No pharmaceutical opinion available for this interaction.
Cobicistat 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 Cobicistat.
3A4 (major) and 2D6 (minor).
3A4 (strong) et 2D6 (moderate), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3.
Possible decrease of the pharmacokinetic boosting effect.
Therefore, resulting in loss of therapeutic effect of associated IP.
Association not recommended. If used, closely monitor clinical effectiveness.
Choose an alternative.
Protease ihnibitor boosted with ritonavir or 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.
Avoid this combination, otherwise a decrease in the dose is necessary.
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 the 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
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.
Ref #3117 : To optimize the monitoring for rifabutin, dosage of this agent, at equilibrium (t1/2 normal; 25hrs), may be necessary. The targeted therapeutic index of 0.3-0.9μg/ml 3-4 post dose (Cmax) and a dose reduction may be necessary from 1 μg/ml depending on the clinical context.
Association not recommended with elvitegravir/cobicistat. See elvitegravir/cobicistat + rifabutin.