Date of report 22 Jun 2020
Reported case interaction between
Cobicistat and CLORAZEPATE

FLS Science

Drugs suspected to be involved in the DDI

Perpetrator
Cobicistat
Daily Dose
150 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Dec. 3, 2019
End date
Ongoing
Victim
CLORAZEPATE
Daily Dose
50 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Ongoing

Complete list of drugs taken by the patient

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

Clorazepate

Clinical case description

Gender
Female
Age
50
eGFR (mL/min)
>60
Liver function impairment
No
Description

50 years old woman diagnosed with HIV in 1997. She had been receiving ART with abacavir, lamivudine and nevirapine maintaining undetectable plasma viral load until September 2019 when she stopped ART during 2 months. In November 2019 ART was reinitiated with FTC/TAF + RAL but it was switched to DRV/c/FTC/TAF because of poor adherence. She was also receiving clorazepate because of a chronic anxiety disorder. Clorazepate is converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Despite nordiazepam plasma concentrations are expected to be increased in combination with a strong inhibitor of CYP3A4 like cobicistat, no adverse events were observed.

Clinical Outcome

No unwanted outcome

Editorial Comment

Darunavir/c is expected to increase nordiazepam exposure due to CYP3A4 Inhibition. Development of adverse effects as a consequence of drug-drug interaction is likely to vary from one person to the other.

University of Liverpool Recommendation

Potential interaction - may require close monitoring, alteration of drug dosage or timing of administration
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