efavirenz/lamivudine/tenofovir DF (Rx)

Brand and Other Names:Symfi, Symfi Lo
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

efavirenz/lamivudine/tenofovir DF (ie, tenofovir disoproxil fumarate)

tablet

  • 400mg/300mg/300mg (Symfi Lo)
  • 600mg/300mg/300mg (Symfi)

HIV Infection

Indicated as a complete antiretroviral (ART) regimen for HIV-1 infection

Combination consists of 2 nucleo(t)side reverse transcriptase inhibitors (NRTIs) (ie, lamivudine and tenofovir) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (ie, efavirenz)

1 tablet (efavirenz 400 mg/lamivudine 300 mg/tenofovir DF 300 mg) PO qHS OR

1 tablet (efavirenz 600 mg/lamivudine 300 mg/tenofovir DF 300 mg) PO qHS

Also see administration

Dosage Modifications

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment necessary
  • Moderate-to-severe (Child-Pugh B or C): Not recommended

Renal impairment

  • CrCl ≥50 mL/min: No dosage adjustment necessary
  • CrCl <50 mL/min or end-stage renal disease (ESRD) requiring hemodialysis: Not recommended because drug is a fixed-dose combination tablet and dose cannot be adjusted

Dosing Considerations

Testing prior to initiation and during treatment

  • Prior to initiation of efavirenz/lamivudine/tenofovir DF, test patients for hepatitis B virus (HBV)
  • Assess serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose, and urine protein in all patients as clinically appropriate
  • Monitor hepatic function

Dosage Forms & Strengths

efavirenz/lamivudine/tenofovir DF (ie, tenofovir disoproxil fumarate)

tablet

  • 400mg/300mg/300mg (Symfi Lo)
  • 600mg/300mg/300mg (Symfi)

HIV Infection

Indicated as a complete antiretroviral (ART) regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children (weight dependent)

Combination consists of 2 nucleo(t)side reverse transcriptase inhibitors (NRTIs) (ie, lamivudine and tenofovir) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (ie, efavirenz)

Also see administration

Symfi Lo

  • <35 kg: Safety and efficacy not established
  • ≥35 kg: 1 tablet (efavirenz 400 mg/lamivudine 300 mg/tenofovir 300 mg) PO qHS

Symfi

  • <40 kg: Safety and efficacy not established
  • ≥40 kg: 1 tablet (efavirenz 600 mg/lamivudine 300 mg/tenofovir DF 300 mg) PO qHS

Dosage Modifications

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment necessary
  • Moderate-to-severe (Child-Pugh B or C): Not recommended

Renal impairment

  • CrCl ≥50 mL/min: No dosage adjustment necessary
  • CrCl <50 mL/min or end-stage renal disease (ESRD) requiring hemodialysis: Not recommended because drug is a fixed-dose combination tablet and dose cannot be adjusted

Dosing Considerations

Testing prior to initiation and during treatment

  • Prior to initiation of efavirenz/lamivudine/tenofovir DF, test patients for hepatitis B virus (HBV)
  • Assess serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose, and urine protein in all patients as clinically appropriate
  • Monitor hepatic function

Clinical trials did not include sufficient number of patients aged ≥65 yr to determine if they respond differently from younger individuals

Exercise caution when administering lamivudine in elderly patients because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy

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Interactions

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            Contraindicated (25)

            • carbamazepine

              carbamazepine, efavirenz. Either decreases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of carbamazepine with NNRTIs may result in a loss of virologic response and possible resistance to the NNRTI. A decrease in AUC is observed for both carbamazepine (27%) and efavirenz (36%) when coadministered.

            • cariprazine

              efavirenz will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • cobimetinib

              efavirenz will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

            • dienogest/estradiol valerate

              efavirenz will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • doravirine

              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.

            • elbasvir/grazoprevir

              efavirenz will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              tenofovir DF, 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.

              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.

              efavirenz, 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.

            • ergonovine

              efavirenz will decrease the level or effect of ergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • etravirine

              efavirenz decreases levels of etravirine by increasing metabolism. Contraindicated. Mfr.'s PI recommends not combining etravirine with other NNRTIs.

            • fostemsavir

              efavirenz will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

            • isavuconazonium sulfate

              efavirenz will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • lefamulin

              lefamulin will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            • lomitapide

              efavirenz increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

            • lonafarnib

              efavirenz will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

            • lorlatinib

              efavirenz will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

            • lumacaftor/ivacaftor

              efavirenz will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.

            • nevirapine

              efavirenz and nevirapine both increase risk of immune reconstitution syndrome. Contraindicated. Coadministration not recommended as this combination has been associated with an increase in adverse reactions and no improvement in efficacy

            • ombitasvir/paritaprevir/ritonavir

              efavirenz will decrease the level or effect of ombitasvir/paritaprevir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir, efavirenz. unspecified interaction mechanism. Contraindicated. Coadministration of avirenz-based regimens with Viekira Pak was poorly tolerated and resulted in liver enzyme elevations.

              efavirenz will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • panobinostat

              efavirenz decreases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers can reduce panobinostat levels by ~70% and lead to treatment failure.

            • praziquantel

              efavirenz decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.

            • rilpivirine

              efavirenz decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be used in combination with NNRTIs.

            • streptozocin

              streptozocin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Contraindicated. Streptozocin should not be used in combination with or concomitantly with other potential nephrotoxins.

            • voriconazole

              voriconazole will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindication applies to efavirenz doses of 400 mg/day or higher. This dose of efavirenz induces CYP3A4 resulting in decreased voriconazole levels. When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg q12hr and efavirenz should be decreased to 300 mg q24hr.

              efavirenz decreases effects of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindication applies to efavirenz doses of 400 mg/day or higher. This dose of efavirenz induces CYP3A4 resulting in decreased voriconazole levels. When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg q12hr and efavirenz should be decreased to 300 mg q24hr.

            Serious - Use Alternative (141)

            • abametapir

              abametapir will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              abametapir will increase the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP2B6 substrates. If not feasible, avoid use of abametapir.

            • abemaciclib

              efavirenz will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

            • adefovir

              adefovir, tenofovir DF. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced nephrotoxicity. Avoid coadministration.

              adefovir increases levels of tenofovir DF by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir. Avoid coadministration.

            • alfuzosin

              efavirenz will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • alpelisib

              efavirenz will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.

            • amiodarone

              efavirenz will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              efavirenz will decrease the level or effect of apalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. No initial dose adjustment

            • apremilast

              efavirenz will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy

            • artemether/lumefantrine

              efavirenz will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

            • atazanavir

              efavirenz will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • atovaquone

              efavirenz decreases levels of atovaquone by unspecified interaction mechanism. Avoid or Use Alternate Drug.

            • axitinib

              efavirenz decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Selection of concomitant medication with no or minimal CYP3A4 induction potential is recommended.

            • bacitracin

              tenofovir DF and bacitracin both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug. Avoid concurrent use of bacitracin with other nephrotoxic drugs

            • bedaquiline

              efavirenz will decrease the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of bedaquiline with strong CYP3A4 inducers due to potential for decreased therapeutic effect

            • bosutinib

              efavirenz decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85% .

            • brigatinib

              efavirenz will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.

            • bromocriptine

              efavirenz increases levels of bromocriptine by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.

            • buprenorphine transdermal

              efavirenz will decrease the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cabergoline

              efavirenz increases levels of cabergoline by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.

            • cabotegravir

              tenofovir DF, 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.

              efavirenz, 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.

            • cabozantinib

              efavirenz will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.

            • cyclosporine

              cyclosporine and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug.

            • capmatinib

              efavirenz will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • carvedilol

              efavirenz will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • ceritinib

              efavirenz decreases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • citalopram

              efavirenz will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clopidogrel

              efavirenz decreases effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Clopidogrel efficacy may be reduced by drugs that inhibit CYP2C19. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19. .

            • cobicistat

              efavirenz will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with efavirenz may result in loss of therapeutic effect and development of resistance to cobicistat.

            • copanlisib

              efavirenz will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

            • dabrafenib

              efavirenz decreases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darolutamide

              efavirenz will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.

            • darunavir

              efavirenz will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with efavirenz may result in loss of therapeutic effect and development of resistance to darunavir

            • deflazacort

              efavirenz will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

            • dihydroergotamine

              efavirenz will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • dihydroergotamine intranasal

              efavirenz will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • dolutegravir

              efavirenz will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Increase dolutegravir dose to 50 mg BID when coadministered with strong UGT1A/CYP3A inducers

            • dronedarone

              efavirenz will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • duvelisib

              efavirenz will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

            • eletriptan

              efavirenz will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eltrombopag

              efavirenz will increase the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • elvitegravir

              efavirenz will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              efavirenz will decrease the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • encorafenib

              efavirenz will decrease the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • entrectinib

              efavirenz and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              efavirenz will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • enzalutamide

              efavirenz will decrease the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              enzalutamide will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erdafitinib

              efavirenz will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              efavirenz will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

            • ergoloid mesylates

              efavirenz increases levels of ergoloid mesylates by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.

            • ergotamine

              efavirenz will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              efavirenz increases levels of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.

            • erythromycin base

              efavirenz will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin ethylsuccinate

              efavirenz will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin lactobionate

              efavirenz will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin stearate

              efavirenz will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ethinylestradiol

              efavirenz will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • ethotoin

              efavirenz will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • etravirine

              efavirenz will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • everolimus

              efavirenz will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • fedratinib

              efavirenz will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • fexinidazole

              efavirenz will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

              fexinidazole will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Coadministration may decrease plasma concentrations of CYP2B6 substrates owing to fexinidazole inducing CYP2B6.

              fexinidazole and efavirenz both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

              fexinidazole will increase the level or effect of efavirenz 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.

            • finerenone

              efavirenz will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fosphenytoin

              efavirenz will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • fostamatinib

              efavirenz will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • glasdegib

              efavirenz will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

              efavirenz and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

            • glecaprevir/pibrentasvir

              efavirenz will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of efavirenz (a strong CYP3A4 inducer) with glecaprevir/pibrentasvir may significantly decrease glecaprevir/pibrentasvir plasma concentrations and AUC. Potential for loss of therapeutic effect.

            • ibrutinib

              efavirenz decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

            • idelalisib

              efavirenz will decrease the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration; strong CYP3A4 inducers significantly decrease idelalisib systemic exposure

              idelalisib will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indinavir

              efavirenz will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • infigratinib

              efavirenz will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irinotecan

              efavirenz will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irinotecan liposomal

              efavirenz will decrease the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • istradefylline

              efavirenz will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

            • itraconazole

              itraconazole will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended 2 weeks before and during itraconazole.

              efavirenz will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended 2 weeks before and during itraconazole.

            • ivabradine

              efavirenz will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.

            • ivacaftor

              efavirenz, ivacaftor. Other (see comment). Avoid or Use Alternate Drug. Comment: Efavirenz decreases levels of ivacaftor by CYP enzyme induction; whereas, ivacaftor increases levels of efavirenz by inhibiting CYP3A4 .

            • ivosidenib

              efavirenz will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

            • ixazomib

              efavirenz will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

            • larotrectinib

              efavirenz will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

            • lemborexant

              efavirenz will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • letermovir

              efavirenz will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.

            • lopinavir

              lopinavir will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lorlatinib

              lorlatinib will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lovastatin

              efavirenz will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lumefantrine

              efavirenz will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

            • lurbinectedin

              efavirenz will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • macimorelin

              efavirenz will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

            • macitentan

              efavirenz will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • methylergonovine

              efavirenz increases levels of methylergonovine by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.

            • metoclopramide intranasal

              efavirenz, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • midostaurin

              efavirenz will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

            • mifepristone

              mifepristone will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              efavirenz will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mobocertinib

              efavirenz will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • naloxegol

              efavirenz will decrease the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use of naloxegol with strong CYP3A4 inducers is not recommended

            • nateglinide

              efavirenz will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • nefazodone

              efavirenz will decrease the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • neratinib

              efavirenz will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

            • netupitant/palonosetron

              efavirenz will decrease the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Netupitant is mainly metabolized by CYP3A4; avoid use in patients who are chronically using a strong CYP3A4 inducer

            • nevirapine

              nevirapine will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration not recommended as this combination has been associated with an increase in adverse reactions and no improvement in efficacy

              efavirenz will decrease the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nisoldipine

              efavirenz will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • norethindrone

              efavirenz will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • norgestrel

              efavirenz will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • olaparib

              efavirenz will decrease the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inducers cannot be avoided, be aware of a potential for decreased efficacy of olaparib

            • osimertinib

              efavirenz will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

            • parecoxib

              efavirenz will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • pemigatinib

              efavirenz will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • perampanel

              efavirenz will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pexidartinib

              efavirenz will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              efavirenz and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

            • pitolisant

              efavirenz and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • pomalidomide

              efavirenz decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pralsetinib

              efavirenz will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

            • pretomanid

              efavirenz will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers.

              efavirenz, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

            • ranolazine

              efavirenz will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • regorafenib

              efavirenz will decrease the level or effect of regorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decrease regorafenib levels and increase exposure of the active metabolite M-5

            • ribociclib

              ribociclib will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifabutin

              efavirenz will decrease the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rimegepant

              efavirenz will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ripretinib

              efavirenz will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.

