Efavirenz

Efavirenz, marketed as Sustiva, is a prescription drug used for the treatment of HIV infection.

Efavirenz belongs to a family of drugs called antiretrovirals. More specifically, efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral. Other members of the NNRTI antiretroviral family include Intelence, Rescriptor and Viramune.

Efavirenz is marketed by Bristol-Myers Squibb.

Uses

Efavirenz was approved by the Food and Drug Administration (FDA) on September 17, 1998, for use with other antiretroviral agents (drugs that work against HIV) in the treatment of HIV infection in adults and children age 3 and older. Efavirenz does not cure HIV infection or AIDS and does not reduce the risk of passing the virus to other people.

How Efavirenz is Taken

Efavirenz is taken by mouth and is available by prescription in the following dosages: 50 or 200 mg capsules and 600 mg tablets.

In adults

The recommended dosage in adults is 600 mg once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs). Taking efavirenz with food in the stomach can lead to increased levels of the drug in the blood; therefore, efavirenz should be taken on an empty stomach, preferably at bedtime.

In children

Efavirenz is to be taken on an empty stomach, preferably at bedtime. The recommended daily dosages for children 3 years of age or older are:

• 22-32 lbs: 200 mg
• 33-43 lbs: 250 mg
• 44-54 lbs: 300 mg
• 55-71.4 lbs: 350 mg
• 71.5-87 lbs: 400 mg
• over 87 lbs: 600 mg

How Efavirenz Works

Efavirenz, the active ingredient in Sustiva, is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1). It has no activity against a related virus, HIV-2.

Efavirenz inhibits HIV-1 reverse transcriptase, an enzyme necessary for HIV-1 to make copies of itself.

How the body affects efavirenz

Peak levels in the blood are reached 3-5 hours after a dose is taken.

Efavirenz is primarily metabolized (broken down) by enzymes in the liver called cytochrome P450 CYP3A4 and CYP2B6.

Approximately 14-34% of the original dose is excreted as metabolites in the urine and 16-61% is excreted as metabolites in the feces.

Side Effects

Serious side effects can occur in people taking efavirenz and the drug may need to be stopped. These include the following:

• Abnormal thinking
• Confusion
• Depression
• Hallucinations
• Memory loss
• Paranoid thinking
• Thoughts of suicide
• Severe rash

Other, less serious side effects have been reported and they may lessen or disappear with continued use of the medicine. These include the following:

• Nausea
• Diarrhea
• Vomiting
• Pain in the abdomen
• Sleep problems
• Abnormal dreams
• Headache
• Dizziness
• Trouble concentrating
• Fatigue
• Anxiety
• Nausea
• Loss of appetite
• Indigestion
• Mild rash
• Abnormal liver tests

Risks and Precautions

Skin Rash

In controlled clinical trials, 26% of people taking 600 mg of efavirenz pre day developed a skin rash compared with 18% of people in a control group (not taking efavirenz). In most people who develop this side effect, efavirenz does not need to be stopped and the rash resolves within one month.

A severe rash associated with blistering, skin shedding, ulceration, or fever, was seen in less than 1% of people taking efavirenz. Stevens-Johnson syndrome, a form of severe rash, was seen in 0.1%. Severe rashes usually resolve without long-term problems once the drug is stopped.

Liver impairment

Efavirenz can cause an increase in the level of liver enzymes measured in the blood. This does not usually mean that the drug needs to be stopped. However, there have been rare reports of liver failure in people with AIDS who were taking efavirenz along with other medications. The exact role of efavirenz in these rare cases is unclear.

Because of the extensive metabolism of efavirenz by the liver, efavirenz may be inappropriate for people with liver impairment, including those with hepatitis B or hepatitis C virus infections.

Convulsions

Convulsions have been observed rarely in patients receiving efavirenz, generally in the presence of a known medical history of seizures. In people with a history of convulsions, an alternative to efavirenz should be used if possible.

Cholesterol

Efavirenz may affect cholesterol and triglyceride levels.

Fat Redistribution

Redistribution of body fat including central obesity, dorsocervical fat enlargement ("buffalo hump"), peripheral or facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy, including efavirenz.

Immune Reconstitution Syndrome

Immune reconstitution syndrome (an aggressive immune response to a hidden, or residual opportunistic infections) has been reported in people treated with combination antiretroviral therapy, including efavirenz.

Nursing Mothers

The Centers for Disease Control and Prevention (CDC) recommends that HIV-infected mothers not breast-feed their infants to avoid risking transmission of HIV, even if they are taking efavirenz and other antiretroviral medications.

Drug Interactions

The following drugs are not to be taken with efavirenz:

• Antihistamines
• Benzodiazepines
• GI motility drugs
• Anti-migraine drugs
• Some antifungal drugs
• Ergot derivatives

Effectiveness

The effectiveness of efavirenz was measured in two clinical trials named Study 006 and ACTG 364:

• Study 006 involved over 1200 patients and compared a efavirenz/zidovudine/lamivudine combination therapy with a efavirenz/indinavir combination therapy and a indinavir/zidovudine/lamivudine combination therapy. For patients treated with efavirenz/zidovudine/lamivudine, efavirenz/indinavir, or indinavir/zidovudine/lamivudine, the percentage of patients with HIV-1 RNA levels < 50 copies/mL was 43%, 31%, and 23%, respectively, through 168 weeks. A post-study data analysis suggests that the response levels continue through 4 years. Therefore, the efavirenz/zidovudine/lamivudine combination is the most effective among the three.^[1]

• ACTG 364 studied 196 patients receiving NRTIs in combination with efavirenz or nelfinavir or efavirenz/nelfinavir combination therapy. There was no significant difference in the mean CD4+ cell count among treatment groups. However, an analysis of time to treatment failure through 72 weeks demonstrates a longer duration of virologic suppression (HIV RNA <500 copies/mL) in the patients treated with efavirenz.^[2]

References

1. ↑ Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999 Dec 16;341(25):1865-73. Abstract | Full Text
2. ↑ Albrecht MA, Bosch RJ, Hammer SM, et al. Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. N Engl J Med. 2001 Aug 9;345(6):398-407. Abstract | Full Text

External Links

• AIDSinfo (NIH): Efavirenz
• AIDSMeds.com: Sustiva
• MedlinePlus: Efavirenz
• Food and Drug Administration (FDA): Efavirenz: Patient Information Sheet
• Drugs.com: Efavirenz
• Rx List: Efavirenz