. renal diseases : to induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome, or that due to lupus erythematosus. respiratory diseases : berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, idiopathic eosinophilic pneumonias, symptomatic sarcoidosis. rheumatic disorders : as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis; acute rheumatic carditis; ankylosing spondylitis; psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy). for the treatment of dermatomyositis, polymyositis, and systemic lupus erythematosus. b. for intra-articular or soft tissue administration ( see warnings) methylprednisolone acetate injectable suspension is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, synovitis of osteoarthritis. c. for intralesional administration methylprednisolone acetate injectable suspension is indicated for intralesional use in alopecia areata, discoid lupus erythematosus; keloids, localized hypertrophic, infiltrated inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus (neurodermatitis) and psoriatic plaques; necrobiosis lipoidica diabeticorum. methylprednisolone acetate injectable suspension also may be useful in cystic tumors of an aponeurosis or tendon (ganglia). methylprednisolone acetate injectable suspension is contraindicated in patients with known hypersensitivity to the product and its constituents. intramuscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura. methylprednisolone acetate injectable suspension is contraindicated for intrathecal administration. this formulation of methylprednisolone acetate has been associated with reports of severe medical events when administered by this route. methylprednisolone acetate injectable suspension is contraindicated in systemic fungal infections, except when administered as an intra-articular injection for localized joint conditions (see warnings: infections, fungal infections ).

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

amneal pharmaceuticals of new york llc - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 20 mg - morphine sulfate extended-release capsules are indicated for the management of severe and persistent pain, that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. limitations of use: - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release opioid formulations/long-acting opioid formulations, [see warnings and precautions (5.1)], reserve morphine sulfate extended-release capsules for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - morphine sulfate extended-release capsules are not indicated as an as-needed (prn) analgesic. morphine sulfate extended-release capsules are contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] -   acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.7)] -   concurrent use of monoamine oxidase inhibitors (maois) or use of maois within the last 14 days [see warnings and precautions (5.8),  drug interactions (7)] -   known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.12)] -   hypersensitivity (e.g., anaphylaxis) to morphine [see adverse reactions (6.2)] risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)]. there are no available data with morphine sulfate extended-release capsules in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see human data] . in published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (hdd) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the hdd in the rabbit, growth retardation at 6 times the hdd in the rat, and axial skeletal fusion and cryptorchidism at 16 times the hdd in the mouse. administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3 to 4 times the hdd; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the hdd [see animal data] . based on animal data, advise pregnant women of the potential risk to a 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. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)]. labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. morphine sulfate extended-release capsules are not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including morphine sulfate extended-release capsules, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data the results from a population-based prospective cohort, including 70 women exposed to morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. however, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and non-randomized study design. animal data formal reproductive and developmental toxicology studies for morphine have not been conducted. exposure margins for the following published study reports are based on human daily dose of 60 mg morphine using a body surface area comparison (hdd). neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of morphine sulfate (35 to 322 mg/kg) on gestation day 8 to pregnant hamsters (4.7 to 43.5 times the hdd). a no adverse effect level was not defined in this study and the findings cannot be clearly attributed to maternal toxicity. neural tube defects (exencephaly), axial skeletal fusions, and cryptorchidism were reported following a single subcutaneous (sc) injection of morphine sulfate to pregnant mice (100 to 500 mg/kg) on gestation day 8 or 9 at 200 mg/kg or greater (16 times the hdd) and fetal resorption at 400 mg/kg or higher (32 times the hdd). no adverse effects were noted following 100 mg/kg morphine in this model (8 times the hdd). in one study, following continuous subcutaneous infusion of doses greater than or equal to 2.72 mg/kg to mice (0.2 times the hdd), exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted. the effects were reduced with increasing daily dose; possibly due to rapid induction of tolerance under these infusion conditions. the clinical significance of this report is not clear. decreased fetal weights were observed in pregnant rats treated with 20 mg/kg/day morphine sulfate (3.2 times the hdd) from gestation day 7 to 9. there was no evidence of malformations despite maternal toxicity (10% mortality). in a second rat study, decreased fetal weight and increased incidences of growth retardation were noted at 35 mg/kg/day (5.7 times the hdd) and there was a reduced number of fetuses at 70 mg/kg/day (11.4 times the hdd) when pregnant rats were treated with 10, 35, or 70 mg/kg/day morphine sulfate via continuous infusion from gestation day 5 to 20. there was no evidence of fetal malformations or maternal toxicity. an increased incidence of abortion was noted in a study in which pregnant rabbits were treated with 2.5 (0.8 times the hdd) to 10 mg/kg morphine sulfate via subcutaneous injection from gestation day 6 to 10. in a second study, decreased fetal body weights were reported following treatment of pregnant rabbits with increasing doses of morphine (10 to 50 mg/kg/day) during the pre-mating period and 50 mg/kg/day (16 times the hdd) throughout the gestation period. no overt malformations were reported in either publication; although only limited endpoints were evaluated. in published studies in rats, exposure to morphine during gestation and/or lactation periods is associated with: decreased pup viability at 12.5 mg/kg/day or greater (2 times the hdd); decreased pup body weights at 15 mg/kg/day or greater (2.4 times the hdd); decreased litter size, decreased absolute brain and cerebellar weights, cyanosis, and hypothermia at 20 mg/kg/day (3.2 times the hdd); alteration of behavioral responses (play, social-interaction) at 1 mg/kg/day or greater (0.2 times the hdd); alteration of maternal behaviors (e.g., decreased nursing and pup retrievals) in mice at 1 mg/kg or higher (0.08 times the hdd) and rats at 1.5 mg/kg/day or higher (0.2 times the hdd); and a host of behavioral abnormalities in the offspring of rats, including altered responsiveness