Cobicistat

Rifabutin

Avoid association.

No pharmaceutical opinion available for this interaction.

Mechanism

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.

Cobicistat

Pharmacodynamic effects

Possible decrease of the pharmacokinetic boosting effect.

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

Recommendations

Association not recommended. If used, closely monitor clinical effectiveness.

Choose an alternative.

Alternative solution(s)

Protease ihnibitor boosted with ritonavir or dolutegravir 50 mg QD or raltegravir 400 mg BID or raltegravir HD 1200 mg QD

Rifabutin

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

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.

Alternative solution(s)

Monitor

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

Tests

Rifabutin

Blood count

Liver function

CD4+

Viral load HIV

Associated PI plasma level

Pharmacokinetic parameters

Comment

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.

Reference
  • 2949
    Cobicistat (Tybost), European public assessment report (EPAR) Product Information, London, United Kingdom, 4 juin 2015.
  • 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.
  • 1096
    Rifabutin (Mycobutin), Pfizer, Québec, Canada, 22 juin 2015.
  • 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.
  • 3151
    AIDS info, Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Disponible : https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Publié le 17 oct. 2017. Consulté le 11 janvier 2018.