HIV/AIDS Update - Updated label information for Sustiva (efavirenz)

The Food and Drug Administration recently approved revisions to the package insert for Sustiva (efavirenz), a non-nucleoside reverse transcriptase inhibitor, for both capsules and tablets, to include updates to the sections described below.

WARNINGS and PRECAUTIONS

Reproductive Risk Potential
Antiretroviral Pregnancy Registry: (updated data) As of July 2009, the Antiretroviral Pregnancy Registry has received prospective reports of 661 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first trimester exposures (606 pregnancies). Birth defects occurred in 14 of 501 live births (first trimester exposure) and 2 of 55 live births (second/third-trimester exposure). One of these prospectively reported defects with first-trimester exposure was a neural tube defect. A single case of anophthalmia with first-trimester exposure to efavirenz has also been prospectively reported; however, this case included severe oblique facial clefts and amniotic banding, a known association with anophthalmia. There have been six retrospective reports of findings consistent with neural tube defects, including meningomyelocele.

Hepatotoxicity
Monitoring of liver enzymes before and during treatment is recommended for patients with underlying hepatic disease, including hepatitis B or C infection; patients with marked transaminase elevations; and patients treated with other medications associated with liver toxicity. A few of the postmarketing reports of hepatic failure occurred in patients with no pre-existing hepatic disease or other identifiable risk factors. Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. In patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range, the benefit of continued therapy with Sustiva needs to be weighed against the unknown risks of significant liver toxicity.

ADVERSE REACTIONS
Postmarketing Experience
Liver and Biliary System:A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing in some cases to transplantation or death.

DRUG INTERACTIONS
Posaconazole: Avoid concomitant use unless the benefit outweighs the risks
Maraviroc: Refer to the full prescribing information for maraviroc for guidance on coadministration with efavirenz.

USE IN SPECIFIC POPULATIONS
Hepatic Impairment
The pharmacokinetics of efavirenz have not been adequately studied in patients with hepatic impairment. Because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with hepatic impairment, caution should be exercised in administering Sustiva to these patients

PATIENT PACKAGE INSERT (PPI)
What are the possible side effects of Sustiva?
Liver problems. Some patients taking Sustiva have experienced serious liver problems including liver failure resulting in transplantation or death. Most of these serious side effects occurred in patients with a chronic liver disease such as hepatitis infection, but there have also been a few reports in patients without any existing liver disease.

The following medicines may need to be replaced with another medicine when taken with Sustiva
Noxafil (posaconazole)
The following medicines may require a change in the dose of either Sustiva or the other medicine
Selzentry (maraviroc)
The complete revised label can be found at http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020972s035,021360s023lbl.pdf
Sustiva is manufactured by Bristol-Myers Squibb.

Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration