Date of report: 23 Dec 2020
Reported case interaction between
 Cobicistat and Rifabutin

FLS Science

Drugs suspected to be involved in the DDI

Drug A
Cobicistat (Perpetrator)
Daily Dose
150 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Unknown
Drug B
Rifabutin (Victim)
Daily Dose
300 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Unknown

Complete list of drugs taken by the patient

Antiretroviral treatment
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir-AF
Complete list of all comedications taken by the patient, included that involved in the DDI
rifabutin

Clinical case description

Gender
Female
Age
63
eGFR (mL/min)
>60
Liver function impairment
Yes
Child-Pugh
Child-Pugh C
Description
A 63-year-old HIV-infected female with a history of latent TB, cirrhosis secodary to non-alcoholic steatohepatitis. The patient has been treated with rifabutin 300 mg daily for a 4 month treatment course 9 months prior. Due to a communication error, the patient was restarted on rifabutin 300 mg daily for 3 months while on treatment with elvitegravir/cobicistat, emtricitabine and tenofovir alafenamide. The patient developed a bilateral panuveitis likely due to the inhibitory effect of cobicistat on rifabutin metabolism leading to high concentrations of rifabutin. Rifabutin-associated uveitis has been recognized as a dosage-dependent side effect. This report was published by Toomey C et al. Case rep Ophthalmol 2020.

Outcome

Toxicity

Drug Interaction Probability Scale (DIPS)

Score
6 - Probable

Editorial Comment

Coadministration is not recommended as it may significantly decrease elvitegravir/cobicistat plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Coadministration of elvitegravir/cobicistat (150 mg/150 mg once daily) and rifabutin (300 mg once daily alone or 150 mg every other day with elvitegravir/cobicistat) decreased elvitegravir Cmin by 67%. Rifabutin exposure was similar to values obtained alone, but 25-O-desacetylrifabutin exposures were 4.8 to 6.3 fold higher. The European SPC suggests that if the combination is needed, to use rifabutin 150 mg 3 times per week on set days (e.g. Monday-Wednesday-Friday) with increased monitoring for rifabutin associated adverse reactions including neutropenia and uveitis due to increased desacetyl rifabutin exposure