Doravirine, Lamivudine, and Tenofovir Disoproxil

Drug class: Antineoplastic Agents

Usage of Doravirine, Lamivudine, and Tenofovir Disoproxil

Treatment of HIV Infection

Treatment of HIV-1 infection in antiretroviral-naive (have not previously received antiretroviral therapy) or antiretroviral-experienced (previously treated) adults.

Fixed combination of doravirine/lamivudine/tenofovir DF used alone as a complete regimen for treatment of HIV-1 infection; use with other antiretrovirals not recommended.

For initial treatment in antiretroviral-naive adults, experts state that doravirine/lamivudine/tenofovir DF is a recommended NNRTI-based regimen in certain clinical situations.

For antiretroviral-experienced adults, manufacturer states that doravirine/lamivudine/tenofovir DF can be used to replace the current antiretroviral regimen in those with plasma HIV-1 RNA levels <50 copies/mL on a stable antiretroviral regimen who have no history of treatment failure and are infected with HIV-1 with no known substitutions associated with resistance to doravirine, lamivudine, or tenofovir DF.

Most appropriate antiretroviral regimen cannot be defined for every clinical scenario; select regimen based on information regarding antiretroviral potency, potential rate of resistance development, known toxicities, potential for pharmacokinetic interactions, and patient's virologic, immunologic, and clinical characteristics. Guidelines for the management of HIV infection, including specific recommendations for initial treatment in antiretroviral-naive patients and recommendations for changing antiretroviral regimens, are available at [Web].

Relate drugs

How to use Doravirine, Lamivudine, and Tenofovir Disoproxil

General

  • Determine Scr, estimated Clcr, urine glucose, and urine protein prior to initiation of doravirine/lamivudine/tenofovir DF and routinely monitor during treatment in all patients as clinically appropriate. Also determine serum phosphorus in patients with chronic kidney disease. (See Renal Impairment under Cautions.)
  • Test for HBV infection prior to initiation. (See HIV-infected Individuals Coinfected with HBV under Cautions.)

    • Administration

    Oral Administration

    Administer orally once daily without regard to food.

    Doravirine/lamivudine/tenofovir DF is used alone as a complete antiretroviral regimen.

    Dosage

    Each fixed-combination tablet of doravirine/lamivudine/tenofovir DF contains doravirine 100 mg, lamivudine 300 mg, and tenofovir DF 300 mg.

    Adults

    Treatment of HIV Infection Antiretroviral-naive or Antiretroviral-experienced Adults Oral

    1 tablet of doravirine/lamivudine/tenofovir DF (doravirine 100 mg, lamivudine 300 mg, tenofovir DF 300 mg) once daily.

    Antiretroviral-naive or Antiretroviral-experienced Adults Receiving Rifabutin Oral

    1 tablet of doravirine/lamivudine/tenofovir DF (doravirine 100 mg, lamivudine 300 mg, tenofovir DF 300 mg) once daily and one 100-mg tablet of single-entity doravirine once daily given approximately 12 hours after the fixed-combination tablet. (See Specific Drugs under Interactions.)

    Special Populations

    Hepatic Impairment

    Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.

    Severe hepatic impairment (Child-Pugh class C): Not studied. (See Hepatic Impairment under Cautions.)

    Renal Impairment

    Estimated Clcr <50 mL/minute: Not recommended. (See Renal Impairment under Cautions.)

    Geriatric Patients

    No specific dosage recommendations; use with caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy. (See Geriatric Use under Cautions.)

    Warnings

    Contraindications

  • Concomitant use with potent CYP3A inducers (e.g., Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, St. John’s wort [Hypericum perforatum]). (See Specific Drugs under Interactions.)
  • History of hypersensitivity reaction to lamivudine.

    • Warnings/Precautions

    Warnings

    HIV-infected Individuals Coinfected with HBV

    Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy.

    In HIV-infected patients with HBV coinfection, severe acute exacerbations of HBV, including liver decompensation and liver failure, reported following discontinuance of lamivudine or tenofovir DF (components of doravirine/lamivudine/tenofovir DF). Such reactions could occur following discontinuance of doravirine/lamivudine/tenofovir DF.

    Closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after doravirine/lamivudine/tenofovir DF is discontinued in patients coinfected with HIV and HBV. If appropriate, initiation of HBV treatment may be warranted, especially in patients with advanced liver disease or cirrhosis.

    Other Warnings and Precautions

    Renal Toxicity

    Renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with hypophosphatemia), reported with tenofovir DF (a component of doravirine/lamivudine/tenofovir DF).

