https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=8362
https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=8362
No pharmaceutical opinion available for this interaction.
Darunavir / 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 Darunavir / ritonavir.
Possible decrease of clinical efficacy and risk of possible development of resistance to antiretroviral class.
No a priori dosage adjustment is recommended.
Monitor the clinical efficacy and appearance of adverse effects.
Dolutegravir 50 mg QD or raltegravir 400 mg BID or raltegravir HD 1200 mg QD : see dolutegravir + rifabutin or raltegravir + rifabutin.
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.
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Rifabutin adverse effects : rash, taste alterations, anorexia, nausea, insomnia, facial paralysis, twitching, peripheral neuritis, neutropenia, thrombocytopenia, arthralgia, uveitis, elevation of liver function tests.
Rifabutin
Blood count
Liver function
Darunavir plasma level
CD4+
Viral load HIV
| Reference number |
|---|
| # patients |
| HIV |
| Dose |
| Frequency |
| AUC |
| Cmax |
| Cmin |
| 2415 |
|---|
| 11 |
| - |
| 150 mg |
| Q48h |
| - 7% * |
| - 28% * |
| + 64% * |
| 2415 |
|---|
| 11 |
| - |
| 600/100 mg |
| BID |
| + 57%/+ 66% |
| + 42% |
| + 75% |
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 #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.
Ref #2415: * Compared to rifabutin 300 mg QD alone.
The AUC, Cmax and Cmin of 25-O-desactyl rifabutin increased by 9.81-fold, 4.77-fold and 27.1-fold, respectively. Dose reduction of rifabutin by at least 75% of the usual dose (300 mg once daily) is recommended (i.e., a maximum dose of 150 mg every other day).