Warfarin, Trimethoprim and a Friday-Night Walk-In Clinic
Mr K is a 78-year-old man with atrial fibrillation who takes warfarin 4 mg daily; his INR has stayed between 2.2 and 2.8 for the past year. His other medicines are bisoprolol, atorvastatin and amiodarone. On Friday at 16:40 he attends a walk-in clinic with dysuria and urinary frequency. The prescriber orders oral trimethoprim 200 mg twice daily for seven days and leaves. Mr K's most recent eGFR is 38 mL/min/1.73 m², and his last INR was 2.4 three weeks ago. He lives alone, drives himself home, and has had one previous gastrointestinal bleed while taking an NSAID. The clinic has no anticoagulation pharmacist on site after 17:00 and no transport service. Mr K asks whether he can start the antibiotic tonight and 'sort out the blood test next week'. The nurse must decide what to say and do before he leaves the building.
1. What is the principal medication-safety problem here, and what must be resolved before Mr K leaves the clinic?
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Main problem: a foreseeable, high-risk warfarin–trimethoprim interaction in a patient with several additional bleeding risk factors.
- Trimethoprim inhibits CYP2C9 and reduces renal tubular secretion of creatinine; it can potentiate warfarin and raise the INR within about 3–5 days. Amiodarone is also a CYP inhibitor with a very long half-life and already increases warfarin exposure. Age 78, eGFR 38 and a previous NSAID-related GI bleed compound the risk.
- A stable INR three weeks ago is not a baseline for starting a new interacting drug. 'Start tonight and check next week' is unsafe because the effect peaks around days 3–5.
Before he leaves:
- Contact the prescriber or on-call clinician; the decision to start, change or delay the antibiotic belongs to the prescriber. Document the conversation.
- Ask the prescriber to review the choice against local guidance and culture results. An alternative with less interaction may be appropriate, but renal function, previous sensitivity and the fact that this is a male UTI must be weighed.
- If trimethoprim proceeds, arrange an INR check within 3–5 days, with a baseline before or at the start if possible, and contact the anticoagulation service the same day.
- Check whether gastroprotection is indicated after the previous GI bleed, and whether repeat urea, creatinine and potassium are due, because trimethoprim can raise potassium in renal impairment.
- Give written safety advice and confirm he can attend for blood tests. Do not let him leave without a named contact and a clear plan.
2. Assuming the prescriber confirms trimethoprim, what counselling and monitoring plan would you give Mr K, including safety-netting?
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Explain in plain language: 'Trimethoprim can make warfarin stronger. That is why we need a blood test in a few days, not next week. Do not change your warfarin dose yourself.'
Monitoring plan
- INR 3–5 days after starting, sooner if any bleeding; repeat as directed by the anticoagulation service. The service manages dose changes; the patient should not self-adjust.
- Repeat urea and electrolytes if he becomes dehydrated or unwell, because trimethoprim can raise creatinine and potassium, particularly at eGFR 38.
- Review urinary symptoms at follow-up. If symptoms worsen or he develops fever or loin pain, he needs reassessment rather than another remote prescription.
Safety-netting - seek same-day help for:
- black, tarry or bloody stools, vomiting blood or coffee-ground material;
- red or brown urine, or any frank haematuria;
- a nosebleed lasting more than 10 minutes or recurring, bleeding gums, unusual bruising or pinpoint rash;
- sudden severe headache, weakness, confusion, or any fall or head injury;
- dizziness, fainting or breathlessness.
Avoid aspirin, ibuprofen and other NSAIDs bought over the counter; paracetamol is preferred for pain. Avoid a sudden large increase in alcohol. Keep the warfarin alert card and clinic number. Ask him to repeat the advice back and document that he did. If he cannot arrange transport or a blood test, escalate to the prescriber or anticoagulation service rather than leaving the plan vague.
3. Two days later Mr K telephones saying he has had a nosebleed lasting 15 minutes and has passed a dark stool. What is your assessment and advice?
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Assessment: this is a red-flag presentation - probable warfarin-related bleeding with a possible upper GI bleed, not a minor epistaxis. Dark stool fits his previous GI bleed and the new interaction. He may be haemodynamically compromised even if he sounds well on the phone.
Advice: do not drive himself. Call emergency services or arrange urgent same-day assessment in an emergency department. While waiting, sit upright, lean forward and pinch the soft part of the nose continuously for 10–15 minutes; spit blood out rather than swallowing it. Do not take another warfarin dose until reviewed. Do not take NSAIDs or aspirin.
What the receiving team needs: time of the last warfarin dose, current INR if known, the date the antibiotic started, all other medicines including amiodarone, and the history of previous GI bleeding. They will check full blood count, INR, renal and liver function and consider reversal according to the INR and haemodynamics.
Escalate immediately if the nosebleed does not stop after 20–30 minutes of pressure, if he feels faint, or if he has haematemesis.
Follow-up: document the call, the advice and the referral; inform the prescriber and anticoagulation service; report it as a medication-related safety incident if local policy requires. The failure mode would be telling him to wait for the planned INR check.