New Zealand - English - Medsafe (Medicines Safety Authority)

janssen-cilag (new zealand) ltd - darunavir ethanolate 650.46mg equivalent to darunavir 600 mg - film coated tablet - 600 mg - active: darunavir ethanolate 650.46mg equivalent to darunavir 600 mg excipient: crospovidone magnesium stearate opadry orange 85f13962 purified water silicified microcrystalline cellulose - adult patients: prezista (with low dose ritonavir as a pharmacokinetic enhancer) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus-1 (hiv-1) infection in adult patients.

New Zealand - English - Medsafe (Medicines Safety Authority)

janssen-cilag (new zealand) ltd - darunavir ethanolate 81.31mg equivalent to darunavir 75 mg - film coated tablet - 75 mg - active: darunavir ethanolate 81.31mg equivalent to darunavir 75 mg excipient: colloidal silicon dioxide crospovidone magnesium stearate opadry white 85f18422 purified water silicified microcrystalline cellulose - adult patients: prezista (with low dose ritonavir as a pharmacokinetic enhancer) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus-1 (hiv-1) infection in adult patients.

New Zealand - English - Medsafe (Medicines Safety Authority)

janssen-cilag (new zealand) ltd - darunavir ethanolate 867.28mg equivalent to darunavir 800 mg - film coated tablet - 800 mg - active: darunavir ethanolate 867.28mg equivalent to darunavir 800 mg excipient: colloidal silicon dioxide crospovidone hypromellose magnesium stearate opadry red 85f150004 purified water silicified microcrystalline cellulose - adult patients: prezista (with low dose ritonavir as a pharmacokinetic enhancer) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus-1 (hiv-1) infection in adult patients.

Israel - English - Ministry of Health

j-c health care ltd - darunavir as ethanolate - film coated tablets - darunavir as ethanolate 400 mg - darunavir - darunavir - prezista , co-administered with 100 mg ritonavir (prezista/rtv), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection for over 18 years of age.

Israel - English - Ministry of Health

j-c health care ltd - darunavir as ethanolate - film coated tablets - darunavir as ethanolate 600 mg - darunavir - darunavir - prezista , co-administered with 100 mg ritonavir (prezista/rtv), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection for over 18 years of age.

Singapore - English - HSA (Health Sciences Authority)

johnson & johnson international (singapore) pte ltd - darunavir ethanolate 650.46 mg eqv darunavir; darunavir ethanolate eqv darunavir - tablet, film coated - 600mg - darunavir ethanolate 650.46 mg eqv darunavir 600mg; darunavir ethanolate eqv darunavir 600mg