            • rolapitant

              efavirenz will decrease the level or effect of rolapitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Long-term coadministration of strong CYP3A4 inducers with rolapitant may significantly decrease rolapitant efficacy.

            • saquinavir

              saquinavir will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selpercatinib

              efavirenz will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selumetinib

              efavirenz will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • silodosin

              efavirenz will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • siponimod

              efavirenz will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              efavirenz will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • sirolimus

              efavirenz will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • sofosbuvir/velpatasvir

              efavirenz will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

            • sonidegib

              efavirenz will decrease the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong or moderate CYP3A4 inducers.

            • sorafenib

              efavirenz will decrease the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • dabigatran

              tenofovir DF will decrease the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration. P-gp inducers reduce systemic exposure of dabigatran

            • edoxaban

              tenofovir DF will decrease the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of edoxaban with potent P-gp inducers

            • lasmiditan

              lasmiditan increases levels of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              lasmiditan increases levels of tenofovir DF by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates.

            • letermovir

              tenofovir DF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • nintedanib

              tenofovir DF decreases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration, particularly for P-gp inducers that are also CYP3A4 inducers; nintedanib is a substrate of P-gp and to a less extent CYP3A4.

            • sotorasib

              sotorasib will decrease the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

              efavirenz will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • stiripentol

              efavirenz will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.

            • suvorexant

              efavirenz will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/day

            • tacrolimus

              efavirenz will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tazemetostat

              efavirenz will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tepotinib

              efavirenz will decrease the level or effect of tepotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              tepotinib will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • tezacaftor

              efavirenz will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate 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.

            Monitor Closely (372)

            • abacavir

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

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

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

            • abiraterone

              efavirenz decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.

            • acalabrutinib

              acalabrutinib increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.

            • acalabrutinib

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

            • alfentanil

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

            • alitretinoin

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

            • almotriptan

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

            • alosetron

              efavirenz will increase the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • alprazolam

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

            • amitriptyline

              efavirenz will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • amlodipine

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

            • apixaban

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

            • apomorphine

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

            • aprepitant

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

            • aripiprazole

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

            • atazanavir

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

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

            • acyclovir

              acyclovir and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              acyclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • atorvastatin

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

            • aldesleukin

              aldesleukin, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              aldesleukin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • amikacin

              amikacin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              amikacin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • amiloride

              tenofovir DF increases levels of amiloride by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • amphotericin B cholesteryl sulfate

              amphotericin B cholesteryl sulfate and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • amphotericin B deoxycholate

              amphotericin B deoxycholate and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • amphotericin B liposomal

              amphotericin B liposomal and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • amphotericin B phospholipid complex

              amphotericin B phospholipid complex and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • apalutamide

              apalutamide will decrease the level or effect of tenofovir DF by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.

            • atazanavir

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

              tenofovir DF decreases levels of atazanavir by unknown mechanism. Use Caution/Monitor. May result in loss of atazanavir antiviral activity; ritonavir boosting may help to compensate.

            • avanafil

              efavirenz will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; increased levels may result in increased associated adverse events; the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours for patients taking concomitant moderate CYP3A4 inhibitors

            • avapritinib

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

            • bazedoxifene/conjugated estrogens

              efavirenz will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of efavirenz 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.

            • benzhydrocodone/acetaminophen

              efavirenz will decrease the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with benzhydrocodone (prodrug of hydrocodone); plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression.

            • berotralstat

              berotralstat will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • bleomycin

              bleomycin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • bortezomib

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

            • bosentan

              efavirenz will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • brentuximab vedotin

              efavirenz will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexanolone

              brexanolone, efavirenz. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brexpiprazole

              efavirenz will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

            • buprenorphine

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

            • buprenorphine buccal

              efavirenz will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine subdermal implant

              efavirenz will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

            • buprenorphine, long-acting injection

              efavirenz will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • bupropion

              efavirenz will decrease the level or effect of bupropion by increasing metabolism. Use Caution/Monitor. Coadministration with hepatic inducers reduced bupropion AUC and Cmax; hydroxybupropion (active metabolite) Cmax was increased

            • buspirone

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

            • cabazitaxel

              efavirenz will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A4 inhibitors.

            • cabozantinib

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

            • calcifediol

              efavirenz, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

            • calcitriol

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

            • cannabidiol

              efavirenz will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              efavirenz will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

              cannabidiol, efavirenz. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • capreomycin

              capreomycin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • carbamazepine

              carbamazepine will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • carboplatin

              carboplatin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • celecoxib

              tenofovir DF, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

              efavirenz will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • cenobamate

              cenobamate will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP2B6 substrate, as needed, when coadministered with cenobamate.

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

              cenobamate, efavirenz. Either increases levels of the other by sedation. Use Caution/Monitor.

            • cidofovir

              cidofovir and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              cidofovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • chlordiazepoxide

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

            • chloroquine

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

            • chlorpheniramine

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

            • cilostazol

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

              efavirenz increases toxicity of cilostazol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider decreasing cilostazol dose; moderate CYP2C19 inhibitors may increase serum levels of 3,4-dehydrocilostazol (active metabolite).

            • cimetidine

              cimetidine, tenofovir DF. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • cinacalcet

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

            • cisplatin

              cisplatin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              cisplatin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clobazam

              efavirenz will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Dosage adjustment may be required; CYP2C19 inhibitors may result in increased exposure to N-desmethylclobazam (active metabolite).

              efavirenz, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clobetasone

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

            • clonazepam

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

            • clopidogrel

              efavirenz decreases effects of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clopidogrel efficacy may be reduced by drugs that inhibit CYP3A4. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP3A4. .

            • clorazepate

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

            • clozapine

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

            • cobicistat

              cobicistat will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • colistin

              colistin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • conivaptan

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

            • conjugated estrogens

              efavirenz will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              efavirenz will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • contrast media (iodinated)

              contrast media (iodinated) and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

            • cortisone

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

            • crizotinib

              efavirenz increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • crofelemer

              crofelemer increases levels of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclophosphamide

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

            • cyclosporine

              efavirenz will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor cyclosporine concentrations when starting, stopping, or adjusting dose of concurrent efavirez, especially within first 2 weeks.

            • dabrafenib

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

            • dantrolene

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

            • dapsone

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

            • darifenacin

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

            • darolutamide

              darolutamide will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).

            • darunavir

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

            • dasatinib

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

            • deferasirox

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

            • dexamethasone

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

            • diazepam

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

            • diazepam intranasal

              efavirenz will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.

              efavirenz will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • dichlorphenamide

              dichlorphenamide and tenofovir DF both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              tenofovir DF, diclofenac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

              efavirenz will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • didanosine

              tenofovir DF increases toxicity of didanosine by decreasing elimination. Use Caution/Monitor. May increase risk of pancreatitis; decrease didanosine dose to 250 mg/day if weight >60 kg and decrease to 200 mg/day if weight <60 kg .

              didanosine, efavirenz. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concomitant administration increases risk of liver toxicity.

