Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis
Table 3. Recommendations for coadministering antiretrovirals with rifabutin in adults* – 2013
Non-nucleoside reverse-transcriptase inhibitors
|
Antiretroviral dose change |
Rifabutin dose change |
Comments |
|
|
Efavirenz
|
No change |
↑ to 600 mg (daily or thrice-weekly) |
If efavirenz is used, the rifamycin of choice is rifampin. Efavirenz reduces rifabutin concentrations, so if rifabutin is to be used, increasing rifabutin dose to 600 mg may compensate for the inducing effect of efavirenz. Employ caution as this strategy has not been tested among patients taking rifabutin daily or thrice-weekly. Efavirenz should not be used during the 1st trimester of pregnancy. |
|
Nevirapine |
No change |
No change (300 mg daily) |
Rifabutin and nevirapine AUC not significantly changed. |
|
Rilpivirine |
Rifabutin and rilpivirine should not be used together |
Rilpivirine AUC ↓ by 46% and Cmin ↓ by 49%. |
|
|
Etravirine |
No change |
No change (300 mg daily) |
No clinical experience; etravirine Cmin ↓ by 35% and rifabutin AUC reduced 17%; these changes are unlikely to be clinically relevant, so no dose adjustment is necessary. Since ritonavir-boosted darunavir and saquinavir also diminish etravirine concentrations, the combination of these boosted PIs, etravirine, and rifabutin is not recommended. |
Single protease inhibitors
|
Antiretroviral dose change |
Rifabutin dose change |
Comments |
|
|
Atazanavir |
No change |
↓ to 150 mg once daily |
No published clinical experience. |
Dual protease inhibitor combinations
|
Antiretroviral dose change |
Rifabutin dose change |
Comments |
|
|
Lopinavir / ritonavir
|
No change |
↓ to 150 mg once daily |
In patients with HIV taking lopinavir/ritonavir, 150 mg once daily of rifabutin produces favorable rifabutin pharmacokinetics. Clinical safety data are limited. Monitor closely for potential rifabutin toxicity – uveitis, hepatotoxicity, and neutropenia. |
|
Fosamprenavir/ritonavir |
No change |
↓ to 150 mg once daily |
In healthy volunteers, a dose of 150 mg every other day of rifabutin given together with standard dose boosted fosamprenavir resulted in an increase in amprenavir AUC and Cmax by 35% and no change in Cmin. Limited clinical data among patients with HIV. Monitor closely for uveitis, hepatotoxicity, and neutropenia. |
| Ritonavir (any dose) with saquinavir, indinavir, amprenavir, fos-amprenavir, atazanavir, tipranavir or darunavir |
No change |
↓ to 150 mg once daily |
Rifabutin AUC ↑ and 25-O-des-acetyl rifabutin AUC ↑, by varying degrees. Monitor closely for uveitis, hepatotoxicity, and neutropenia. . |
CCR-5 receptor antagonists
|
Maraviroc |
No change |
No change |
No clinical experience; a significant interaction is unlikely, but this has not yet been studied |
integrase inhibitors
|
Raltegravir |
No change |
No change |
When given with standard-dose rifabutin (300 mg daily), raltegravir AUC increased 19%, Cmin decreased 20%, and Cmax increased 39%. These changes are unlikely to be clinically-significant. |
| Elvitegravir co-formulated with cobicistat, tenofovir, and emtricitabine (Stribild™) |
Stribild™ and rifabutin should not be used together
|
When given with rifabutin 150 mg thrice-weekly, elvitegravir Cmin reduced 64%, cobicistat Cmin reduced 71%, and 25-O-desacetylrifabutin AUC increased 6-fold. | |