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. |
| Molecular Weight | 238.16 |
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 | Contraindicated due to risk of hemolytic anemia in the fetus; theoretical risk of neural tube defects. |
| 2nd trimester | Use only if clearly needed; avoid near term due to risk of hemolytic anemia. |
| 3rd trimester | Contraindicated at term (38-42 weeks) due to risk of hemolytic anemia in the newborn. |
Clinical note
Antacids may decrease absorption Can cause pulmonary fibrosis and peripheral neuropathy with long-term use.
| FDA category | Positive |
| Placental transfer | Crosses the placenta; measurable fetal plasma concentrations. |
| Breastfeeding | Excreted into breast milk in low concentrations; considered compatible with breastfeeding due to low infant plasma levels. Observe infant for diarrhea or rash. |
■ 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 |
AnuriaOliguriaSignificant renal impairment (CrCl <30 mL/min or eGFR <30 mL/min/1.73 m2)Pregnancy at term (38-42 weeks)Glucose-6-phosphate dehydrogenase (G6PD) deficiency (relative, but often considered absolute)
| 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 |
Loading safety data…
| Lactation Rating | L2 (Probably Compatible) |
| 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. |
| 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. |
| Food/Dietary | Take with food or milk to enhance absorption and reduce GI upset. Avoid antacids containing magnesium trisilicate within 1 hour of dosing. No specific dietary restrictions otherwise, but maintaining adequate hydration is recommended. |
| Clinical Pearls | Nitrofurantoin monohydrate/macrocrystals is a first-line agent for uncomplicated urinary tract infections (UTIs) caused by susceptible organisms such as Escherichia coli. It is contraindicated in patients with CrCl <30 mL/min due to risk of accumulation and neurotoxicity. Avoid use in late pregnancy (38-42 weeks) and during labor due to potential neonatal hemolysis. Monitor for pulmonary reactions (acute, subacute, or chronic) and hepatic injury; discontinue immediately if symptoms occur. Take with food to enhance absorption and reduce gastrointestinal upset. The macrocrystalline form improves GI tolerance. Not effective for pyelonephritis or perinephric abscess due to poor tissue penetration. |
| Patient Advice | Take this medication with food or milk to reduce stomach upset and improve absorption. · Do not take with antacids containing magnesium trisilicate, as they may decrease absorption. · Complete the full course of therapy even if symptoms improve before the prescription is finished. · Report immediately any signs of pulmonary toxicity: cough, chest pain, difficulty breathing, or fever. · Report any signs of liver injury: yellowing of skin or eyes, dark urine, or persistent nausea/vomiting. · This medication may cause your urine to turn a harmless brown or rust-yellow color. · Avoid alcohol during therapy as it may increase the risk of side effects. · Inform your healthcare provider if you have kidney disease, anemia, diabetes, or a history of nerve damage. · Do not use if you are pregnant at term (38-42 weeks) or while breastfeeding if the infant has G6PD deficiency. · Store at room temperature away from moisture and heat. |