            • diflunisal

              tenofovir DF, diflunisal. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • diltiazem

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

            • digoxin

              tenofovir DF increases levels of digoxin by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • docetaxel

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

            • dofetilide

              tenofovir DF increases levels of dofetilide by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • doxorubicin

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

            • doxorubicin liposomal

              efavirenz will decrease the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dronabinol

              efavirenz will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

            • dronedarone

              dronedarone will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May decrease dronedarone levels.

            • duvelisib

              tenofovir DF will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • efavirenz

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

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

            • elagolix

              elagolix will decrease the level or effect of efavirenz 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.

              elagolix will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

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

            • eliglustat

              efavirenz will decrease the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A inducers significantly decreases eliglustat exposure; coadministration not recommended

            • emtricitabine

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

            • enfuvirtide

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

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

            • emtricitabine

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

            • entecavir

              tenofovir DF increases levels of entecavir by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. Both drugs are excreted by active tubular secretion.

            • encorafenib

              encorafenib, efavirenz. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enfuvirtide

              efavirenz and enfuvirtide 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.

            • erlotinib

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

            • erythromycin base

              erythromycin base will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • escitalopram

              efavirenz will increase the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • esketamine intranasal

              esketamine intranasal, efavirenz. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esomeprazole

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

            • estradiol

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

            • estradiol vaginal

              efavirenz will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens conjugated synthetic

              efavirenz will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens esterified

              efavirenz will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estropipate

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

            • eszopiclone

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

            • ethosuximide

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

            • etodolac

              tenofovir DF, etodolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • etonogestrel

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

            • etoposide

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

            • etravirine

              efavirenz will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • exemestane

              efavirenz will decrease the level or effect of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients receiving exemestane with a potent CYP3A4 inducer the recommended dose of exemestane is 50 mg daily after a meal.

            • famciclovir

              tenofovir DF increases levels of famciclovir by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • fedratinib

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

            • felbamate

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

            • felodipine

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

            • fenofibrate

              fenofibrate increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Increased risk of myopathy.

            • fenofibrate micronized

              fenofibrate micronized increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Increased risk of myopathy.

            • fenofibric acid

              fenofibric acid increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Increased risk of myopathy.

            • fenoprofen

              tenofovir DF, fenoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • fentanyl

              efavirenz will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • fentanyl intranasal

              efavirenz will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • fentanyl transdermal

              efavirenz will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • fentanyl transmucosal

              efavirenz will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

            • fesoterodine

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

            • flibanserin

              efavirenz will decrease the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers substantially decrease flibanserin systemic exposure.

            • flucytosine

              flucytosine, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              flucytosine increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • fludrocortisone

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

            • flurazepam

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

            • flurbiprofen

              efavirenz will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              tenofovir DF, flurbiprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • fluvastatin

              efavirenz will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • fosamprenavir

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

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

            • fluvoxamine

              fluvoxamine will increase the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • fosamprenavir

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

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

            • foscarnet

              foscarnet and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • fostemsavir

              efavirenz and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • ganciclovir

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

            • fostamatinib

              fostamatinib will increase the level or effect of tenofovir DF by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • ganciclovir

              ganciclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • gefitinib

              efavirenz will decrease the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase gefitinib to 500 mg daily if coadministered with a strong CYP3A4 inducer. Resume gefitinib dose at 250 mg/day 7 days after discontinuing the strong inducer.

            • gentamicin

              gentamicin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              gentamicin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir will increase the level or effect of tenofovir DF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • guanfacine

              efavirenz will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

            • haloperidol

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

            • hydrocodone

              efavirenz will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • hydrocortisone

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

            • hydroxyprogesterone caproate

              efavirenz will decrease the level or effect of hydroxyprogesterone caproate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ibuprofen

              efavirenz will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              tenofovir DF, ibuprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • ibuprofen IV

              tenofovir DF, ibuprofen IV. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

              efavirenz will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • ifosfamide

              efavirenz increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

              efavirenz increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.

            • indinavir

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

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

            • iloperidone

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

              iloperidone increases levels of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imipramine

              efavirenz will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • indinavir

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

            • indomethacin

              tenofovir DF, indomethacin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • 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 efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isosorbide dinitrate

              efavirenz will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isosorbide mononitrate

              efavirenz will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isradipine

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

            • istradefylline

              istradefylline will increase the level or effect of efavirenz 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.

              istradefylline will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • ivacaftor

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

            • ketoprofen

              tenofovir DF, ketoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • ivosidenib

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

            • ixabepilone

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

            • ketamine

              efavirenz will increase the level or effect of ketamine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

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

            • ketoconazole

              ketoconazole will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketorolac

              tenofovir DF, ketorolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • lamivudine

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

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

            • lansoprazole

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

            • ledipasvir/sofosbuvir

              ledipasvir/sofosbuvir will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              ledipasvir/sofosbuvir will increase the level or effect of tenofovir DF by unspecified interaction mechanism. Use Caution/Monitor.

            • lapatinib

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

            • lasmiditan

              lasmiditan, efavirenz. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor CYP2B6 substrate for adequate clinical response. Consider increasing the CYP2B6 substrate dose according to specific prescribing recommendations.

            • letermovir

              letermovir increases levels of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levamlodipine

              efavirenz will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

            • levonorgestrel intrauterine

              efavirenz decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levonorgestrel oral

              efavirenz decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              efavirenz will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

            • linagliptin

              efavirenz will decrease the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer.

              efavirenz will decrease the level or effect of linagliptin by Other (see comment). Use Caution/Monitor. Reports of hyperglycemia due to insulin resistance with protease inhibitors.

            • lonafarnib

              lonafarnib will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

            • lopinavir

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

            • loratadine

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

            • losartan

              efavirenz will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.

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

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, efavirenz. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

            • lurasidone

              efavirenz decreases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. It may be necessary to increase the lurasidone dose after chronic treatment (ie, 7 days or more) with moderate CYP3A inducers.

              lurasidone, efavirenz. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maraviroc

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

            • marijuana

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

            • meclofenamate

              tenofovir DF, meclofenamate. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • medroxyprogesterone

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

            • mefenamic acid

              tenofovir DF, mefenamic acid. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • mefloquine

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

            • meloxicam

              efavirenz will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              tenofovir DF, meloxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • memantine

              tenofovir DF increases levels of memantine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • meperidine

              efavirenz will decrease the level or effect of meperidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased toxic metabolite formation.

