Moderate
Tramadol × Warfarin
Other opioids×Vitamin K antagonist anticoagulants
Mechanism
Tramadol indirectly affects CYP2C9-mediated warfarin metabolism via CYP2D6. INR increases of 1–2 points have been reported, especially in older patients.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.
Management
On tramadol start, check INR at 5–7 days. For pronounced pain, alternatives: paracetamol up to 2 g/day or a short tramadol course at 50 mg at night. High-dose opioids and NSAIDs are less preferred.