Atazanavir

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

Atazanavir can decrease the P-gp and increase the plasma concentration of Edoxaban.

Atazanavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Edoxaban

Pharmacodynamic effects

Possible increase of adverse effects.

Recommendations

A decrease in the dose should be considered.

Monitor closely clinical efficacy and appearance of adverse effects.

See comments.

Alternative solution(s)

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.