Can Macrobid (nitrofurantoin) cause impaired renal function?

Macrobid (Nitrofurantoin) and Renal Function

Macrobid (nitrofurantoin) should not be used in patients with creatinine clearance below 30 mL/min due to increased risk of toxicity and reduced efficacy, but is generally safe in patients with mild to moderate renal impairment (CrCl 30-60 mL/min). 1, 2

Relationship Between Nitrofurantoin and Renal Function

Nitrofurantoin's relationship with renal function involves two key concerns:

1. Efficacy concerns: Historically, it was believed that nitrofurantoin would not achieve adequate urinary concentrations in patients with reduced renal function, potentially leading to treatment failure.

2. Safety concerns: Reduced renal clearance could potentially lead to higher systemic concentrations and increased risk of adverse effects.

Current Evidence on Safety and Efficacy

The FDA drug label clearly states that nitrofurantoin is contraindicated in patients with creatinine clearance under 60 mL/min or clinically significant elevated serum creatinine due to increased risk of peripheral neuropathy 1. However, more recent evidence has challenged this strict cutoff:

• A 2018 study found that nitrofurantoin was not associated with increased risk of adverse outcomes in patients with eGFR <60 mL/min/1.73 m², and was actually associated with lower odds of hospitalization for acute kidney injury compared to trimethoprim 3.

• A 2015 Canadian study of older women with relatively low kidney function (median eGFR 38 mL/min/1.73 m²) found that while treatment failure rates were higher with nitrofurantoin compared to other antibiotics, similar rates were observed in women with higher eGFRs, suggesting factors other than renal function may be responsible 4.

Current Recommendations

Based on the most recent evidence:

• For eGFR 30-60 mL/min: Nitrofurantoin can be used with appropriate monitoring 2, 3.

• For eGFR <30 mL/min: Nitrofurantoin should be avoided due to both reduced efficacy and increased toxicity risk 2.

Potential Adverse Effects Related to Renal Function

When used in patients with significant renal impairment, nitrofurantoin may cause:

1. Peripheral neuropathy: More likely in patients with renal impairment, can become severe or irreversible 1.

2. Pulmonary reactions: A 2013 study found a significantly increased risk of pulmonary adverse events leading to hospitalization in patients with renal impairment <50 mL/min/1.73 m² (HR 4.1,95% CI 1.31-13.09) 5.

3. Hepatic reactions: Including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis (rare) 1.

Clinical Approach

When considering nitrofurantoin in patients with potential renal impairment:

1. Assess renal function: Calculate eGFR or creatinine clearance before prescribing.

2. Use alternative agents if eGFR <30 mL/min: Consider fosfomycin, trimethoprim-sulfamethoxazole (with dose adjustment), or cephalosporins 2.

3. Monitor patients with eGFR 30-60 mL/min for:

   • Signs of peripheral neuropathy (numbness, tingling)
   • Pulmonary symptoms (cough, dyspnea, chest pain)
   • Treatment response

Common Pitfalls to Avoid

1. Outdated contraindication thresholds: The historical contraindication at eGFR <60 mL/min appears overly conservative based on recent evidence 6, 3.

2. Ignoring other risk factors: Patients with anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases have increased risk of peripheral neuropathy with nitrofurantoin regardless of renal function 1.

3. Prolonged treatment courses: Adverse effects are more common with extended treatment, particularly in those with reduced renal function 6.

In conclusion, while nitrofurantoin has historically been contraindicated in patients with reduced renal function, more recent evidence suggests it can be used safely in patients with mild to moderate renal impairment (eGFR 30-60 mL/min). However, it should still be avoided in patients with severe renal impairment (eGFR <30 mL/min) due to both efficacy and safety concerns.