to opioids at 4 mg/kg/day (0.7 times the hdd) or greater. fetal and/or postnatal exposure to morphine in mice and rats has been shown to result in morphological changes in fetal and neonatal brain and neuronal cell loss, alteration of a number of neurotransmitter and neuromodulator systems, including opioid and non-opioid systems, and impairment in various learning and memory tests that appear to persist into adulthood. these studies were conducted with morphine treatment usually in the range of 4 to 20 mg/kg/day (0.7 to 3.2 times the hdd). additionally, delayed sexual maturation and decreased sexual behaviors in female offspring at 20 mg/kg/day (3.2 times the hdd), and decreased plasma and testicular levels of luteinizing hormone and testosterone, decreased testes weights, seminiferous tubule shrinkage, germinal cell aplasia, and decreased spermatogenesis in male offspring were also observed at 20 mg/kg/day (3.2 times the hdd). decreased litter size and viability were observed in the offspring of male rats that were intraperitoneally administered morphine sulfate for 1 day prior to mating at 25 mg/kg/day (4.1 times the hdd) and mated to untreated females. decreased viability and body weight and/or movement deficits in both first and second generation offspring were reported when male mice were treated for 5 days with escalating doses of 120 to 240 mg/kg/day morphine sulfate (9.7 to 19.5 times the hdd) or when female mice treated with escalating doses of 60 to 240 mg/kg/day (4.9 to 19.5 times the hdd) followed by a 5-day treatment-free recovery period prior to mating. similar multigenerational findings were also seen in female rats pre-gestationally treated with escalating doses of 10 to 22 mg/kg/day morphine (1.6 to 3.6 times the hdd). risk summary morphine is present in breast milk. published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine auc ratio of 2.5:1 measured in one lactation study. however, there is insufficient information to determine the effects of morphine on the breastfed infant and the effects of morphine on milk production. lactation studies have not been conducted with extended–release morphine, including morphine sulfate extended-release capsules. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with morphine sulfate extended-release capsules. clinical considerations monitor infants exposed to morphine sulfate extended-release capsules through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of morphine is stopped, or when breastfeeding is stopped. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2)]. in published animal studies, morphine administration adversely effected fertility and reproductive endpoints in male rats and prolonged estrus cycle in female rats [see nonclinical toxicology (13)] . the safety and efficacy of morphine sulfate extended-release capsules in patients less than 18 years have not been established. clinical studies of morphine sulfate extended-release capsules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. elderly patients (aged 65 years or older) may have increased sensitivity to morphine. in general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of morphine sulfate extended-release capsules slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.7)] . this drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. morphine pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. start these patients with a lower than usual dosage of morphine sulfate extended-release capsules and titrate slowly while regularly evaluate for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine pharmacokinetics are altered in patients with renal failure. start these patients with a lower than usual dosage of morphine sulfate extended-release capsules and titrate slowly while regularly evaluate for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine sulfate extended-release capsules contain morphine, a schedule ii controlled substance. morphine sulfate extended-release capsules contains morphine, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)] . misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. 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. misuse and abuse of morphine sulfate extended-release capsules increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of morphine sulfate extended-release capsules with alcohol and other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of morphine sulfate extended-release capsules abuse include those with a history of prolonged use of any opioid, including products containing morphine, those with a history of drug or alcohol abuse, or those who use morphine sulfate extended-release capsules in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. morphine sulfate extended-release capsules, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of morphine sulfate extended-release capsules abuse of morphine sulfate extended-release capsules poses a risk of overdose and death. this risk is increased with concurrent use of morphine sulfate extended-release capsules with alcohol and/or other cns depressants. taking cut, broken chewed, crushed, or dissolved morphine sulfate extended-release capsules enhances drug release and increases the risk of overdose and death. morphine sulfate extended-release capsules are approved for oral use only. inappropriate intravenous, intramuscular, or subcutaneous use of morphine sulfate extended-release capsules can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid 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). physical dependence is a state that develops as a result of a 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. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue morphine sulfate extended-release capsules in a patient physically dependent on opioids. rapid tapering of morphine sulfate extended-release capsules in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing morphine sulfate extended-release capsules, gradually taper the dosage using a patient-specific plan that considers the following: the dose of morphine sulfate extended-release capsules the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.5), and warnings and precautions (5.15)] . infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)] . morphine sulfate (mor’ feen sul’ fate) extended-release capsules, usp, cii if you cannot swallow morphine sulfate extended-release capsules, tell your healthcare provider. there may be another way to take morphine sulfate extended-release capsules that may be right for you. if your healthcare provider tells you that you can take morphine sulfate extended-release capsules using this other way, follow these steps: morphine sulfate extended-release capsules can be opened and the pellets inside the capsule can be sprinkled over applesauce, as follows: figure 1 - open the morphine sulfate extended-release capsule and sprinkle the pellets over about one tablespoon of applesauce. (see figure 1) figure 2 - swallow all of the applesauce and pellets right away. do not save any of the applesauce and pellets for another dose. (see figure 2) figure 3 - rinse your mouth to make sure you have swallowed all of the pellets. do not chew the pellets. (see figure 3) figure 4 - flush the empty capsule down the toilet right away. (see figure 4) you should not receive morphine sulfate extended-release capsules through a nasogastric tube. this instructions for use has been approved by the u.s. food and drug administration. manufactured by: amneal pharmaceuticals of ny, llc brookhaven, ny 11719 distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 12-2021-03 dispense with medication guide available at: documents.amneal.com/mg/morphine-sulfate-er-cap.pdf