Idvynso (Doravirine, Islatravir): Uses, Dosage, Side Effects & Warnings

Q: Who makes Idvynso?

Idvynso is listed by 1 labeler in the FDA NDC directory, including Merck Sharp & Dohme LLC.

Uses

1 INDICATIONS AND USAGE IDVYNSO™ is indicated as a complete two-drug regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine [see Microbiology (12.4) and Clinical Studies (14) ]. IDVYNSO is a two-drug combination of doravirine, a HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI), and islatravir, a nucleoside analog reverse transcriptase inhibitor (NRTI), and is indicated as a complete regimen for the treatment of HIV-1 infection in adults 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 virologic treatment failure and no known substitutions associated with resistance to doravirine. ( 1 )

Dosage and administration

Recommended dosage: One tablet taken orally once daily with or without food in adults. ( 2.1 ) Dosage adjustment with rifabutin: Take one tablet of IDVYNSO once daily, followed by one tablet of doravirine (PIFELTRO) 100 mg approximately 12 hours after the dose of IDVYNSO. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of IDVYNSO is one tablet taken orally once daily with or without food [see Clinical Pharmacology (12.3) ] . One tablet of IDVYNSO contains 100 mg doravirine and 0.25 mg islatravir. 2.2 Dosage Adjustment with Rifabutin If IDVYNSO is co-administered with rifabutin, take one tablet of IDVYNSO once daily as recommended, followed by one tablet of doravirine (PIFELTRO) 100 mg approximately 12 hours after the dose of IDVYNSO for the duration of rifabutin co-administration [see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ].

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS IDVYNSO film-coated tablets are pink, oval-shaped, and debossed with 772 on one side and are plain on the other side. Each tablet contains 100 mg doravirine and 0.25 mg islatravir. Tablets: 100 mg doravirine and 0.25 mg islatravir. ( 3 )

Contraindications

4 CONTRAINDICATIONS IDVYNSO 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 IDVYNSO [see Warnings and Precautions (5.2) , Drug Interactions (7.2) , and Clinical Pharmacology (12.3) ] . lamivudine (3TC) or emtricitabine (FTC) as significant decreases in islatravir-triphosphate (ISL-TP) concentrations may occur, which may decrease the effectiveness of IDVYNSO [see Warnings and Precautions (5.2) , Drug Interactions (7.2) and Clinical Pharmacology (12.3) ] . IDVYNSO 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 IDVYNSO. ( 4 ) IDVYNSO is contraindicated when co-administered with lamivudine (3TC) or emtricitabine (FTC), which are deoxycytidine kinase (dCK) substrates, as a decrease in islatravir-triphosphate (ISL-TP) levels may occur, which may decrease the effectiveness of IDVYNSO. ( 4 )

Warnings and precautions

Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), have been reported. Discontinue IDVYNSO immediately if signs or symptoms of severe skin reactions develop. ( 5.1 ) 5.1 Skin and Hypersensitivity Reactions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during postmarketing experience with doravirine-containing regimens [see Adverse Reactions (6.2) ] . In addition, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) was reported with IDVYNSO in a clinical trial [see Adverse Reactions (6.1) ] . Discontinue IDVYNSO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement, a progressive severe rash, or a rash with constitutional symptoms, eosinophilia, lymphadenopathy, or other organ involvement develops. Clinical status should be closely monitored, and appropriate therapy should be initiated. 5.2 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions The concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to [see Dosage and Administration (2.2) , Contraindications (4) , Drug Interactions (7.2) , and Clinical Pharmacology (12.3) ]: Loss of therapeutic effect of IDVYNSO and possible development of resistance. Possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO . See Table 3 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during IDVYNSO therapy, review concomitant medications during IDVYNSO therapy, and monitor for adverse reactions.