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

dr.reddys laboratories inc - darunavir (unii: yo603y8113) (darunavir - unii:yo603y8113) - darunavir tablets, co-administered with ritonavir (darunavir/ritonavir), in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (hiv-1) infection in adult and pediatric patients 3 years of age and older [see use in specific populations ( 8.4) and clinical studies ( 14)]. co-administration of darunavir/ritonavir is contraindicated with drugs that are highly dependent on cyp3a for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). examples of these drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed below [see drug interactions ( 7.3)] . due to the need for co-administration of darunavir with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications. - alpha 1-adrenoreceptor antagonist: alfuzosin - anti-gout: colchicine, in patients with renal and/or hepatic impairment - antimycobacterial: rifampin - antipsychotics: lurasidone, pimozide - cardiac disorders: dronedarone, ivabradine, ranolazine - ergot derivatives, e.g. dihydroergotamine, ergotamine, methylergonovine  - herbal product: st. john’s wort (hypericum perforatum) - hepatitis c direct acting antiviral: elbasvir/grazoprevir - lipid modifying agents: lomitapide, lovastatin, simvastatin - opioid antagonist: naloxegol - pde-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension - sedatives/hypnotics: orally administered midazolam, triazolam pregnancy exposure registry   there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to darunavir during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) 1-800-258-4263.   risk summary   prospective pregnancy data from the apr are not sufficient to adequately assess the risk of birth defects or miscarriage. available limited data from the apr show no statistically significant difference in the overall risk of major birth defects for darunavir compared with the background rate for major birth defects of 2.7% in a u.s. reference population of the metropolitan atlanta congenital defects program (macdp) [see data] . the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15 to 20%. the background risk of major birth defects and miscarriage for the indicated population is unknown. studies in animals did not show evidence of developmental toxicity. exposures (based on auc) in rats were 3-fold higher, whereas in mice and rabbits, exposures were lower (less than 1-fold) than human exposures at the recommended daily dose [see data] .  clinical considerations   the recommended dosage in pregnant patients is darunavir 600 mg taken with ritonavir 100 mg twice daily with food.   darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (hiv-1 rna less than 50 copies per ml), and in whom a change to twice daily darunavir 600 mg with ritonavir 100 mg may compromise tolerability or compliance [see dosage and administration ( 2.4) and clinical pharmacology ( 12.3)]. data   human data   darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 36 pregnant women during the second and third trimesters, and postpartum. eighteen subjects were enrolled in each bid and qd treatment arms. twenty-nine subjects completed the trial through the postpartum period (6 to 12 weeks after delivery) and 7 subjects discontinued before trial completion, 5 subjects in the bid arm and 2 subjects in the qd arm. the pharmacokinetic data demonstrate that exposure to darunavir and ritonavir as part of an antiretroviral regimen was lower during pregnancy compared with postpartum (6 to 12 weeks). exposure reductions during pregnancy were greater for the once daily regimen as compared to the twice daily regimen [see clinical pharmacology ( 12.3)] . virologic response was preserved. in the bid arm, the proportion of subjects with hiv-1 rna <50 copies/ml were 39% (7/18) at baseline, 61% (11/18) through the third trimester visit, and 61% (11/18) through the 6 to 12 week postpartum visit. virologic outcomes during the third trimester visit showed hiv-1 rna ≥50 copies/ml for 11% (2/18) of subjects and were missing for 5 subjects (1 subject discontinued prematurely due to virologic failure). in the qd arm, the proportion of subjects with hiv-1 rna <50 copies/ml were 61% (11/18) at baseline, 83% (15/18) through the third trimester visit, and 78% (14/18) through the 6 to 12 week postpartum visit. virologic outcomes during the third trimester visit showed hiv-1 rna ≥50 copies/ml for none of the subjects and were missing for 3 subjects (1 subject discontinued prematurely due to virologic failure). darunavir/ritonavir was well tolerated during pregnancy and postpartum. there were no new clinically relevant safety findings compared with the known safety profile of darunavir/ritonavir in hiv-1­-infected adults.  among the 31 infants with hiv test results available data, born to the 31 hiv-infected pregnant women who completed trial through delivery or postpartum period, all 31 infants had test results that were negative for hiv-1 at the time of delivery and/or through 16 weeks postpartum. all 31 infants received antiretroviral prophylactic treatment containing zidovudine. based on prospective reports to the apr of over 980 exposures to darunavir-containing regimens during pregnancy resulting in live births (including over 660 exposed in the first trimester and over 320 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.6% (95% ci: 2.3% to 5.3%) with first trimester exposure to darunavir-containing regimens and 2.5% (95% ci: 1.1% to 4.8%) with second/third trimester exposure to darunavir-containing regimens.   animal data   reproduction studies conducted with darunavir showed no embryotoxicity or teratogenicity in mice (doses up to 1,000 mg/kg from gestation day (gd) 6 to 15 with darunavir alone) and rats (doses up to 1,000 mg/kg from gd 7 to 19 in the presence or absence of ritonavir) as well as in rabbits (doses up to 1,000 mg/kg/day from gd 8 to 20 with darunavir alone). in these studies, darunavir exposures (based on auc) were higher in rats (3-fold), whereas in mice and rabbits, exposures were lower (less than 1-fold) compared to those obtained in humans at the recommended clinical dose of darunavir boosted with ritonavir. risk summary the centers for disease control and prevention recommend that hiv-infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv.   there are no data on the presence of darunavir in human milk, the effects on the breastfed infant, or the effects on milk production. darunavir is present in the milk of lactating rats [see data] . because of the potential for (1) hiv transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants) and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving darunavir [see use in specific populations ( 8.4)] . data   animal data   studies in rats (with darunavir alone or with ritonavir) have demonstrated that darunavir is secreted in the milk. in the rat pre- and postnatal development study, a reduction in pup body weight gain was observed due to exposure of pups to drug substances via milk. the maximal maternal plasma exposures achieved with darunavir (up to 1,000 mg/kg with ritonavir) were approximately 50% of those obtained in humans at the recommended clinical dose with ritonavir. contraception   use of darunavir may reduce the efficacy of combined hormonal contraceptives and the progestin only pill. advise patients to use an effective alternative (non-hormonal) contraceptive method or add a barrier method of contraception. for co-administration with drospirenone, clinical monitoring is recommended due to the potential for hyperkalemia [see drug interactions ( 7.3)] . darunavir/ritonavir is not recommended in pediatric patients below 3 years of age because of toxicity and mortality observed in juvenile rats dosed with darunavir (from 20 mg/kg to 1,000 mg/kg) up to days 23 to 26 of age [see warnings and precautions ( 5.10), use in specific populations ( 8.1) and clinical pharmacology ( 12.3)].   the safety, pharmacokinetic profile, and virologic and immunologic responses of darunavir/ritonavir administered twice daily were evaluated in treatment-experienced hiv-1­-infected pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg. these subjects were evaluated in clinical trials tmc114-c212 (80 subjects, 6 to less than 18 years of age) and tmc114-228 (21 subjects, 3 to less than 6 years of age) [see adverse reactions ( 6.1), clinical pharmacology ( 12.3) and clinical studies ( 14.4)] . frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see adverse reactions ( 6.1)] . refer to dosage and administration ( 2.5) for twice-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg.   in clinical trial tmc114-c230, the safety, pharmacokinetic profile and virologic and immunologic responses of darunavir/ritonavir administered once daily were evaluated in treatment-naïve hiv-1 infected pediatric subjects 12 to less than 18 years of age (12 subjects) [see adverse reactions ( 6.1), clinical pharmacology ( 12.3) and clinical studies ( 14.4)] . frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see adverse reactions ( 6.1)] . once daily dosing recommendations for pediatric patients 3 to less than 12 years of age were derived using population pharmacokinetic modeling and simulation. although a darunavir/ritonavir once daily dosing pediatric trial was not conducted in children less than 12 years of age, there is sufficient clinical safety data to support the predicted darunavir exposures for the dosing recommendations in this age group [see clinical pharmacology ( 12.3)] . please see dosage and administration ( 2.5) for once-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg.   juvenile animal data   in a juvenile toxicity study where rats were directly dosed with darunavir (up to 1,000 mg/kg), deaths occurred from post-natal day 5 at plasma exposure levels ranging from 0.1 to 1 of the human exposure levels. in a 4-week rat toxicology study, when dosing was initiated on post-natal day 23 (the human equivalent of 2 to 3 years of age), no deaths were observed with a plasma exposure (in combination with ritonavir) 2 times the human plasma exposure levels. clinical studies of darunavir did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. in general, caution should be exercised in the administration and monitoring of darunavir in elderly patients, reflecting the greater frequency of decreased hepatic function, and of concomitant disease or other drug therapy [see clinical pharmacology ( 12.3)]. no dosage adjustment of darunavir/ritonavir is necessary for patients with either mild or moderate hepatic impairment. no pharmacokinetic or safety data are available regarding the use of darunavir/ritonavir in subjects with severe hepatic impairment. therefore, darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment [see dosage and administration ( 2.6) and clinical pharmacology ( 12.3)]. population pharmacokinetic analysis showed that the pharmacokinetics of darunavir were not significantly affected in hiv-infected subjects with moderate renal impairment (crcl between 30 to 60 ml/min, n=20). no pharmacokinetic data are available in hiv-1-infected patients with severe renal impairment or end stage renal disease; however, because the renal clearance of darunavir is limited, a decrease in total body clearance is not expected in patients with renal impairment. as darunavir and ritonavir are highly bound to plasma proteins, it is unlikely that they will be significantly removed by hemodialysis or peritoneal dialysis [see clinical pharmacology ( 12.3)] .