    Determine Scr, estimated Clcr, urine glucose, and urine protein prior to initiation of doravirine/lamivudine/tenofovir DF and routinely monitor as clinically appropriate during treatment in all patients. Also determine serum phosphorus in those with chronic kidney disease. (See Renal Impairment under Cautions.)

    Discontinue doravirine/lamivudine/tenofovir DF if clinically important decreases in renal function or evidence of Fanconi syndrome occurs or if estimated Clcr decreases to <50 mL/minute.

    Because persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy, promptly evaluate renal function in patients at risk for renal dysfunction who present with such symptoms. (See Bone Effects under Cautions.)

    Avoid doravirine/lamivudine/tenofovir DF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs). Acute renal failure reported after initiation of high-dose or multiple NSAIAs in HIV-infected patients at risk for renal dysfunction who appeared stable while receiving tenofovir DF; hospitalization and renal replacement therapy required in some patients. Consider alternatives to NSAIAs in patients at risk for renal dysfunction.

    Bone Effects

    Decreases in bone mineral density (BMD) from baseline at lumbar spine and hip, increases in several biochemical markers of bone metabolism, and increased serum parathyroid hormone and 1,25 vitamin D levels reported in patients receiving tenofovir DF (a component of doravirine/lamivudine/tenofovir DF). Effects of tenofovir-associated changes in BMD on long-term bone health and future fracture risk unknown.

    Osteomalacia associated with proximal renal tubulopathy, which may contribute to fractures, reported in patients receiving tenofovir DF. Arthralgia and muscle pain or weakness also reported in cases of proximal renal tubulopathy. Consider hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving preparations containing tenofovir DF.

    Consider BMD monitoring in adults with history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Effect of calcium and vitamin D supplementation not studied, but may be beneficial for all patients. If bone abnormalities suspected, obtain appropriate consultation.

    Interactions

    Concomitant use with certain drugs may result in known or potentially clinically important drug interactions, some of which may lead to loss of therapeutic effect of the antiretrovirals and possible development of resistance or may increase plasma concentrations of the antiretroviral agents and/or concomitant drugs leading to clinically important adverse reactions.

    Consider potential for drug interactions prior to and during doravirine/lamivudine/tenofovir DF therapy; review concomitant drugs during doravirine/lamivudine/tenofovir DF therapy and monitor for adverse effects. (See Interactions.)

    Immune Reconstitution Syndrome

    Immune reconstitution syndrome reported in HIV-infected patients receiving multiple-drug antiretroviral therapy. During the initial phase of treatment, HIV-infected patients whose immune systems respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii], tuberculosis); such responses may necessitate further evaluation and treatment.

    Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) also reported in the setting of immune reconstitution; however, time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

    Use of Fixed Combinations

    Consider cautions, precautions, contraindications, and interactions associated with each component of doravirine/lamivudine/tenofovir DF. Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.

    Doravirine/lamivudine/tenofovir DF is used alone as a complete regimen; use in conjunction with other antiretrovirals not recommended.

    Specific Populations

    Pregnancy

    Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

    Doravirine/lamivudine/tenofovir DF: Insufficient data in pregnant women to assess the risk of birth defects and miscarriage.

    Doravirine: Human data not available to establish whether or not doravirine poses a risk to pregnancy outcomes. In animal reproduction studies, no adverse developmental effects observed in rabbits or rats at exposures 8 or 9 times higher, respectively, than human exposures at recommended human dosage. In pregnant rabbits and rats, doravirine crossed the placenta resulting in fetal plasma concentrations up to 40 and 52%, respectively, of maternal concentrations observed on gestation day 20.

    Lamivudine: Available human data show no difference in the overall risk of major birth defects. In pregnant rabbits, oral administration during organogenesis resulted in embryolethality at systemic exposures similar to the recommended clinical dose; no adverse development effects observed in rats and rabbits with oral administration during organogenesis at peak plasma concentrations approximately 35 times higher than human exposure at the recommended clinical dose.

    Tenofovir DF: Available human data show no difference in the overall risk of major birth defects. No adverse developmental effects observed in pregnant rats and rabbits at doses up to 14 and 19 times higher, respectively, than recommended human dosage.

    Lactation

    Doravirine: Not known whether distributed into human milk. Distributed into milk of lactating rats (milk concentrations approximately 1.5 times higher than maternal plasma concentrations at 2 hours after a dose on lactation day 14).

