Darunavir / ritonavir

Edoxaban

Dose adjustment and closer monitoring are required.

Available pharmaceutical opinion

Document made available to the pharmacist to communicate a drug interaction to the doctor.

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Mechanism

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

Darunavir / ritonavir

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.
Canadian 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.

Ref #3527 : However, according to clinical information, when performing this dose reduction in the presence of P-gp inhibitors, it was observed in the ENGAGE AF-TIMI study that the plasma levels of edoxaban were lower compared to patients who were receiving the standard dose. Consequently, no dose reduction is recommended for concomitant P-gp inhibitor use.

Reference
  • 3396
    Edoxaban (Lixiana), Servier, Québec, Canada, 12 février 2020.
  • 3527
    Edoxaban (Savaysa), Prescribing Information, Daiichi Sankyo Inc. NJ USA, April 2020.
  • 3528
    Wiggins BS, Dixon DL Neyens RR, Page RL et al. Select Drug-Drug Interactions With Direct Oral Anticoagulants: JACC Review Topic of the Week. J Am Coll Cardiol. 2020 Mar 24; 75 (11): 1341-50.