After the recent death of a patient who had been taking warfarin and tramadol together, British health authorities have issued an alert on using the two medications concurrently, saying this can cause harmful drug interactions, raise the International Normalised Ratio (INR), and result in severe bruising and bleeding, which in some patients could be fatal.
The Medicines and Healthcare products Regulatory Agency (MRHA) said there was concern that the interaction between the two drugs was not well known and that there was a need to highlight this interaction to healthcare professionals.
Warfarin is a coumarin-derived vitamin K antagonist used for prevention and treatment of blood clots: to prevent embolisation in rheumatic heart disease and atrial fibrillation and after insertion of prosthetic heart valves. It is also used in the prevention and treatment of venous thrombosis and pulmonary embolism and treatment of transient ischaemic attacks.
The medication has a low therapeutic index, meaning 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. This 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 like 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.
Gov.UK article – Warning over Warfarin interaction with tramadol (Open access)
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