Date of report 21 Jun 2019

Reported case interaction between
Cobicistat and Quetiapine

In this case a DRV/Cobi dose 800/150 mg every 12 hours was used, maybe to overcome PI resistance, for compliance reasons and taking into consideration the potential interaction between DRV/cobi and etravirine (see below). However, this is not the recommended dose of DRV/cobi, and this limits the generalization of this report. If DRV/cobi (instead of DRV/r) is to be used with etravirine, there is a potential DDI that could markedly decrease DRV concentrations (Moltó J et al. JAC 2018; 73:732-7) with potential risk of virological failure (However, that study was done with DRV/cobi once-daily, but not with DRV/cobi twice-daily). Quetiapine trough concentrations were within the normal range (although close to the lower margin). However, quetiapine daily doses in this patient were of 25 mg/daily, which are far below the usual dose (200-800 mg/daily). Although the European product label for quetiapine contraindicates the drug with CYP3A4 inhibitors (such as cobicistat), the US product label recommends reducing quetiapine to 1/6 of the original dose in that setting. However, the 25 mg daily dose used in this case is even lower than 1/6 of the lowest usual dose. Of note, a multidirectional DDI with quetiapine and ARV might be possible in this patient, as etravirine can act as a CYP3A4 inducer, potentially lowering quetiapine concentrations (and partially compensating the cobi inhibitory effect; quality of evidence: very low).