NITROFURANTOIN
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 inactivate or inhibit bacterial ribosomal proteins, DNA, RNA, and metabolic enzymes, leading to bacterial cell death.
| Metabolism | Primarily metabolized in the liver and various tissues; reduced by xanthine oxidase and aldehyde oxidase; approximately 60-80% of a dose is rapidly metabolized. |
| Excretion | Renal: ~40% unchanged via glomerular filtration and tubular secretion, biliary/fecal: <1% |
| Half-life | Normal renal function: 20-60 minutes; impaired function: prolonged up to 1-2 hours, clinically significant due to urinary concentration requirement |
| Protein binding | ~40-60% bound to albumin and globulins |
| Volume of Distribution | 0.3-0.8 L/kg, distributes into tissues but low tissue levels; high urine concentrations provide antibacterial effect |
| Bioavailability | Oral: 90-95% (macrocrystals 87%); food enhances absorption |
| Onset of Action | Oral: 30-45 minutes; intravenous: not available clinically |
| Duration of Action | 6-8 hours, limited by rapid renal excretion and short half-life; requires q6h dosing for urinary tract infections |
| Molecular Weight | 238.16 |
100 mg orally twice daily for 5-7 days (uncomplicated UTI); 50-100 mg orally four times daily for 7 days (symptomatic uncomplicated UTI). Extended-release: 100 mg orally twice daily for 7 days.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl <60 mL/min: contraindicated (risk of peripheral neuropathy, inadequate urine concentration). CrCl 30-60 mL/min: avoid use. CrCl <30 mL/min: contraindicated. |
| Liver impairment | No specific Child-Pugh based adjustments established. Use with caution in severe hepatic impairment (Child-Pugh class C) due to risk of hepatotoxicity. Monitor liver function. |
| Pediatric use | Infants ≥1 month: 5-7 mg/kg/day divided every 6 hours (maximum 400 mg/day). Children ≥1 month: 5-7 mg/kg/day divided every 6 hours for symptomatic UTI; 3-4 mg/kg/day divided every 6 hours for suppressive therapy. Extended-release not recommended for children <12 years. |
| Geriatric use | Caution due to age-related renal impairment. