European Union - English - EMA (European Medicines Agency)

viiv healthcare b.v. - cabotegavir sodium, cabotegravir - hiv infections - antivirals for systemic use - vocabria tablets are indicated in combination with rilpivirine tablets for the short-term treatment of human immunodeficiency virus type 1 (hiv-1) infection in adults who are virologically suppressed (hiv-1 rna

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

merck sharp & dohme (australia) pty ltd - raltegravir potassium, quantity: 651.6 mg (equivalent: raltegravir, qty 600 mg) - tablet, film coated - excipient ingredients: hypromellose; croscarmellose sodium; magnesium stearate; microcrystalline cellulose; carnauba wax; titanium dioxide; lactose monohydrate; triacetin; iron oxide yellow; iron oxide black - isentress or isentress hd, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection in adults, adolescents and children from the age of 2 years.,this indication is based on analyses of plasma hiv-1 rna levels in controlled studies of isentress (see section 5.1).,the indication in paediatric patients is based on the evaluation of safety, tolerability, pharmacokinetic parameters and efficacy of isentress through at least 24 weeks in a multicentre, open label, noncomparative study in hiv-1 infected, treatment-experienced children and adolescents 2 to 18 years of age.,the use of other active antiretroviral agents in combination with isentress is associated with a greater likelihood of treatment response (see section 5.1).,there are no study results demonstrating the effect of isentress on clinical progression of hiv-1 infection.

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

merck sharp & dohme (australia) pty ltd - raltegravir potassium, quantity: 434.4 mg (equivalent: raltegravir, qty 400 mg) - tablet, film coated - excipient ingredients: microcrystalline cellulose; lactose monohydrate; calcium hydrogen phosphate; hypromellose; poloxamer; sodium stearylfumarate; magnesium stearate; butylated hydroxytoluene; titanium dioxide; purified talc; iron oxide red; polyvinyl alcohol; macrogol 3350; iron oxide black - isentress or isentress hd, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection in adults, adolescents and children from the age of 2 years.,this indication is based on analyses of plasma hiv-1 rna levels in controlled studies of isentress (see section 5.1).,the indication in paediatric patients is based on the evaluation of safety, tolerability, pharmacokinetic parameters and efficacy of isentress through at least 24 weeks in a multicentre, open label, noncomparative study in hiv-1 infected, treatment-experienced children and adolescents 2 to 18 years of age.,the use of other active antiretroviral agents in combination with isentress is associated with a greater likelihood of treatment response (see section 5.1).,there are no study results demonstrating the effect of isentress on clinical progression of hiv-1 infection.

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

merck sharp & dohme (australia) pty ltd - raltegravir potassium, quantity: 108.6 mg (equivalent: raltegravir, qty 100 mg) - tablet, chewable - excipient ingredients: hyprolose; sucralose; saccharin sodium; sodium citrate dihydrate; mannitol; sodium stearylfumarate; magnesium stearate; iron oxide yellow; crospovidone; iron oxide red; purified water; strong ammonia solution; ethylcellulose; oleic acid; medium chain triglycerides; sorbitol; ammonium glycyrrhizinate; fructose; flavour; hypromellose; macrogol 400 - isentress or isentress hd, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection in adults, adolescents and children from the age of 2 years.,this indication is based on analyses of plasma hiv-1 rna levels in controlled studies of isentress (see section 5.1).,the indication in paediatric patients is based on the evaluation of safety, tolerability, pharmacokinetic parameters and efficacy of isentress through at least 24 weeks in a multicentre, open label, noncomparative study in hiv-1 infected, treatment-experienced children and adolescents 2 to 18 years of age.,the use of other active antiretroviral agents in combination with isentress is associated with a greater likelihood of treatment response (see section 5.1).,there are no study results demonstrating the effect of isentress on clinical progression of hiv-1 infection.