Side effects

The following serious adverse reactions are described in greater detail in other sections of the labeling: Skin and Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Most common adverse reactions (incidence greater than or equal to 2%, all grades): diarrhea, dizziness, fatigue, abdominal distension, headache, and weight increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Virologically-Suppressed Adults Living with HIV-1 Who Switched to IDVYNSO The safety assessment of IDVYNSO in virologically-suppressed (HIV-1 RNA less than 50 copies/mL) participants living with HIV was based on Week 48 data from two Phase 3, randomized trials, Trial 051 and Trial 052. A total of 708 participants received once-daily IDVYNSO [see Clinical Studies (14) ] . In Trial 051, an open-label trial with 551 participants, 366 participants were switched to IDVYNSO and 185 participants continued their baseline antiretroviral therapy (ART). By Week 48, 0.5% in the IDVYNSO group and 2% in the baseline ART group had adverse events leading to discontinuation of study medication. In Trial 052, a double-blinded trial with 513 participants, 342 participants were switched to IDVYNSO and 171 participants continued on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). By Week 48, 3% in the IDVYNSO group and 2% in the BIC/FTC/TAF group had adverse events leading to discontinuation of study medication. Among participants who received IDVYNSO and experienced at least one adverse event in Trial 051 or Trial 052, 88% experienced only adverse events that were mild (Grade 1) or moderate (Grade 2). The most common adverse reactions (all grades) reported in greater than or equal to 2% of participants in any treatment group from Trial 051 and Trial 052 through Week 48 are presented in Table 1 . Table 1: Adverse Reactions Frequencies based on all adverse events attributed to study drugs by the investigator (All Grades) Reported in ≥2% of Participants in Any Treatment Group in Trials 051 and 052 in HIV-1 Virologically-Suppressed Adults (Week 48) Adverse Reactions Trial 051 Trial 052 IDVYNSO N=366 Baseline ART N=185 IDVYNSO N=342 BIC/FTC/TAF N=171 Diarrhea 3% 0 1% 1% Dizziness 2% 1% 1% 0 Fatigue Fatigue includes fatigue and asthenia. 2% 1% 1% 1% Abdominal distension 2% 0 1% 0 Headache 2% 1% 1% 0 Weight increased The mean change in weight from baseline at Week 48 was 0.94 kg in the IDVYNSO group vs. -0.15 kg in the baseline ART group in Trial 051, and -0.03 kg in the IDVYNSO group vs. 0.28 kg in the BIC/FTC/TAF group in Trial 052. 2% 4 of the 6 participants with adverse reactions of weight increased switched from a baseline ART regimen containing efavirenz and/or tenofovir disoproxil fumarate in Trial 051. 0 <1% 0 A single case of severe immune thrombocytopenia (platelet count nadir of 2 x10 9 /L) characterized by abrupt onset of subcutaneous hematoma, petechiae, and hematuria was reported in a participant 32 days after initiating IDVYNSO in Trial 052. This serious adverse reaction resolved with discontinuation of IDVYNSO, in conjunction with treatments including corticosteroids and IVIG. Among all participants in Trial 051 and Trial 052, there were no patterns of platelet decreases over time with IDVYNSO and no differences between treatment arms in mean change from baseline in platelet count. Less Common Adverse Reactions The following select adverse reactions were observed in less than 2% of participants administered IDVYNSO: Gastrointestinal disorders : Abdominal pain (includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort), flatulence, nausea Psychiatric disorders: Abnormal dreams, Insomnia (includes insomnia, initial insomnia, middle insomnia and terminal insomnia) Skin and Subcutaneous Tissue Disorders : Pruritus, Rash (includes rash, rash papular, rash maculo-papular and rash pruritic) In an ongoing clinical trial, a participant developed Grade 4 DRESS syndrome ten weeks after starting IDVYNSO that was characterized by a diffuse pruritic maculopapular rash covering 60% of the body, lymphadenopathy, eosinophilia (peak 20,000 cells/µL), and an episode of hypotension. This serious adverse reaction resolved with discontinuation of IDVYNSO [see Warnings and Precautions (5.1) ]. Laboratory Abnormalities Hepatic laboratory data from Trials 051 and Trial 052 are presented in Table 2 . The hepatic laboratory abnormalities were generally asymptomatic and resolved without discontinuation of IDVYNSO. Table 2: Hepatic Laboratory Abnormalities (Grades 2-4) Worsened from Baseline Reported in Adults Receiving IDVYNSO in Trial 051 and Trial 052 Laboratory Parameter Trial 051 Trial 052 IDVYNSO N=366 Baseline ART N=185 IDVYNSO N=340 BIC/FTC/TAF N=171 Alanine Aminotransferase Grade 2: 2.5 - <5.0 x ULN 2% 1% 1% 1% Grade 3: 5.0 - <10.0 x ULN <1% 0 0 0 Grade 4: ≥10.0 x ULN 0 1% 1% 0 Aspartate Aminotransferase Grade 2: 2.5 - <5.0 x ULN 2% 2% 2% 1% Grade 3: 5.0 - <10.0 x ULN 0 0 <1% 0 Grade 4: ≥10.0 x ULN 0 1% 1% 1% Total Bilirubin Grade 2: 1.6 - <2.6 x ULN 1% 1% 1% 1% Grade 3: 2.6 - <5.0 x ULN <1% 0 1% 0 Grade 4: ≥5.0 x ULN 0 0 0 0 Across the clinical development program for the combination of doravirine and islatravir, there were 3 participants with elevations in alanine aminotransferase and/or aspartate aminotransferase greater than 10X ULN attributed to study drug that resolved with discontinuation of treatment.

