Nitrofurantoin Prescribed at an eGFR of 26 in a Warfarin-Treated Older Adult
Mrs. D., 78, brings a new electronic prescription to your community pharmacy: nitrofurantoin monohydrate/macrocrystals 100 mg PO BID for 7 days, from a walk-in clinic physician. She reports 2 days of dysuria and urinary frequency, no fever, no flank pain, and no vomiting. Her medication list includes warfarin 4 mg daily (INR 2.6 last week; target 2.0–3.0 for atrial fibrillation), ramipril 5 mg daily, metformin 500 mg BID and atorvastatin 20 mg daily. A lab report she printed from her family physician's portal shows eGFR 26 mL/min/1.73 m², hemoglobin 104 g/L and platelets 210 × 10⁹/L. She weighs 52 kg. The clinic note reads "empiric therapy; no urine culture obtained." She asks whether the new antibiotic is safe with her warfarin and whether she needs to come back to the clinic.
1. List the concerns you would raise with this prescription before dispensing, and state what you would do next.
Read the worked answer
Do not dispense as written. Concerns, in order of urgency:
- Nitrofurantoin is the wrong drug at this eGFR. The Canadian product monograph contraindicates nitrofurantoin when CrCl is below 30 mL/min (some references use <30–40), because inadequate urinary concentrations reduce efficacy and systemic accumulation increases the risk of pulmonary fibrosis, hepatotoxicity, peripheral neuropathy and hemolysis. Her eGFR is 26 mL/min/1.73 m².
- No culture. Empiric therapy in an older adult with reduced renal function and anemia should be guided by a urine culture and susceptibility; the note says none was sent.
- Warfarin. Nitrofurantoin has been reported to potentiate warfarin; more importantly, any acute infection and antibiotic change can destabilize the INR. Her INR is 2.6, so she has little headroom.
- Anemia (Hb 104). Consider G6PD deficiency and other causes before any nitrofurantoin exposure; hemolysis is a recognized risk.
- Red flags. No fever or flank pain today, so outpatient management is reasonable - but she needs to know what would change that.
Action: hold the prescription, telephone the prescriber, describe the eGFR and the alternative you suggest, document the conversation, and tell Mrs. D. not to start the antibiotic until she hears back. Offer to arrange a urine culture.
2. Recommend an alternative regimen, including what information you need and how you would justify it to the prescriber.
Read the worked answer
Recommended alternative: send a urine culture, then treat with an agent that achieves urinary concentrations and is safe at eGFR 26.
- First choice if she prefers a single dose and is not pregnant: fosfomycin trometamol 3 g PO once. It concentrates in urine, is given as one dose, and avoids the warfarin interaction seen with TMP-SMX. Its efficacy is somewhat reduced in advanced CKD, so culture follow-up matters.
- If culture grows a susceptible organism: cephalexin 500 mg PO BID–q8h (renally adjusted) or amoxicillin 500 mg PO TID for 5–7 days, guided by susceptibility.
- Avoid: TMP-SMX (hyperkalemia with ramipril, renal impairment, warfarin interaction), fluoroquinolones (tendinopathy, aortic risk, warfarin, renal dosing), and nitrofurantoin.
- If she develops fever, rigors, flank pain or vomiting: treat as pyelonephritis and refer urgently; do not manage with oral cystitis therapy.
Justification to the prescriber: 'Her eGFR is 26; nitrofurantoin is contraindicated and likely ineffective. Culture is needed. I suggest fosfomycin 3 g once, or a susceptibility-guided beta-lactam, with an INR check in 3–5 days because she is on warfarin.'
3. What would you document, and what follow-up would you arrange?
Read the worked answer
Document: the prescription as received, the eGFR and lab values used, the prescriber contact time and person, the recommendation made, the prescriber's decision, and the patient counseling given. Note that the drug was not dispensed and why.
Follow-up:
- Urine culture result in 48–72 h; if the organism is resistant to the chosen agent, call the prescriber again.
- INR in 3–5 days, sooner if bruising or bleeding.
- Symptom check at 48–72 h: dysuria, fever, flank pain, confusion.
- Return precautions: fever ≥38 °C, rigors, flank pain, vomiting, inability to keep fluids down, new confusion.
- Hydration and voiding advice; review ramipril and metformin sick-day rules if she becomes dehydrated.
- Reassess the need for prophylaxis if this is a recurrent UTI; address modifiable risk factors.
If the prescriber insists on nitrofurantoin, escalate to the pharmacist-in-charge or medical director and document the refusal to dispense on safety grounds.