IDVYNSO

IDVYNSO is an FDA-registered drug product whose active ingredient is DORAVIRINE, ISLATRAVIR. It is labelled by Merck Sharp & Dohme LLC taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 0006-5092, application NDA216964, label effective 20260420. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing DORAVIRINE, ISLATRAVIR are most often described in connection with: antiretroviral regimen, indicated complete, hiv- infection, adults replace, rna less, history virologic, treatment failure, known substitutions. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

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 )

2 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) ].

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 )

6 ADVERSE REACTIONS 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. Of the 3 participants, one received doravirine 100 mg with islatravir 0.75 mg (three times the recommended dosage of islatravir) and had transient elevation in total bilirubin 2X ULN and Grade 1 (mild) nausea. The other 2 participants received IDVYNSO and were asymptomatic. 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing experience in patients receiving doravirine-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Doravirine: Hepatobiliary Disorders: hepatitis Investigations: hepatic enzyme increased Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)

2 FDA recall record(s) match this product name or manufacturer. A match means the firm or product name appears in the enforcement report; confirm lot numbers and dates against the official FDA notice before acting.

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 …

Who makes IDVYNSO?
Merck Sharp & Dohme LLC is the labeler of record for IDVYNSO.

What form does IDVYNSO come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is IDVYNSO prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has IDVYNSO been recalled?
2 FDA recall record(s) match this product name or manufacturer. Review the recall and safety notices section on this page and confirm lot numbers against the official FDA enforcement report.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.