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.
3A4 and 2D6 (major), 1A2 and 2B6 (minor), 5 metabolites, one of which has a weak concentration of an active metabolite (M-2), transporters: MRP1, MRP2, P-gp
2B6, 2C8, 2C9, 1A2, 2C19 (moderate) UGT (moderate)
3A4 (potent) and 2D6 (moderate), transporters: BCRP, OATP1A2, OATP1B1, OATP1B3, MRP1, MRP2, OCT1, OCT2, P-gp
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.
Dolutegravir 50 mg QD or raltegravir 400 mg BID or raltegravir HD 1200 mg QD
3A4, cholibestérase, Un des métabolites est métabolisé CYP 3A4 (25-O-desacetyl rifabutine = activité similaire à la rifabutine)
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.
Rifabutin adverse effects : rash, taste alterations, anorexia, nausea, insomnia, facial paralysis, twitching, peripheral neuritis, neutropenia, thrombocytopenia, arthralgia, uveitis, elevation of liver function tests.
Viral load HIV
Associated PI plasma level
|+ 4 x|
|+ 2.5 x|
|+ 6 x|
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.