    Lamivudine and tenofovir DF: Distributed into human milk.

    Doravirine/lamivudine/tenofovir DF: Not known whether the fixed combination or individual drug components affect human milk production or affect the breast-fed infant.

    Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

    Pediatric Use

    Safety and efficacy not established in pediatric patients <18 years of age.

    Geriatric Use

    Experience in patients ≥65 years of age insufficient to determine whether they respond differently than younger adults.

    Use with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

    Hepatic Impairment

    Doravirine: No clinically important differences in doravirine pharmacokinetics in patients with moderate hepatic impairment (Child-Pugh class B). Not studied in those with severe hepatic impairment (Child-Pugh class C).

    Lamivudine: Pharmacokinetics not substantially affected by diminishing hepatic function. Safety and efficacy not established in patients with decompensated liver disease.

    Tenofovir: Pharmacokinetics not substantially affected by any degree of hepatic impairment.

    Renal Impairment

    Not recommended in patients with estimated Clcr <50 mL/minute because dosage of lamivudine and tenofovir DF (components of doravirine/lamivudine/tenofovir DF) cannot be adjusted for renal impairment.

    Common Adverse Effects

    Dizziness, nausea, abnormal dreams.

    What other drugs will affect Doravirine, Lamivudine, and Tenofovir Disoproxil

    The following drug interactions are based on studies using the individual components of doravirine/lamivudine/tenofovir DF. Consider interactions associated with each drug in the fixed combination.

    Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

    Doravirine: Primarily metabolized by CYP3A. In vitro, does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4; not likely to induce CYP1A2, 2B6, or 3A4. Concomitant use of doravirine and CYP3A inducers may decrease doravirine plasma concentrations and may reduce efficacy of doravirine. Concomitant use of doravirine/lamivudine/tenofovir DF with CYP3A inhibitors may increase doravirine plasma concentrations. Not likely to have a clinically important effect on the exposure of drugs metabolized by CYP isoenzymes.

    Lamivudine: Not substantially metabolized by CYP isoenzymes; does not inhibit or induce CYP isoenzymes. Clinically important CYP-mediated drug interactions unlikely.

    Tenofovir DF: Not a substrate of CYP isoenzymes. In vitro, does not inhibit CYP isoenzymes 3A4, 2D6, 2C9, or 2E1; may have a slight inhibitory effect on CYP1A. Pharmacokinetic interactions with inhibitors or substrates of CYP isoenzymes unlikely.

    Drugs Affecting or Metabolized by UGT

    Doravirine: In vitro, does not inhibit UGT1A1.

    Drugs Affecting or Affected by Other Transporters

    Doravirine: Based on in vitro studies, not likely to inhibit P-glycoprotein (P-gp) transport system, organic anion transport polypeptide (OATP) 1B1, OATP1B3, bile salt export pump (BSEP), organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, multidrug and toxin extrusion transporter (MATE) 1, or MATE2K. Not a substrate of breast cancer resistance protein (BCRP); unlikely to be a substrate of OATP1B1 or 1B3.

    Lamivudine: Primarily eliminated in urine by active organic cationic secretion. Potential pharmacokinetic interactions with drugs that are primarily eliminated by active renal secretion via organic cationic transport.

    Drugs Affecting Renal Function

    Drugs that reduce renal function or compete for active tubular secretion: Potential increased concentrations of lamivudine, tenofovir, and/or concomitant drug.

    Specific Drugs

    Drug

    Interaction

    Comments

    Adefovir dipivoxil

    Tenofovir DF: Data not available

    Tenofovir DF: Do not use concomitantly with adefovir dipivoxil

    α1-Adrenergic blocking agents

    Alfuzosin, doxazosin, silodosin, tamsulosin: No effect on α1-adrenergic blocking agent concentrations expected if used with doravirine

    Dosage adjustments not needed if used with doravirine

    Antacids

    Antacid containing aluminum hydroxide, magnesium hydroxide, and simethicone: No clinically important effect on doravirine concentrations

    Dosage adjustments not needed if used with doravirine

    Anticoagulants

    Apixaban, betrixaban, dabigatran, edoxaban, rivaroxaban: No effect on anticoagulant concentrations expected if used with doravirine

    Warfarin: No effect on warfarin concentrations expected if used with doravirine

    Apixaban, betrixaban, dabigatran, edoxaban, rivaroxaban: Experts state dosage adjustments not needed if used with doravirine

