Drug Interaction Report

GENERALLY AVOID: Thrombotic events have been reported in fitusiran-treated patients, and concurrent use of hormonal contraceptives may increase the risk. Estrogen based hormonal contraceptives are an established risk factor for thrombosis in patients with inherited antithrombin (AT) deficiency.

MANAGEMENT: Concomitant use of fitusiran with estrogen based hormonal contraceptives should generally be avoided. Patients using hormonal contraceptives are advised to use alternative non-hormonal contraception prior to starting treatment with and while receiving fitusiran.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.