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Efavirenz is a strong inducer of the CYP340 system and, because of its long half-life, may have lasting effects on the metabolism of other drugs even after it is discontinued. A recent study examined the pharmacokinetic effects of recent efavirenz exposure on the metabolism of rilpivirine, the recently approved NNRTI.

This open-label trial involved 17 healthy volunteers who received rilpivirine 25 mg daily for 14 days (period 1) followed by a 14- to 21-day washout, then efavirenz 600 mg daily for 14 days, followed immediately by rilpivirine 25 mg daily for 28 days (period 2). Pharmacokinetic evaluations were conducted during the two rilpivirine dosing periods. During period 2, when rilpivirine was initiated immediately after efavirenz discontinuation, levels of rilpivirine were reduced in comparison with levels for period 1: rilpivirine C_min was 28% lower on days 1 and 14, and remained 25% lower on day 28, compared with the C_min during period 1 of rilpivirine treatment.

It is not currently known whether this prolonged reduction in rilpivirine C_min will have any significant effect on virologic suppression or resistance development, but because it is likely that patients may be switched from efavirenz to rilpivirine, it is important to develop strategies for managing this interaction. Pending further study, direct switches from efavirenz to rilpivirine should be done cautiously and with close monitoring.

References

1. Crauwels H, Vingerhoets J, Ryan R, et al. Pharmacokinetic parameters of once-daily TMC278 following administration of EFV in healthy volunteers. In: Program and abstracts of the 18th Conference on Retroviruses and Opportunistic Infections; February 27-March 2, 2011; Boston. Abstract 630.