    Warfarin: Dosage adjustments not needed if used with doravirine

    Anticonvulsants

    Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: Decreased doravirine concentrations expected; possible decreased doravirine efficacy

    Eslicarbazepine: Possible decreased doravirine concentrations

    Ethosuximide, lacosamide, lamotrigine, tiagabine, zonisamide: No effect on anticonvulsant concentrations expected if used with doravirine

    Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: Concomitant use contraindicated; do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after anticonvulsant discontinued; experts state consider alternative anticonvulsant

    Eslicarbazepine: If used concomitantly, experts state monitor virologic outcomes and consider doravirine plasma concentration monitoring; alternatively, consider different antiretroviral or anticonvulsant

    Ethosuximide, lacosamide, lamotrigine, tiagabine, zonisamide: Dosage adjustments not needed if used with doravirine

    Antidiabetic agents

    Canagliflozin, dapagliflozin, empagliflozin: No effect on antidiabetic agent concentrations expected if used with doravirine

    Linagliptin, saxagliptin, sitagliptin: No effect on antidiabetic agent concentrations expected if used with doravirine

    Metformin: No clinically important effect on metformin concentrations when used with doravirine; possible decreased doravirine concentrations and AUC

    Canagliflozin, dapagliflozin, empagliflozin: Dosage adjustments not needed if used with doravirine

    Linagliptin, saxagliptin, sitagliptin: Dosage adjustments not needed if used with doravirine

    Metformin: Dosage adjustments not needed if used with doravirine

    Antifungals, azoles

    Fluconazole, isavuconazonium sulfate [prodrug of isavuconazole], itraconazole, voriconazole: Possible increased doravirine concentrations

    Ketoconazole: Increased doravirine exposures and peak plasma concentrations; not considered clinically important

    Posaconazole: Possible increased doravirine concentrations

    Fluconazole, isavuconazonium sulfate, itraconazole, voriconazole: Dosage adjustments not needed if used with doravirine

    Posaconazole: Experts state monitor for doravirine-associated toxicities

    Antimalarial and antiprotozoal agents

    Atovaquone: Data not available regarding use with doravirine

    Fixed combination of artemether and lumefantrine (artemether/lumefantrine): No effect on antimalarial agent concentrations expected if used with doravirine

    Fixed combination of atovaquone and proguanil (atovaquone/proguanil): Data not available regarding use with doravirine

    Atovaquone: Experts recommend monitoring for antiprotozoal efficacy if used with doravirine

    Artemether/lumefantrine: Dosage adjustments not needed if used with doravirine

    Atovaquone/proguanil: Experts recommend monitoring for antimalarial efficacy if used with doravirine

    Antimycobacterials (Bedaquiline, rifamycins)

    Bedaquiline: No effect on bedaquiline concentrations expected if used with doravirine

    Rifabutin: Decreased doravirine AUC and trough plasma concentrations; peak plasma concentrations not affected

    Rifampin: Decreased doravirine AUC, peak plasma concentrations, and trough plasma concentrations; possible decreased doravirine efficacy

    Rifapentine: Decreased doravirine concentrations expected; possible decreased efficacy of doravirine

    Bedaquiline: Dosage adjustments not needed if used with doravirine

    Rifabutin: Increase doravirine dosage by using doravirine/lamivudine/tenofovir DF in conjunction with single-entity doravirine (see Antiretroviral-naive or Antiretroviral-experienced Adults Receiving Rifabutin under Dosage and Administration)

    Rifampin, rifapentine: Concomitant use contraindicated; do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after rifampin or rifapentine discontinued

    Antiplatelet agents

    Ticagrelor, vorapaxar: No effect on antiplatelet agent concentrations expected if used with doravirine

    Ticagrelor, vorapaxar: Dosage adjustments not needed if used with doravirine

    Antipsychotic agents

    Aripiprazole, brexpiprazole, Cariprazine, lurasidone, pimavanserin, pimozide, quetiapine: No effect on antipsychotic agent concentrations expected

    Aripiprazole, brexpiprazole, cariprazine, lurasidone, pimavanserin, pimozide, quetiapine: Dosage adjustments not needed if used with doravirine

    Benzodiazepines

    Alprazolam, diazepam, lorazepam, triazolam: No effect on benzodiazepine concentrations expected if used with doravirine

    Midazolam: No clinically important pharmacokinetic interactions with doravirine

    Alprazolam, diazepam, lorazepam, midazolam, triazolam: Dosage adjustments not needed if used with doravirine

    Buprenorphine

    Doravirine: No effect on buprenorphine concentrations expected if used with doravirine

