Israel - English - Ministry of Health

merck sharp & dohme (israel - 1996) company ltd, israel - doravirine; lamivudine; tenofovir disoproxil as fumarate - film coated tablets - doravirine 100 mg; lamivudine 300 mg; tenofovir disoproxil as fumarate 245 mg - lamivudine,tenofovir disoproxil and doravirine - delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) is indicated as a complete regimen for the treatment of human immunodeficiency virus-1 (hiv-1) infection in adults without past or present evidence of viral resistance to doravirine, lamivudine, or tenofovir.

Israel - English - Ministry of Health

merck sharp & dohme (israel - 1996) company ltd, israel - doravirine - film coated tablets - doravirine 100 mg - doravirine - pifeltro is indicated, in combination with other antiretroviral medicinal products, for the treatment of adults infected with hiv-1 without past or present evidence of viral resistance to doravirine.

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

merck sharp & dohme llc - doravirine (unii: 913p6lk81m) (doravirine - unii:913p6lk81m), lamivudine (unii: 2t8q726o95) (lamivudine - unii:2t8q726o95), tenofovir disoproxil fumarate (unii: ott9j7900i) (tenofovir anhydrous - unii:w4hfe001u5) - delstrigo® is indicated as a complete regimen for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 35 kg: - with no prior 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 with no history of treatment failure and no known substitutions associated with resistance to the individual components of delstrigo [see clinical studies (14)] . - delstrigo is contraindicated when co-administered with drugs that are strong cytochrome p450 (cyp)3a enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of delstrigo [see warnings and precautions (5.3), drug interactions (7.2), and clinical pharmacology (12.3)] . these drugs include, but are not limited to, the following: - the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin - the androgen receptor inhibitor enzalutamide - the antimycobacterials rifampin, rifapentine - the cytotoxic agent mitotane - st. john's wort (hypericum perforatum) - delstrigo is contraindicated in patients with a previous hypersensitivity reaction to lamivudine. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to delstrigo during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary there is insufficient prospective pregnancy data from the apr to adequately assess the risk of birth defects and miscarriage. doravirine use in individuals during pregnancy has not been evaluated; however, lamivudine and tdf use during pregnancy has been evaluated in a limited number of individuals reported to the apr. available data from the apr show no difference in the overall risk of major birth defects for lamivudine and tdf compared with the background rate for major birth defects of 2.7% in the u.s. reference population of the metropolitan atlanta congenital defects program (macdp) (see data ). the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in the clinically recognized pregnancies in the u.s. general population is 15-20%. methodological limitations of the apr include the use of macdp as the external comparator group. the macdp population is not disease-specific, evaluates individuals and infants from the limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. in animal reproduction studies, oral administration of lamivudine to pregnant rabbits during organogenesis resulted in embryolethality at systemic exposure (auc) similar to the recommended clinical dose; however, no adverse development effects were observed with oral administration of lamivudine to pregnant rats during organogenesis at plasma concentrations (cmax ) 35 times the recommended clinical dose. no adverse developmental effects were observed when doravirine and tdf were administered separately at doses/exposures ≥8 (doravirine) and ≥14 (tdf) times those of the recommended human dose (rhd) of delstrigo (see data ). data human data lamivudine : the apr has received a total of over 13,000 prospective reports with follow-up data of possible exposure to lamivudine-containing regimens; over 5,900 reports in the first trimester; over 5,600 reports in the second trimester; and over 1,800 reports in the third trimester. birth defects occurred in 170 of 5,472 (3.1%, 95% ci: 2.7% to 3.6%) live births for lamivudine-containing regimens (first trimester exposure); and 218 of 7,513 (2.9%, 95% ci: 2.5% to 3.3%) live births for lamivudine-containing regimens (second/third trimester exposure). among pregnant mothers in the u.s. reference population, the background rate of birth defects is 2.7%. there was no association between lamivudine and overall birth defects observed in the apr. tdf : the apr has received a total of over 7,000 prospective reports with follow-up data of possible exposure to tenofovir disoproxil-containing regimens; over 5,100 reports in the first trimester; over 1,300 reports in the second trimester; and over 600 reports in the third trimester. birth defects occurred in 113 of 4,576 (2.5%, 95% ci: 2.0% to 3.0%) live births for