Nitrofurantoin (Macrobid) Should Not Be Used in CKD with eGFR 36
Do not prescribe nitrofurantoin to this patient with an eGFR of 36 mL/min/1.73 m². The drug is contraindicated at this level of renal function, and alternative antibiotics should be selected for urinary tract infections.
Rationale for Contraindication
Nitrofurantoin is explicitly contraindicated in patients with eGFR <60 mL/min/1.73 m² according to current FDA labeling, though the evidence basis for this cutoff has been questioned 1
Expert consensus from nephrology, geriatric, and primary care pharmacists unanimously identified nitrofurantoin as a top medication to avoid in patients with eGFR <30 mL/min/1.73 m², emphasizing its importance in medication safety 2
Prescribing nitrofurantoin in advanced CKD (eGFR <30) is exceedingly common but represents a significant dosing error, with studies showing it was prescribed 169 times in patients with stage 4-5 CKD despite contraindication 3
Why the Contraindication Exists
Inadequate urinary drug concentrations occur when eGFR falls below 60 mL/min/1.73 m², as nitrofurantoin requires renal excretion to achieve therapeutic levels in the urine 1
The contraindication stems from 1968 pharmacokinetic data showing minimal drug recovery in urine when CrCl <60 mL/min, though this study had significant methodological limitations including small sample size and lack of clinical efficacy endpoints 1
The FDA labeling changed between 1988 (when the cutoff was CrCl 40 mL/min) and 2003 (when it became <60 mL/min), likely following the pharmacokinetic concerns about urinary drug concentrations 1
Nuances and Contradictory Evidence
While the contraindication is clear, recent evidence suggests the situation may be more complex:
A 2018 retrospective cohort study of 116,945 older patients found that nitrofurantoin prescribing in patients with eGFR <60 mL/min was associated with LOWER odds of hospitalization for acute kidney injury compared to trimethoprim (adjusted OR 0.62 for eGFR 45-59, and 0.45 for eGFR <30) 4
Nitrofurantoin was not associated with increased risk of any adverse outcome (including treatment failure, sepsis, or death) in patients with reduced eGFR in this large real-world study 4
The evidence supporting the contraindication is weak, with no well-designed clinical trials measuring urinary concentrations and clinical efficacy endpoints in patients with varying degrees of renal impairment 1
Clinical Decision for Your Patient
Despite the contradictory research evidence suggesting potential safety, you should follow current FDA labeling and expert consensus:
With an eGFR of 36 mL/min/1.73 m², this patient is in CKD Stage 3b, well below the contraindication threshold of 60 mL/min/1.73 m² 5
Alternative antibiotics for UTI in this patient include: ciprofloxacin (though also flagged for caution in advanced CKD), trimethoprim-sulfamethoxazole with dose adjustment, or cephalosporins with appropriate renal dosing 2
The risk-benefit calculation favors avoiding nitrofurantoin given regulatory contraindication, medicolegal considerations, and availability of alternatives, even though recent data suggest the drug may be safer than previously thought 4
Common Pitfalls to Avoid
Do not rely solely on automated prescribing systems, as dosing errors for antibiotics in CKD remain exceedingly common (64-68 per 100 prescriptions) despite eGFR reporting 3
Verify the eGFR is current (within 3 months) before prescribing any renally-cleared antibiotic, as kidney function can decline rapidly in older patients 5
Consider nephrology referral for this patient, as eGFR 36 represents CKD Stage 3b and meets criteria for specialist evaluation to optimize medication management 5