Idvynso (doravirine/islatravir)
Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor Oral Tablet
Last reviewed · Source: First Databank (FDB) drug data
Overview
Doravirine and islatravir (doravirine/islatravir) is a fixed-combination antiretroviral agent containing doravirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) and islatravir, an HIV-1 nucleoside analog reverse transcriptase inhibitor (NRTI).
Doravirine and islatravir (doravirine/islatravir) is a fixed-dose combination antiretroviral agent containing doravirine and islatravir. Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Islatravir is a deoxyadenosine nucleoside analog reverse transcriptase inhibitor (NRTI).
Islatravir is phosphorylated by cellular kinases to form the pharmacologically active metabolite islatravir-triphosphate (ISL-TP). ISL-TP inhibits RT by blocking translocation after incorporation into viral DNA (immediate chain termination) and by preventing further nucleotide incorporation through structural changes in the viral DNA (delayed chain termination).
The absolute bioavailability of doravirine is 64% while the bioavailability of islatravir is unknown. The time to maximum absorption under the fasted state is 4 hours for doravirine and 1 hour for islatravir. Doravirine is 76% protein bound and islatravir is 3% protein bound.
The elimination half-lives of doravirine and islatravir are 15 and 21 hours, respectively. Doravirine is primarily metabolized by cytochrome P-450 (CYP) 3A, while islatravir is primarily metabolized by oxidative deamination by adenosine deaminase (ADA). Unchanged doravirine and islatravir accounted for 6% and 32% of the administered dose recovered in urine, respectively.
USES: This combination product is used by itself to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life.
This product contains 2 drugs: doravirine and islatravir. Doravirine belongs to a class of drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Islatravir belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs).
This medication is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor. Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor.
Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.
Generic name: doravirine/islatravir
Pronunciation: (DOR-a-VIR-een/is-LAT-ra-vir)
Drug class: Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor
Therapeutic class: Anti-Infective Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Idvynso
Indications
The following indications are listed for Idvynso:
- Hiv Infection
Also known as: Human Immunodeficiency Virus Disease, Human Immunodeficiency Virus Infection.
Dosing
The islatravir component of doravirine/islatravir is commercially available as islatravir anhydrous; dosage is expressed in terms of islatravir.
If doravirine/islatravir is co-administered with rifabutin, administer doravirine 100 mg/islatravir 0.25 mg (1 tablet) once daily, followed by doravirine 100 mg (1 tablet) approximately 12 hours later, for the duration of rifabutin co-administration.
No dosing information is available for this tab.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Idvynso 100 Mg-0.25 Mg Tablet | Maintenance | Take 1 tablet by oral route once daily. |
No dosing information is available for this tab.
Drug interactions
In vitro, doravirine does not inhibit major drug metabolizing enzymes, including cytochrome P-450 (CYP) 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.
Doravirine is not likely to be an inducer of CYP1A2, CYP2B6, or CYP3A4, and is not likely to be an inhibitor of organic anion transporter polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), bile salt export pump (BSEP), organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT) 2, multidrug and toxin extrusion transporter (MATE) 1, and MATE2K.
Islatravir is not a substrate for OAT1, OAT3, OCT2, MATE1, MATE2K, or P-gp. Islatravir is a substrate of breast cancer resistance protein (BCRP).
Islatravir does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, UGT1A1, UGT2B7, OATP1B1, OATP1B3, OCT1, OAT1, MATE1, MATE2K, P-gp, BSEP, multidrug resistance protein (MRP) 2, MRP3, or MRP 4. Islatravir inhibits OCT2, OAT3, and BCRP. Islatravir does not induce CYP3A4, CYP1A2, or CYP2B6, in vitro.
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Anti-Retrovirals/Atidarsagene Autotemcel
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells.
CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells.
DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1)
Anti-Retrovirals/Elivaldogene Autotemcel
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells.
CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells.
DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1)
Anti-Retrovirals/Etuvetidigene Autotemcel
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Etuvetidigene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating HIV-based lentiviral vector. Antiretrovirals may interfere with the manufacturing of the apheresed cells.
CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of etuvetidigene autotemcel.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Patients should not take antiretrovirals for at least one month prior to mobilization and until at least 7 days after etuvetidigene autotemcel infusion.(1) If a patient requires antiretroviral agents for HIV post-exposure prophylaxis, etuvetidigene autotemcel treatment should be delayed until HIV testing is negative at 6 months post-exposure.(1)
DISCUSSION: Antiretroviral medications may interfere with the manufacturing of etuvetidigene autotemcel therapy.(1)
Anti-Retrovirals/Lovotibeglogene Autotemcel
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells.
CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1)
DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1)
Anti-Retrovirals; Hydroxyurea/Betibeglogene Autotemcel
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1)
CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells.
DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1)
Doravirine/Strong Cyp3a4 Inducers
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Strong inducers of CYP3A4 are expected to increase the metabolism of doravirine.(1)
CLINICAL EFFECTS: Concurrent or recent use of strong inducers of CYP3A4 may result in decreased levels and effectiveness of doravirine.(3)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: Concurrent administration of strong inducers of CYP3A4 with doravirine is contraindicated. A washout period of 4 weeks for the CYP3A4 inducer is recommended prior to initiation of doravirine.(1)
DISCUSSION: Doravirine is metabolized by CYP3A4. Strong inducers of CYP3A4 are expected to reduce doravirine levels, which may lead to loss of response.(1) In a study in 10 subjects, rifampin (600 mg daily), a strong inducer of CYP3A4, decreased the area-under-curve (AUC), maximum concentration (Cmax), and 24 hour concentration (C24) of a single dose of doravirine (100 mg) by 88%, 57%, and 97% respectively.(1) Strong inducers of CYP3A4 include apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, oxcarbazepine, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(1)
Islatravir/Emtricitabine; Lamivudine
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Emtricitabine and lamivudine may inhibit the intracellular phosphorylation of islatravir by deoxycytidine kinase (dCK).(1)
CLINICAL EFFECTS: Concurrent administration of emtricitabine or lamivudine with islatravir may result in decreased clinical efficacy of islatravir.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of the doravirine-islatravir fixed-dose combination states that co-administration with emtricitabine or lamivudine is contraindicated.(1)
DISCUSSION: Islatravir undergoes a series of phosphorylations to its active metabolites.(1) In a clinical study in healthy participants, co-administration of multiple daily doses of 300 mg lamivudine and a single dose of 2 mg islatravir (8 times the recommended dosage) decreased intracellular ISL-TP (islatravir active metabolite) area under the curve (AUC) level by 87% and maximum concentration (Cmax) by 76% relative to islatravir alone. A similar effect is anticipated when islatravir is co-administered with emtricitabine.(1,2) Compounds phosphorylated by dCK and linked to this monograph include: emtricitabine and lamivudine.
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Anti-Retrovirals/Marnetegragene Autotemcel
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Marnetegragene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of transduced cells.
CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of marnetegragene autotemcel.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the antiretrovirals) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells.(1)
DISCUSSION: Antiretroviral medications may interfere with the manufacturing of marnetegragene autotemcel.(1)
Doravirine/Efavirenz;Etravirine;Nevirapine
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Efavirenz, etravirine, and nevirapine may induce the metabolism of doravirine via CYP3A4.(1)
CLINICAL EFFECTS: Concurrent use of efavirenz, etravirine, or nevirapine may result in subtherapeutic levels of doravirine.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Coadministration of doravirine with efavirenz, etravirine, or nevirapine is not recommended.(1)
DISCUSSION: In a study in 17 healthy subjects, coadministration of efavirenz (600 mg daily) with a single dose of doravirine (100 mg) decreased doravirine's area-under-curve (AUC), maximum concentration (Cmax), and 24 hour concentration (C24) by 62%, 35%, and 85%, respectively.(1)
Doravirine/Moderate Cyp3a4 Inducers
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Moderate CYP3A4 inducers are expected to increase the metabolism of doravirine.(1-3)
CLINICAL EFFECTS: Concurrent or recent use of a moderate CYP3A4 inducer may result in decreased levels and effectiveness of doravirine.(1-3)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: Recommendations for concurrent use of moderate CYP3A4 inducers with doravirine vary depending on the reference. The manufacturer of the fixed dose combination of doravirine-islatravir states concurrent use with moderate CYP3A4 inducers is not recommended.(3) The DHHS HIV guidelines state when coadministering doravirine with bosentan, dexamethasone, and eslicarbazepine (moderate CYP3A4 inducers): consider an alternative antiretroviral or alternative drug to the moderate CYP3A4 inducer. It would be prudent to consider alternative drugs to other moderate CYP3A4 inducers. If co-administration is necessary monitor virologic response.(4) The University of Liverpool HIV Drug Interactions Database states concurrent use with moderate CYP3A4 inducers should be avoided. If concurrent use cannot be avoided, dose adjustment of doravirine to 100 mg twice daily is recommended and should be maintained for at least 2 weeks following cessation of the moderate CYP3A4 inducer. If a patient is on eslicarbazepine, doravirine should not be coadministered.(5) The manufacturer of single ingredient doravirine and the fixed dose combination of doravirine-lamivudine-tenofovir does not have a recommendation for concurrent use with moderate CYP3A4 inducers.(1,3)
