Taking warfarin and tramadol together can cause harmful drug interactions, which can raise the International Normalized Ratio (INR), and result in severe bruising and bleeding, which in some patients could be fatal. As MHRA has received a Coroner’s report following the death of a patient who died from a bleed on the brain, following concurrent treatment with warfarin and tramadol. Taking warfarin and tramadol together may increase a patient’s INR and increase the risk of bleeding. The Coroner raised concerns that the interaction between warfarin and tramadol was not well known and emphasized the need to highlight this interaction to healthcare professionals.

Warfarin is a coumarin-derived vitamin K antagonist used for prevention and treatment of blood clots. It is used to prevent embolization in rheumatic heart disease and, atrial fibrillation and after insertion of prosthetic heart valves. Warfarin is also used in the prevention and treatment of venous thrombosis and pulmonary embolism and treatment of transient ischaemic attacks. Warfarin has a low therapeutic index, which means care is required when taking co-prescribed medicines due to the possibility of interactions that could lead to an increased risk of bleeding. The product information for warfarin advises that healthcare professionals should refer to the product information of any new concomitant medicines for specific guidance on use with warfarin and whether a dose adjustment or therapeutic monitoring is required. The product information will be updated to include the interaction in due course.

Tramadol is a non-selective opioid analgesic, which acts as an agonist at the mu, delta and kappa opioid receptors. Section 4.5 of the tramadol Summary of Product Characteristics (SmPC) states that caution should be exercised during concomitant treatment with coumarin derivatives such as warfarin due to reports of increased INR with major bleeding and bruising in some patients. While the risk of major bleeding with warfarin treatment is rare, the risk may be increased with concurrent use of tramadol.

Report any suspected adverse drug reactions

Please continue to report suspected adverse drug reactions (ADRs) to the Yellow Card scheme. Reporting suspected ADRs, even those known to occur, adds to knowledge about the frequency and severity of these reactions and can be used to identify patients who are most at risk. Your report helps the safer use of medicines. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

• The Yellow Card scheme website
• The Yellow Card app; download from the Apple App Storeor Google Play Store
• Some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)

When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, and product brand name.

Learn more about the advice for healthcare professionals at: Warfarin: be alert to the risk of drug interactions with tramadol - GOV.UK (www.gov.uk)