IDVYNSO Doravirine, Islatravir 100 mg; .25 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Doravirine and islatravir is used to treat human immunodeficiency virus (HIV) infection. Doravirine is in a class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Islatravir is in a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). The combination of doravirine and islatravir works by decreasing the amount of HIV in the body. Although the combination of doravirine and islatravir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses. Taking these medicati...
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII H0G9379FGK
Calcium carbonate is a white mineral powder used as a filler and buffering agent in medicines. It helps give tablets their bulk and size while neutralizing stomach acid in some formulations.
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A natural wax derived from a Brazilian palm tree, used as a coating and polish on tablets and capsules. It creates a smooth, shiny finish that protects the medicine and improves appearance.
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Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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Hypromellose 2910 is a plant-based thickening agent derived from cellulose. In medicines, it forms a protective coating on tablets or capsules and controls how quickly the drug dissolves and releases into your body.
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Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
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UNII A7ZHS2RJ34
A cellulose-derived polymer made by chemically modifying plant fiber. It acts as a film-former and enteric coating to protect medicine from stomach acid and control where it dissolves in the digestive tract.
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Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII XHX3C3X673
Triacetin is a clear, oily liquid made from glycerin and acetic acid. It works as a plasticizer and solvent in medicines, helping soften coatings and improve how liquids mix together in formulations.
13 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Idvynso 100 mg/1; .25 mgthis 00006-5092-01 | Merck | 30 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 8486975 ↗ | Drug substance | U-4527 | Aug 30, 2032 |
| US 7339053 ↗ | Drug substance | — | May 31, 2027 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Apr 20, 2031 |
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🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
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Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00006-5092-01 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (0006-5092-01) | 2026-04-23 | Active |
| 00006-5092-59 | 14 TABLET, FILM COATED in 1 BOTTLE (0006-5092-59) | 2026-04-23 | Active |
You're viewing the largest of 2 pack sizes for this product.
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🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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 ▾
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 )
2.1Recommended 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.
2.2Dosage 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 Cautions ▾
5 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 )
5.1Skin 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.
5.2Risk 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.
🤒 Adverse Reactions ▾
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 .
6.1Clinical 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, a…
🔄 Drug Interactions ▾
7 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 )
7.1Concomitant 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.
7.2Effects 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 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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.
8.2Lactation 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) ] .
8.4Pediatric Use The safety and effectiveness of IDVYNSO have not been established in pediatric patien…
🤰 Pregnancy ▾
8.1Pregnancy 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 ▾
8.4Pediatric 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 ▾
8.5Geriatric 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 ▾
10 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action IDVYNSO is a fixed-dose combination of the antiretroviral drugs doravirine and islatravir [see Microbiology (12.4) ].
12.2Pharmacodynamics In a Phase 2 trial evaluating doravirine over a dose range of 0.25 to 2 times the recommended dose of doravirine (in combination with FTC and TDF), in participants with no antiretroviral treatment history, no exposure-response relationship for efficacy was identified for doravirine. In a Phase 2 trial evaluating islatravir over a dose range of 1 to 9 times the recommended dose of islatravir (in combination with doravirine and 3TC), in participants with no antiretroviral treatment history, no exposure-response relationship for efficacy was identified for islatravir.
Exposure-response modeling of data from Phase 2 and Phase 3 studies, including studies evaluating islatravir at daily doses from 0.25 mg to 2.25 mg (9 times the recommended daily dosage), demonstrated a relationship between islatravir exposure and decreases in lymphocytes and CD4+ T-cells. No clinically meaningful reduction in lymphocytes or CD4+ T-cells was observed at exposures associated with the recommended daily islatravir dose of 0.25 mg. Cardiac Electrophysiology At 12 times the maximum recommended doravirine dose, clinically significant QTc interval prolongation was not observed.
At 960 times the maximum recommended islatravir dose, clinically significant QTc interval prolongation was not observed.
12.3Pharmacokinetics Single-dose administration of one IDVYNSO tablet to healthy adult participants under fasted conditions provided comparable exposures of doravirine and islatravir to administration of a doravirine tablet (100 mg) plus an islatravir capsule (0.25 mg). No clinically significant difference in pharmacokinetics was observed between healthy participants and participants living with HIV-1. Plasma pharmacokinetic properties of the components of IDVYNSO are provided in Table 4 .
Table 4: Pharmacokinetic Properties of the Components of IDVYNSO Parameter Doravirine Islatravir Abbreviations: AUC=area under the time concentration curve; C max =maximum concentration; C 24 =concentration at 24 hours; T max =time to C max ; Vd/F=apparent volume of distribution; t 1/2 =half-life; CL/F=apparent clearance; ADA= adenosine deaminase General Steady State Exposure AUC 0-24 Reported as geometric mean (%CV: geometric coefficient of variation) 37.8 (29) μM•hr Doravirine 100 mg once daily to participants living with HIV 31.4 (15.3) nM•hr IDVYNSO once daily to participants living with HIV C max 2.26 (19) μM 3.45 (5.5) nM C 24 0.930 (63) μM 0.779 (22.3) nM Time to Steady State (d) 2 7 Accumulation Ratio 1.2 to 1.4
1.8Absorption Absolute Bioavailability 64% unknown T max (hr) Under fasted conditions 4 1 Effect of Food Geometric mean ratio [high-fat meal/fasting] and (90% confidence interval) for pharmacokinetic parameters. High fat meal is approximately 1000 kcal, 50% fat. The effect of food is not clinically relevant.
AUC Ratio 1.17 (1.10, 1.24) 1.13 (1.07, 1.19) C max Ratio 1.18 (1.11, 1.25) 0.80 (0.71, 0.91) Distribution V d /F (L) Based on population pharmacokinetic modeling and reported as the population mean (%CV) 162 (32.6) 264 Plasma protein binding 76% 3% Elimination t 1/2 (h) 15 21 Reported as the effective half-life of islatravir. The terminal half-life of islatravir is approximately 230 hours. The terminal half-life of intracellular ISL-TP is approximately 186 hours.
CL/F (L/hr) 6.34 (35.2) 27.7 (15.1) Metabolism Primary Pathway(s) CYP3A Oxidative deamination by ADA Excretion Major route of elimination Metabolism Metabolism Urine (unchanged) 6% 32% Biliary/Fecal (unchanged) Minor Minor Specific Populations No clinically significant differences in the pharmacokinetics of doravirine were observed based on age (18 to 78 years), sex, race/ethnicity (White, Black or African American, Asian, and other), mild to severe renal impairment (creatinine clearance (CLcr) > 15 mL/min), an…
🧬 Mechanism of Action ▾
12.1Mechanism of Action IDVYNSO is a fixed-dose combination of the antiretroviral drugs doravirine and islatravir [see Microbiology (12.4) ].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 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].
📋 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
💬 Information for Patients ▾
17 PATIENT COUNSELING 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) ] .