Spojené štáty - angličtina - NLM (National Library of Medicine)

remedyrepack inc. - darunavir ethanolate (unii: 33o78xf0bw) (darunavir - unii:yo603y8113), cobicistat (unii: lw2e03m5pg) (cobicistat - unii:lw2e03m5pg) - darunavir 800 mg - prezcobix ® is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv-1) infection in treatment-naïve and treatment-experienced adults with no darunavir resistance-associated substitutions (v11i, v32i, l33f, i47v, i50v, i54l, i54m, t74p, l76v, i84v, l89v). prezcobix is contraindicated in patients receiving the following co-administered drugs prezcobix is contraindicated in patients receiving the following co-administered drugs [see drug interactions (7.3) and clinical pharmacology (12.3)]. - alpha 1-adrenoreceptor antagonist: alfuzosin - anticonvulsants: carbamazepine, phenobarbital, phenytoin - anti-gout: colchicine, in patients with renal and/or hepatic impairment - antimycobacterial: rifampin - antipsychotics: lurasidone, pimozide - cardiac disorders: dronedarone, ivabradine, ranolazinecardiac disorders: dronedarone, ivabradine, ranolazine - ergot derivatives, e.g. dihydroergotamine, ergotamine, methylergonovine - gi motility agent: cisapride - he

Spojené štáty - angličtina - NLM (National Library of Medicine)