    Lamivudine or tenofovir DF: No clinically important pharmacokinetic interactions

    Doravirine: Dosage adjustments not needed

    Lamivudine or tenofovir DF: Dosage adjustments not needed

    Bupropion

    No effect on bupropion concentrations expected if used with doravirine

    Dosage adjustments not needed if used with doravirine

    Calcium-channel blocking agents

    Dihydropyridine calcium-channel blocking agents: No effect on concentrations of these calcium-channel blocking agents expected if used with doravirine

    Diltiazem, verapamil: Possible increased doravirine concentrations; no effect on diltiazem or verapamil concentrations expected if used with doravirine

    Dihydropyridine calcium-channel blocking agents, diltiazem, verapamil: Dosage adjustments not needed if used with doravirine

    Co-trimoxazole

    Lamivudine: Increased lamivudine AUC and decreased lamivudine oral clearance; no effect on pharmacokinetics of trimethoprim or sulfamethoxazole

    Dasabuvir

    Dasabuvir used with the fixed combination of ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/ritonavir): Possible increased doravirine concentrations

    Dasabuvir used with ombitasvir/paritaprevir/ritonavir: Dosage adjustments not needed if used with doravirine

    Dexamethasone

    Doravirine: Possible decreased doravirine concentrations

    Doravirine: Experts state consider an alternative corticosteroid for long-term use; if used concomitantly, monitor virologic response

    Dutasteride

    Doravirine: Pharmacokinetic interactions not expected

    Elbasvir and grazoprevir

    Elbasvir and grazoprevir: No clinically important pharmacokinetic interactions with doravirine

    Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Dosage adjustments not needed if used with doravirine

    Entecavir

    Tenofovir DF: No clinically important pharmacokinetic interactions

    Enzalutamide

    Decreased doravirine concentrations expected; possible decreased doravirine efficacy

    Concomitant use contraindicated; do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after enzalutamide discontinued

    Estrogens and progestins

    Contraceptives containing ethinyl estradiol or levonorgestrel (oral): No effect on ethinyl estradiol or levonorgestrel concentrations expected if used with doravirine or tenofovir DF

    Contraceptives containing etonogestrel or levonorgestrel (transdermal systems) and contraceptives containing ethinyl estradiol and etonogestrel or segesterone (vaginal rings): No effect on concentrations of these hormones expected if used with doravirine

    Medroxyprogesterone: No effect on concentrations of the hormone expected if used with doravirine

    Contraceptives containing ethinyl estradiol and levonorgestrel (oral): Dosage adjustments not needed if used with doravirine

    Contraceptives containing etonogestrel or levonorgestrel (transdermal systems) and contraceptives containing ethinyl estradiol and etonogestrel or segesterone (vaginal rings): Dosage adjustments not needed if used with doravirine

    Medroxyprogesterone: Dosage adjustments not needed if used with doravirine

    Ganciclovir and valganciclovir

    Tenofovir DF: Concomitant use with ganciclovir or valganciclovir may result in increased tenofovir and/or ganciclovir concentrations

    Tenofovir DF: Monitor for dose-related toxicities of tenofovir and/or ganciclovir

    Glecaprevir and pibrentasvir

    Fixed combination of glecaprevir and pibrentasvir (glecaprevir/pibrentasvir): Possible increased doravirine concentrations; no clinically important effect on tenofovir concentrations

    Glecaprevir/pibrentasvir: Dosage adjustments not needed if used with doravirine or tenofovir DF

    Histamine H2-receptor antagonists

    No effect on doravirine concentrations expected

    Dosage adjustments not needed if used with doravirine

    HMG-CoA reductase inhibitors (statins)

    Atorvastatin: No clinically important effect on atorvastatin concentrations when used with doravirine

    Fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin: No effect on statin concentrations expected if used with doravirine

    Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin: Dosage adjustments not needed if used with doravirine

    Immunosuppressive agents

    Cyclosporine: Possible increased doravirine concentrations; no effect on cyclosporine concentrations expected if used with doravirine

    Everolimus, sirolimus, tacrolimus: No effect on immunosuppressive agent concentrations expected if used with doravirine

    Tenofovir DF: No clinically important pharmacokinetic interactions with tacrolimus

    Cyclosporine, everolimus, sirolimus, tacrolimus: Dosage adjustments not needed if used with doravirine

    Lamivudine

    No clinically important pharmacokinetic interactions between doravirine, lamivudine, and tenofovir DF

