Darunavir / ritonavir

Rifampin

Contraindicated.

No pharmaceutical opinion available for this interaction.

Mechanism

Rifampin increases the metabolism (CYP 3A4) and decreases the plasma concentration of Darunavir / ritonavir.

Darunavir / ritonavir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Risk of a possible development of resistance to antiretroviral class.

Recommendations

Alternative solution(s)

Rifampin

Pharmacodynamic effects

Increased risk of hepatotoxicity.

Recommendations

Use an alternative.

Alternative solution(s)

Rifabutin either 150 mg QD, every 2 days or 3 times a week (see rifabutin with PIs) or choose an antibiotic that does not interact with PIs.

Monitor

Tests

Pharmacokinetic parameters

Comment

Co-administration of rifampicin 600 mg QD with protease inhibitors such as lopinavir/ritonavir, darunavir/ritonavir, atazanavir/ritonavir and atazanavir alone causes a decrease in AUC and Cmin of approximately 75% to 80%.

Ref #3571 : This study evaluated the safety and pharmacokinetic profile of adjusted doses of darunavir/ritonavir (1600/200 mg QD and 800/100 mg BID) with rifampicin in virologically suppressed PLWH without TB. The study was stopped early because adjusted doses of darunavir/ritonavir with rifampicin had unacceptable risk of hepatotoxicity. Darunavir trough concentrations were markedly reduced with the daily adjusted dose.

Ref #3425 : This In vitro inhibition study investigates the complex interplay between CYP3A induction, inhibition, metabolism and hepatic transport using the HepatopacTM system which displays a singular capacity in capturing all relevant pathways. Addition of 600 mg rifampicin resulted in a pronounced decrease of darunavir Cmax, AUC24h, and Ctrough in the various simulated regimens (800/100 mg QD DRV/r, 1600/200 mg QD DRV/r and 800/100 mg BID DRV/r). Based on their findings, changing the darunavir/ritonavir regimen from 800/100 mg QD to 800/100 mg BID was identified as the most promising regimen to counter the interaction of 600 mg QD rifampicin in HIV patients co-infected with TB.

Ref #3116 : To increase the chance of achieving therapeutic serum levels and reduce the development of resistance and treatment failures some experts, as well as the CDC, recommend a 150mg QD dose. See rifabutin + PIs.

Reference
  • 2386
    Darunavir (Prezista), Janssen, Ontario, Canada, 23 mai 2018.
  • 3571
    Ebrahim I, Maartens G, Wiesner L, Orrell C, Smythe W, et al. Pharmacokinetic profile and safety of adjusted doses of darunavir/ritonavir with rifampicin in people living with HIV. J Antimicrob Chemother. 2020 Apr 1; 75(4): 1019-1025.
  • 3426
    Jacobs F, Van Delft Y, Crauwels 1, Lachau-Durand S, Mohammed P et al. Predicted Pharmacokinetic Interactions of Rifampicin with Ritonavir-Boosted Darunavir. 19th International Workshop on Clinical Pharmacology of Antiviral Therapy. May 22-24 2018, Baltimore, USA, Abstract 37.
  • 3116
    Center for Disease Control and prevention. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis. Disponible: http://www.cdc.gov/tb/publications/guidelines/tb_hiv_drugs/recommendations03.htm Publié le 22 sept 2014. Consulté le 11 janvier 2018.