DuPont applies to FDA for approval of one-tablet, once daily formulation of efavirenz

DuPont Pharmaceuticals Company announced this week that it has applied to the US Food and Drug Administration (FDA) for approval of both a 600 and a 300 mg tablet formulation of its anti-HIV drug efavirenz (Sustiva).

Efavirenz is a once-daily anti-HIV treatment, a non nucleoside reverse transcriptase inhibitor, used in combination with other antiretroviral drugs for the treatment of HIV infection. The new formulation of efavirenz, if approved by FDA, will provide patients in the US with the option to take one 600 mg efavirenz tablet once daily instead of the currently approved three 200 mg capsules once daily. The “new” 600 mg tablet is approximately the same size as an efavirenz 200 mg capsule.

The availability of efavirenz as one or two pills per day as part of a combination regimen may help patients cut down the number of pills required per day. Pending FDA approval, DuPont Pharmaceuticals hopes to launch the 600 and 300 mg formulations in early 2002 and will continue to manufacture the 200 mg capsules for those who still need to take efavirenz as three capsules once-daily.

Efavirenz Adverse Events

Efavirenz is generally well tolerated. The most common adverse events are nervous system symptoms (e.g., dizziness, insomnia, impaired concentration, somnolence, and abnormal dreaming), and mild to moderate rash. These symptoms occur early in treatment and generally resolve within two to four weeks. In a small number of patients, serious psychiatric adverse experiences have been reported. In controlled trials, serious psychiatric symptoms observed were severe depression (0.9%), suicidal ideation or attempts (0.5%), aggressive behaviour (0.3%), paranoid reactions (0.2%), and manic reactions (0.1%).

These problems were seen at a similar frequency in control groups and tended to occur more often in patients with a history of mental illness, where the frequency of each of these events was approximately one percent. A few suicides have been reported; however, a causal relationship to efavirenz has not been established. Patients with serious psychiatric experiences should contact their physician. Women should not become pregnant while taking efavirenz because birth defects have been seen in animals given efavirenz. Patients should be cautioned not to operate hazardous machinery or drive if they experience nervous system symptoms.

Drug Interactions

Efavirenz is administered currently as three 200 mg capsules once-daily. Efavirenz should not be administered concurrently with Hismanal (astemizole), Propulsid (cisapride), Versed (midazolam), Halcion (triazolam) or ergot derivatives. Current treatment guidelines recommend against the use of any antiretroviral agent as monotherapy. Therefore, efavirenz must not be used as a single agent to treat HIV or added on as a sole agent to a failing regimen. The choice of new antiretroviral agents to be used in combination with efavirenz should take into consideration the potential for viral cross-resistance. Efavirenz therapy should always be initiated in combination with at least one other antiretroviral agent to which the patient has not been previously exposed.