Efavirenz Dosage

Usual Adult Dose for HIV Infection

600 mg orally once a day

Usual Adult Dose for Nonoccupational Exposure

(Not approved by FDA)

Centers for Disease Control and Prevention (CDC) recommendations: 600 mg orally once a day, in combination with (lamivudine or emtricitabine) plus (zidovudine or tenofovir)

Duration: 28 days

Prophylaxis should be initiated as soon as possible, within 72 hours of exposure.

Usual Adult Dose for Occupational Exposure

(Not approved by FDA)

CDC recommendations:
Alternate expanded regimen for HIV postexposure prophylaxis: 600 mg orally once a day, in combination with (lamivudine plus zidovudine) or (emtricitabine plus zidovudine) or (lamivudine plus tenofovir) or (emtricitabine plus tenofovir)

Duration: Generally 28 days; however, the exact duration of therapy may differ based on the institution's protocol.

Prophylaxis should be initiated immediately, preferably within hours after exposure.

Usual Pediatric Dose for HIV Infection

3 years or older:
10 to less than 15 kg: 200 mg orally once a day
15 to less than 20 kg: 250 mg orally once a day
20 to less than 25 kg: 300 mg orally once a day
25 to less than 32.5 kg: 350 mg orally once a day
32.5 to less than 40 kg: 400 mg orally once a day
40 kg or more: 600 mg orally once a day

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Mild hepatic impairment: The manufacturer recommends caution when administering this drug to patients with this degree of liver dysfunction.

Moderate to severe hepatic impairment: Not recommended.

Dose Adjustments

Concomitant voriconazole: The efavirenz dose should be decreased to 300 mg orally once a day using the capsule formulation.

Concomitant rifampin:
Patients weighing 50 kg or more: The efavirenz dose should be increased to 800 mg orally once a day.

Precautions

The concomitant administration of efavirenz with many other drugs is either contraindicated or not recommended. Patients should be advised to inform their healthcare providers of all other prescription and nonprescription drugs and supplements that they are taking.

Efavirenz has been associated with severe psychiatric adverse effects during clinical trials including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions. Delusions, psychosis-like behavior, and death by suicide have been reported during postmarketing use. The risk may be increased in patients with a history of injectable drug use, psychiatric history, or use of psychiatric medications. Patients should seek immediate medical attention if they experience serious psychiatric effects. The potential benefits versus the risk of continued treatment should be carefully evaluated.

Patients should be cautioned that efavirenz may impair the mental abilities necessary for performing potentially hazardous tasks such as driving or operating machinery and that the central nervous system effects may be additive with concomitant use of alcohol or psychoactive drugs.

Convulsions have occurred during efavirenz treatment, generally in patients with a history of seizures. Caution is recommended in all patients with a seizure history and plasma level monitoring may be recommended in patients concomitantly taking anticonvulsive medications metabolized by the liver.

The manufacturer recommends avoiding pregnancy during treatment with efavirenz. Barrier contraception must always be used in combination with other methods of contraception (e.g., hormonal) during efavirenz treatment. Use of adequate contraception for 12 weeks following efavirenz discontinuation is recommended. Pregnancy testing is recommended for women of childbearing potential prior to starting efavirenz therapy. Patients should be advised of the potential harm to the fetus if they become pregnant while taking efavirenz or if it is administered during the first trimester.

Patients should notify their physician if a rash develops. Efavirenz should be withdrawn if the rash is severe, such as that associated with blistering, desquamation, mucosal involvement, or fever. However, in most adult patients who developed a rash during clinical trials (26%), the rash was usually a mild or moderate maculopapular skin eruption that occurred within the first two weeks of therapy and resolved within one month despite continued use of the drug. Efavirenz can be reinitiated following interruption due to rash. The use of antihistamines and/or corticosteroids may improve tolerability and hasten resolution of rash. For patients who have had a life-threatening cutaneous reaction (e.g., Stevens-Johnson syndrome), alternative therapy should be considered.

Monitoring of liver enzymes before and during efavirenz therapy is recommended in patients treated concomitantly with hepatotoxic drugs, in patients with underlying liver disease (including hepatitis B or C infection), and in patients with marked transaminase elevations. Monitoring of liver enzymes should be considered in patients without preexisting liver dysfunction or other risk factors. The benefit of continued therapy with efavirenz should be weighed against the unknown risks of significant hepatotoxicity in patients with persistent serum transaminase elevations (to greater than 5 times the upper limit of normal).

Monitoring of triglycerides and cholesterol is recommended prior to starting efavirenz and periodically during therapy.

Immune reconstitution syndrome has occurred during combination antiretroviral therapy. Patients responding to therapy may develop an inflammatory response to indolent or residual opportunistic infections and require evaluation and treatment.

Efavirenz must not be used alone for the treatment of HIV-1 or added on as a sole agent to a failing regimen. Resistant virus, which also demonstrates cross-resistance to other nonnucleoside reverse transcriptase inhibitors (NNRTIs), emerges rapidly when efavirenz is used as monotherapy. The potential for viral cross-resistance should be considered when choosing new antiretroviral agents to be used in combination with efavirenz.

The potential for HIV-1 cross-resistance among NNRTIs exists but has not been fully explored. It is unknown what effect efavirenz therapy will have on the activity of subsequently administered NNRTIs. Selection of antiretroviral agents for a patient's medication regimen should be done carefully.

Since it is one of the active components, efavirenz should not be coadministered with efavirenz/emtricitabine/tenofovir unless needed for dose adjustment (e.g., with rifampin).

Safety and effectiveness have not been established in pediatric patients less than 3 years of age or less than 13 kg.

Dialysis

No adjustment recommended.

Other Comments

Efavirenz should be taken on an empty stomach. Administration with food has been shown to increase efavirenz concentrations and may lead to an increased incidence of adverse reactions. Efavirenz should be taken at bedtime to improve the tolerability of central nervous system adverse effects.

Efavirenz should always be used in combination with other antiretroviral agents.

See also...