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

merck sharp & dohme (australia) pty ltd - raltegravir potassium, quantity: 27.16 mg (equivalent: raltegravir, qty 25 mg) - tablet, chewable - excipient ingredients: hyprolose; sucralose; saccharin sodium; sodium citrate dihydrate; mannitol; sodium stearylfumarate; magnesium stearate; iron oxide yellow; crospovidone; purified water; strong ammonia solution; ethylcellulose; oleic acid; medium chain triglycerides; sorbitol; ammonium glycyrrhizinate; fructose; flavour; hypromellose; macrogol 400 - isentress or isentress hd, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (hiv-1) infection in adults, adolescents and children from the age of 2 years.,this indication is based on analyses of plasma hiv-1 rna levels in controlled studies of isentress (see section 5.1).,the indication in paediatric patients is based on the evaluation of safety, tolerability, pharmacokinetic parameters and efficacy of isentress through at least 24 weeks in a multicentre, open label, noncomparative study in hiv-1 infected, treatment-experienced children and adolescents 2 to 18 years of age.,the use of other active antiretroviral agents in combination with isentress is associated with a greater likelihood of treatment response (see section 5.1).,there are no study results demonstrating the effect of isentress on clinical progression of hiv-1 infection.

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

viiv healthcare pty ltd - cabotegravir, quantity: 30 mg (equivalent: cabotegravir sodium, qty mg) - tablet, film coated - excipient ingredients: titanium dioxide; magnesium stearate; hypromellose; lactose monohydrate; microcrystalline cellulose; sodium starch glycollate type a; macrogol 3350 - vocabria tablets are indicated in combination with rilpivirine tablets for the short-term treatment of human immunodeficiency virus type 1 (hiv-1) infection in adults who are virologically suppressed (hiv-1 rna <50 copies/ml) and have no known or suspected resistance to either cabotegravir or rilpivirine (see sections 4.2 dose and method of administration and 5.1 pharmacodynamic properties, clinical trials) for: ? oral lead in to assess tolerability of cabotegravir prior to administration of cabotegravir prolonged-release suspension for injection plus rilpivirine prolonged-release suspension for injection. ? oral therapy for adults who will miss planned dosing with cabotegravir prolonged-release suspension for injection.

New Zealand - English - Medsafe (Medicines Safety Authority)

merck sharp & dohme (new zealand) limited - raltegravir potassium 434.4mg equivalent to raltegravir 400 mg;   - film coated tablet - 400 mg - active: raltegravir potassium 434.4mg equivalent to raltegravir 400 mg   excipient: calcium hydrogen phosphate hypromellose lactose monohydrate magnesium stearate microcrystalline cellulose opadry pink poloxamer 407 sodium stearyl fumarate - isentress is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv-1) infection.

