Date of report 19 May 2023

Reported case interaction between
Cobicistat and TICAGRELOR

74 years old man living with HIV since 1986. Heavily treatment experienced because of virological failures and selection of resistance-associated mutations. Salvage therapy in 2007 with TDF/FTC, DRV/r an RAL achieving undetectable viral load. Current ART TAF/FTC, DRV/cobi, DTG (start date unknown).

Comorbidities: Hypertension; ischemic cardiomiopathy (AMI in 2011); Benign prostatic hyperplasia; depression.

In December 2022 he was hospitalized because a new AMI. He required coronary angioplasty and stent insertion and after this procedure, the inhibitor of platelet aggregation ticagrelor was initiated. During the following 2 months, no bleeding events were observed.  However, in February 2023, ticagrelor was switched to prasugrel.

Coadministration of ticagrleor and strong inhibitors of CYP3A4 such as cobicistat is contraindicated, as it may lead to a substantial increase in exposure to ticagrelor and bleeding risk.

Of note, other potential drug-drug interactions were also detected in this patient:

• Atorvastatin and solifenacin are metabolized by CYP3A4 and concentrations are expected to increase due to inhibition of CYP3A4 by cobicistat.
• Sacubitril is converted to the active metabolite LBQ657 by carboxylesterases. LBQ657 is a substrate of OATP1B1/3, OAT1 and darunavir/cobicistat may inhibit OATP1B1 and therefore increase the exposure of sacubitril’s active metabolite.

However, signs of toxicity related with these drugs was neither detected.