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

aurobindo pharma limited - darunavir propylene glycolate (unii: 6m6d7f3vc7) (darunavir - unii:yo603y8113) - darunavir tablets, co-administered with ritonavir (darunavir/ritonavir), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection in adult and pediatric patients 3 years of age and older [see use in specific populations (8.4) and clinical studies (14)] . co-administration of darunavir/ritonavir is contraindicated with drugs that are highly dependent on cyp3a for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). examples of these drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed below [see drug interactions (7.3)] . due to the need for co-administration of darunavir with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications. - alpha 1-adrenoreceptor antagonist: alfuzosin - anti-gout: colchicine, in patients with renal and/or hepatic impairment - antimycobacterial: rifampin - antipsychotics: lurasidone, pimozide - cardiac disorders: dronedarone, ivabradine, ranolazine - ergot derivatives, e.g., dihydroergotamine, ergotamine, methylergonovine - herbal product: st. john’s wort (hypericum perforatum ) - hepatitis c direct acting antiviral: elbasvir/grazoprevir - lipid modifying agents: lomitapide, lovastatin, simvastatin - opioid antagonist: naloxegol - pde-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension - sedatives/hypnotics: orally administered midazolam, triazolam pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to darunavir during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) 1-800-258-4263. risk summary prospective pregnancy data from the apr are not sufficient to adequately assess the risk of birth defects or miscarriage. available limited data from the apr show no statistically significant difference in the overall risk of major birth defects for darunavir compared with the background rate for major birth defects of 2.7% in a u.s. reference population of the metropolitan atlanta congenital defects program (macdp) [see data] . the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15 to 20%. the background risk of major birth defects and miscarriage for the indicated population is unknown. studies in animals did not show evidence of developmental toxicity. exposures (based on auc) in rats were 3-fold higher, whereas in mice and rabbits, exposures were lower (less than 1-fold) than human exposures at the recommended daily dose [see data] . clinical considerations the recommended dosage in pregnant patients is darunavir 600 mg taken with ritonavir 100 mg twice daily with food. darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (hiv-1 rna less than 50 copies per ml), and in whom a change to twice daily darunavir 600 mg with ritonavir 100 mg may compromise tolerability or compliance [see dosage and administration (2.4) and clinical pharmacology (12.3)] . data human data darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 36 pregnant women during the second and third trimesters, and postpartum. eighteen subjects were enrolled in each bid and qd treatment arms. twenty-nine subjects completed the trial through the postpartum period (6 to 12 weeks after delivery) and 7 subjects discontinued before trial completion, 5 subjects in the bid arm and 2 subjects in the qd arm. the pharmacokinetic data demonstrate that exposure to darunavir and ritonavir as part of an antiretroviral regimen was lower during pregnancy compared with postpartum (6 to 12 weeks). exposure reductions during pregnancy were greater for the once daily regimen as compared to the twice daily regimen [see clinical pharmacology (12.3)]. virologic response was preserved. in the bid arm, the proportion of subjects with hiv-1 rna <50 copies/ml were 39% (7/18) at baseline, 61% (11/18) through the third trimester visit, and 61% (11/18) through the 6 to 12 week postpartum visit. virologic outcomes during the third trimester visit showed hiv-1 rna ≥50 copies/ml for 11% (2/18) of subjects and were missing for 5 subjects (1 subject discontinued prematurely due to virologic failure). in the qd arm, the proportion of subjects with hiv-1 rna <50 copies/ml were 61% (11/18) at baseline, 83% (15/18) through the third trimester visit, and 78% (14/18) through the 6 to 12 week postpartum visit. virologic outcomes during the third trimester visit showed hiv-1 rna ≥50 copies/ml for none of the subjects and were missing for 3 subjects (1 subject discontinued prematurely due to virologic failure). darunavir/ritonavir was well tolerated during pregnancy and postpartum. there were no new clinically relevant safety findings compared with the known safety profile of darunavir/ritonavir in hiv-1-infected adults. among the 31 infants with hiv test results available data, born to the 31 hiv-infected pregnant women who completed trial through delivery or postpartum period, all 31 infants had test results that were negative for hiv-1 at the time of delivery and/or through 16 weeks postpartum. all 31 infants received antiretroviral prophylactic treatment containing zidovudine. based on prospective reports to the apr of over 980 exposures to darunavir-containing regimens during pregnancy resulting in live births (including over 660 exposed in the first trimester and over 320 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.6.% (95% ci: 2.3% to 5.3.