Delavirdine Interaction Studies--Caution!!! 9/14/96

An announcement has been released by Upjohn & Pharmacia's discussing recent results from the interaction study they have been conducting of their new non-nucleoside RT inhibitor called delavirdine with 3 approved protease inhibitors--saquinavir, ritonavir and indinavir.

These results are preliminary data and not complete. The research was conducted by Upjohn and the 3 protease inhibitor manufacturers did not participate in the studies. Merck will be conducting its own interaction studies to confirm the Upjohn data, and I presume so will Abbott and Roche. Without this confirmation, you may be taking a risk by making treatment decisions based on the preliminary Upjohn data.

Combining a NNRTI with a protease inhibitor may alter the blood concentrations of either or both drugs. The amount of alteration is unknown without adequate research to properly explore the question. If you alter the blood concentration of the NNRTI (delavirdine or nevirapine) or the protease inhibitor, you may acheive undesired blood concentrations. In effect, you could be over- or underdosing either or both of the drugs (the NNRTI and the protease inhibitor). Underdosing can be equivalent to taking to low a dose of for example indinavir, saquinavir, the NNRTI or ritonavir. As you know, that can cause resistance and subsequent cross-resistance. Overdosing could be the equivalent of taking more than prescribed of ritonavir, the NNRTI or indinavir. Dangerous side effects or toxicities could result from overdosing.

Another concern to be aware of is the potential for NNRTI cross-resistance. If resistance develops from underdosing of one NNRTI, you could develop cross-resistance to other NNRTIs. At the nevirapine FDA Advisory Committee hearing, Dr. Maureen Myers said nevirapine can be cross-resistant with delavirdine.

So, I would advise to be circumspect and patient. Stay tuned for further developments.

Related articles:

• post-Vancouver article on nevirapine (9/14/96)
• pre-Vancouver article on nevirapine (6/9/96)
• delavirdine and drug interactions (4/4/96)