Liverpool HIV Interactions

Potential Weak Interaction

Rilpivirine (RPV)

Ketoconazole

Quality of Evidence: Low

Summary:

Coadministration may increase rilpivirine concentrations. No dose adjustment is required for rilpivirine when co-administered with azole antifungal agents, but clinical monitoring for breakthrough fungal infections is recommended when azole antifungals are co-administered with rilpivirine. Coadministration of rilpivirine (150 mg once daily) and ketoconazole (400 mg once daily) increased rilpivirine Cmax, AUC and Cmin by 30%, 49% and 76%, respectively. Ketoconazole Cmax, AUC and Cmin decreased by 15%, 24% and 66%, respectively. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.] Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with ketoconazole. However, the product labels for rilpivirine indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Ketoconazole has a conditional risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Description:

Coadministration of ketoconazole (400 mg once daily) and a higher than the recommended dose of rilpivirine decreased ketoconazole AUC and Cmin by 24% and 66%, but had no effect on Cmax. This was due to induction of CYP3A due to high rilpivirine dose in the study. Rilpivirine AUC, Cmin and Cmax increased by 49%, 76% and 30%, respectively, due to inhibition of CYP 3A enzymes. At the recommended dose of 25 mg once daily, no dose adjustment is required when rilpivirine is co-administered with ketoconazole.

Edurant Summary of Product Characteristics, Janssen-Cilag Ltd, January 2019.

Concomitant use of rilpivirine with azole antifungal agents may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No rilpivirine dose adjustment is required when rilpivirine is co-administered with azole antifungal agents. Clinically monitor for breakthrough fungal infections when azole antifungals are co-administered with rilpivirine. Coadministration of rilpivirine (150 mg once daily) and ketoconazole (400 mg once daily) was studied in 15 subjects. Rilpivirine Cmax, AUC and Cmin increased by 30%, 49% and 76%, respectively. Ketoconazole Cmax, AUC and Cmin decreased by 15%, 24% and 66%, respectively.

Edurant US Prescribing Information, Janssen Therapeutics, May 2019.

Coadministration of rilpivirine (150 mg once daily) and ketoconazole (400 mg once daily) was studied in 15 HIV-negative subjects. Rilpivirine Cmax, AUC and Cmin increased by 30%, 49% and 76%, respectively. Ketoconazole Cmax, AUC and Cmin decreased by 15%, 24% and 66%, respectively.
van Heeswijk R, et al. The pharmacokinetic interaction between ketoconazole and TMC278, an investigational non-nucleoside reverse transcriptase inhibitor, in healthy HIV-negative subjects. 16th International AIDS Conference, Toronto, August 2006, abstract TUPE0087.

View all available interactions with Rilpivirine (RPV) by clicking here.