Do Not Coadminister
Quality of Evidence: Moderate
Coadministration is not recommended as it may significantly decrease ritonavir concentrations and consequently those of protease inhibitors being boosted, leading to loss of therapeutic effect and possible development of resistance.
Although rifampicin may induce metabolism of ritonavir, limited data indicate that when high doses of ritonavir (600 mg twice daily) is co-administered with rifampicin, the additional inducing effect of rifampicin (next to that of ritonavir itself) is small and may have no clinical relevant effect on ritonavir levels in high-dose ritonavir therapy. The effect of ritonavir on rifampicin is not known.
Norvir Summary of Product Characteristics, AbbVie Ltd, September 2016.
The coadministration of ritonavir (500 mg every 12 hours for 20 days) with rifampicin (600 or 300 mg daily for 10 days) was investigated using a study with parallel group design. Ritonavir AUC, Cmax and Cmin were decreased by 35%, 25% and 49%, respectively. Coadministration of rifampicin and ritonavir may lead to loss of virologic response. Alternative antimycobacterial agents, such as rifabutin, should be considered.
Norvir Prescribing Information, AbbVie Inc, December 2016.
A study was performed in eight HIV+ subjects receiving ritonavir (600 mg twice daily) and anti-TB therapy which included rifampicin (600 mg daily) with isoniazid and pyrazinamide. After 8 weeks, trough plasma concentrations ranged from 350 ng/ml to 5630 ng/ml and were stated to be above the IC95 (650 ng/ml –LHPG: this value is lower than the generally accepted MEC for ritonavir – there is still need for caution) in all but one subject. The authors conclude that ritonavir and rifampicin can be administered concomitantly in HIV+ subjects with TB and result in a good clinical, immunological and virological response.
Treatment of tuberculosis in HIV-infected patients: safety and antiretroviral efficacy of the concomitant use of ritonavir and rifampin. Moreno S, Podzamczer D, Blazquez R, et al. AIDS, 2001, 15:1185-7.
A study was conducted on three HIV negative TB patients receiving rifampicin and indinavir/ritonavir (800/100 mg) and six healthy volunteers receiving indinavir/ritonavir (800/100 mg) without rifampicin. The AUCs of indinavir and ritonavir were decreased by 81 and 89%, respectively. The AUCs of rifampicin and its active metabolite were increased by 25 and 63% but their peak and trough concentrations were not influenced.
Double trouble: A pharmacokinetic study of indinavir/ritonavir (800+100 mg bid) and rifampicin for patients co-infected with TB and HIV. de Gast M, Burger D, van Crevel R, et al. 2nd International Workshop on Clinical Pharmacology of HIV Therapy, Noordwijk, the Netherlands, 2001, abstract 1.10.