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

viiv healthcare company - cabotegravir sodium (unii: 3l12pt535m) (cabotegravir - unii:hmh0132z1q) -       vocabria is indicated in combination with edurant (rilpivirine) tablets for short-term treatment of hiv-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg who are virologically suppressed (hiv-1 rna <50 copies/ml) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, for use as [see microbiology (12.4), clinical studies (14.1)] : vocabria is indicated in at-risk adults and adolescents weighing at least 35 kg for short-term pre-exposure prophylaxis (prep) to reduce the risk of sexually acquired hiv-1 infection. individuals must have a negative hiv-1 test prior to initiating vocabria for hiv-1 prep. vocabria may be used as [see dosage and administration (2.2), contraindications (4), warnings and precautions (5.1), clinical studies (14.2)] : treatment of hiv-1 infection vocabria is contraindicated in patients: prior to initiation of vocabria, note that use of cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) with rifabutin is contraindicated. since vocabria is taken in combination with edurant tablets, the prescribing information for edurant should be consulted for additional contraindications. hiv-1 pre-exposure prophylaxis vocabria is contraindicated in individuals: pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to vocabria during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary there are insufficient human data on the use of vocabria during pregnancy to adequately assess a drug-associated risk of birth defects and miscarriage. while there are insufficient human data to assess the risk of neural tube defects (ntds) with exposure to vocabria during pregnancy, ntds were associated with dolutegravir, another integrase inhibitor. discuss the benefit-risk of using vocabria with individuals of childbearing potential or during pregnancy. the apr has been established to monitor for birth defects following prenatal exposure to antiretrovirals. the rate of miscarriage is not reported in the apr. the background risk for major birth defects and miscarriage for the indicated population is unknown. the background rate for major birth defects in a united states (u.s.) reference population of the metropolitan atlanta congenital defects program (macdp) is 2.7%. the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15% to 20%. the apr uses the macdp as the u.s. reference population for birth defects in the general population. the macdp evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at <20 weeks’ gestation. in animal reproduction studies with oral cabotegravir, a delay in the onset of parturition and increased stillbirths and neonatal deaths were observed in a rat pre- and postnatal development study at >28 times the exposure at the recommended human dose (rhd). no evidence of adverse developmental outcomes was observed with oral cabotegravir in rats or rabbits (>28 times or similar to the exposure at the rhd, respectively) given during organogenesis (see data) . data human data: data from a birth outcome surveillance study in botswana showed that dolutegravir, another integrase inhibitor, was associated with increased risk of ntds when administered at the time of conception and in early pregnancy. data from clinical trials are insufficient to address this risk with cabotegravir. animal data: cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from 15 days before cohabitation, during cohabitation, and from gestation days 0 to 17. there were no effects on fetal viability when fetuses were delivered by caesarean, although a minor decrease in fetal body weight was observed at 1,000 mg/kg/day (>28 times the exposure in humans at the rhd). no drug-related fetal toxicities were observed at 5 mg/kg/day (approximately 13 times the exposure in humans at the rhd), and no drug-related fetal malformations were observed at any dose. cabotegravir was administered orally to pregnant rabbits at 0, 30, 500, or 2,000 mg/kg/day from gestation days 7 to 19. no drug-related fetal toxicities were observed at 2,000 mg/kg/day (approximately 0.7 times the exposure in humans at the rhd). in a rat pre- and postnatal development study, cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from gestation day 6 to lactation day 21. a delay in the onset of parturition and increases in the number of stillbirths and neonatal deaths by lactation day 4 were observed at 1,000 mg/kg/day (>28 times the exposure in humans at the rhd); there were no alterations to growth and development of surviving offspring. in a cross-fostering study, similar incidences of stillbirths and early postnatal deaths were observed when rat pups born to cabotegravir-treated mothers were nursed from birth by control mothers. there was no effect on neonatal survival of control pups nursed from birth by cabotegravir-treated mothers. a lower dose of 5 mg/kg/day (13 times the exposure at the rhd) was not associated with delayed parturition or neonatal mortality in rats. studies in pregnant rats showed that cabotegravir crosses the placenta and can be detected in fetal tissue. risk summary there are no data on the presence of cabotegravir in human milk, the effects on the breastfed infant, or the effects on milk production. cabotegravir is present in animal milk (see data) . when a drug is present in animal milk, it is likely that the drug will be present in human milk. potential risks of breastfeeding include: (1) hiv‑1 transmission (in hiv-1–negative infants), (2) developing viral resistance (in hiv-1–positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults. in hiv-1–uninfected mothers, the developmental and health benefits of breastfeeding and the mother’s clinical need for vocabria for hiv-1 prep