Warfarin, an OTC NSAID, and co-trimoxazole: bleeding gums and an INR of 6.4
A 58-year-old man with a mechanical mitral valve on warfarin 3 mg daily comes to a Ulaanbaatar pharmacy with gum bleeding for three days and new bruises on both forearms. His last INR was 2.6, six weeks ago. He has taken warfarin every day without interruption but has not attended the anticoagulation clinic since. For five days he has taken diclofenac 50 mg three times daily, bought without a prescription at another pharmacy for a painful knee. He also finished a seven-day course of co-trimoxazole 960 mg twice daily for a urinary infection four days ago. He denies melena, haematuria, or headache, and feels otherwise well. Blood pressure is 138/84 and heart rate 78. The laboratory in the same building can return an INR in 40 minutes. He asks you to sell him something stronger for the knee and says he should probably double his warfarin because the valve 'needs protection'.
1. Identify every factor raising this patient's bleeding risk and explain the mechanism of each.
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1. Warfarin itself, unmonitored. A mechanical mitral valve needs an INR usually 2.5–3.5, but after six weeks without measurement the current INR is unknown; adherence without monitoring is not safety.
2. Diclofenac (NSAID) - two mechanisms.
- Pharmacodynamic: NSAIDs inhibit platelet cyclo-oxygenase, impairing platelet aggregation; this happens even at normal INR and is enough to cause mucosal bleeding.
- Pharmacokinetic: diclofenac is metabolised by CYP2C9, the same enzyme that clears S-warfarin, so it can raise warfarin exposure. It also damages gastric mucosa, adding a local bleeding source.
3. Co-trimoxazole - potentiation.
- Metabolic: the sulfamethoxazole component inhibits CYP2C9, reducing warfarin metabolism and raising INR within days; the effect can persist after the course ends.
- Protein binding: sulfonamides can displace warfarin from albumin, transiently increasing free drug.
- Floral effect: broad-spectrum antibiotics reduce gut vitamin K-producing flora, lowering vitamin K availability.
4. Age and comorbidity risk factors - over 65 is a recognised bleeding risk, and the knee pain may signal reduced mobility and falls risk.
5. Visible bleeding already present (gums, bruises) means the interaction is clinically expressed, not theoretical.
2. The INR returns at 6.4 with no major bleeding. Outline your recommendation, including whether to give vitamin K, what to do about warfarin, and how to handle the knee pain.
Read the worked answer
Triage first: the patient is haemodynamically stable, with no melena, haematuria, or neurological signs - so this is minor mucosal bleeding, not a major haemorrhage, and he does not need emergency reversal with prothrombin complex concentrate.
Warfarin and vitamin K - reasoned answer
- Withhold warfarin for one to two doses and recheck INR in 24 hours.
- For an INR of 6.4 without bleeding, guidelines advise against routine vitamin K. With visible gum bleeding and bruising, a small oral dose of vitamin K1, 1–2 mg, is reasonable - but keep it small. In a patient with a mechanical mitral valve, an oversized dose makes him warfarin-refractory for days and exposes the valve to thrombosis risk; 10 mg would be a mistake.
- Restart at a reduced dose (e.g. 2–2.5 mg daily, or his usual 3 mg if the INR falls below 2.5) only after the INR is back in the target range, and recheck in 2–3 days and then weekly until stable.
- Refer him back to the anticoagulation clinic and record the missed monitoring as a system failure, not just a patient failure.
Knee pain
- Refuse any oral NSAID, including 'stronger' ones and aspirin-containing products.
- Offer paracetamol, short term, at no more than about 2 g/day and with an INR check after several days - high-dose regular paracetamol can itself raise the INR.
- Consider a topical NSAID gel (much lower systemic exposure, though not zero), plus heat, weight management, physiotherapy referral, and a walking aid review.
- Explain why: the combination he just used is what caused the bleeding.
3. Write the counselling you would give before he leaves, including how you would address self-medication in a Mongolian community pharmacy setting.
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Explain the cause in plain words: 'The pain tablets you bought thin your blood in a second way and irritate the stomach, and the infection antibiotic slowed the removal of warfarin from your body. The result is an INR of 6.4 when you need about 3.'
Safety rules to state explicitly, and check by teach-back
- Never buy painkillers, cold remedies, or 'blood-thinning' products without telling the pharmacist you take warfarin. Many combination cold and pain products contain NSAIDs or aspirin without saying so clearly on the front of the pack.
- Every antibiotic needs an INR check - ask for one, because many antibiotics raise the INR.
- Keep green leafy vegetables and herbal teas consistent rather than avoiding them; sudden changes in vitamin K intake destabilise the INR.
- Avoid alcohol binges; report black stools, blood in urine, nosebleeds that will not stop, unusual headache, or weakness on one side immediately.
- Carry a card or phone note: 'I take warfarin for a mechanical heart valve, target INR 2.5–3.5.'
Practical points for this setting Ask, as a habit, 'What else are you taking, including anything bought elsewhere?' - self-medication across several pharmacies is common and is the main way these interactions are missed. Offer to phone the anticoagulation clinic, write the next INR date on the box in large script, and give the family member who collects his medicines the same message. Document the counselling and the refusal of an NSAID in the pharmacy record.