INR 5.8 After an Antibiotic and an NSAID
Mrs K, 74, takes warfarin 5 mg daily for atrial fibrillation with a target INR of 2.0–3.0. Four days ago her GP prescribed trimethoprim–sulfamethoxazole (TMP-SMX) double strength twice daily for a urinary tract infection. She has also been taking over-the-counter ibuprofen 400 mg three times daily for knee pain. Today's INR is 5.8; four days ago it was 3.1. She feels well, reports mild gum bleeding when brushing her teeth, and has no melena, haematuria or new bruising beyond a small forearm ecchymosis. BP 138/76, HR 82 irregularly irregular, RR 16, temperature 36.8 °C. Haemoglobin 118 g/L (baseline 124), platelets 210 × 10⁹/L, creatinine 96 µmol/L (baseline 88). The chart carries a standing order: 'Hold warfarin if INR > 4.0 and repeat INR in 24 hours.'
1. Explain why the INR has risen, and why simply following the standing order would be inadequate.
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Two interactions are stacking.
- TMP-SMX inhibits CYP2C9, the principal enzyme metabolising S-warfarin, and also displaces warfarin from albumin and suppresses vitamin K-producing gut flora. The INR rise typically appears 3–7 days after starting - exactly the timeline here (3.1 → 5.8 on day 4).
- Ibuprofen barely changes the INR but is the more immediately dangerous drug: it inhibits platelet cyclo-oxygenase and is directly gastroduodenal irritant. A patient at INR 5.8 taking regular ibuprofen has a substantially increased risk of gastrointestinal bleeding, and the small fall in haemoglobin (124 → 118 g/L) must be treated as possibly significant rather than as noise.
Why the standing order is not enough: it was written for a stable patient with an unexplained mild elevation. It (a) ignores the cause, while both interacting drugs continue; (b) contains no bleeding assessment; (c) does not require prescriber review; and (d) permits a 24-hour delay in rechecking a value that may still be climbing given that the antibiotic continues. Following it without escalation would be technically compliant and clinically negligent.
2. What are your immediate assessments and actions, and what exactly would you communicate to the prescriber?
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Assess first, then escalate.
- Bleeding assessment: gum bleeding, epistaxis, haematuria, melena or haematochezia, haemoptysis, new headache or focal neurology (intracranial bleed), abdominal or flank pain, new bruising, postural dizziness. Check postural BP and HR for volume loss and repeat the haemoglobin if bleeding is suspected.
- Medication history: confirm actual doses and timings of warfarin, TMP-SMX and ibuprofen; ask about other OTC or herbal products, alcohol intake, and any recent change in vitamin K-rich foods.
- Hold tonight's warfarin as the order directs and repeat the INR - but do not stop there.
- Stop the ibuprofen now. This does not need to wait for a call-back; advise paracetamol within safe dose and discuss alternatives for knee pain.
- Contact the prescriber with the numbers and the cause: 'INR 5.8, up from 3.1, on day 4 of TMP-SMX plus regular ibuprofen; no major bleeding, minor gum bleeding, Hb 118 from 124. I have held tonight's dose and stopped the ibuprofen. I need advice on whether oral vitamin K is indicated, whether the antibiotic can be changed, and when to recheck.' Ask specifically for a documented decision.
Guidance generally reserves vitamin K for INR ≥5 with additional bleeding risk, or higher values, or active bleeding - but that is the prescriber's decision to make and to document. Record the advice, who gave it, and the time.
3. What teaching and monitoring plan would you put in place before she leaves? Include how you would confirm understanding.
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Teach-back, not a leaflet.
- Warfarin: why the INR is checked, the target range, that the dose is not fixed, and that every new medicine - including OTC, herbal and complementary products - must be checked with the pharmacist or prescriber first. Explain that antibiotics are a classic cause of INR swings, so the same thing can recur.
- NSAIDs: why ibuprofen is particularly risky with warfarin (gastrointestinal bleeding) and what to use instead for her knee.
- Bleeding red flags: black tarry stools, blood in urine, vomiting blood or coffee grounds, severe or sudden headache, uncontrolled nosebleed, unusual bruising - seek urgent care the same day, not next week.
- Consistency: keep vitamin K-rich foods steady rather than eliminating them; limit alcohol; use a soft toothbrush and an electric razor while the INR is high.
- Monitoring plan: repeat INR in 24 hours, then at a frequency set by the result; arrange a further check after the antibiotic course finishes, because the interaction resolves as the antibiotic clears. Book the next INR before she leaves.
- Written record: update her anticoagulant alert card and give a written summary of what happened and when to seek help.
Confirm understanding by asking her to explain back, in her own words, what she will do if her stools turn black and what she will do before taking any new painkiller. Document that this was done and what she demonstrated.