Drugs suspected to be involved in the DDI-summary
Complete list of drugs taken by the patient
Quetiapine, Mirtazapine, Clonazepam, Desvenlafaxine
Clinical case description
55 years old HIV+ man with severe chronic depression. For this reason, quetiapine was initiated in July 2016, while he was on ART with EVG/c/FTC/TDF (Stribild). The initial dose of quetiapine was 100-25-25 mg and it was increased progressively (100-25-50 mg, 100-100-200 mg) until the current dose (since December 2016): 300 mg twice daily. In July 2017 ART was switched to EVG/c/FTC/TAF (Genvoya). He has never presented quetiapine toxicity related symptoms.
It is important to note that in the European SPC both EVG/c/FTC/TDF and EVG/c/FTC/TAF are contraindicated with quetiapine due to the known inhibition of CYP3A4 metabolism by cobicistat and therefore potential increase in quetiapine exposure. In the US prescribing information the recommendation is to dose reduce the quetiapine to 1/6th of the dose. Individualization of dosing to manage a drug interaction is an important principle of patient management. The interesting point about this case is that the dose of quetiapine was progressively increased over a period of time and at the current dose of 600 mg there have been no apparent adverse effects due to supra therapeutic concentrations of quetiapine. Despite this particular case it is important to be very cautious about this interaction. Note that quetiapine can be administered over a range of doses and the greatest concern will be at higher doses when the implications of increasing the exposure is greatest.