Darunavir / cobicistat

Edoxaban

Dose adjustment and closer monitoring are required.

No pharmaceutical opinion available for this interaction.

Mechanism

Darunavir / cobicistat can decrease the P-gp and increase the plasma concentration of Edoxaban.

Darunavir / cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Edoxaban

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

Use with caution or choose an alternative.

A decrease in the dose should be considered.

Monitor closely clinical efficacy and appearance of adverse effects.

See comments.

Alternative solution(s)

Prefer warfarin or potentially dabigatran or low molecular weight heparin (LMWH).

Monitor

Effectiveness and safety (signs and symptoms of bleeding : anemia, hematoma, hematuria, epistaxis, gastrointestinal disorders, urinary and digestive haemorrhage) and, particularly in patients with bleeding risk factors (old person, low body weight, impaired kidney function).

Tests

Pharmacokinetic parameters

Comment

Ref #3396 : In a study, a single concomitant dose of edoxaban 60 mg with ketoconazole 400 mg QD, increased edoxaban AUC and Cmax by 87% and 89%, respectively.
The product monograph states that HIV protease inhibitors such as darunavir/ritonavir or lopinavir/ritonavir can inhibit P-gp and potentially increase edoxaban exposure by 1.5 to 2-fold. They also say that concomitant use with potent P-gp inhibitors, such as ketoconazole or erythromycin, requires edoxaban dose reduction to 30 mg QD.

Reference
  • 3396
    Edoxaban (Lixiana), Servier, Québec, Canada, 26 juil 2017.
  • 3437
    Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza), Janssen Inc, Ontario, Canada, 3 octobre 2018.