%) with first trimester exposure to darunavir-containing regimens and 2.5% (95% ci: 1.1% to 4.8%) with second/third trimester exposure to darunavir-containing regimens. animal data reproduction studies conducted with darunavir showed no embryotoxicity or teratogenicity in mice (doses up to 1000 mg/kg from gestation day (gd) 6 to 15 with darunavir alone) and rats (doses up to 1000 mg/kg from gd 7 to 19 in the presence or absence of ritonavir) as well as in rabbits (doses up to 1000 mg/kg/day from gd 8 to 20 with darunavir alone). in these studies, darunavir exposures (based on auc) were higher in rats (3-fold), whereas in mice and rabbits, exposures were lower (less than 1-fold) compared to those obtained in humans at the recommended clinical dose of darunavir boosted with ritonavir. risk summary the centers for disease control and prevention recommend that hiv-infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv. there are no data on the presence of darunavir in human milk, the effects on the breastfed infant, or the effects on milk production. darunavir is present in the milk of lactating rats [see data] . because of the potential for (1) hiv transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants) and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving darunavir [see use in specific populations (8.4)] . data animal data studies in rats (with darunavir alone or with ritonavir) have demonstrated that darunavir is secreted in the milk. in the rat pre- and postnatal development study, a reduction in pup body weight gain was observed due to exposure of pups to drug substances via milk. the maximal maternal plasma exposures achieved with darunavir (up to 1000 mg/kg with ritonavir) were approximately 50% of those obtained in humans at the recommended clinical dose with ritonavir. contraception use of darunavir may reduce the efficacy of combined hormonal contraceptives and the progestin only pill. advise patients to use an effective alternative (non-hormonal) contraceptive method or add a barrier method of contraception. for co-administration with drospirenone, clinical monitoring is recommended due to the potential for hyperkalemia [see drug interactions (7.3)] . darunavir/ritonavir is not recommended in pediatric patients below 3 years of age because of toxicity and mortality observed in juvenile rats dosed with darunavir (from 20 mg/kg to 1000 mg/kg) up to days 23 to 26 of age [see warnings and precautions (5.10) , use in specific populations (8.1) and clinical pharmacology (12.3)] . the safety, pharmacokinetic profile, and virologic and immunologic responses of darunavir/ritonavir administered twice daily were evaluated in treatment-experienced hiv-1-infected pediatric subjects 3 to less than 18 years of age and weighting at least 10 kg. these subjects were evaluated in clinical trials tmc114-c212 (80 subjects, 6 to less than 18 years of age) and tmc114-228 (21 subjects, 3 to less than 6 years of age) [see adverse reactions (6.1) , clinical pharmacology (12.3) and clinical studies (14.4)] . frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see adverse reactions (6.1)] . refer to dosage and administration (2.5)  for twice-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg. in clinical trial tmc114-c230, the safety, pharmacokinetic profile and virologic and immunologic responses of darunavir/ritonavir administered once daily were evaluated in treatment-naïve hiv-1 infected pediatric subjects 12 to less than 18 years of age (12 subjects) [see adverse reactions (6.1) , clinical pharmacology (12.3) and clinical studies (14.4)] . frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see adverse reactions (6.1)] . once daily dosing recommendations for pediatric patients 3 to less than 12 years of age were derived using population pharmacokinetic modeling and simulation. although a darunavir/ritonavir once daily dosing pediatric trial was not conducted in children less than 12 years of age, there is sufficient clinical safety data to support the predicted darunavir exposures for the dosing recommendations in this age group [see clinical pharmacology (12.3)] . please see dosage and administration (2.5)  for once-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg. juvenile animal data   in a juvenile toxicity study where rats were directly dosed with darunavir (up to 1000 mg/kg), deaths occurred from post-natal day 5 at plasma exposure levels ranging from 0.1 to 1.0 of the human exposure levels. in a 4-week rat toxicology study, when dosing was initiated on post-natal day 23 (the human equivalent of 2 to 3 years of age), no deaths were observed with a plasma exposure (in combination with ritonavir) 2 times the human plasma exposure levels. clinical studies of darunavir did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. in general, caution should be exercised in the administration and monitoring of darunavir in elderly patients, reflecting the greater frequency of decreased hepatic function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3)] . no dosage adjustment of darunavir/ritonavir is necessary for patients with either mild or moderate hepatic impairment. no pharmacokinetic or safety data are available regarding the use of darunavir/ritonavir in subjects with severe hepatic impairment. therefore, darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment [see dosage and administration (2.6) and clinical pharmacology (12.3)] . population pharmacokinetic analysis showed that the pharmacokinetics of darunavir were not significantly affected in hiv-infected subjects with moderate renal impairment (crcl between 30 to 60 ml/min, n=20). no pharmacokinetic data are available in hiv-1-infected patients with severe renal impairment or end stage renal disease; however, because the renal clearance of darunavir is limited, a decrease in total body clearance is not expected in patients with renal impairment. as darunavir and ritonavir are highly bound to plasma proteins, it is unlikely that they will be significantly removed by hemodialysis or peritoneal dialysis [see clinical pharmacology (12.3)] .