DISCUSSION: Doravirine is metabolized by CYP3A4. Moderate CYP3A4 inducers are expected to reduce doravirine levels, which may lead to loss of response.(1) In a study in 12 subjects, rifabutin (300 mg daily), a moderate CYP3A4 inducer, decreased the area-under-curve (AUC) and 24 hour concentration (C24) of a single dose of doravirine (100 mg) by 50% and 68%, respectively.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dexamethasone, dipyrone, elagolix, eslicarbazepine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat, thioridazine and tovorafenib.(3-4)
Islatravir/Selected Deoxycytidine Kinase Substrates
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Clofarabine, cytarabine, fludarabine, gemcitabine, molnupiravir, nelarabine and zalcitabine may inhibit the intracellular phosphorylation of islatravir by deoxycytidine kinase (dCK).(1)
CLINICAL EFFECTS: Concurrent administration of clofarabine, cytarabine, fludarabine, gemcitabine, molnupiravir, nelarabine, or zalcitabine with islatravir may result in decreased clinical efficacy of islatravir.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of the doravirine-islatravir fixed-dose combination states that co-administration with dCK substrates is not recommended.(1)
DISCUSSION: Islatravir undergoes a series of phosphorylations to its active metabolite.(1) In a clinical study in healthy participants, co-administration of multiple daily doses of 300 mg lamivudine and a single dose of 2 mg islatravir (8 times the recommended dosage) decreased intracellular ISL-TP (islatravir active metabolite) area under the curve (AUC) level by 87% and maximum concentration (Cmax) by 76% relative to islatravir alone.(1) It is expected that co-administration with other compounds phosphorylated by dCK may result in a decrease in ISL-TP exposures.(1,2) Compounds phosphorylated by dCK include: clofarabine, cytarabine, fludarabine, gemcitabine, molnupiravir, nelarabine and zalcitabine.
Selected Protease Inhibitors And Nnrtis/Garlic
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: The exact mechanism is unknown. Garlic may induce the metabolism of protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) by CYP3A4. P-glycoproteins may also be involved.(1,2)
CLINICAL EFFECTS: Concurrent use of garlic and a protease inhibitor or NNRTI may result in decreased levels and effectiveness of the protease inhibitor or NNRTI therapy.(2-3)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Patients taking a protease inhibitor or NNRTI should avoid taking garlic supplements. Garlic from food sources is not likely to cause a problem, although there may be some concern if patients are ingesting a large quantity of garlic on a regular basis.
DISCUSSION: A study in nine HIV-negative subjects examined the effects of the concurrent use of a garlic supplement (taken twice daily) on saquinavir (1200 mg twice daily). Concurrent use resulted in a decrease in saquinavir area-under-curve (AUC), maximum concentration (Cmax), and trough concentration (Cmin) by 51%, 49%, and 54%, respectively, when compared to the administration of saquinavir alone. Following a garlic washout period, saquinavir levels only returned to 60-70% of baseline.(2) In a study in 10 healthy subjects, the administration of garlic (10 mg twice daily) for four days had no significant effects on a single dose of ritonavir (400 mg). Ritonavir AUC and Cmax decreased by 17% and by 25%, respectively. However, the authors cautioned that their results should not be extrapolated to steady-state conditions.(4)
Moderate Interaction: Assess the risk to the patient and take action as needed.
Doravirine/Rifabutin
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Rifabutin may induce the metabolism of doravirine by CYP3A4.(1-3)
CLINICAL EFFECTS: Concurrent or recent use of rifabutin may result in decreased levels and effectiveness of doravirine.(1-3)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: If concurrent therapy is necessary, increase doravirine dosage to one tablet twice daily for the duration of coadministration with rifabutin.(1) Patients on the fixed-dose combination of doravirine-lamivudine-tenofovir should take 1 tablet (100 mg) of doravirine about 12 hours after their dose of doravirine-lamivudine-tenofovir for the duration of rifabutin co-administration.(2) Patients on the fixed-dose combination of doravirine-islatravir should take 1 tablet (100 mg) of doravirine about 12 hours after their dose of doravirine-islatravir for the duration of rifabutin co-administration.(3)
DISCUSSION: Doravirine is metabolized by CYP3A4. Moderate inducers of CYP3A4 such as rifabutin are expected to reduce doravirine levels, which may lead to loss of response.(1) In a study in 12 subjects, rifabutin (300 mg daily), a moderate inducer of CYP3A4, decreased the area-under-curve (AUC) and 24 hour concentration (C24) of a single dose of doravirine (100 mg) by 50% and 68%, respectively.(1) In a study of 15 patients, doravirine 100 mg twice daily given concurrently with rifabutin 300 mg once daily resulted in similar doravirine levels and exposure as doravirine 100 mg once daily alone.(3)
Doravirine/Tecovirimat
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Tecovirimat may induce the metabolism of doravirine via CYP3A4.(1-4)
CLINICAL EFFECTS: Concurrent or recent use of tecovirimat may result in decreased levels and effectiveness of doravirine, as well as the development of resistance.(1-4)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Coadministration of doravirine with tecovirimat should be approached with caution. Some experts state that dose adjustment of either drug is not necessary while others suggest the following dosage change: For adult and pediatric patients weighing at least 35 kg, consider increasing doravirine to 100 mg twice daily during treatment with tecovirimat and for approximately 2 weeks after the end of treatment.(1-4)