            • mestranol

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

            • metaxalone

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

            • metformin

              tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.

            • methadone

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

            • methylprednisolone

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

            • midazolam

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

            • midazolam intranasal

              midazolam intranasal, efavirenz. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • midodrine

              tenofovir DF increases levels of midodrine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • mifepristone

              efavirenz, mifepristone. Other (see comment). Use Caution/Monitor. Comment: Efavirenz shown in vitro to induce CYP3A4 and CYP2B6, but in vitro has been shown to inhibit CYP3A4 and therefore may affect mifepristone levels/effect; mifepristone inhibits CYP2B6, therefore increasing exposure of efavirenz.

            • mirtazapine

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

            • mitomycin

              mitomycin, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              mitomycin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • modafinil

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

            • morphine

              tenofovir DF increases levels of morphine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • nabumetone

              tenofovir DF, nabumetone. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • nafcillin

              nafcillin will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may increase metabolism of CYP3A4 substrates

            • naldemedine

              efavirenz will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Simulation using physiologically-based pharmacokinetic modeling suggests that concomitant use of moderated CYP3A4 inducers decrease exposure to naldemedine. The clinical consequence of this decreased exposure is unknown.

            • naproxen

              tenofovir DF, naproxen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • nefazodone

              nefazodone will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nelfinavir

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

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

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

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

            • neomycin PO

              neomycin PO and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              neomycin PO increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • nicardipine

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

            • nevirapine

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

            • nevirapine

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

            • nifedipine

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

            • nilotinib

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

            • oliceridine

              efavirenz will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.

            • omeprazole

              efavirenz will increase the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • ondansetron

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

            • orlistat

              orlistat will decrease the level or effect of efavirenz 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.

              orlistat will decrease the level or effect of tenofovir DF 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.

              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.

            • osilodrostat

              efavirenz will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

              osilodrostat and efavirenz both increase QTc interval. Use Caution/Monitor.

            • oxaliplatin

              oxaliplatin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • ospemifene

              efavirenz decreases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxaliplatin

              oxaliplatin will increase the level or effect of efavirenz by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

            • oxcarbazepine

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

            • oxycodone

              efavirenz decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • palbociclib

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

            • paricalcitol

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

            • pazopanib

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

            • peginterferon alfa 2a

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

            • oxaprozin

              tenofovir DF, oxaprozin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • pamidronate

              pamidronate increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Combination may increase risk of nephrotoxicity.

            • peginterferon alfa 2b

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

            • pemetrexed

              pemetrexed, tenofovir DF. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

              pemetrexed, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • penicillamine

              penicillamine, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              penicillamine increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • pentamidine

              pentamidine and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • peramivir

              tenofovir DF increases levels of peramivir by decreasing renal clearance. Use Caution/Monitor. Caution when peramivir coadministered with nephrotoxic drugs.

            • phenytoin

              efavirenz will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              phenytoin will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When given together, periodic monitoring for reduced efavirenz efficacy and phenytoin plasma concentrations are recommended .

              phenytoin will increase the level or effect of efavirenz by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • pimavanserin

              efavirenz will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.

            • pimozide

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

            • piroxicam

              tenofovir DF, piroxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

              efavirenz will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • pitolisant

              efavirenz will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

            • pramipexole

              tenofovir DF increases levels of pramipexole by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • polatuzumab vedotin

              efavirenz will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

            • prednisolone

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

            • prednisone

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

            • primaquine

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

            • probenecid

              probenecid increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • procainamide

              tenofovir DF increases levels of procainamide by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • progesterone intravaginal gel

              efavirenz will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • progesterone micronized

              efavirenz will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • progesterone, natural

              efavirenz will decrease the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • proguanil

              efavirenz decreases levels of proguanil by unspecified interaction mechanism. Use Caution/Monitor. May decrease serum concentrations of the active metabolite of proguanil.

            • quazepam

              quazepam will increase the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

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

            • quetiapine

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

            • quinidine

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

              tenofovir DF, quinidine. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • ramelteon

              efavirenz will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • regorafenib

              regorafenib will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.

            • repaglinide

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

            • ribavirin

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

            • ribociclib

              efavirenz will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

            • rifabutin

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

            • rifampin

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

              rifampin will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • riociguat

              efavirenz will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment

            • risperidone

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

            • ritonavir

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

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

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

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

              ritonavir increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • rivaroxaban

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

            • safinamide

              safinamide will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • roflumilast

              efavirenz will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness

            • romidepsin

              efavirenz will decrease the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with strong 3A4 inducers should be avoided if possible.

            • rucaparib

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

            • ruxolitinib

              efavirenz will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saquinavir

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

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

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

            • saquinavir

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

            • selexipag

              efavirenz will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

            • sarecycline

              sarecycline will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • sertraline

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

            • sildenafil

              efavirenz will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levels

            • simvastatin

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

            • sirolimus

              sirolimus, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              sirolimus increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • sitagliptin

              tenofovir DF, sitagliptin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • sofosbuvir

              sofosbuvir will increase the level or effect of tenofovir DF by unspecified interaction mechanism. Use Caution/Monitor.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF

            • solifenacin

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

            • sorafenib

              efavirenz decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

            • stavudine

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

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

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

            • stiripentol

              stiripentol will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

              stiripentol, efavirenz. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

              stiripentol, efavirenz. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP2B6 inhibitor and inducer. Monitor CYP2B6 substrates coadministered with stiripentol for increased or decreased effects. CYP2B6 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.

              stiripentol, efavirenz. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • sufentanil SL

              efavirenz decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.

            • streptomycin

              streptomycin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              streptomycin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • sulindac

              tenofovir DF, sulindac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • tacrolimus

              tacrolimus and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

            • tafamidis

              tafamidis will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • tafamidis meglumine

              tafamidis meglumine will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • telavancin

              telavancin, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              telavancin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • tenofovir DF

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

            • sulfamethoxazole

              efavirenz will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • sunitinib

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

            • tadalafil

              efavirenz will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.

            • tamoxifen

              efavirenz, tamoxifen. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. CYP2C9/10 inhibition decreases tamoxifen metabolism to active metabolites.

              efavirenz, tamoxifen. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

            • tamsulosin

              efavirenz increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • tasimelteon

              efavirenz will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducers

            • tazemetostat

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

            • tecovirimat

              tecovirimat will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Consider increasing dosage of interacting drug, if necessary

            • temsirolimus

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

            • teniposide

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

            • tenofovir DF

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

            • terbinafine

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

            • tetracycline

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

            • theophylline

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

            • tiagabine

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

            • ticagrelor

              efavirenz decreases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid use of ticagrelor with potent CYP3A inducers.

