Sirolimus and Voriconazole interaction

Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp Avoid concomitant use of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampin or rifabutin) [ see Drug Interactions (7.2) ].

Strong Inducers and Strong Inhibitors of CYP3A4 and P-gp Avoid concomitant use of sirolimus with strong inducers (e.g., rifampin, rifabutin) and strong inhibitors (e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin) of CYP3A4 and P-gp.

Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.

Use with Cyclosporine Cyclosporine, a substrate and inhibitor of CYP3A4 and P-gp, was demonstrated to increase sirolimus concentrations when co-administered with sirolimus.

Weak and Moderate Inducers or Inhibitors of CYP3A4 and P-gp Exercise caution when using sirolimus with drugs or agents that are modulators of CYP3A4 and P-gp.

…• Ergot alkaloids (e.g., ergotamine, dihydroergotamine) • Finerenone • Ivabradine • Lurasidone • Naloxegol • Pimozide • Quinidine • Rifabutin [see Clinical Pharmacology (12.3) ] • Sirolimus [see Clinical Pharmacology (12.3) ] • Tolvaptan • Venetoclax: Coadministration at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic…

…Drugs [see Clinical Pharmacology (12.3)] Drug/Drug Class (Mechanism of Interaction by Voriconazole) Drug Plasma Exposure (C max and AUC τ ) Prevention or Management Recommendations Sirolimus Results based on in vivo clinical studies generally following repeat oral dosing with 200 mg BID voriconazole to healthy subjects (CYP3A4 Inhibition) Significantly Increased…