Date of report: 22 Jun 2020
Reported case interaction between
Cobicistat and Clorazepate
Cobicistat and Clorazepate
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
Dec. 3, 2019
End date
Ongoing
Drug B
Clorazepate
(Victim)
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.
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.