tdf-containing regimens (first trimester exposure); and 51 of 1,965 (2.6%, 95% ci: 1.9% to 3.4%) live births for tdf-containing regimens (second/third trimester exposure). among pregnant mothers in the u.s. reference population, the background rate of birth defects is 2.7%. there was no association between tenofovir and overall birth defects observed in the apr. animal data doravirine : doravirine was administered orally to pregnant rabbits (up to 300 mg/kg/day on gestation days (gd) 7 to 20) and rats (up to 450 mg/kg/day on gd 6 to 20 and separately from gd 6 to lactation/postpartum day 20). no significant toxicological effects on embryo-fetal (rats and rabbits) or pre/post-natal (rats) development were observed at exposures (auc) approximately 9 times (rats) and 8 times (rabbits) the exposure in humans at the rhd. doravirine was transferred to the fetus through the placenta in embryo-fetal studies, with fetal plasma concentrations of up to 40% (rabbits) and 52% (rats) that of maternal concentrations observed on gd 20. lamivudine : lamivudine was administered orally to pregnant rats (at 90, 600, and 4,000 mg per kg per day) and rabbits (at 90, 300, and 1,000 mg per kg per day and at 15, 40, and 90 mg per kg per day) during organogenesis (on gd 7 through 16 [rat] and 8 through 20 [rabbit]). no evidence of fetal malformations due to lamivudine was observed in rats and rabbits at doses producing plasma concentrations (cmax ) approximately 35 times higher than human exposure at the recommended daily dose. evidence of early embryolethality was seen in the rabbit at system exposures (auc) similar to those observed in humans, but there was no indication of this effect in the rat at plasma concentrations (cmax ) 35 times higher than human exposure at the recommended daily dose. studies in pregnant rats showed that lamivudine is transferred to the fetus through the placenta. in the fertility/pre- and postnatal development study in rats, lamivudine was administered orally at doses of 180, 900, and 4,000 mg per kg per day (from prior to mating through postnatal day 20). in the study, development of the offspring, including fertility and reproductive performance, was not affected by maternal administration of lamivudine. tdf : reproduction studies have been performed in rats and rabbits at doses up to 14 and 19 times the human dose based on body surface area comparisons and revealed no evidence of harm to the fetus. risk summary the centers for disease control and prevention recommend that hiv-1-infected mothers in the united states not breastfeed their infants to avoid risking potential transmission of hiv-1 infection. based on limited published data, both lamivudine and tenofovir are present in human milk. it is unknown whether doravirine is present in human milk, but doravirine is present in the milk of lactating rats (see data ). it is not known whether delstrigo or the components of delstrigo affects human milk production, or has effects on the breastfed infant. because of the potential for (1) hiv-1 transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants), and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving delstrigo. data doravirine : doravirine was excreted into the milk of lactating rats following oral administration (450 mg/kg/day) from gd 6 to lactation day 14, with milk concentrations approximately 1.5 times that of maternal plasma concentrations observed 2 hours post dose on lactation day 14. the safety and efficacy of delstrigo for the treatment of hiv-1 infection have been established in pediatric patients weighing at least 35 kg [see indications and usage (1) and dosage and administration (2.2)] . use of delstrigo in this group is supported by evidence from adequate and well-controlled trials in adults with additional pharmacokinetic, safety, and efficacy data from an open-label trial in virologically-suppressed or treatment-naïve pediatric subjects 12 to less than 18 years of age. the safety and efficacy of delstrigo in these pediatric subjects were similar to that in adults, and there was no clinically significant difference in exposure for the components of delstrigo. [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.3).] safety and efficacy of delstrigo in pediatric patients weighing less than 35 kg have not been established. clinical trials of doravirine, lamivudine, or tdf did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. in general, caution should be exercised in the administration of delstrigo in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3)]. because delstrigo is a fixed-dose combination tablet and the dosage of lamivudine and tdf, both components of delstrigo, cannot be altered, delstrigo is not recommended in patients with estimated creatinine clearance less than 50 ml/min [see warnings and precautions (5.2) and clinical pharmacology (12.3)] . no dosage adjustment of delstrigo is required in patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. delstrigo has not been studied in patients with severe hepatic impairment (child-pugh class c) [see clinical pharmacology (12.3)] .