    No in vitro evidence of antagonistic antiretroviral effects between doravirine and lamivudine or tenofovir DF

    Ledipasvir and sofosbuvir

    Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): No clinically important pharmacokinetic interactions with doravirine; increased tenofovir exposures

    Ledipasvir/sofosbuvir: Dosage adjustments not needed if used with doravirine/lamivudine/tenofovir DF; monitor for tenofovir-associated adverse effects

    Lofexidine

    No effect on lofexidine concentrations expected if used with doravirine

    Dosage adjustments not needed if used with doravirine

    Macrolides

    Azithromycin: No effect on azithromycin concentrations expected if used with doravirine

    Clarithromycin: Possible increased doravirine concentrations; no effect on clarithromycin concentrations expected if used with doravirine

    Erythromycin: Possible increased doravirine concentrations

    Azithromycin: Dosage adjustments not needed if used with doravirine

    Clarithromycin: Experts state consider alternative (e.g., azithromycin) for prophylaxis or treatment of M. avium complex (MAC) infections in patients receiving doravirine

    Erythromycin: Experts state monitor for doravirine tolerability

    Methadone

    Doravirine and tenofovir DF: No clinically important effects on pharmacokinetics of methadone or either antiretroviral

    Dosage adjustments not needed if used with doravirine

    Mitotane

    Decreased doravirine concentrations expected; possible decreased doravirine efficacy

    Concomitant use contraindicated; do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after mitotane discontinued

    Nefazodone

    Doravirine: Possible increased doravirine concentrations

    Doravirine: Experts state monitor for doravirine-associated adverse effects

    NSAIAs

    High-dose or multiple NSAIAs: Possible increased concentrations of lamivudine, tenofovir, and/or the NSAIAs

    Avoid doravirine/lamivudine/tenofovir DF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs)

    Olanzapine

    Doravirine: No clinically important effect on olanzapine concentrations expected

    Doravirine: Experts state dosage adjustments not needed

    Phosphodiesterase type 5 (PDE5) inhibitors

    Avanafil, sildenafil, tadalafil, vardenafil: No effect on PDE5 inhibitor concentrations expected

    Avanafil, sildenafil, tadalafil, vardenafil: Dosage adjustments not needed if used with doravirine

    Platelet-aggregation inhibitors

    Clopidogrel, prasugrel: No effect on platelet-aggregation inhibitor concentrations expected if used with doravirine

    Clopidogrel, prasugrel: Dosage adjustments not needed if used with doravirine

    Proton-pump inhibitors

    Pantoprazole: No clinically important effect on doravirine concentrations

    Other proton-pump inhibitors: No effect on doravirine concentrations expected

    Pantoprazole and other proton-pump inhibitors: Dosage adjustments not needed if used with doravirine

    Ribavirin

    Tenofovir DF: No clinically important pharmacokinetic interactions

    Tenofovir DF: Dosage adjustment not needed

    St. John's wort (Hypericum perforatum)

    Decreased doravirine concentrations expected; possible decreased doravirine efficacy

    Concomitant use contraindicated; do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after St. John's wort discontinued

    Sofosbuvir

    Tenofovir DF: No clinically important pharmacokinetic interactions

    Sofosbuvir and velpatasvir

    Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): Possible increased tenofovir concentrations and AUC; no clinically important pharmacokinetic interactions with doravirine expected

    Sofosbuvir/velpatasvir: Monitor for tenofovir-associated adverse effects

    Sofosbuvir, velpatasvir, and voxilaprevir

    Fixed combination of sofosbuvir, velpatasvir, and voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir): Possible increased tenofovir concentrations and AUC; no clinically important pharmacokinetic interactions with doravirine expected

    Sofosbuvir/velpatasvir/voxilaprevir: Monitor for tenofovir-associated adverse effects

    Sorbitol

    Lamivudine: Decreased lamivudine AUC and peak plasma concentrations

    Avoid concomitant use of doravirine/lamivudine/tenofovir DF and sorbitol-containing drugs

    SSRIs

    Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline: No effect on SSRI concentrations expected if used with doravirine

    Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline: Dosage adjustments not needed if used with doravirine

    Tenofovir

    No clinically important pharmacokinetic interactions between doravirine, lamivudine, and tenofovir DF

    No in vitro evidence of antagonistic antiretroviral effects between doravirine and lamivudine or tenofovir DF

    Trazodone

    No effect on trazodone concentrations expected if used with doravirine

    Dosage adjustments not needed if used with doravirine

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