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Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis

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Table 2a. Recommendations for coadministering antiretroviral drugs with rifampin in adults – 2013

 

Non-nucleoside reverse transcriptase inhibitors

 

Recommended change in dose of antiretroviral drug

Recommended change in dose of rifampin

Comments

 

Efavirenz

 

 

None;
some clinicians may increase the dose to 800mg in persons weighing >50kg.

 

No change
(600 mg/day)

 

Effect on efavirenz AUC is highly variable.  Efavirenz should not be used during the 1st trimester of pregnancy. 

 

   Nevirapine

 

Initiate at a dose of 200 mg twice daily rather than 200 mg once daily (use the same maintenance dose of 200 mg twice daily)

 

 

No change
(600 mg/day)

 

Efavirenz is preferred, but if nevirapine must be used, lead-in dosing at 200 mg once-daily should be avoided, as this may increase risk of virologic failure. Because of this risk, monitoring of adherence and viral load is recommended.  If available, consider therapeutic drug monitoring.

 

   Rilpivirine

 

Rifampin and rilpivirine should not be used together

 

Rilpivirine AUC ¯ by 80%, Cmin decreased 89%

   Etravirine

 

Etravirine and rifampin should not be used together

 

Marked decrease in etravirine predicted, based on data on the interaction with rifabutin

 

Single protease inhibitors

 

Recommended change in dose of antiretroviral drug

Recommended change in dose of rifampin

 

Comments

 

   Atazanavir

 

Rifampin and atazanavir should not be used together

 

Atazanavir AUC ¯ by >95%. Increasing the dose to 300 mg twice daily or 400 mg twice daily still resulted in subtherapeutic atazanavir concentrations.

 

Ritonavir-boosted protease inhibitors

 

Recommended change in dose of antiretroviral drug

Recommended change in dose of rifampin

Comments

 

Lopinavir / ritonavir (Kaletra)

Lopinavir  800 mg plus ritonavir 200 mg twice daily (double dose)

No change
(600 mg/day)

Use with caution; this combination resulted in hepatotoxicity in all adult healthy volunteers in an initial study. It was better-tolerated among adult patients already taking lopinavir/ritonavir based ART with increase to 600 mg/150 mg after one week, then 800 mg/200 mg one week later.

“Super-boosted” lopinavir / ritonavir
   (Kaletra)

Lopinavir  400 mg plus ritonavir 400 mg twice daily (super boosting)

No change
(600 mg/day)

Use with caution; this combination resulted in hepatotoxicity among adult healthy volunteers.  It has not been adequately tested in patients with HIV.

Atazanavir / ritonavir

Rifampin and atazanavir/ritonavir should not be used together.

Atazanavir trough concentration ¯ by > 90%. Doubling the dose to 300/100 twice daily resulted in hepatotoxicity in healthy volunteers.

Darunavir / ritonavir

Rifampin and darunavir/ritonavir should not be used together

No drug interaction studies of darunavir and rifampin have been conducted.

Fosamprenavir/ritonavir

Rifampin and fosamprenavir/ritonavir should not be used together

Fosamprenavir Cmax decreased by 70%, AUC decreased 82%, trough decreased 92%

Saquinavir / ritonavir

Rifampin and saquinavir/ritonavir should not be used together. 

The combination of saquinavir (1000 mg twice-daily), ritonavir (100 mg twice-daily), and rifampin caused unacceptable rates of hepatotoxicity among healthy volunteers. In tuberculosis patients, 400/400 twice daily caused similar rates of hepatotoxicity.

 

CCR-5 receptor antagonists

 

Recommended change in dose of antiretroviral drug

Recommended change in dose of rifampin

Comments

Maraviroc

Increase maraviroc to 600 mg twice-daily

No change
(600 mg/day)

The reductions in maraviroc concentrations related to rifampin co-administration may be overcome by increasing the dose, though the 600 mg twice-daily dose has not been formally tested.  Use with caution, as there is no reported clinical experience with increased dose of maraviroc with rifampin

 

Integrase inhibitors

 

Recommended change in dose of antiretroviral drug

Recommended change in dose of rifampin

Comments

Raltegravir

Increase dose to 800 mg twice daily

No change
(600 mg/day)

Raltegravir trough concentrations reduced by 53% even with increased dose to 800 mg twice daily despite reasonable overall exposures. The clinical significance of this is unknown. Use this dose with caution and employ viral load monitoring, if available.

Elvitegravir co-formulated with cobicistat, tenofovir, and emtricitabine (Stribild™)

 

Stribild and rifampin should not be used together

 

Marked decrease in elvitegravir and cobicistat concentrations predicted based on metabolic pathways of these drugs

 

 
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