            • ticlopidine

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

              ticlopidine will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • tinidazole

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

            • tipranavir

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

              tipranavir will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

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

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

            • tobramycin

              tenofovir DF and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              tobramycin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • tofacitinib

              efavirenz increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Loss of, or decreased response to tofacitinib may occur when coadministered with potent CYP3A4 inducers.

            • tolbutamide

              efavirenz will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • tolterodine

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

            • toremifene

              efavirenz decreases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers increase rate of toremifene metabolism, lowering the steady-state concentration in serum.

            • tramadol

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

            • trazodone

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

            • triamcinolone acetonide injectable suspension

              efavirenz will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triazolam

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

            • trimethoprim

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

            • tolmetin

              tenofovir DF, tolmetin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • trimipramine

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

              efavirenz will decrease the level or effect of trimipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • trospium chloride

              tenofovir DF, trospium chloride. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • tucatinib

              tucatinib will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • umeclidinium bromide/vilanterol inhaled

              efavirenz will decrease the level or effect of umeclidinium bromide/vilanterol inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • valacyclovir

              valacyclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • valganciclovir

              valganciclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

              valganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.

            • vancomycin

              tenofovir DF and vancomycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • vardenafil

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

            • venlafaxine

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

            • verapamil

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

            • vilanterol/fluticasone furoate inhaled

              efavirenz will decrease the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid or Use Alternate Drug.

            • vilazodone

              efavirenz decreases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider increasing vilazodone dose up to 2-fold (not to exceed 80 mg/day) when coadministered with strong CYP3A4 inducers for >14 days.

            • vorapaxar

              efavirenz decreases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vortioxetine

              efavirenz decreases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.

            • warfarin

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

            • zidovudine

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

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

            • zonisamide

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

            Minor (89)

            • alosetron

              efavirenz will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ambrisentan

              efavirenz will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amobarbital

              amobarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • aprepitant

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

            • armodafinil

              armodafinil will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              efavirenz will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • atazanavir

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

              efavirenz decreases levels of atazanavir by unspecified interaction mechanism. Minor/Significance Unknown. May be coadministered; see atazanavir monograph for dosing info.

            • black cohosh

              black cohosh, tenofovir DF. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hepatoxicity.

            • bosentan

              bosentan will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              efavirenz will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • butabarbital

              butabarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • butalbital

              butalbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • caspofungin

              efavirenz decreases levels of caspofungin by increasing metabolism. Minor/Significance Unknown.

            • cevimeline

              efavirenz will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cimetidine

              efavirenz will increase the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • clarithromycin

              efavirenz will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • clomipramine

              efavirenz will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cocaine

              efavirenz will increase the level or effect of cocaine by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

            • colchicine

              efavirenz will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • conivaptan

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

            • cortisone

              cortisone will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclosporine

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

            • darifenacin

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

            • darunavir

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

            • dasatinib

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

            • desipramine

              efavirenz will decrease the level or effect of desipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dexamethasone

              dexamethasone will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • diazepam

              efavirenz will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • disopyramide

              efavirenz will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • donepezil

              efavirenz will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dutasteride

              efavirenz will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eplerenone

              efavirenz will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • esomeprazole

              efavirenz will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • etravirine

              etravirine will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eucalyptus

              efavirenz will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • finasteride

              efavirenz will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fluconazole

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

            • fludrocortisone

              fludrocortisone will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fosamprenavir

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

            • fosphenytoin

              fosphenytoin will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • galantamine

              efavirenz will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • grapefruit

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

            • griseofulvin

              griseofulvin will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • imatinib

              efavirenz will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • imipramine

              efavirenz will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • indinavir

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

            • ketoconazole

              efavirenz will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lansoprazole

              efavirenz will increase the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • lapatinib

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

            • losartan

              efavirenz decreases effects of losartan by decreasing metabolism. Minor/Significance Unknown. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.

            • lumefantrine

              lumefantrine will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • marijuana

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

            • methylprednisolone

              methylprednisolone will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metronidazole

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

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • modafinil

              modafinil will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • montelukast

              efavirenz will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nelfinavir

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

            • nifedipine

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

            • nilotinib

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

            • nimodipine

              efavirenz will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nitrendipine

              efavirenz will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • oxybutynin

              efavirenz will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel

              efavirenz will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel protein bound

              efavirenz will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pantoprazole

              efavirenz will increase the level or effect of pantoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • parecoxib

              efavirenz will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paromomycin

              paromomycin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.

              paromomycin increases levels of tenofovir DF by decreasing elimination. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pioglitazone

              efavirenz will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ponatinib

              efavirenz decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.

            • posaconazole

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

            • prednisone

              prednisone will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • primidone

              primidone will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • propafenone

              efavirenz will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • quinine

              efavirenz will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rabeprazole

              efavirenz will increase the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              efavirenz will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ramelteon

              efavirenz will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rifapentine

              rifapentine will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ritonavir

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

            • rufinamide

              rufinamide will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • saxagliptin

              efavirenz will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sufentanil

              efavirenz will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sulfamethoxazole

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

            • topiramate

              topiramate will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            Listed adverse reactions are Grade 2-4 unless specified

            >10%

            Rash (18%)

            Headache (14%)

            Pain (13%)

            Diarrhea (11%)

            Depression (11%)

            Grade 3-4 laboratory abnormalities

            • Fasting cholesterol >250 mg/dL (19%)
            • Creatine kinase (males: >990 U/L; females >845 U/L) (12%)

            1-10%

            Fever (8%)

            Abdominal pain (7%)

            Asthenia (6%)

            Anxiety (6%)

            Arthralgia (5%)

            Insomnia (5%)

            Pneumonia (5%)

            Myalgia (3%)

            Dizziness (3%)

            Lipodystrophy (1%)

            Peripheral neuropathy (1%)

            Grade 3-4 laboratory abnormalities

            • Serum amylase >175 U/L (9%)
            • AST elevated (5%)
            • ALT elevated (4%)
            • Hematuria >100 RBC/HPF (7%)
            • Neutrophils <750 mg/dL (3%)
            • Fasting triglycerides >750 mg/dL (1%)

            Postmarketing Reports

            Efavirenz

            • Body as a whole: Allergic reactions, asthenia, redistribution/accumulation of body fat
            • Central and peripheral nervous system: Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, vertigo
            • Endocrine: Gynecomastia
            • Gastrointestinal: Constipation, malabsorption
            • Cardiovascular: Flushing, palpitations
            • Liver and biliary system: Hepatic enzyme increase, hepatic failure, hepatitis
            • Metabolic and nutritional: Hypercholesterolemia, hypertriglyceridemia
            • Musculoskeletal: Arthralgia, myalgia, myopathy
            • Psychiatric: Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide, catatonia
            • Respiratory: Dyspnea
            • Skin and appendages: Erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome
            • Special senses: Abnormal vision, tinnitus

