Major
fluvoxamine × Warfarin
SSRI×Vitamin K antagonist anticoagulants
Mechanism
Fluvoxamine inhibits CYP2C19 and CYP1A2 – minor warfarin clearance routes. INR rises within 1–2 weeks of co-administration. Fluvoxamine (an SSRI) also depletes the platelet serotonin pool, impairing primary haemostasis.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
After starting fluvoxamine, check INR at 1 and 2 weeks, then monthly. If INR rises above target, reduce warfarin by 10–20%. Alternative antidepressants without CYP1A2/CYP2C19 effect: sertraline or escitalopram with pantoprazole cover.