Apalutamide is a moderate to strong CYP3A4 inducer and this may lead to a decreased exposure of nirmatrelvir/ritonavir and potential loss of virologic response. In addition, serum concentrations of apalutamide may be increased when coadministered with ritonavir resulting in the potential for serious adverse events including seizure. Concomitant use of Paxlovid with apalutamide is not recommended.

Apalutamide is a moderate to strong CYP3A4 inducer and this may lead to a decreased exposure of nirmatrelvir/ritonavir and potential loss of virologic response. In addition, serum concentrations of apalutamide may be increased when coadministered with ritonavir resulting in the potential for serious adverse events including seizure. Concomitant use of Paxlovid with apalutamide 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 apalutamide due to the delayed offset of the recently discontinued CYP3A inducer.