Drug interactions between Luvox CR and Miradon

anisindione ↔ fluvoxamine

Applies to:Miradon (anisindione) and Luvox CR (fluvoxamine)

MONITOR: Coadministration with fluvoxamine may increase the plasma concentrations and hypoprothrombinemic effect of warfarin and similar anticoagulants. The proposed mechanism is fluvoxamine inhibition of multiple CYP450 enzymes that are involved in the metabolism of oral anticoagulants. According to the manufacturer, coadministration of fluvoxamine (50 mg three times a day) and warfarin for two weeks resulted in a 98% increase in warfarin plasma concentrations and prolonged prothrombin times. In one case report, an elderly woman stabilized on warfarin developed an elevated INR shortly after citalopram was changed to fluvoxamine during a hospitalization. The INR elevation persisted for 7 days, even several days after fluvoxamine has been discontinued. The prolonged effect may be due to the relatively long half-life of fluvoxamine, particularly in the elderly.

MANAGEMENT: Caution is advised if fluvoxamine must be used with warfarin or other oral anticoagulants. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of fluvoxamine in patients who are stabilized on their anticoagulant regimen. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools. Alternatively, fluvoxamine may be substituted with an antidepressant that is less likely to interfere with CYP450 metabolism, such as citalopram, sertraline, or venlafaxine.