No pharmaceutical opinion available for this interaction.
Rifabutin can induce the metabolism (CYP 3A4) and decrease the plasma concentration of Elvitegravir / Cobicistat.
Elvitegravir / Cobicistat may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Rifabutin.
Elvitegravir 3A4 and then UGT1A1/3; Cobicistat 3A4 (major) and 2D6 (minor)
Elvitegravir : 2C9 (moderate)
Cobicistat : 3A4 and 2D6 (potent), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3
Possible decrease of clinical efficacy.
Avoid association. Choose an alternative.
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)
Increase of adverse effects.
Antibiotic not interacting with elvitegravir/cobicistat.
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
Elvitegravir plasma level
|150/150 mg||150/150 mg|
|- 67%||+ 59%|
|150 mg||150 mg|
|+ 525% *|
|+ 394% *||+ 41%|
|+ 384% *|
Ref #2721 : * Refer to 25-O-desacetyl rifabutin.
There was a similar exposure to rifabutin. The antimycobacterial effect observed was 21% higher with elvitegravir/cobicistat association. Further studies are in progress.
Ref #3067 : Twice daily administration of cobicistat with once daily elvitegravir mitigated the effect of rifabutin induction upon their coadministration. Elvitegravir and rifabutin exposures (AUC and Cmax) were within the predefined boundary, while EVG and RFB Cmin were higher, 59% for elvitegravir and 41% for rifabutin. Importantly, elvitegravir Cmin, the parameter best associated with antiviral activity, was >10-fold above the IC95 (45 ng/mL). Consistent with rifabutin coadministration with boosted-protease inhibitor regimens, the exposure of 25-O-desacetylrifabutin were markedly higher (~12-fold). However, the total increase in antimycobacterial activity was less than 2-fold.
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.