Dosage adjustment is recommended.

No pharmaceutical opinion available for this interaction.


Ritonavir can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Rifabutin.

Rifabutin can induce the metabolism (CYP 3A4) and decrease the plasma concentration of Ritonavir.


Pharmacodynamic effects

Possible decrease of clinical efficacy.

Therefore, resulting in loss of therapeutic effect of associated IP.


No a priori dosage adjustment is recommended.

Monitor for clinical efficacy and adjust the dosage if necessary.

Alternative solution(s)

Dolutegravir 50 mg QD or raltegravir 400 mg BID or raltegravir HD 1200 mg QD


Pharmacodynamic effects

Possible increase of adverse effects.


Dose reduction suggested of up to 75% (e.g., 150 mg every other day).

To increase the probabilities of achieving therapeutic serum levels and reduce the development of resistance and treatment failures some experts, as well as the DHHS, recommend a rifabutin dose of 150mg QD.

Monitor closely clinical efficacy and appearance of adverse effects.

Alternative solution(s)


Rifabutin adverse effects : rash, taste alterations, anorexia, nausea, insomnia, facial paralysis, twitching, peripheral neuritis, neutropenia, thrombocytopenia, arthralgia, uveitis, elevation of liver function tests.



Blood count

Liver function


Viral load HIV

Associated PI plasma level

Pharmacokinetic parameters
Reference number
# patients
AUC 0-24h
Duration (days)
+ 4 x
+ 2.5 x
+ 6 x
150 mg
500 mg

Several studies were initially done with healthy subjects with the combination of protease inhibitors and rifabutin. These studies demonstrated that a dose of rifabutin 150 mg 3 times/week associated with protease inhibitors was approximately equivalent to a dose of rifabutin 300 mg QD.
Subsequently, studies in subjects co-infected with HIV and tuberculosis demonstrated that the dose of 150 mg 3 times/week was insufficient for some subjects. Therefore, the dose of rifabutin 150 mg QD in combination with PIs is currently recommended in the guidelines.

Rifabutin dosage at steady-state (t1/2 normal; 25hrs) : targeted therapeutic index of 0.3-0.9μg/ml 3-4 post dose (Cmax) and a dose reduction may be necessary from 1μg/ml depending on the clinical context.

Ref #307: The AUC 0-24h, Cmax and Cmin of 25-O-desacetyl rifabutine increased by 35x, 16x and 200x, respectively. Because ritonavir may induce its own metabolism, it is possible to observe an increase in rifabutine metabolism right after stopping ritonavir.

Ref #3117 : Concomitant administration of a protease inhibitor and rifabutin increases the plasma concentrations of rifabutin and 25-O-desacetyl rifabutin. The addition of a protease inhibitor slightly increases the concentrations of rifabutin, but increases the concentrations of 25-O-deacetyl rifabutin by 5 to 10-fold. In return, rifabutin does not significantly affect the plasma concentrations of protease inhibitors.

  • 122
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 5 juillet 2021.
  • 307
    Cato A 3rd, Cavanaugh J, Shi H et al. The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin. Clin Pharmacol Ther 1998;63:414-421.
  • 328
    Gallicano K, Khaliq Y, Seguin I et al. A pharmacokinetic study of intermittent rifabutin dosing with a combination of ritonavir and saquinavir in HIV patients. 8th Annual Canadian Conference on HIV/AIDS Research 1999. Abstract B-204.
  • 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.
  • 3117
    Regazzi M, Carvalho AC, Villani P, Matteelli A. Treatment Optimization in Patients Co-Infected with HIV and Mycobacterium tuberculosis Infections: Focus on Drug–Drug Interactions with Rifamycins. Clinical Pharmacokinetics, June 2014, 53 (6), 489-507.
  • 2449
    Naiker S, Conolly C, Weisner L, Kellerman T, Reddy T et al.Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy. BMC Pharmacol Toxicol. 2014; 15: 61.
  • 1096
    Rifabutin (Mycobutin), Pfizer, Québec, Canada, 22 juin 2015.
  • 3151
    U.S. Department of Health and Human services (DHHS) : Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Disponible : https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines. Publié le 16 août 2021. Consulté le 16 septembre 2021.