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

amneal pharmaceuticals ny llc - darunavir (unii: yo603y8113) (darunavir - unii:yo603y8113) - darunavir, co-administered with ritonavir (darunavir/ritonavir), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection in adult and pediatric patients 3 years of age and older [see use in specific populations (8.4)  and clinical studies (14)] . co-administration of darunavir/ritonavir is contraindicated with drugs that are highly dependent on cyp3a for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). examples of these drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed below [see drug interactions (7.3)] . due to the need for co-administration of darunavir with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications. - alpha 1-adrenoreceptor antagonist: alfuzosin - anti-gout: colchicine, in patients with renal and/or hepatic impairment - antimycobacterial: rifampin - antipsychotics: lurasidone, pimozide - cardiac disorders: dronedarone, ivabradine, ranolazine - ergot derivatives, e.g., dihydroergotamine, ergotamine, methylergonovine -  herbal product: st. john’s wort (hypericum perforatum ) - hepatitis c direct acting antiviral: elbasvir/grazoprevir - lipid modifying agents: lomitapide, lovastatin, simvastatin - opioid antagonist: naloxegol - pde-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension - sedatives/hypnotics: orally administered midazolam, triazolam pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to darunavir during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) 1-800-258-4263. risk summary prospective pregnancy data from the apr are not sufficient to adequately assess the risk of birth defects or miscarriage. available limited data from the apr show no statistically significant difference in the overall risk of major birth defects for darunavir compared with the background rate for major birth defects of 2.7% in a u.s. reference population of the metropolitan atlanta congenital defects program (macdp) [see data] .  the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15% to 20%. the background risk of major birth defects and miscarriage for the indicated population is unknown. studies in animals did not show evidence of developmental toxicity. exposures (based on auc) in rats were 3-fold higher, whereas in mice and rabbits, exposures were lower (less than 1-fold) than human exposures at the recommended daily dose [see data] . clinical considerations the recommended dosage in pregnant patients is darunavir 600 mg taken with ritonavir 100 mg twice daily with food. darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (hiv-1 rna less than 50 copies per ml), and in whom a change to twice daily darunavir 600 mg with ritonavir 100 mg may compromise tolerability or compliance [see dosage and administration (2.4) and clinical pharmacology (12.3)] . data human data darunavir/ritonavir (600 mg/100 mg twice daily or 800 mg/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 36 pregnant women during the second and third trimesters, and postpartum. eighteen subjects were enrolled in each bid and qd treatment arms. twenty-nine subjects completed the trial through the postpartum period (6 to 12 weeks after delivery) and 7 subjects discontinued before trial completion, 5 subjects in the bid arm and 2 subjects in the qd arm. the pharmacokinetic data demonstrate that exposure to darunavir and ritonavir as part of an antiretroviral regimen was lower during pregnancy compared with postpartum (6 to 12 weeks). exposure reductions during pregnancy were greater for the once daily regimen as compared to the twice daily regimen [see clinical pharmacology (12.3)]. virologic response was preserved. in the bid arm, the proportion of subjects with hiv-1 rna < 50 copies/ml were 39% (7/18) at baseline, 61% (11/18) through the third trimester visit, and 61% (11/18) through the 6 to 12 week postpartum visit. virologic outcomes during the third trimester visit showed hiv-1 rna ≥ 50 copies/ml for 11% (2/18) of subjects and were missing for 5 subjects (1 subject discontinued prematurely due to virologic failure). in the qd arm, the proportion of subjects with hiv-1 rna < 50 copies/ml were 61% (11/18) at baseline, 83% (15/18) through the third trimester visit, and 78% (14/18) through the 6 to 12 week postpartum visit. virologic outcomes during the third trimester visit showed hiv-1 rna ≥ 50 copies/ml for none of the subjects and were missing for 3 subjects (1 subject discontinued prematurely due to virologic failure). darunavir/ritonavir was well tolerated during pregnancy and postpartum. there were no new clinically relevant safety findings compared with the known safety profile of darunavir/ritonavir in hiv-1-infected adults. among the 31 infants with hiv test results available data, born to the 31 hiv-infected pregnant women who completed trial through delivery or postpartum period, all 31 infants had test results that were negative for hiv-1 at the time of delivery and/or through 16 weeks postpartum. all 31 infants received antiretroviral prophylactic treatment containing zidovudine. based on prospective reports to the apr of over 980 exposures to darunavir-containing regimens during pregnancy resulting in live births (including over 660 exposed in the first trimester and over 320 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.6% (95% ci: 2.3% to 5.3%) with first trimester exposure to darunavir-containing regimens and 2.5% (95% ci: 1.1% to 4.8%) with second/third trimester exposure to darunavir-containing regimens. animal data reproduction studies conducted with darunavir showed no embryotoxicity or teratogenicity in mice (doses up to 1,000 mg/kg from gestation day (gd) 6 to 15 with darunavir alone) and rats (doses up to 1,000 mg/kg from gd 7 to 19 in the presence or absence of ritonavir) as well as in rabbits (doses up to 1,000 mg/kg/day from gd 8 to 20 with darunavir alone). in these studies, darunavir exposures (based on auc) were higher in rats (3-fold), whereas in mice and rabbits, exposures were lower (less than 1-fold) compared to those obtained in humans at the recommended clinical dose of darunavir boosted with ritonavir. risk summary the centers for disease control and prevention recommend that hiv-infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv. there are no data on the presence of darunavir in human milk, the effects on the breastfed infant, or the effects on milk production. darunavir is present in the milk of lactating rats [see data] . because of the potential for (1) hiv transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants) and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving darunavir [see use in specific populations (8.4)] . data animal data studies in rats (with darunavir alone or with ritonavir) have demonstrated that darunavir is secreted in the milk. in the rat pre- and postnatal development study, a reduction in pup body weight gain was observed due to exposure of pups to drug substances via milk. the maximal maternal plasma exposures achieved with darunavir (up to 1,000 mg/kg with ritonavir) were approximately 50% of those obtained in humans at the recommended clinical dose with ritonavir. contraception use of darunavir may reduce the efficacy of combined hormonal contraceptives and the progestin only pill. advise patients to use an effective alternative (non-hormonal) contraceptive method or add a barrier method of contraception. for co-administration with drospirenone, clinical monitoring is recommended due to the potential for hyperkalemia [see drug interactions (7.3)] . darunavir/ritonavir is not recommended in pediatric patients below 3 years of age because of toxicity and mortality observed in juvenile rats dosed with darunavir (from 20 mg/kg to 1,000 mg/kg) up to days 23 to 26 of age [see warnings and precautions (5.10) , use in specific populations (8.1) and clinical pharmacology (12.3)] . the safety, pharmacokinetic profile, and virologic and immunologic responses of darunavir/ritonavir administered twice daily were evaluated in treatment-experienced hiv-1-infected pediatric subjects 3 to less than 18 