Ritonavir: Expanded Access Begins, Warning on Drug Interactions

The new protease inhibitor ritonavir is now becoming available through an expanded access program from Abbott Laboratories. This drug must be used very carefully, because it has strong interactions with many other drugs. The main problem is that ritonavir blocks a liver enzyme which normally destroys certain drugs, causing normal doses of the other drug to accumulate to toxic levels. Doses of the other drug may need to be greatly reduced -- and in many cases they should not be used together with ritonavir at all.

This same kind of effect is caused by some other drugs, such as ketoconazole. But the effect is much stronger with ritonavir than with any other drug physicians have experience with. This is a critical time in the development of ritonavir, as the drug has previously been used only in tightly controlled clinical trials, and is now moving into the less controlled expanded access program.

The concern was increased by the unexpected death of Philadelphia treatment activist Jonathan Lax on January 11, a day and a half after he switched to taking open-label ritonavir, after participating in a placebo-controlled trial during which he was convinced he was receiving the placebo. He was reportedly taking many other medications, although we do not know which ones. We do not know whether ritonavir had anything to do with his death; about 1500 people have taken ritonavir so far, and no similar case has ever been reported. Still, this incident emphasizes the need for caution. Abbott is working closely with the medical examiner's office in Philadelphia to determine the cause of death.

A partial list of over 20 drugs which should not be taken together with ritonavir is available from Project Inform. For a current copy of the list, contact the Project Inform hotline at 800/822-7422, or 415/558-9051, 10 a.m. to 4 p.m. Pacific time, Monday through Saturday. Persons using ritonavir need to talk with their physicians, who should have the latest information from Abbott concerning dose adjustments, or drugs which must be avoided entirely.