Warfarin, a Urinary Tract Infection, and New Bleeding
A 78-year-old woman with atrial fibrillation takes warfarin 5 mg daily; her INR has been stable at 2.4 for three months. She presents to an urgent care clinic with dysuria, frequency, and a temperature of 38.1°C. The clinic e-prescribes trimethoprim-sulfamethoxazole DS one tablet PO twice daily for 7 days and ibuprofen 600 mg PO every 6 hours as needed for pain. She calls your pharmacy two days later reporting gum bleeding and new bruises on both forearms. She denies melena, hematemesis, and severe headache. Her most recent INR, drawn yesterday, is 5.8. She asks whether she should stop the antibiotic or the warfarin.
1. What is the most likely cause of the elevated INR and bleeding, and what should you do first?
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The likely cause is the TMP-SMX–warfarin interaction, compounded by ibuprofen. TMP-SMX inhibits CYP2C9 (the warfarin S-enantiomer), displaces warfarin from albumin, and can reduce vitamin K–producing gut flora; ibuprofen adds antiplatelet and GI mucosal risk. An INR of 5.8 with gum bleeding and bruising is clinically significant even without melena or hematemesis. Do not independently tell the patient to stop warfarin or the antibiotic. Triage for major bleeding (hemodynamic instability, melena, hematemesis, severe headache, neurologic change); if present, send to emergency care. Otherwise contact the prescriber urgently, recommend holding warfarin and same-day INR/clinical assessment, and discuss oral vitamin K per protocol. Document the interaction, advice, and follow-up.
2. Recommend an alternative antibiotic and analgesic, with rationale.
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For uncomplicated cystitis, prefer an agent without a major warfarin interaction. Nitrofurantoin 100 mg PO BID for 5 days is reasonable if CrCl is at least 30 mL/min and there is no pyelonephritis; fosfomycin 3 g PO once is another option. Avoid TMP-SMX and fluoroquinolones if alternatives exist. For analgesia, use acetaminophen 500–1000 mg PO every 6 hours as needed, with a maximum of 3 g/day (lower if hepatic impairment or alcohol use). Avoid ibuprofen and other NSAIDs because of additive bleeding risk and GI injury. Confirm the patient’s renal function and allergies before recommending nitrofurantoin, and remind the prescriber that the antibiotic change does not eliminate the need to monitor INR after warfarin is resumed.
3. What monitoring and counseling should you provide?
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Counsel the patient to seek emergency care for black stools, vomiting blood, severe headache, weakness, or uncontrolled bleeding. Check INR within 2–3 days after holding or restarting warfarin, and more often after any antibiotic change. Reinforce consistent vitamin K intake, avoidance of new OTC NSAIDs and interacting supplements, and use of acetaminophen instead of ibuprofen. Review all prescriptions for other CYP2C9 inhibitors. Document the interaction, the prescriber contact, and the monitoring plan. Do not restart warfarin until the prescriber has reviewed the INR and bleeding assessment.