            Lamivudine

            • Body as a whole: Redistribution/accumulation of body fat
            • Endocrine and metabolic: Hyperglycemia
            • General: Weakness
            • Hemic and lymphatic: Anemia (including pure red blood cell aplasia and severe anemias progressing on therapy)
            • Hepatic and pancreatic: Lactic acidosis and hepatic steatosis, posttreatment exacerbation 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
            • Renal and urinary disorders: Renal insufficiency, 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
            • Hepatobiliary disorders: Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)
            • Skin and subcutaneous tissue disorders: Rash
            • Musculoskeletal and connective-tissue disorders: Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy
            • General disorders and administration site conditions: Asthenia
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            Warnings

            Black Box Warnings

            Severe acute exacerbations of hepatitis B reported in patients coinfected with HBV and HIV-1 and who have discontinued lamivudine or tenofovir DF, 2 components of Symfi Lo

            Closely monitor hepatic function in these patients and initiate antihepatitis B treatment if necessary

            Contraindications

            Documented hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to any components contained in the formulation

            Coadministration with elbasvir and grazoprevir

            Cautions

            Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with the use of nucleoside analogs and other ARTs; suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity

            Not approved for chronic hepatitis B virus (HBV) infection and the safety and efficacy have not been established in patients coinfected with HBV and HIV-1; if treatment with Epivir-HBV, tenofovir DF, or a tenofovir AF-containing product is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment (see Black Box Warnings and Dosing Considerations)

            Risk of serious psychiatric events (eg, depression, suicidality, paranoia, manic episodes); immediate medical evaluation recommended for serious psychiatric symptoms such as severe depression or suicidal ideation; there have been occasional postmarketing reports of death by suicide, delusions, psychosis like behavior and catatonia; a causal relationship to the use of efavirenz cannot be determined from these reports (see Adverse Effects)

            CNS symptoms reported (eg, dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, hallucinations); nervous system symptoms (NSSs) are frequent and usually begin 1-2 days after initiating therapy and resolve in 2-4 weeks; dosing at bedtime may improve tolerability; NSSs are not predictive of onset of psychiatric symptoms

            Risk of rash; rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 2 weeks of initiating therapy with efavirenz (median time to onset of rash in adults was 11 days) and, in most patients continuing therapy with efavirenz, rash resolves within 1 month

            Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman (see Pregnancy)

            Postmarketing cases of hepatitis, including fulminant hepatitis progressing to liver failure requiring transplantation or resulting in death, reported in patients treated with efavirenz; reports included patients with underlying hepatic disease, including coinfection with hepatitis B or C, and patients without preexisting hepatic disease or other identifiable risk factors; monitoring of liver enzymes before and during treatment is recommended for all patients; consider discontinuing treatment in patients with persistent elevations of serum transaminases to greater than 5x ULN; discontinue treatment if elevation of serum transaminases is accompanied by clinical signs or symptoms of hepatitis or hepatic decompensations

            Hepatic decompensation, some fatal, reported in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy and interferon and ribavirin-based regimens; monitor for treatment-associated toxicities; discontinue therapy, as medically appropriate, and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both

            Immune reconstitution syndrome reported in HIV-infected patients treated with combination ART; during initial phase of combination ART, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), tuberculosis), and further evaluation and treatment may be necessary

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

            In HIV-infected patients, redistribution/accumulation of body fat (eg, central obesity, dorsocervical fat enlargement [buffalo hump], peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance) observed in patients receiving combination ART

            Treatment with efavirenz has resulted in increases in total cholesterol and triglycerides; perform cholesterol and triglyceride testing before initiating efavirenz therapy and at periodic intervals during therapy

            Convulsions observed in patients receiving efavirenz, generally in the presence of known medical history of seizures; exercise caution in any patient with a history of seizures

            In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, lamivudine should be used with caution

            Late-onset neurotoxicity

            • Ataxia and encephalopathy (impaired consciousness, confusion, psychomotor slowing, psychosis, delirium), may occur months to years after beginning therapy
            • Some events of late-onset neurotoxicity have occurred in patients with CYP2B6 genetic polymorphisms which are associated with increased drug levels despite standard dosing therapy
            • Evaluate promptly patients presenting with signs and symptoms of serious neurologic adverse experiences to assess the possibility that these events may be related to therapy, and whether discontinuation is warranted
            • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with use of nucleoside analogs and other antiretrovirals; female sex and obesity may be risk factors for development of lactic acidosis and severe hepatomegaly with steatosis in patients treated with antiretroviral nucleoside analogues

            Bone effects of tenofovir

            • In clinical trials, tenofovir DF was associated with slightly greater decreases in bone mineral density and increases in biochemical markers of bone metabolism
            • Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, reported
            • Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients
            • Effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults and pediatric subjects 2 years and older are unknown
            • Long-term effect of lower spine and total body BMD on skeletal growth in pediatric patients, and in particular, effects of long-duration exposure in younger children unknown
            • Consider assessment of BMD for adult and pediatric patients who have history of pathologic bone fracture or other risk factors for osteoporosis or bone loss; if bone abnormalities are suspected obtain appropriate consultation

            New onset or worsening renal impairment

            • Renal impairment (eg, cases of acute renal failure and Fanconi syndrome [eg, renal tubular injury with severe hypophosphatemia]) reported with the use of tenofovir DF
            • Assess estimated CrCl in all patients prior to initiating therapy and as clinically appropriate during therapy with tenofovir DF; in patients at risk of renal dysfunction, assess estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein prior to initiation of tenofovir disoproxil fumarate and periodically during tenofovir DF therapy
            • Cases of acute renal failure after initiation of high-dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDs) reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir DF; some patients required hospitalization and renal replacement therapy

            Drug interactions overview

            • Coadministration of Symfi Lo and other ARTs for HIV-1 should be avoided since Symfi Lo is a complete HIV infection
            • Concomitant use with other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effects, possible development of resistance, or possible increased effects/toxicities of concomitant drugs
            • Since tenofovir is primarily eliminated by the kidneys, coadministration of efavirenz/lamivudine/tenofovir DF with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir and/or increase the concentrations of other renally eliminated drugs; avoid efavirenz/lamivudine/tenofovir DF with concurrent or recent use of a nephrotoxic agent (eg, high-dose or multiple NSAIDs); consider alternatives to NSAIDs, if needed, in patients at risk for renal dysfunction
            • QTc prolongation observed with the use of efavirenz; consider alternatives to efavirenz-containing products when coadministered with a drug with a known risk of torsade de pointes or with patients at higher risk of torsade de pointes
            • Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels
            • False-positive urine cannabinoid test results reported with some screening assays in uninfected and HIV-infected subjects receiving efavirenz; confirmation of positive screening tests for cannabinoids by a more specific method is recommended Efavirenz has been shown in vivo to induce CYP3A and CYP2B6; efavirenz coadministered with CYP3A or CYP2B6 substrates may result in decreased plasma concentrations
            • Drugs that induce CYP3A activity (eg, rifampin, rifabutin) would be expected to increase the clearance of efavirenz, resulting in lowered plasma concentrations; this may lead to loss of virologic response and possibly resistance
            • Lamivudine is predominantly eliminated in the urine by active organic cationic secretion; coadministration with drugs eliminated via organic cationic transport system (eg, trimethoprim) may interact with lamivudine
            • Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures; when possible, avoid use of sorbitol-containing medicines with lamivudine
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            Pregnancy & Lactation

            Pregnancy

            Advise pregnant women of the potential risk to a fetus

            Owing to the potential teratogenic effects, avoid pregnancy in women receiving Symfi Lo

            Females of reproductive potential should undergo pregnancy testing before initiation

            An ART pregnancy registry has been established (1-800-258-4263); prospective pregnancy data from the Antiviral Pregnancy Registry (APR) not sufficient to adequately assess risk of birth defects or miscarriage

            Retrospective case reports of neural tube defects in infants whose mothers were exposed to efavirenz-containing regimens in the first trimester of pregnancy; similar malformations observed in studies conducted in monkeys at doses similar to the human dose; fetal and embryonic toxicities occurred in rats at a dose 10 times less than the human exposure at recommended clinical dose; owing to the potential risk of neural tube defects, do not use in the first trimester of pregnancy

            Lamivudine produced embryonic toxicity in rabbits at a dose that produced similar human exposures as the recommended clinical dose; relevance of animal findings to human pregnancy registry data is not known; there are no adequate and well-controlled studies with tenofovir DF in pregnant women; tenofovir DF should be used during pregnancy only if clearly needed

            Contraception

            • Females of reproductive potential should use effective contraception during and for 12 weeks after discontinuing treatment, owing to the long half-life of efavirenz
            • Always use barrier contraception in combination with other methods of contraception
            • Hormonal methods that contain progesterone may have decreased effectiveness

            Lactation

            The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection

            Efavirenz has been shown to pass into human breast milk; no information available on the effects of efavirenz on the breastfed infant or the effects of efavirenz on milk production

            Lamivudine is excreted into human milk

            Samples of breast milk obtained from five HIV-1-infected mothers in the first postpartum week show that tenofovir is excreted in human milk at low levels; impact of this exposure in breastfed infants is unknown and the effects of tenofovir DF on milk production is unknown

            Owing to the potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed

            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

            Tenofovir: NRTI; following hydrolysis and phosphorylation, inhibits HIV-1 reverse transcriptase by competing with AMP as substrate

            Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog

            Efavirenz: NNRTI; activity against HIV-1 by binding to reverse transcriptase and consequently blocking the RNA-dependent and DNA-dependent DNA polymerase activities including HIV-1 replication; it does not require intracellular phosphorylation for antiviral activity

            Absorption

            Efavirenz

            • Peak plasma time: 3-5 hr
            • Steady-state plasma concentration reached in 6-10 days

            Lamivudine

            • Peak plasma concentration: 1.5 mcg/mL (2 mg/kg BID)
            • Bioavailability: 87% (oral solution)
            • Peak plasma concentration
              • CrCl >60 mL/min, single 300-mg dose: 2.6 mcg/mL
              • CrCl 10-30 mL/min, single 300-mg dose: 3.6 mcg/mL
              • CrCl <10 mL/min, single 300-mg dose: 6 mcg/mL
            • AUC
              • CrCl >60 mL/min, single 300-mg dose: 11 mcg•hr/mL
              • CrCl 10-30 mL/min, single 300-mg dose: 48 mcg•hr/mL
              • CrCl <10 mL/min, single 300-mg dose: 157 mcg•hr/mL

            Tenofovir DF

            • Peak plasma time: 1 hr
            • Bioavailability: ~25% (fasted)
            • Peak plasma concentration
              • Fasted; single 300-mg dose: 296 ng/mL
              • CrCl >80 mL/min, single 300-mg dose: 0.34 mcg/mL
              • CrCl >80 mL/min, single 300-mg dose: 0.34 mcg/mL
              • CrCl 50-80 mL/min, single 300-mg dose: 0.33 mcg/mL
              • CrCl 30-49 mL/min, single 300-mg dose: 0.37 mcg/mL
              • CrCl 12-29 mL/min, single 300-mg dose: 0.6 mcg/mL
            • AUC
              • Fasted; single 300-mg dose: 2287 ng•hr/mL
              • CrCl >80 mL/min, single 300-mg dose: 2.18 mcg•hr/mL
              • CrCl 50-80 mL/min, single 300-mg dose: 3.06 mcg•hr/mL
              • CrCl 30-49 mL/min, single 300-mg dose: 6.01 mcg•hr/mL
              • CrCl 12-29 mL/min, single 300-mg dose: 15.98 mcg•hr/mL

            Distribution

            Efavirenz

            • Protein bound: ~99.5-99.75% (human plasma proteins, predominantly albumin)

            Lamivudine

            • Protein bound: <36%

            Tenofovir DF

            • Protein bound: <7% (0.01-25 mcg/mL)

            Metabolism

            Efavirenz

            • In vitro studies suggest CYP3A and CYP2B6 are major isozymes responsible for efavirenz metabolism; also shown to induce CYP enzymes, resulting in induction of its own metabolism

            Tenofovir DF

            • Not by CYP; converted intracellularly by hydrolysis to tenofovir, then phosphorylated to active tenofovir diphosphate

            Excretion

            Efavirenz

            • Half-life: 52-76 hr (single doses); 40-55 hr (multiple doses)
            • Excretion: Feces (16-68%)

            Lamivudine

            • Excretion, trans-sulfoxide metabolite: Urine (5.2%)
            • Majority of lamivudine is eliminated unchanged in urine by active organic cationic secretion
            • Half-life: 5-7 hr

            Tenofovir DF

            • Excretion: Urine (~70-80% [unchanged drug])
            • Half-life: ~17 hr
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            Administration

            Oral Administration

            Oral use only

            Take on an empty stomach, preferably at bedtime; dosing at bedtime may improve tolerability of neurologic symptoms

            Missed dose

            • Missed dose: Take dose as soon as possible
            • If it is almost time for next dose, skip missed dose and take next dose at your regular time

            Storage

            Tablets: Store below 30°C (86°F)

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            Images

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            Patient Handout

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

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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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.