DISCUSSION: In a study in 17 healthy subjects, coadministration of efavirenz (600 mg daily) with a single dose of doravirine (100 mg) decreased doravirine's area-under-curve (AUC), maximum concentration (Cmax), and 24 hour concentration (C24) by 62%, 35%, and 85%, respectively.(1) In a pharmacokinetic study, tecovirimat decreased the Cmax and AUC of midazolam by 39% and 32%, respectively.(2-3)
Islatravir/Adenosine Deaminase Inhibitors
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Islatravir is a substrate of adenosine deaminase (ADA). ADA inhibitors may inhibit the metabolism of islatravir.(1)
CLINICAL EFFECTS: Concurrent administration of islatravir with ADA inhibitors may result in elevated levels of islatravir and adverse events such as headache.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of the fixed-dose combination doravirine-islatravir states that co-administration with ADA inhibitors is not recommended.(1)
DISCUSSION: The coadministration of islatravir with ADA inhibitors has not been evaluated clinically. Islatravir is eliminated by renal excretion (approximately 32%) and ADA-mediated metabolism (approximately 53%). Coadministration of ADA inhibitors like pentostatin with islatravir may result in an increase in plasma concentration of islatravir.(1) ADA inhibitors linked to this monograph include: pentostatin.(1)
Contraindications
*Concomitant use 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 doravirine/islatravir.
*Concomitant use with lamivudine or emtricitabine, which are deoxycytidine kinase (dCK) substrates, as a decrease in islatravir-triphosphate (ISL-TP) levels may occur, which may decrease the effectiveness of doravirine/islatravir.
- Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
- Chronic kidney disease stage 5 (failure) GFr<15 ml/min
There are no severe contraindications for this drug.
- Viral hepatitis B
Adverse reactions
The most common adverse reactions (>=2%, all grades) to doravirine/islatravir were diarrhea, dizziness, fatigue, abdominal distension, headache, and increased weight.
Rare or Very Rare
- DRESS syndrome
- Hepatitis
- Idiopathic thrombocytopenic purpura
- Stevens-johnson syndrome
- Toxic epidermal necrolysis
Less Frequent
- Abdominal distension
- Abnormal hepatic function tests
- Diarrhea
- Dizziness
- Fatigue
- Headache disorder
- Hyperbilirubinemia
- Increased alanine transaminase
- Increased aspartate transaminase
- Weight gain
Rare or Very Rare
- Acute abdominal pain
- Dream disorder
- Flatulence
- Insomnia
- Nausea
- Pruritus of skin
- Skin rash
Precautions
No enhanced messaging available.
The safety and effectiveness of doravirine/islatravir have not been established in pediatric patients <18 years of age.
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in females exposed to doravirine/islatravir during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263.
There are no adequate data regarding use of doravirine/islatravir in pregnant women. In animal reproductive studies, no developmental effects were observed when doravirine or islatravir was administered at an AUC of at least 8 (doravirine) and 500 (islatravir) times the exposure at the recommended human dose.
It is not known whether doravirine/islatravir is distributed into human milk, or if the drug has any effects on the breastfed infant or on milk production. Doravirine is present in the milk of lactating rats, while islatravir was detected in the plasma of nursing pups from lactating rats administered islatravir. Potential risks of breastfeeding include HIV-1 transmission (in infants without HIV-1), developing viral resistance (in infants with HIV-1), and serious adverse reactions in breastfed infants.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Among the patients who received doravirine/islatravir in clinical trials, 81 (11%) were >=65 years of age and 10 (1%) were >=75 years of age. No overall differences in safety or efficacy were observed between these patients and younger patients; however, greater sensitivity of some older adults cannot be ruled out.
ICD codes
| Code | Type | Description |
|---|---|---|
| HIV infection | ||
| B20 | ICD10CM | Human immunodeficiency virus [HIv] disease |
| B97.35 | ICD10CM | Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere |
| O98.7 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium |
| O98.71 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy |
| O98.711 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester |
| O98.712 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester |
| O98.713 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester |
| O98.719 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester |
| O98.72 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating childbirth |
| O98.73 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating the puerperium |
| Z21 | ICD10CM | Asymptomatic human immunodeficiency virus [HIv] infection status |
ICD code information from First Databank (FDB).
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Last reviewed · Source: First Databank (FDB) drug data
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