should be considered along with any potential adverse reactions on the breastfed child from vocabria and the risk of hiv-1 acquisition due to nonadherence and subsequent mother to child transmission. mothers should not breastfeed if acute hiv-1 infection is suspected because of the risk of hiv-1 transmission to the infant. data animal lactation studies with cabotegravir have not been conducted. however, cabotegravir was detected in the plasma of nursing pups on lactation day 10 in the rat pre- and postnatal development study. treatment of hiv-1 infection the safety and effectiveness of vocabria have been established in adolescents aged 12 to younger than 18 years and weighing at least 35 kg, which is supported by the following: mocha trial the safety, tolerability, and pharmacokinetics of oral and injectable cabotegravir and oral and injectable rilpivirine are being assessed in an ongoing phase 1/2 multicenter, open-label, non-comparative study, mocha (impaact 2017). data are available from the week 16 interim analysis from mocha. the primary objective at week 16 was to confirm the use of the adult dose, through the evaluation of safety and pharmacokinetics, for oral and injectable cabotegravir and injectable rilpivirine in 23 hiv-1–infected virologically suppressed adolescents (aged 12 to younger than 18 years and weighing at least 35 kg) receiving background antiretroviral therapy. a total of 8 hiv-1–infected pediatric participants 12 years of age and older and weighing at least 35 kg and receiving background antiretroviral therapy received oral cabotegravir. the safety of vocabria in adolescents is expected to be similar to adults, as there was no clinically significant difference in drug exposure [see adverse reactions (6.1), clinical pharmacology (12.3)] . please refer to the cabenuva prescribing information for additional information. the safety, efficacy, and pharmacokinetics of vocabria have not been established in pediatric patients younger than 12 years of age or weighing <35 kg. hiv-1 pre-exposure prophylaxis the safety and effectiveness of vocabria for hiv-1 prep in at-risk adolescents weighing at least 35 kg is supported by data from 2 adequate and well-controlled trials of vocabria for hiv-1 prep in adults with additional safety and pharmacokinetic data from studies in hiv-1–infected adults who were administered cabenuva and in hiv-1–infected pediatric subjects who were administered separate components of cabenuva in addition to their current antiretroviral therapy [see dosage and administration (2.2), adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2)] . apretude for hiv-1 prep is being evaluated in 2 open-label multicenter clinical trials in adolescent individuals. fifty-nine adolescents have been enrolled. of these, 54 adolescent participants received one or more injections after receiving vocabria. in adolescents receiving vocabria and apretude for hiv-1 prep, the safety data were comparable to the safety data reported in adults receiving apretude for hiv-1 prep. while using apretude, hiv-1 testing should be conducted prior to initiating apretude (with or without an oral lead-in with oral cabotegravir) and prior to each injection of apretude. adolescents may benefit from more frequent visits and counseling to support adherence to the dosing schedule [see dosage and administration (2.2), warnings and precautions (5.1)]. the safety, efficacy, and pharmacokinetics of vocabria in pediatric participants younger than 12 years of age or weighing <35 kg have not been established. clinical trials of vocabria did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. in general, caution should be exercised in administration of vocabria in elderly patients, reflecting 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 vocabria is necessary for patients with mild to moderate (creatinine clearance equal to 30 ml/min to <90 ml/min) or severe renal impairment (creatinine clearance <30 ml/min) [see clinical pharmacology (12.3)] . the effect of end-stage renal disease (creatinine clearance <15 ml/min) on the pharmacokinetics of cabotegravir is unknown. as cabotegravir is >99% protein bound, dialysis is not expected to alter exposures of cabotegravir. since vocabria is taken in combination with edurant for the treatment of hiv-1 infection, the prescribing information for edurant should be consulted for additional recommendations in patients with severe impairment or end-stage renal disease. no dosage adjustment of vocabria is necessary for patients with mild or moderate hepatic impairment (child-pugh a or b). the effect of severe hepatic impairment (child-pugh c) on the pharmacokinetics of cabotegravir is unknown [see clinical pharmacology (12.3)] .

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

viiv healthcare pty ltd - cabotegravir sodium, quantity: 31.62 mg (equivalent: cabotegravir, qty 30 mg) - tablet, film coated - excipient ingredients: lactose monohydrate; microcrystalline cellulose; hypromellose; sodium starch glycollate type a; magnesium stearate; titanium dioxide; macrogol 3350 - apretude is indicated in at-risk adults and adolescents (at least 12 years of age) and weighing at least 35 kg for pre-exposure prophylaxis (prep) to reduce the risk of sexually acquired hiv-1 infection.,apretude tablets may be used as an oral lead-in to assess tolerability of cabotegravir prior to administration of cabotegravir injections or as short-term oral prep in individuals who will miss planned dosing with cabotegravir injections.,individuals must have a documented negative hiv-1 test prior to initiating apretude for hiv-1 prep.

Canada - English - Health Canada

merck canada inc - raltegravir (raltegravir potassium) - tablet - 400mg - raltegravir (raltegravir potassium) 400mg - hiv integrase inhibitors