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

merck sharp & dohme llc - doravirine (unii: 913p6lk81m) (doravirine - unii:913p6lk81m) - pifeltro® is indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 35 kg: - with no prior 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 with no history of treatment failure and no known substitutions associated with resistance to doravirine [see clinical studies (14)] . pifeltro is contraindicated when co-administered with drugs that are strong cytochrome p450 (cyp)3a enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of pifeltro [see warnings and precautions (5.1), drug interactions (7.1), and clinical pharmacology (12.3)] . these drugs include, but are not limited to, the following: - the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin - the androgen receptor inhibitor enzalutamide - the antimycobacterials rifampin, rifapentine - the cytotoxic agent mitotane - st. john's wort (hypericum perforatum) pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to pifeltro during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary no adequate human data are available to establish whether or not pifeltro poses a risk to pregnancy outcomes. in animal reproduction studies, no adverse developmental effects were observed when doravirine was administered at exposures ≥8 times the exposure in humans at the recommended human dose (rhd) of pifeltro (see data ). the background rate of major birth defects is 2.7% in a u.s. reference population of the metropolitan atlanta congenital defects program (macdp). the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in the clinically recognized pregnancies in the u.s. general population is 15-20%. methodological limitations of the apr include the use of macdp as the external comparator group. the macdp population is not disease-specific, evaluates individuals and infants from the limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. data animal data doravirine was administered orally to pregnant rabbits (up to 300 mg/kg/day on gestation days (gd) 7 to 20) and rats (up to 450 mg/kg/day on gd 6 to 20 and separately from gd 6 to lactation/postpartum day 20). no significant toxicological effects on embryo-fetal (rats and rabbits) or pre/post-natal (rats) development were observed at exposures (auc) approximately 9 times (rats) and 8 times (rabbits) the exposure in humans at the rhd. doravirine was transferred to the fetus through the placenta in embryo-fetal studies, with fetal plasma concentrations of up to 40% (rabbits) and 52% (rats) that of maternal concentrations observed on gd 20. risk summary the centers for disease control and prevention recommend that hiv-1-infected mothers in the united states not breastfeed their infants to avoid risking potential transmission of hiv-1 infection. it is unknown whether doravirine is present in human milk, affects human milk production, or has effects on the breastfed infant. doravirine is present in the milk of lactating rats (see data ). because of the potential for (1) hiv-1 transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants), and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving pifeltro. data doravirine was excreted into the milk of lactating rats following oral administration (450 mg/kg/day) from gd 6 to lactation day 14, with milk concentrations approximately 1.5 times that of maternal plasma concentrations observed 2 hours post dose on lactation day 14. the safety and efficacy of pifeltro for the treatment of hiv-1 infection have been established in pediatric patients weighing at least 35 kg [see indications and usage (1) and dosage and administration (2.1)]. use of pifeltro in this group is supported by evidence from adequate and well-controlled trials in adults and an open-label trial in virologically-suppressed or treatment-naïve pediatric subjects 12 to less than 18 years of age. the safety, efficacy, and exposure of doravirine in these pediatric subjects were similar to that in adults. [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.3).] safety and efficacy of pifeltro in pediatric patients weighing less than 35 kg have not been established. clinical trials of pifeltro did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. in general, caution should be exercised in the administration of pifeltro in elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3)] . no dosage adjustment of pifeltro is required in patients with mild, moderate, or severe renal impairment. pifeltro has not been adequately studied in patients with end-stage renal disease and has not been studied in dialysis patients [see clinical pharmacology (12.3)] . no dosage adjustment of pifeltro is required in patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. pifeltro has not been studied in patients with severe hepatic impairment (child-pugh class c) [see clinical pharmacology (12.3)] .

