Darunavir / cobicistat

Trazodone

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Darunavir / cobicistat may possibly inhibit the metabolism (CYP 2D6 and 3A4) and consequently increase the concentration of Trazodone.

Darunavir / cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Trazodone

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

If antiretroviral therapy is going on, start with a small dose and gradually increase depending on efficacy and safety.

If patient already on trazodone and antiretroviral therapy is started, reduce the dose by 50% and gradually increase depending on efficacy and safety.

In patients already being treated with this combination and tolerating it, if deemed appropriate, keep actual treatment and exercise close monitoring of adverse effects.

Alternative solution(s)

Monitor

Trazodone toxicity: dizziness, fatigue, sweating, orthostatic hypotension, syncope, priapism.

Anticholinergic adverse effects: xerostomia, constipation, urinary retention, sedation, drowsiness, blurred vision, akathisia, convulsions, tachycardia, hypotension, etc.

Tests

Pharmacokinetic parameters

Comment

Ref #1515 : When co-administering a single dose of trazodone with ritonavir 200 mg BID an increase was observed in trazodone AUC and Cmax of 140% and 34%, respectively. Cases of patients showing symptoms as nausea, dizziness, fatigue, performance issues, hypotension and syncope have been reported.

Reference
  • 1515
    Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone. J Clin Pharmacol 2003;43(4):414-422.
  • 1308
    Zalma A, von Moltke LL, Granda BW, et al. In vitro metabolism of trazodone by CYP 3A: Inhibition by ketoconazole and human immunodeficiency viral protease inhibitors. Biol Psychiatry 2000;47:655-661.
  • 1514
    Trazodone (Desyrel), Novopharm, Ontario, Canada, mars 2011.
  • 3071
    Darunavir/cobicistat (Prezcobix), Janssen, Ontario, Canada, 7 avril 2017.
  • 3437
    Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza), Janssen Inc, Ontario, Canada, 3 octobre 2018.