INR 5.8 After a New Antibiotic and an Over-the-Counter NSAID

Three separate mechanisms are stacking on top of each other:

1. Trimethoprim–sulfamethoxazole → warfarin. Sulfamethoxazole inhibits CYP2C9, the enzyme that clears the more potent S-enantiomer of warfarin, so warfarin clearance falls and INR rises. The effect typically appears within days of starting and peaks in the first week - matching the 10-day history.
2. Ibuprofen → warfarin. NSAIDs inhibit platelet cyclo-oxygenase, impairing platelet aggregation even when the INR is therapeutic, and they displace warfarin from albumin. They also injure the gastric mucosa. The result is a bleeding risk that is higher than the INR alone suggests.
3. Ibuprofen → gut. The single black tarry stool is the important detail: melena suggests upper gastrointestinal bleeding, which is exactly the site NSAIDs plus anticoagulation endanger.

Add the clinical context: he is not unreliable - he took a GP-issued antibiotic and an 'everyday' painkiller. The failure here is interaction screening and counselling at the point of prescribing and dispensing, not adherence.

Risk stratification: INR 5.8 without major bleeding is 'supratherapeutic with minor bleeding' (gum bleeding, melena) - not a routine dose tweak, because melena is a possible GI bleed that needs assessment, not just a reduced dose.

Immediate actions (in order):

1. Do not give the next warfarin dose - hold it and record the reason.
2. Assess for bleeding properly: ask about haematemesis, melena volume and frequency, haematuria, epistaxis, headache or focal neurology, and inspect for bruising or pallor; check postural BP and HR.
3. Contact the prescriber/anticoagulation service now and state the INR, the interacting drugs and the melena.
4. Arrange urgent investigations: repeat INR, CBC, renal and liver function, group and screen, and consider referral to the emergency department for evaluation of the GI bleed.
5. Stop the ibuprofen and agree an alternative analgesic (see next task).
6. Document the INR, the advice received, and the plan with a recheck date.

Is vitamin K indicated?

• For an INR above 5 with minor bleeding, guidelines support holding warfarin and considering low-dose oral vitamin K (typically 1–2.5 mg) in discussion with the prescriber - it lowers the INR faster than holding alone.
• It is not an automatic 'give vitamin K' situation, and it is not given IV here: IV vitamin K is reserved for major bleeding, and oral routes are preferred for non-emergency correction.
• Major bleeding (haemodynamic instability, large GI bleed, intracranial bleed) would need urgent reversal with IV vitamin K plus prothrombin complex concentrate and emergency transfer - that is a different pathway.

The safe answer is: hold, assess, escalate, and let the prescriber confirm the reversal plan - but do not send him home with only 'skip two doses'.

Teach the mechanism, not just the rule. He needs to understand why 'a UTI antibiotic' and 'a knee pain tablet' were dangerous, or it will happen again.

Teaching points:

• Every new medicine must be checked against warfarin - including antibiotics, antifungals, OTC painkillers and herbal products. Ask the pharmacist every time.
• No NSAIDs (ibuprofen, naproxen, aspirin unless prescribed). Agree an alternative for his knee: topical NSAID is generally lower risk but still needs checking; paracetamol is preferred - and note that regular paracetamol at higher doses (e.g. >2 g/day for several days) can also raise INR, so it needs INR monitoring too.
• Bleeding warning signs that mean 'go now', not 'wait and see': black tarry stools, vomiting blood or 'coffee grounds', blood in urine, prolonged nosebleed, unusual headache, any fall or head strike.
• Consistency: keep vitamin K-rich foods steady rather than avoiding them, limit alcohol, use a soft toothbrush and an electric razor.
• Carry an anticoagulant alert card; tell any dentist, surgeon or new prescriber.

Monitoring plan:

• Recheck INR in 2–3 days after stopping the interacting drugs, then again within a week, and resume standard intervals once stable in range.
• Give a written anticoagulation record with the next test date and who to call.
• Notify the anticoagulation service and the GP of the interaction and the new plan, so the same antibiotic is not re-prescribed without cover next time.