Drug Detail

Efavirenz

Last Updated June 10, 2016

Trade Names

  • Efavirenz: Stocrin, Aspen Efavirenz, Cipla-Efavirenz, Adco-Efavirenz, Erige, Efavirenz Winthrop, Sonke Efavirenz, Efrin (Mylan),Viref, Efamat;
  • Tenofovir/emtricitabine/efavirenz: Atripla, Odimune (Cipla Medpro),Citenvir, Atroiza (Mylan), Eftenem;
  • Zidovudine/lamivudine plus efavirenz: Cipla-Duovir/Cipla Efavirenz copack;
  • Tenofovir/lamivudine/efavirenz: Tenarenz (Aspen), Eflaten

Drug Classification

Nonnucleoside reverse transcriptase inhibitor antiretroviral

Formulations

  • Efavirenz: 50 mg, 200 mg capsules; 200 mg, 600 mg tablets
  • Tenofovir/emtricitabine/efavirenz: 300/200/600 mg tablet
  • Zidovudine/lamivudine plus efavirenz: 300/150 mg plus 600 mg tablets
  • Tenofovir/lamivudine/efavirenz: 300/300/600 mg tablets

Indications and Pharmacology

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%.

Dosage

Adult Dose: 600 mg once daily at bedtime; take on an empty stomach.

No dose adjustment with rifampicin. If dosed concomitantly with rifabutin, rifabutin dose should be increased(see Drug–Drug Interactions).

Use in Renal or Hepatic Insufficiency:

  • No dose adjustments needed in renal insufficiency.
  • Contraindicated in patients with severe liver disease.

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):

  • 13-15 kg: 200 mg once daily.
  • 15-20 kg: 250 mg once daily.
  • 20-25 kg: 300 mg once daily.
  • 25.0-32.5 kg: 350 mg once daily.
  • 32.5-40.0 kg: 400 mg once daily.
  • ≥ 40 kg: 600 mg once daily.

Warnings

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.

Drug–Drug Interactions

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:

Considerations for Special Populations

  • Recommended for HIV-positive pregnant women, breastfeeding women, and women of childbearing age who initiate antiretroviral therapy.
  • Should not be used in children < 3 years or < 13 kg.

Adverse Effects

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.