Document made available to the pharmacist to communicate a drug interaction to the doctor.DOWNLOAD
Elvitegravir / Cobicistat can decrease the P-gp and increase the plasma concentration of Edoxaban.
Elvitegravir 3A4 and then UGT1A1/3; Cobicistat 3A4 (major) and 2D6 (minor)
Elvitegravir : 2C9 (moderate)
Cobicistat : 3A4 and 2D6 (potent), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3
P-gp, 3A4 (less than 10%)
Possible increase of adverse effects.
Use with caution or choose an alternative.
A decrease in the dose should be considered.
Monitor closely clinical efficacy and appearance of adverse effects.
Prefer warfarin or potentially dabigatran or low molecular weight heparin (LMWH).
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).
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 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.