Based on theoretical considerations darunavir/cobicistat is expected to increase nifedipine plasma concentrations (CYP3A and/or CYP2D6 inhibition). Clinical monitoring of therapeutic and adverse effects is recommended when these medicines are co-administered with darunavir/cobicistat.

Coadministration is expected to increase concentrations of nifedipine. Clinical monitoring is recommended for co-administration with calcium channel blockers metabolized by CYP3A.

PBPK/PD models for 3 formations of nifedipine were developed based on the Simcyp nifedipine model and the models were verified using published data. The effects of ritonavir on nifedipine exposure and systolic blood pressure (SBP) were assessed for instant-release, sustained-release and controlled-release formulations in patients. The predicted maximum concentration (Cmax), area under plasma concentration-time curve (AUC), maximum reduction in SBP and area under effect-time curve were all within 0.5-2.0-fold of the observed data. Model simulations showed that the inhibitory effect of ritonavir on CYP3A4 increased the Cmax of nifedipine 17.92-48.85-fold and the AUC 63.30-84.01-fold at steady state and decreased the SBP by >40 mmHg. Thus, the combination of nifedipine and ritonavir could lead to severe hypotension. It is not recommended for patients to take nifedipine- and ritonavir-containing regimens simultaneously.