Last Updated June 10, 2016
Nonnucleoside reverse transcriptase inhibitor antiretroviral
Indication: treatment of HIV infection in combination with other antiretrovirals; postexposure prophylaxis in combination with other antiretrovirals.
Mechanism of action*: binds directly to reverse transcriptase, which interferes with HIV viral RNA–dependent DNA polymerase inhibiting viral replication.
Pharmacokinetics: metabolized in the liver by CYP 2B6 and 3A4. CYP 3A4 mixed inhibitor/inducer. Half-life: 40-55 hours. Administration with a high-fat meal increases bioavailability by 50%.
Adult Dose: 600 mg once daily at bedtime; take on an empty stomach.
Use in Renal or Hepatic Insufficiency:
Use in Pregnancy and Breastfeeding: Category D. Can be used in HIV-positive pregnant women and in women of childbearing age who initiate antiretroviral therapy (ART); can be continued in HIV-positive women who become pregnant on efavirenz-containing ART.
Excreted into breast milk. Safety with breastfeeding has not been established.
Use in Children: Safety and efficacy in children < 3 years or < 13 kg not established.
Children ≥ 3 years (oral doses):
Skin rashes are more common in children than adults.
Central nervous system adverse effects may be worsened by concomitant use of psychoactive drugs or alcohol.
Taking with a high-fat meal increases bioavailability by 50% and is not recommended.
Efavirenz has a long half-life; if treatment is to be discontinued, stopping efavirenz 1-2 weeks before stopping the rest of the regimen may reduce the risk of resistance development. Alternatively, efavirenz may be replaced by a PI before interrupting therapy.
Increased concentrations of concomitant medication*: warfarin.
Decreased concentrations of concomitant medication*: methadone, warfarin, carbamazepine, phenobarbital, phenytoin, bupropion, sertraline, itraconazole, posaconazole, voriconazole, ketoconazole, clarithromycin, rifabutin (rifabutin dose should be increased to 450 mg/day), diltiazem, verapamil, felodipine, nicardipine, nifedipine, boceprevir, levonorgestrel, norelgestromin, etonogestrel, norgestimate, atorvastatin, simvastatin, pravastatin, simeprevir, cyclosporine, tacrolimus, sirolimus, artemether, lumefantrine, atovaquone, proguanil.
Increased concentrations of efavirenz with concomitant medication*: voriconazole.
Decreased concentrations of efavirenz with concomitant medication*: carbamazepine, phenobarbital, phenytoin, rifampicin (increase efavirenz dose to 800 mg once daily for patients weighing ≥ 50 kg).
Drug interactions between efavirenz and other antiretrovirals:
Neuropsychiatric symptoms (drowsiness, dizziness, insomnia, confusion, abnormal dreams, amnesia, hallucinations), particularly in first 2-6 weeks of therapy; mild to moderate maculopapular rash; increased liver function tests; hyperlipidaemia; false positive cannabinoid drug screening.*
*Information from US prescribing information.
†South African National Department of Health Consolidated Guidelines, 2015.