Drug interactions

Because IDVYNSO is a complete regimen, co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. ( 7.1 ) Consult the full prescribing information prior to and during treatment for important potential drug-drug interactions. ( 2.2 , 4 , 5.2 , 7 , 12.3 ) 7.1 Concomitant Use with Other Antiretroviral Medications Because IDVYNSO is a complete regimen for the treatment of HIV-1 infection, co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. 7.2 Effects of Other Drugs on IDVYNSO Doravirine Co-administration of IDVYNSO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce the efficacy of IDVYNSO [see Contraindications (4) , Warnings and Precautions (5.2) , and Clinical Pharmacology (12.3) ] . Co-administration of IDVYNSO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. Islatravir Islatravir requires phosphorylation by cellular kinases to form the pharmacologically active ISL-TP. Co-administration of IDVYNSO and drugs that are substrates of dCK (e.g., certain nucleoside antiviral agents and nucleoside antimetabolites) may result in a decrease in ISL-TP concentrations and may reduce the therapeutic effect of islatravir [see Contraindications (4) , Warnings and Precautions (5.2) , and Clinical Pharmacology (12.3) ] . Islatravir is subject to ADA-mediated metabolism (approximately 53%). Co-administration of IDVYNSO and drugs that are ADA inhibitors (e.g., pentostatin) may result in increased plasma concentrations of islatravir and may increase the risk of adverse reactions [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . The drug interactions described in Table 3 are based on studies conducted with IDVYNSO, its components, or are predicted drug interactions that may occur with IDVYNSO. Table 3: Drug Interactions with IDVYNSO This table is not all inclusive. Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comment ↑ = increase, ↓ = decrease Strong CYP3A Inducers ↓ doravirine Co-administration with strong CYP3A inducers is contraindicated At least a 4-week cessation period is recommended prior to initiation of IDVYNSO. Moderate CYP3A Inducers ↓ doravirine If IDVYNSO is co-administered with rifabutin Interactions were evaluated in clinical studies. All other drug-drug interactions are predicted. , one tablet of doravirine (PIFELTRO) should be taken approximately 12 hours after the dose of IDVYNSO [see Dosage and Administration (2.2) ] . Co-administration with other moderate CYP3A inducers is not recommended. dCK Substrates May include other nucleoside drugs Anti-virals lamivudine emtricitabine ↓ ISL-TP Co-administration is contraindicated with lamivudine or emtricitabine. Nucleoside Antimetabolites cladribine clofarabine cytarabine fludarabine gemcitabine ↓ ISL-TP Co-administration with these nucleoside antimetabolites is not recommended as dCK substrates may cause a decrease in the intracellular concentration of ISL-TP. ADA Inhibitors pentostatin ↑ islatravir Co-administration with pentostatin is not recommended as it may cause an increase in plasma concentrations of islatravir.

Use in specific populations

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to IDVYNSO 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 IDVYNSO during pregnancy to inform a drug-associated risk of birth defects and miscarriage. In animal reproduction studies, no developmental effects were observed when the components of IDVYNSO were administered separately at exposures (AUC) at least 8 (doravirine) and 500 (islatravir) times the exposure at the recommended human dose (RHD) of these components in IDVYNSO (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 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. Islatravir Islatravir was administered orally to pregnant rabbits (up to 10 mg/kg/day on GD 7 to 20) and rats (up to 50 mg/kg/day on GD 6 to 20 and separately up to 10 mg/kg 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 500 times (rats) and 1300 times (rabbits) the exposure in humans at the RHD. In rats, islatravir was transferred to the fetus through the placenta in rats, with fetal plasma concentrations of up to 88% that of maternal concentrations observed on GD 20. 8.2 Lactation Risk Summary It is unknown whether IDVYNSO or any of the components of IDVYNSO 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, while islatravir was detected in the plasma of nursing pups from lactating rats administered islatravir ( see Data ). Potential risks of breastfeeding include (1) HIV-1 transmission (in infants without HIV-1), (2) developing viral resistance (in infants with HIV-1), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. Data Doravirine: Doravirine was excreted into the milk of lactating rats following oral administration (450 mg/kg/day) from GD 6 to Lactation Day (LD) 14, with milk concentrations approximately 1.5 times that of maternal plasma concentrations observed 2 hours post dose on LD 14. Islatravir: Islatravir was detected in the plasma of nursing pups (LD 10) from lactating rats following oral administration (10 mg/kg) from GD 6 to LD 10, with concentrations 0.1% and 1.5% the maternal plasma concentrations observed 1 and 3 hours post dose on LD 10, respectively [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The safety and effectiveness of IDVYNSO have not been established in pediatric patients less than 18 years of age [see Clinical Pharmacology (12.3) ]. 8.5 Geriatric Use Clinical trials in virologically-suppressed participants who received IDVYNSO (Trial 051 and Trial 052) included 81 (11%) participants aged 65 years and older, including 10 (1%) aged 75 years and older [see Clinical Studies (14) ] . No overall differences in safety or effectiveness were observed between these participants and younger participants, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Renal Impairment No dosage adjustment of IDVYNSO is required in patients with eGFR ≥30 mL/min/1.73 m 2 . IDVYNSO is not recommended in patients with eGFR <30 mL/min/1.73 m 2 . IDVYNSO has not been studied in participants undergoing dialysis [see Clinical Pharmacology (12.3) ] . 8.7 Hepatic Impairment No dosage adjustment of IDVYNSO is recommended in patients with mild or moderate hepatic impairment (Child-Pugh Class A or B). IDVYNSO has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and therefore is not recommended in these patients [see Clinical Pharmacology (12.3) ] . 8.8 HBV Co-Infection IDVYNSO does not have activity against hepatitis B virus (HBV). Patients with HBV coinfection who switch to IDVYNSO from an antiretroviral regimen with activity against HBV, and patients on IDVYNSO who are newly diagnosed with HBV coinfection, should be closely monitored and specific anti-HBV therapy should be considered, as clinically appropriate.

Pregnancy

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to IDVYNSO 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 IDVYNSO during pregnancy to inform a drug-associated risk of birth defects and miscarriage. In animal reproduction studies, no developmental effects were observed when the components of IDVYNSO were administered separately at exposures (AUC) at least 8 (doravirine) and 500 (islatravir) times the exposure at the recommended human dose (RHD) of these components in IDVYNSO (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 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. Islatravir Islatravir was administered orally to pregnant rabbits (up to 10 mg/kg/day on GD 7 to 20) and rats (up to 50 mg/kg/day on GD 6 to 20 and separately up to 10 mg/kg 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 500 times (rats) and 1300 times (rabbits) the exposure in humans at the RHD. In rats, islatravir was transferred to the fetus through the placenta in rats, with fetal plasma concentrations of up to 88% that of maternal concentrations observed on GD 20.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of IDVYNSO have not been established in pediatric patients less than 18 years of age [see Clinical Pharmacology (12.3) ].

Geriatric use

8.5 Geriatric Use Clinical trials in virologically-suppressed participants who received IDVYNSO (Trial 051 and Trial 052) included 81 (11%) participants aged 65 years and older, including 10 (1%) aged 75 years and older [see Clinical Studies (14) ] . No overall differences in safety or effectiveness were observed between these participants and younger participants, but greater sensitivity of some older individuals cannot be ruled out.

Overdosage

No data are available on overdose of IDVYNSO and there is no known specific treatment for overdose with IDVYNSO. If overdose occurs, the person should be monitored, and standard supportive treatment applied as required.

Description

11 DESCRIPTION IDVYNSO is a fixed-dose combination tablet for oral administration containing doravirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI), and islatravir, an HIV-1 nucleoside analog reverse transcriptase inhibitor (NRTI). Each film-coated tablet contains 100 mg of doravirine and 0.25 mg islatravir as active ingredients. The tablets include the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The tablets are film coated with a coating material containing the following inactive ingredients: calcium carbonate, ferric oxide, ferrosoferric oxide, hypromellose, lactose monohydrate, and triacetin. The coated tablets are polished with carnauba wax. Doravirine The chemical name for doravirine is 3-chloro-5-[[1-[(4,5-dihydro-4-methyl-5-oxo-1 H -1,2,4-triazol-3-yl)methyl]-1,2-dihydro-2-oxo-4-(trifluoromethyl)-3-pyridinyl]oxy]benzonitrile. The molecular formula is C 17 H 11 ClF 3 N 5 O 3 and the molecular weight is 425.75. Doravirine is practically insoluble in water and has the following structural formula: Islatravir Islatravir is a crystalline monohydrate. The chemical name for islatravir is 2′-deoxy-4′- C -ethynyl-2-fluoroadenosine hydrate (1:1). The molecular formula is C 12 H 12 FN 5 O 3 .H 2 O and the molecular weight is 311.27. Islatravir monohydrate is very slightly soluble in water and has the following structural formula: Chemical Structure - Doravirine Chemical Structure - Islatravir

Mechanism of action

12.1 Mechanism of Action IDVYNSO is a fixed-dose combination of the antiretroviral drugs doravirine and islatravir [see Microbiology (12.4) ].

How supplied

Each IDVYNSO tablet contains 100 mg of doravirine and 0.25 mg of islatravir, is pink, oval-shaped and film-coated, and is debossed with 772 on one side and plain on the other side. Each bottle contains 30 tablets (NDC 0006-5092-01) with desiccant and is closed with a child-resistant closure. Store IDVYNSO in the original bottle. Keep the bottle tightly closed to protect from moisture. Do not remove the desiccant. Store IDVYNSO at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Patient information

Advise patients to read the FDA-approved patient labeling ( Patient Information ). Skin and Hypersensitivity Reactions Inform patients that severe skin reactions including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported with doravirine-containing regimens. Advise patients to immediately contact their healthcare provider if they develop a rash. Instruct patients to immediately stop taking IDVYNSO and seek medical attention if a painful rash with mucosal involvement or a rash with constitutional symptoms develops [see Warnings and Precautions (5.1) ] . Drug Interactions Inform patients that IDVYNSO may interact with certain other drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St. John’s wort [see Contraindications (4) , Warnings and Precautions (5.2) , and Drug Interactions (7.2) ]. For patients concomitantly receiving rifabutin, take one tablet of doravirine (PIFELTRO) 100 mg approximately 12 hours after the dose of IDVYNSO [see Dosage and Administration (2.2) ] . Dosing Instructions Advise patients to take IDVYNSO every day at a regularly scheduled time with or without food. Inform patients that it is important not to miss or skip doses as it can result in development of resistance. If patients forget to take IDVYNSO, tell patients to take the missed dose right away, unless it is almost time for the next dose [see Dosage and Administration (2.1) ] . Pregnancy Registry Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes in pregnant individuals exposed to IDVYNSO [see Use in Specific Populations (8.1) ]. Lactation Inform patients that the potential risks of breastfeeding include: (1) HIV-1 transmission (in infants without HIV-1), (2) developing viral resistance (in infants with HIV-1), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults [see Use in Specific Populations (8.2) ] .

Active ingredients

Doravirine in 1 product
Islatravir Anhydrous in 1 product

Idvynso NDC products (1)

NDC	Strength & form	Labeler	Type
0006-5092	Doravirine 100 mg/1; Islatravir Anhydrous .25 mg/1 Tablet, Film Coated	Merck Sharp & Dohme LLC	NDA

Frequently asked questions

What is Idvynso used for?

1 INDICATIONS AND USAGE IDVYNSO™ is indicated as a complete two-drug regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions…

What are the side effects of Idvynso?

The following serious adverse reactions are described in greater detail in other sections of the labeling: Skin and Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Most common adverse reactions (incidence greater than or equal to 2%, all grades): diarrhea, dizziness, fatigue, abdominal distension, headache, and weight increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS,… See the full label for the complete list.

Who makes Idvynso?

Idvynso is listed by 1 labeler in the FDA NDC directory, including Merck Sharp & Dohme LLC.