a-s medication solutions - darunavir ethanolate (unii: 33o78xf0bw) (darunavir - unii:yo603y8113), cobicistat (unii: lw2e03m5pg) (cobicistat - unii:lw2e03m5pg) - darunavir 800 mg - prezcobix is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv-1) infection in treatment-naïve and treatment-experienced adults and pediatric patients weighing at least 40 kg with no darunavir resistance-associated substitutions (v11i, v32i, l33f, i47v, i50v, i54l, i54m, t74p, l76v, i84v, l89v). darunavir and cobicistat are both inhibitors of the cytochrome p450 3a (cyp3a) isoform. prezcobix should not be co-administered with medicinal products that are highly dependent on cyp3a for clearance and for which increased plasma concentrations are associated with serious and/or life threatening events (narrow therapeutic index). darunavir and cobicistat are both substrates of the cytochrome p450 3a (cyp3a) isoform. co-administration of prezcobix with cyp3a inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance. examples of drugs that are contraindicated for co-administration with prezcobix [see drug interactions (7.3)and clinical pharmacology (12.3)] are listed below. - alpha 1-adrenoreceptor antagonist: alfuzosin - anticonvulsants: carbamazepine, phenobarbital, phenytoin - 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 individuals exposed to prezcobix during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) 1-800-258-4263. risk summary prezcobix is not recommended during pregnancy because of substantially lower exposures of darunavir and cobicistat during the second and third trimesters [see dosage and administration (2.5)] . a study evaluating the pharmacokinetics of antiretrovirals during pregnancy demonstrated substantially lower exposures of darunavir and cobicistat in the second and third trimesters compared to the post-partum period (see data) and [see clinical pharmacology (12.3)]. prospective pregnancy data from the apr are not sufficient to adequately assess the risk of birth defects or miscarriage. however, available data from the apr show no statistically significant difference in the overall risk of major birth defects for darunavir and cobicistat compared with the background rate for major birth defects of 2.7% in a u.s. reference population of the metropolitan atlanta congenital defects program (macdp) (see data) . the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15–20%. the background risk of major birth defects and miscarriage for the indicated population is unknown. in animal reproduction studies, no adverse developmental effects were observed when the components of prezcobix were administered separately at darunavir exposures less than 1 (mice and rabbits) and 3-times (rats), and at cobicistat exposures 1.6 (rats) and 3.8 (rabbits) times human exposures at the recommended daily dose of these components in prezcobix (see data) . no adverse developmental effects were seen when cobicistat was administered to rats through lactation at cobicistat exposures up to 1.2 times the human exposure at the recommended therapeutic dose. clinical considerations not recommended during pregnancy prezcobix is not recommended for use during pregnancy because of substantially lower exposures of darunavir and cobicistat during pregnancy (see data) and [see clinical pharmacology (12.3)] . prezcobix should not be initiated in pregnant individuals. an alternative regimen is recommended for individuals who become pregnant during therapy with prezcobix. data human data prezcobix in combination with a background regimen was evaluated in a clinical trial of 7 pregnant individuals taking prezcobix prior to enrollment and who were willing to remain on prezcobix throughout the study. the study period included the second and third trimesters, and through 12 weeks postpartum. six pregnant individuals completed the trial. exposure to darunavir and cobicistat as part of an antiretroviral regimen was substantially lower during the second and third trimesters of pregnancy compared with postpartum [see clinical pharmacology (12.3)] . one out of 6 pregnant individuals who completed the study experienced virologic failure with hiv-1 rna >1,000 copies/ml from the third trimester visit through the postpartum period. five pregnant individuals had sustained virologic response (hiv rna <50 copies/ml) throughout the study period. there are no clinical data on the virologic response when prezcobix is initiated during pregnancy. prospective reports from the apr of overall major birth defects in pregnancies exposed to the components of prezcobix are compared with a u.s. background major birth defect rate. methodological limitations of the apr include the use of macdp as the external comparator group. limitations of using an external comparator include differences in methodology and populations, as well as confounding due to the underlying disease. there were no new clinically relevant safety findings compared with the known safety profile of prezcobix in adults with hiv-1 infection. darunavir : 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. cobicistat : based on prospective reports to the apr of over 570 exposures to cobicistat-containing regimens during pregnancy resulting in live births (including over 480 exposed in the first trimester and over 80 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.7% (95% ci: 2.2% to 5.7%) and 1.1% (95% ci: 0.0% to 6.2%) with first and second/third trimester, respectively, to cobicistat-containing regimens. animal data darunavir : reproduction studies conducted with darunavir showed no embryotoxicity or teratogenicity in mice (doses up to 1000 mg/kg from gestation day (gd) 6–15 with darunavir alone) and rats (doses up to 1000 mg/kg from gd 7–19 in the presence or absence of ritonavir) as well as in rabbits (doses up to 1000 mg/kg/day from gd 8–20 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 co-administered with ritonavir. cobicistat : cobicistat was administered orally to pregnant rats at doses up to 125 mg/kg/day on gd 6–17. increases in post-implantation loss and decreased fetal weights were observed at a maternal toxic dose of 125 mg/kg/day. no malformations were noted at doses up to 125 mg/kg/day. systemic exposures (auc) at 50 mg/kg/day in pregnant females were 1.6 times higher than human exposures at the recommended daily dose of cobicistat. in pregnant rabbits, cobicistat was administered orally at doses up to 100 mg/kg/day during gd 7–20. no maternal or embryo/fetal effects were noted at the highest dose of 100 mg/kg/day. systemic exposures (auc) at 100 mg/kg/day were 3.8 times higher than human exposures at the recommended daily dose of cobicistat. in a pre/postnatal developmental study in rats, cobicistat was administered orally at doses up to 75 mg/kg from gd 6 to postnatal day 20, 21, or 22. at doses of 75 mg/kg/day, neither maternal nor developmental toxicity was noted. systemic exposures (auc) at this dose were 1.2 times the human exposures at the recommended daily dose of cobicistat. risk summary the centers for disease control and prevention recommend that hiv infected mothers in the united states not breastfeed their infants to avoid risking postnatal transmission of hiv. there are no data on the presence of darunavir or cobicistat in human milk, the effects on the breastfed infant, or the effects on milk production. darunavir and cobicistat are 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 breastfed infants, instruct mothers not to breastfeed if they are receiving prezcobix. data animal data darunavir : studies in rats (with darunavir alone or with ritonavir) have demonstrated that darunavir is excreted in 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 of darunavir with ritonavir. cobicistat : during the pre/postnatal developmental toxicology study at doses up to 75 mg/kg/day, mean cobicistat milk to plasma ratio of up to 1.9 was measured 2 hours after administration to rats on lactation day 10. contraception additional or alternative (non-hormonal) forms of contraception should be considered when estrogen-containing contraceptives are co-administered with prezcobix. for co-administration with drospirenone, clinical monitoring is recommended due to the potential for hyperkalemia. no data are available to make recommendations on co-administration with other hormonal contraceptives [see drug interactions (7.3)]. the safety and effectiveness of prezcobix for the treatment of hiv-1 infection in pediatric patients weighing at least 40 kg was established through a trial with components of prezcobix. use of prezcobix in this group is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic, safety, and virologic data from a study of components of prezcobix (trial gs-us-216-0128) in pediatric subjects with hiv-1 infection aged 12 to less than 18 years [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.2)] . the safety and effectiveness of prezcobix have not been established in pediatric patients weighing less than 40 kg. darunavir, a component of prezcobix is not recommended in pediatric patients below 3 years of age because of toxicity and mortality observed in juvenile rats dosed with darunavir. juvenile animal toxicity data darunavir: 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 trials of prezcobix did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. in general, caution should be exercised in the administration and monitoring of prezcobix 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 clinical trials were conducted with darunavir co-administered with cobicistat in hepatically impaired subjects and the effect of hepatic impairment on darunavir exposure when co-administered with cobicistat has not been evaluated. based on the recommendations for darunavir co-administered with ritonavir, a dose adjustment for patients with mild or moderate hepatic impairment is not necessary. no pharmacokinetic or safety data are available regarding the use of darunavir in subjects with severe hepatic impairment. therefore, prezcobix is not recommended for use in patients with severe hepatic impairment [see clinical pharmacology (12.3)] . a renal impairment trial was not conducted for darunavir co-administered with cobicistat [see clinical pharmacology (12.3)] . cobicistat has been shown to decrease estimated creatinine clearance without affecting actual renal glomerular function. dosing recommendations are not available for drugs that require dosage adjustment for renal impairment when used in combination with prezcobix [see warnings and precautions (5.3)and clinical pharmacology (12.2)] .