years of age and weighting at least 10 kg. these subjects were evaluated in clinical trials tmc114-c212 (80 subjects, 6 to less than 18 years of age) and tmc114-228 (21 subjects, 3 to less than 6 years of age) [see adverse reactions (6.1) , clinical pharmacology (12.3)  and clinical studies (14.4)] . frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see adverse reactions (6.1)] . refer to dosage and administration (2.5)  for twice-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg. in clinical trial tmc114-c230, the safety, pharmacokinetic profile and virologic and immunologic responses of darunavir/ritonavir administered once daily were evaluated in treatment-naïve hiv-1 infected pediatric subjects 12 to less than 18 years of age (12 subjects) [see adverse reactions (6.1) , clinical pharmacology (12.3)  andclinical studies (14.4)] . frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see adverse reactions (6.1)] . once daily dosing recommendations for pediatric patients 3 to less than 12 years of age were derived using population pharmacokinetic modeling and simulation. although a darunavir/ritonavir once daily dosing pediatric trial was not conducted in children less than 12 years of age, there is sufficient clinical safety data to support the predicted darunavir exposures for the dosing recommendations in this age group [see clinical pharmacology (12.3)] . please see dosage and administration (2.5)  for once-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg. juvenile animal data in a juvenile toxicity study where rats were directly dosed with darunavir (up to 1,000 mg/kg), deaths occurred from post-natal day 5 at plasma exposure levels ranging from 0.1 to 1.0 of the human exposure levels. in a 4-week rat toxicology study, when dosing was initiated on post-natal day 23 (the human equivalent of 2 to 3 years of age), no deaths were observed with a plasma exposure (in combination with ritonavir) 2 times the human plasma exposure levels. clinical studies of darunavir did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. in general, caution should be exercised in the administration and monitoring of darunavir in elderly patients, reflecting the greater frequency of decreased hepatic function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3)] . no dosage adjustment of darunavir/ritonavir is necessary for patients with either mild or moderate hepatic impairment. no pharmacokinetic or safety data are available regarding the use of darunavir/ritonavir in subjects with severe hepatic impairment. therefore, darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment [see dosage and administration (2.6) and clinical pharmacology (12.3)] . population pharmacokinetic analysis showed that the pharmacokinetics of darunavir were not significantly affected in hiv-infected subjects with moderate renal impairment (crcl between 30 to 60 ml/min, n=20). no pharmacokinetic data are available in hiv-1-infected patients with severe renal impairment or end stage renal disease; however, because the renal clearance of darunavir is limited, a decrease in total body clearance is not expected in patients with renal impairment. as darunavir and ritonavir are highly bound to plasma proteins, it is unlikely that they will be significantly removed by hemodialysis or peritoneal dialysis [see clinical pharmacology (12.3)] .

Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - darunavir, quantity: 800 mg - tablet, film coated - excipient ingredients: crospovidone; magnesium stearate; microcrystalline cellulose; colloidal anhydrous silica; titanium dioxide; purified talc; iron oxide red; polyvinyl alcohol; macrogol 3350 - adult patients darunavir (with low dose ritonavir as a pharmacokinetic enhancer) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus-1 (hiv-1) infection in adult patients.,paediatric patients darunavir (with low dose ritonavir as a pharmacokinetic enhancer) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv) infection in treatment-experienced paediatric patients aged 6 years and older, weighing at least 20 kg.