NITROFURANTOIN (MONOHYDRATE/MACROCRYSTALS)
Clinical safety rating: avoid
Antacids may decrease absorption Can cause pulmonary fibrosis and peripheral neuropathy with long-term use.
Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates that inhibit bacterial cell wall synthesis, protein synthesis, and DNA/RNA synthesis. It is bacteriostatic at low concentrations and bactericidal at higher concentrations.
| Metabolism | Primarily metabolized in the liver and tissues by various enzymes, including aldehyde oxidase and xanthine oxidase. The major metabolic pathway is reduction to aminofurantoin. Approximately 20-25% of the drug is excreted unchanged in urine. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 40% of the dose; tubular reabsorption occurs. Biliary/fecal elimination is minimal (<5%). |
| Half-life | Terminal elimination half-life: 20-60 minutes (average ~30 min) in patients with normal renal function; prolonged in renal impairment (e.g., CrCl <60 mL/min). |
| Protein binding | Approximately 60-70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd: Approximately 0.3-0.7 L/kg, indicating distribution mainly into extracellular fluids and tissues, with minimal intracellular penetration. |
| Bioavailability | Oral bioavailability: ~90% (macrocrystals) to 100% (monohydrate) when taken with food; absorption is enhanced by food. |
| Onset of Action | Oral: Therapeutic effect typically begins within 30-60 minutes due to rapid absorption and urinary concentration. |
| Duration of Action | Duration: Approximately 6-12 hours based on urinary bactericidal concentrations, which persist above MIC for common uropathogens for this period with twice-daily dosing. |
100 mg orally twice daily for 5-7 days; for uncomplicated urinary tract infection.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated if CrCl < 30 mL/min or GFR < 30 mL/min/1.73 m²; no adjustment needed for CrCl ≥ 30 mL/min. |
| Liver impairment | No specific adjustment recommended; contraindicated in patients with significant hepatic impairment (Child-Pugh class C) due to risk of hepatotoxicity. |
| Pediatric use | For patients ≥ 1 month: 5-7 mg/kg/day orally divided every 6 hours; maximum 400 mg/day. For acute therapy: 5-7 mg/kg/day for 7 days. |
| Geriatric use | Use with caution due to age-related decline in renal function; monitor renal status; avoid if CrCl < 30 mL/min; increased risk of pulmonary and hepatic adverse reactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Antacids may decrease absorption Can cause pulmonary fibrosis and peripheral neuropathy with long-term use.
| FDA category | Positive |
| Breastfeeding | Excreted into breast milk in small amounts (M/P ratio approximately 0.02-0.06). Considered compatible with breastfeeding by the American Academy of Pediatrics. Caution in infants with G6PD deficiency or hyperbilirubinemia due to theoretical risk of hemolysis. |
| Teratogenic Risk | First trimester: Avoid use due to possible teratogenic effects (increased risk of neural tube defects, oral clefts) based on some observational studies. Second and third trimesters: Generally considered safe but may be associated with neonatal hemolysis if used near term due to immature erythrocyte enzyme systems. Contraindicated at term (38-42 weeks) due to risk of hemolytic anemia in the newborn. |
■ FDA Black Box Warning
None.
| Common Effects | Blurred vision Decreased blood pressure Dizziness Headache Increased heart rate Lightheadedness Paresthesia tingling or pricking sensation |
| Serious Effects |
["Hypersensitivity to nitrofurantoin or any component of the formulation","Significant renal impairment (creatinine clearance <30 mL/min or oliguria/anuria)","Pregnancy at term (38-42 weeks gestation) or during labor and delivery","Infants less than 1 month of age (risk of hemolytic anemia due to immature erythrocyte enzyme systems)","Concurrent use with drugs that may inhibit metronidazole metabolism (e.g., disulfiram-like reactions)"]
| Precautions | ["Pulmonary reactions (acute, subacute, chronic) including pulmonary fibrosis; monitor for cough, dyspnea, and pulmonary infiltrates","Hepatotoxicity including hepatic necrosis; discontinue if hepatitis occurs","Peripheral neuropathy (may become severe or irreversible); use caution in patients with renal impairment, anemia, diabetes, electrolyte imbalance, or vitamin B deficiency","Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency","Pseudomembranous colitis (Clostridioides difficile-associated diarrhea)","Superinfection with resistant organisms, including Pseudomonas or Candida","Use in pregnancy should be avoided at term (38-42 weeks gestation) due to risk of neonatal hemolysis"] |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN) due to reliance on renal excretion. Monitor for peripheral neuropathy, pulmonary reactions (fever, cough, dyspnea). In pregnancy, fetal ultrasound for anomaly detection if used in first trimester. For use near term, monitor neonate for jaundice and hemolysis. |
| Fertility Effects | No known adverse effects on fertility in males or females based on available data. Reversible impairment of spermatogenesis reported in animal studies at high doses, not confirmed in humans. |