Efavirenz (Sustiva) May Interact with Anticonvulsant Drug Phenytoin (Dilantin)

The non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva) may interact with the anticonvulsant medication phenytoin (Dilantin), leading to dangerously reduced levels of efavirenz, according to a case report in the January 2 issue of AIDS. Efavirenz is also a component of the widely used fixed-dose combination pill Atripla (efavirenz/tenofovir/emtricitabine).

The case report concerns a 35-year-old HIV positive Seattle man with a history of epilepsy who had been taking phenytoin plus pregabalin (Lyrica) to control his seizures. He was diagnosed with HIV after presenting with oral/esophageal candidiasis (thrush) and wasting, and was found to have a very low CD4 cell count (11 cells/mm3).

The patient was first treated with fluconazole (Diflucan) for candidiasis and prophylactic drugs for other opportunistic infections, then was started on an antiretroviral regimen containing efavirenz plus tenofovir/emtricitabine (Truvada).

Although he received a higher than usual dose of efavirenz due to a known interaction with rifampin (used as prophylaxis for Mycobacterium avium complex), he had no measurable efavirenz in his blood 4 and 14 days after starting the drug. Nevertheless, he experienced a decrease in HIV RNA, likely due to the other drugs in his antiretroviral regimen.

At 14 days, the study authors further increased the patient's efavirenz dose (to 600 mg twice daily) and switched him from phenytoin to different anticonvulsants. After 2 more weeks, his efavirenz blood concentration was near the expected level and his viral load continued to decrease; at that point, his efavirenz dose was lowered.

Based on this case report, clinicians should exercise caution when combining efavirenz and phenytoin, since subtherapeutic levels of efavirenz can lead to loss of virological control and emergence of drug-resistant virus.

01/11/08

Reference
CW Spak, S Dhanireddy, and BW Kosel. Clinical interaction between efavirenz and phenytoin. AIDS 22(1): 164-165. January 2, 2008.