Európska únia - angličtina - EMA (European Medicines Agency)

gilead sciences ireland uc - elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate - hiv infections - antivirals for treatment of hiv infections, combinations, antivirals for systemic use - treatment of human immunodeficiency virus 1 (hiv 1) infection in adults aged 18 years and over who are antiretroviral treatment-naïve or are infected with hiv 1 without known mutations associated with resistance to any of the three antiretroviral agents in stribild.

Spojené kráľovstvo - angličtina - MHRA (Medicines & Healthcare Products Regulatory Agency)

bristol-myers squibb pharmaceuticals ltd - atazanavir sulfate; cobicistat - tablet - 300mg ; 150mg

Spojené štáty - angličtina - NLM (National Library of Medicine)

e.r. squibb & sons, l.l.c. - atazanavir sulfate (unii: 4mt4vie29p) (atazanavir - unii:qzu4h47a3s), cobicistat (unii: lw2e03m5pg) (cobicistat - unii:lw2e03m5pg) - atazanavir 300 mg - evotaz® is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv-1) infection in the following populations [see dosage and administration (2.2, 2.3)] : use of evotaz in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions [see clinical pharmacology (12.4) ] . the concomitant use of evotaz and the following drugs in table 1, are contraindicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect [see warnings and precautions (5.8, 5.9), drug interactions (7), and clinical pharmacology (12.3)]. evotaz is contraindicated: table 1: drugs contraindicated with evotaz alpha 1-adrenoreceptor antagonist alfuzosin antianginal ranolazine antiarrhythmics dronedarone anticonvulsants carbamazepine, phenobarbital, phenytoin antigout colchicine (when used in patients with hepatic and/or renal impairment) antimycobacterials rifampin antineoplastics irino

Spojené štáty - angličtina - NLM (National Library of Medicine)

remedyrepack inc. - elvitegravir (unii: 4gdq854u53) (elvitegravir - unii:4gdq854u53), cobicistat (unii: lw2e03m5pg) (cobicistat - unii:lw2e03m5pg), emtricitabine (unii: g70b4etf4s) (emtricitabine - unii:g70b4etf4s), tenofovir alafenamide fumarate (unii: fwf6q91tzo) (tenofovir anhydrous - unii:w4hfe001u5) - elvitegravir 150 mg - genvoya is indicated as a complete regimen for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 25 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (hiv-1 rna less than 50 copies per ml) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of genvoya [see clinical studies (14)]. coadministration of genvoya 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. these drugs and other contraindicated drugs (which may lead to reduced efficacy of genvoya and possible resistance) are listed below [see drug interactions (7.5) and clinical pharmacology (12.3)]

Singapur - angličtina - HSA (Health Sciences Authority)

gilead sciences singapore pte. ltd. - cobicistat on silicon dioxide 288.5mg eqv cobicistat; elvitegravir; emtricitabine; tenofovir disoproxil fumarate 300.0mg eqv tenofovir disoproxil - tablet, film coated - cobicistat on silicon dioxide 288.5mg eqv cobicistat 150.0mg; elvitegravir 150.0mg; emtricitabine 200.0mg; tenofovir disoproxil fumarate 300.0mg eqv tenofovir disoproxil 245.0 mg

Singapur - angličtina - HSA (Health Sciences Authority)

gilead sciences singapore pte. ltd. - cobicistat on silicon dioxide 288.5mg eqv cobicistat; elvitegravir; emtricitabine; tenofovir alafenamide fumarate 11.2mg eqv tenofovir alafenamide fumarate free base - tablet, film coated - cobicistat on silicon dioxide 288.5mg eqv cobicistat 150mg; elvitegravir 150.0mg; emtricitabine 200.0mg; tenofovir alafenamide fumarate 11.2mg eqv tenofovir alafenamide fumarate free base 10.0mg

Kanada - angličtina - Health Canada

janssen inc - darunavir (darunavir ethanolate); cobicistat; emtricitabine; tenofovir alafenamide (tenofovir alafenamide hemifumarate) - tablet - 800mg; 150mg; 200mg; 10mg - darunavir (darunavir ethanolate) 800mg; cobicistat 150mg; emtricitabine 200mg; tenofovir alafenamide (tenofovir alafenamide hemifumarate) 10mg - antiretrovirals

Spojené kráľovstvo - angličtina - MHRA (Medicines & Healthcare Products Regulatory Agency)

gilead sciences international ltd - tenofovir disoproxil fumarate; emtricitabine; cobicistat; elvitegravir - tablet - 245mg ; 200mg ; 150mg ; 150mg