Enzalutamide is a strong CYP3A4 inducer, and this may lead to decreased exposure of Paxlovid, potential loss of virologic response, and possible resistance. Concomitant use of enzalutamide with Paxlovid is contraindicated. Paxlovid cannot be started immediately after discontinuation of CYP3A4 inducers due to the delayed offset of the recently discontinued CYP3A4 inducer. A multi-disciplinary approach (e.g., involving physicians and specialists in clinical pharmacology) should be considered to determine the adequate timing for Paxlovid initiation taking into account the delayed offset of the recently discontinued CYP3A inducer and the need to initiate Paxlovid within 5 days of symptom onset.

Co-administration may decrease nirmatrelvir/ritonavir concentrations. Paxlovid is contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. Paxlovid cannot be started immediately after discontinuation of enzalutamide due to the delayed offset of the recently discontinued CYP3A inducer.