Efavirenz Gets Expanded Indication for HIV

Megan Brooks


May 07, 2013

The US Food and Drug Administration (FDA) has expanded the approval of efavirenz (Sustiva, Bristol-Myers Squibb) to HIV-1 infected children as young as 3 months and weighing at least 3.5 kg, the agency announced on May 2.

For pediatric patients who cannot swallow capsules, the capsule contents can be sprinkled on a small amount of food (1 - 2 teaspoons) or put in infant formula, the FDA said. However, use of infant formula for mixing should only be considered for those young infants who cannot reliably consume solid foods. Detailed information about the "capsule sprinkle" method will be provided in the instructions for use at the end of the patient information section of the package insert.

The updated labeling includes a table for once-daily dosing along with the corresponding number of capsules or tablets and strength to administer. Capsules can be administered intact or as sprinkles. Tablets must not be crushed.

Table. Recommended dosing

Body weight Daily dose Number of capsules or tablets and strength to administer
3.5 to less than 5 kg 100 mg Two 50-mg capsules
5 to less than 7.5 kg 150 mg Three 50-mg capsules
7.5 to less than 15 kg 200 mg One 200-mg capsule
15 to less than 20 kg 250 mg One 200-mg + one 50-mg capsule
20 to less than 25 kg 300 mg One 200-mg + two 50-mg capsules
25 to less than 32.5 kg 350 mg One 200-mg + three 50-mg capsules
32.5 to less than 40 kg 400 mg Two 200-mg capsules
At least 40 kg 600 mg One 600-mg tablet or three 200-mg capsules

Efavirenz, a non-nucleoside reverse transcriptase inhibitor, was approved in the United States in 1998 to treat HIV-1 infected children 3 years of age or older and weighing at least 10 kg.

According to the FDA, the new indication for efavirenz was based on results from 3 open-label studies of the drug in combination with other antiretroviral agents in 182 HIV-1 infected pediatric patients aged 3 months to 21 years. Virologic and immunologic response was observed across all ages at the end of the studies, as measured by HIV RNA and CD4 cell count.

The FDA said adverse reactions observed in the 3 pediatric trials were similar to those observed in adult clinical trials, except for rash, which was more common in pediatric patients and more severe.

Rash was reported in 59 (32%) of 182 pediatric patients treated with efavirenz; 2 pediatric patients experienced grade 3 rash (confluent rash with fever, generalized rash), and 4 had grade 4 rash (erythema multiforme). Five pediatric patients (2.7%) discontinued from the study because of rash. Prophylaxis with appropriate antihistamines before initiating therapy with efavirenz in pediatric patients should be considered, the FDA advises.

The agency also says use of efavirenz in patients younger than 3 months or less than 3.5 kg body weight is not recommended because its safety, pharmacokinetics, and antiretroviral activity have not been evaluated in this age group and there is a risk of developing HIV resistance if efavirenz is underdosed.

The FDA said the complete revised labeling will be posted soon on Drugs@FDA.