What are the contraindications to Macrobid (nitrofurantoin)?

Contraindications to Nitrofurantoin (Macrobid)

Nitrofurantoin is contraindicated in patients with significant renal impairment (creatinine clearance <60 mL/min) due to increased risk of toxicity from drug accumulation and reduced efficacy due to insufficient urinary concentrations. 1

Absolute Contraindications

1. Renal Impairment:

   • Creatinine clearance <60 mL/min 1
   • Clinically significant elevated serum creatinine 2
   • Reduced renal function leads to:
     • Insufficient urinary drug concentrations (reduced efficacy)
     • Increased systemic exposure (increased toxicity risk)

2. Pregnancy at Term (38-42 weeks):

   • Risk of hemolytic anemia in the newborn

3. Infants Under 4 Months:

   • Risk of hemolytic anemia due to immature enzyme systems 1

4. G6PD Deficiency:

   • Can cause hemolytic anemia of the primaquine-sensitivity type 2
   • This deficiency is found in 10% of Black individuals and a small percentage of ethnic groups of Mediterranean and Near-Eastern origin 2

5. History of Nitrofurantoin-Associated Pulmonary Reactions:

   • Previous acute, subacute, or chronic pulmonary hypersensitivity reactions 2

6. History of Nitrofurantoin-Associated Hepatic Reactions:

   • Previous hepatitis, cholestatic jaundice, chronic active hepatitis, or hepatic necrosis 2

Relative Contraindications/Use with Caution

1. Conditions that Increase Risk of Peripheral Neuropathy:

   • Anemia
   • Diabetes mellitus
   • Electrolyte imbalance
   • Vitamin B deficiency
   • Debilitating disease 2

2. Pulmonary Disease:

   • Pre-existing pulmonary conditions may increase risk of pulmonary reactions

3. Hepatic Impairment:

   • Increased risk of hepatotoxicity

4. Long-term Use:

   • Chronic pulmonary reactions generally occur in patients receiving continuous treatment for six months or longer 2
   • Close monitoring required for long-term therapy

5. Drug Interactions:

   • Concomitant use with:
     • Antacids containing magnesium trisilicate
     • Probenecid
     • Sulfonylurea hypoglycemics
     • Medications that impair renal function 1

Monitoring Requirements When Using Nitrofurantoin

1. Renal Function:

   • Baseline and periodic monitoring of creatinine clearance

2. Pulmonary Function:

   • Monitor for symptoms like cough, dyspnea, chest pain, fever
   • Consider pulmonary function tests for long-term therapy

3. Hepatic Function:

   • Periodic liver function tests, especially for extended use

4. Neurological Assessment:

   • Monitor for signs of peripheral neuropathy (numbness, tingling)

Important Adverse Effects to Monitor

1. Pulmonary Reactions:

   • Acute, subacute, or chronic pulmonary hypersensitivity reactions
   • Can be severe and potentially fatal 2
   • Manifestations include malaise, dyspnea, cough, altered pulmonary function

2. Hepatotoxicity:

   • Hepatitis, cholestatic jaundice, chronic active hepatitis, hepatic necrosis 2

3. Peripheral Neuropathy:

   • Can become severe or irreversible
   • Fatalities have been reported 2

4. Hematologic Effects:

   • Hemolytic anemia (especially in G6PD deficiency)
   • Agranulocytosis, leukopenia, thrombocytopenia 2

5. Gastrointestinal Effects:

   • Nausea, vomiting, anorexia (most common)
   • Abdominal pain, diarrhea
   • Potential for C. difficile-associated diarrhea 2

Nitrofurantoin remains an effective first-line option for uncomplicated UTIs in patients with normal renal function, but careful patient selection and monitoring are essential to minimize the risk of serious adverse effects.