doravirine/lamivudine/tenofovir DF (Rx)

Brand and Other Names:Delstrigo
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

doravirine/lamivudine/tenofovir DF

tablet

  • 100mg/300mg/300mg

HIV Infection

Indicated as a complete regimen for treatment of HIV-1 infection in adults

  • Without prior antiretroviral therapy (ART) treatment history, OR
  • To replace a current ART regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ART regimen with no history of treatment failure and no known substitutions associated with resistance to the individual drug components

1 tablet PO qDay with or without food

Dosage Modifications

Renal impairment

  • Estimated CrCl <50 mL/min: Use not recommended (unable to adjust fixed-dose combination)

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Not studied

Coadministration with rifabutin

  • If coadministered with rifabutin, 1 tablet (ie, 100 mg) of doravirine (Pifeltro) should be taken ~12 hr after Delstrigo dose

Dosing Considerations

Monitoring

  • Obtain baseline test for hepatitis B virus (HBV) infection (see Black Box Warnings)
  • Patients with chronic kidney disease: Obtain baseline serum phosphorus and periodically assess during treatment
  • Obtain the following tests at baseline and periodically assess during treatment for all patients
    • Serum creatinine
    • Estimated CrCl
    • Urine glucose
    • Urine protein

<18 years: Safety and efficacy not established

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Interactions

Interaction Checker

and doravirine/lamivudine/tenofovir DF

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            Contraindicated (15)

            • amobarbital

              amobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • apalutamide

              apalutamide will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • armodafinil

              armodafinil will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • bexarotene

              bexarotene will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • bosentan

              bosentan will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • brigatinib

              brigatinib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • butabarbital

              butabarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • butalbital

              butalbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • carbamazepine

              carbamazepine will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • clobazam

              clobazam will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • dabrafenib

              dabrafenib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • efavirenz

              efavirenz will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              lamivudine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.

            • emtricitabine

              emtricitabine and lamivudine both increase risk of immune reconstitution syndrome. Contraindicated. Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.

              emtricitabine, lamivudine. Other (see comment). Contraindicated. Comment: Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.

            • encorafenib

              encorafenib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            Serious - Use Alternative (6)

            • cabotegravir

              doravirine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

              lamivudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • fexinidazole

              fexinidazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • sorbitol

              sorbitol will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Sorbitol-containing solution decreased systemic exposure of lamivudine oral solution in a pediatric study (ARROW trial). Results showed lower rates of virologic suppression, lower plasma lamivudine exposure, and development of viral resistance more frequently than children receiving lamivudine tablets.

            • tafenoquine

              tafenoquine will increase the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

            • trilaciclib

              trilaciclib will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

            • tucatinib

              tucatinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            Monitor Closely (48)

            • abacavir

              abacavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • atazanavir

              atazanavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              atazanavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • cabozantinib

              lamivudine will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity

            • cenobamate

              cenobamate will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • chloramphenicol

              chloramphenicol will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • clarithromycin

              clarithromycin will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • cobicistat

              cobicistat will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • conivaptan

              conivaptan will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • darunavir

              darunavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • efavirenz

              efavirenz and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • elagolix

              elagolix will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • enfuvirtide

              enfuvirtide and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • erdafitinib

              lamivudine increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

            • fedratinib

              fedratinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fosamprenavir

              fosamprenavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              fosamprenavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • ganciclovir

              ganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Increased risk of hematologic toxicity.

            • grapefruit

              grapefruit will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • idelalisib

              idelalisib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • imatinib

              imatinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • indinavir

              indinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              indinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • interferon alfa 2b

              interferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • isoniazid

              isoniazid will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • istradefylline

              istradefylline will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • ketoconazole

              ketoconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • lopinavir

              lopinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • lorlatinib

              lorlatinib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mifepristone

              mifepristone will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • nefazodone

              nefazodone will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • nelfinavir

              nelfinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              nelfinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • nevirapine

              lamivudine and nevirapine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • orlistat

              orlistat will decrease the level or effect of lamivudine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.

            • peginterferon alfa 2a

              peginterferon alfa 2a, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • peginterferon alfa 2b

              peginterferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • ribavirin

              ribavirin increases toxicity of lamivudine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of lactic acidosis.

            • ritonavir

              ritonavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              ritonavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • saquinavir

              saquinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • saquinavir

              saquinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • stavudine

              lamivudine and stavudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • stiripentol

              stiripentol will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • tazemetostat

              tazemetostat will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • tenofovir DF

              lamivudine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • tipranavir

              tipranavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              tipranavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • trimethoprim

              trimethoprim increases effects of lamivudine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Potential for increased toxicity.

            • voriconazole

              voriconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            Minor (3)

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of lamivudine by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.

            • ribociclib

              ribociclib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole increases levels of lamivudine by decreasing renal clearance. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Sleep disorders and disturbances (12%)

            1-10%

            Dizziness (9%)

            Nausea (7%)

            Headache (6%)

            Fatigue (6%)

            Diarrhea (5%)

            Abdominal pain (5%)

            Total bilirubin 1.1 to <1.6x ULN (5%)

            Altered sensorium (4%)

            AST 2.5 to <5x ULN (4%)

            Lipase 1.5 to <3x ULN (4%)

            Creatinine >1.3 to 1.8x ULN (3%)

            ALT 2.5 to <5x ULN (3%)

            Lipase ≥3x ULN (3%)

            Creatine kinase ≥10x ULN (3%)

            Rash (2%)

            Total bilirubin 1.6 to <2.6x ULN (2%)

            Creatinine >1.8x ULN (2%)

            Creatine kinase 6 to <10x ULN (2%)

            Abnormal dreams (1%)

            Insomnia (1%)

            ALT ≥5x ULN (1%)

            <1%

            AST ≥5x ULN

            Alkaline phosphatase 2.5 to <5x ULN

            LDL cholesterol, fasted ≥190 mg/dL

            Triglycerides, fasted >500 mg/dL

            Postmarketing Reports

            Lamivudine

            • Body as a whole: Redistribution/accumulation of body fat
            • Endocrine and metabolic: Hyperglycemia
            • General: Weakness
            • Hemic and lymphatic: Anemia (eg, pure red cell aplasia and severe anemias progressing on therapy)
            • Hepatic and pancreatic: Lactic acidosis and hepatic steatosis, posttreatment exacerbations of hepatitis B
            • Hypersensitivity: Anaphylaxis, urticaria
            • Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis
            • Skin: Alopecia, pruritus

            Tenofovir DF

            • Immune system disorders: Allergic reaction, including angioedema
            • Metabolism and nutrition disorders: Lactic acidosis, hypokalemia, hypophosphatemia
            • Respiratory, thoracic, and mediastinal disorders: Dyspnea
            • Gastrointestinal disorders: Pancreatitis, increased amylase, abdominal pain
            • Hepatobiliary disorders: Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)
            • Skin and SC tissue disorders: Rash
            • Musculoskeletal and connective tissue disorders: Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy
            • Renal and urinary disorders: Acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria
            • General disorders and administration site conditions: Asthenia
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            Warnings

            Black Box Warnings

            Test all patients for HBV before initiating ARTs

            Severe acute hepatitis B exacerbations reported in patients coinfected with HIV-1 and HBV who have discontinued lamivudine or tenofovir DF

            Monitor both clinical and laboratory values for several months after discontinuing Delstrigo in patients who are coinfected with HIV-1 and HBV

            If appropriate, initiate antihepatitis B therapy

            Contraindications

            Hypersensitivity to lamivudine

            Strong CYP3A inducers

            • Doravirine is contraindicated with strong CYP3A inducers, which may decrease effectiveness
            • Strong CYP3A inducer examples
              • Anticonvulsants (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin)
              • Antimycobacterials (eg, rifampin, rifapentine)
              • Enzalutamide
              • Mitotane
              • St. John’s wort (Hypericum perforatum)

            Cautions

            Severe acute exacerbations of hepatitis B (eg, liver decompensated, liver failure) reported in patients coinfected with HIV-1 and HBV and who have discontinued products containing lamivudine and/or tenofovir DF

            Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), reported with tenofovir DF; avoid with concurrent or recent use of nephrotoxic agents (eg, high-dose or multiple NSAIDs)

            Discontinue if CrCl declines below 50 mL/min

            Tenofovir DF associated with decreased bone mineral density (BMD) and increased biochemical markers of bone metabolism; consider assessing BMD in patients at risk

            Immune reconstitution syndrome reported with combination ART

            Autoimmune disorders (eg, Grave disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) reported to occur in the setting of immune reconstitution; however, time to onset varies and can occur many months after initiation of treatment

            Drug interaction overview

            • Coadministration of doravirine with strong CYP3A inducers may decrease systemic exposure and lead to loss of therapeutic effect and possible HIV resistance
            • Since Delstrigo is a complete regimen for HIV-1 infection, coadministration with other antiretroviral medications for HIV-1 infection not recommended; information regarding potential drug-drug interactions with other antiretroviral medications is not provided
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            Pregnancy

            Pregnancy

            Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263; pregnancy exposure registry monitors pregnancy outcomes in individuals exposed during pregnancy

            Data are not available to establish drug-associated risks to pregnancy outcomes

            Doravirine has not been evaluated in pregnancy; however, lamivudine and tenofovir DF use during pregnancy has been evaluated in a limited number of individuals reported to the APR; available data from the APR show no difference in the overall risk of major birth defects for lamivudine and TDF compared with the background rate for major birth defects of 2.7% in the US reference population

            Lactation

            The Centers for Disease Control and Prevention do not recommend HIV-infected women breastfeed their infants, owing to potential risk for postnatal transmission of HIV

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Doravirine: Non-nucleoside reverse transcriptase inhibitor (NNRTI); inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase

            Lamivudine: Nucleoside reverse transcriptase inhibitor (NRTI); following phosphorylation to active metabolite, inhibits HIV reverse transcriptase via DNA chain termination after incorporation

            Tenofovir DF: NRTI; following hydrolysis and subsequent phosphorylation, inhibits HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine 5′-triphosphate (ATP) and, after incorporation into DNA, by DNA chain termination

            Absorption

            Bioavailability

            • Doravirine: 64%
            • Lamivudine: 86%
            • Tenofovir AF: 25%

            Peak plasma time

            • Doravirine: 2 hr
            • Tenofovir AF: 1 hr

            Peak plasma concentration

            • Doravirine: 0.962 mcg/mL
            • Lamivudine: 2.04 mcg/mL
            • Tenofovir AF: 0.3 mcg/mL

            AUC

            • Doravirine: 16.1 mcg·h/mL
            • Lamivudine: 8.87 mcg·h/mL
            • Tenofovir AF: 2.29 mcg·h/mL

            Distribution

            Protein bound

            • Doravirine: 76%
            • Lamivudine: <36%
            • Tenofovir AF: <0.7%

            Vd

            • Doravirine: 60.5 L
            • Lamivudine: 1.3 L/kg
            • Tenofovir AF: 1.3 L/kg

            Metabolism

            Doravirine: CYP3A (primary)

            Lamivudine: CYP3A (minor)

            Tenofovir AF: No CYP metabolism

            Elimination

            Half-life

            • Doravirine: 15 hr
            • Lamivudine: 5-7 hr
            • Tenofovir AF: 17 hr

            Renal clearance

            • Doravirine: 9.3 mL/min
            • Lamivudine: 199.7 mL/min
            • Tenofovir AF: 243.5 mL/min

            Total clearance

            • Doravirine: 106 mL/min
            • Lamivudine: 398.5 mL/min
            • Tenofovir AF: 1043.7 mL/min

            Excretion

            • Major elimination route
              • Doravirine: Metabolism
              • Lamivudine and tenofovir AF: Glomerular filtration and active tubular secretion
            • Urine (unchanged)
              • Doravirine: 6%
              • Lamivudine: 71%
              • Tenofovir AF: 70-80%
            • Biliary/fecal (unchanged)
              • Doravirine: Minor
              • Lamivudine and tenofovir AF: Not applicable
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            Administration

            Oral Administration

            Complete regimen for HIV in adults without prior ART treatment history; do not prescribe with other ARTs

            Instruct patient to take at a regularly scheduled time of the day

            May take with or without food

            Missed dose

            • If patient forgets dose, instruct them to take the missed dose right away, unless it is almost time for the next dose
            • If time nearer to next dose, advise not to take 2 doses at once and to take the next dose at the regularly scheduled time

            Storage

            Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

            Store in original bottle

            Keep bottle tightly closed to protect from moisture; do not remove desiccants

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.