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

a-s medication solutions - doravirine (unii: 913p6lk81m) (doravirine - unii:913p6lk81m) - pifeltro® is indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 35 kg: - with no prior 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 with no history of treatment failure and no known substitutions associated with resistance to doravirine [see clinical studies (14)] . pifeltro is contraindicated when co-administered with drugs that are strong cytochrome p450 (cyp)3a enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of pifeltro [see warnings and precautions (5.1), drug interactions (7.1), and clinical pharmacology (12.3)] . these drugs include, but are not limited to, the following: - the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin - the androgen receptor inhibitor enzalutamide - the antimycobacterials rifampin, rifapentine - the cytotoxic agent mitotane - st. john's wort (hypericum perforatum) pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to pifeltro during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary no adequate human data are available to establish whether or not pifeltro poses a risk to pregnancy outcomes. in animal reproduction studies, no adverse developmental effects were observed when doravirine was administered at exposures ≥8 times the exposure in humans at the recommended human dose (rhd) of pifeltro (see data ). the background rate of major birth defects is 2.7% in a u.s. reference population of the metropolitan atlanta congenital defects program (macdp). the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in the clinically recognized pregnancies in the u.s. general population is 15-20%. methodological limitations of the apr include the use of macdp as the external comparator group. the macdp population is not disease-specific, evaluates individuals and infants from the limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. data animal data doravirine was administered orally to pregnant rabbits (up to 300 mg/kg/day on gestation days (gd) 7 to 20) and rats (up to 450 mg/kg/day on gd 6 to 20 and separately from gd 6 to lactation/postpartum day 20). no significant toxicological effects on embryo-fetal (rats and rabbits) or pre/post-natal (rats) development were observed at exposures (auc) approximately 9 times (rats) and 8 times (rabbits) the exposure in humans at the rhd. doravirine was transferred to the fetus through the placenta in embryo-fetal studies, with fetal plasma concentrations of up to 40% (rabbits) and 52% (rats) that of maternal concentrations observed on gd 20. risk summary the centers for disease control and prevention recommend that hiv-1-infected mothers in the united states not breastfeed their infants to avoid risking potential transmission of hiv-1 infection. it is unknown whether doravirine is present in human milk, affects human milk production, or has effects on the breastfed infant. doravirine is present in the milk of lactating rats (see data ). because of the potential for (1) hiv-1 transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants), and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving pifeltro. data doravirine was excreted into the milk of lactating rats following oral administration (450 mg/kg/day) from gd 6 to lactation day 14, with milk concentrations approximately 1.5 times that of maternal plasma concentrations observed 2 hours post dose on lactation day 14. the safety and efficacy of pifeltro for the treatment of hiv-1 infection have been established in pediatric patients weighing at least 35 kg [see indications and usage (1) and dosage and administration (2.1)]. use of pifeltro in this group is supported by evidence from adequate and well-controlled trials in adults and an open-label trial in virologically-suppressed or treatment-naïve pediatric subjects 12 to less than 18 years of age. the safety, efficacy, and exposure of doravirine in these pediatric subjects were similar to that in adults. [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.3).] safety and efficacy of pifeltro in pediatric patients weighing less than 35 kg have not been established. clinical trials of pifeltro did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. in general, caution should be exercised in the administration of pifeltro in elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see clinical pharmacology (12.3)] . no dosage adjustment of pifeltro is required in patients with mild, moderate, or severe renal impairment. pifeltro has not been adequately studied in patients with end-stage renal disease and has not been studied in dialysis patients [see clinical pharmacology (12.3)] . no dosage adjustment of pifeltro is required in patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. pifeltro has not been studied in patients with severe hepatic impairment (child-pugh class c) [see clinical pharmacology (12.3)] .

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

a-s medication solutions - doravirine (unii: 913p6lk81m) (doravirine - unii:913p6lk81m) - pifeltro™ is indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients weighing at least 35 kg: - with no prior 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 with no history of treatment failure and no known substitutions associated with resistance to doravirine [see clinical studies (14)] . pifeltro is contraindicated when co-administered with drugs that are strong cytochrome p450 (cyp)3a enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of pifeltro [see warnings and precautions (5.1), drug interactions (7.1), and clinical pharmacology (12.3)] . these drugs include, but are not limited to, the following: - the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin - the androgen

European Union - English - EMA (European Medicines Agency)

merck sharp & dohme b.v. - doravirine, lamivudine, tenofovir disoproxil fumarate - hiv infections - antivirals for treatment of hiv infections, combinations - delstrigo is indicated for the treatment of adults infected with hiv 1 without past or present evidence of resistance to the nnrti class, lamivudine, or tenofovir.delstrigo is also indicated for the treatment of adolescents aged 12 years and older weighing at least 35 kg who are infected with hiv-1 without past or present evidence of resistance to the nnrti class, lamivudine, or tenofovir and who have experienced toxicities which preclude the use of other regimens that do not contain tenofovir disoproxil.

Singapore - English - HSA (Health Sciences Authority)

msd pharma (singapore) pte. ltd. - doravirine - tablet, film coated - doravirine 100.0mg

European Union - English - EMA (European Medicines Agency)

merck sharp & dohme b.v. - doravirine - hiv infections - antivirals for systemic use - pifeltro is indicated, in combination with other antiretroviral medicinal products, for the treatment of adults, and adolescents aged 12 years and older weighing at least 35 kg infected with hiv 1 without past or present evidence of resistance to the nnrti class.

Canada - English - Health Canada

merck canada inc - doravirine - tablet - 100mg - doravirine 100mg - nonnucleoside reverse transcriptase inhibitors