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Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis

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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
(Kaletra™)

 

 

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.

 

*Pediatric formulation and pharmacokinetic data are not available in children.

 

 
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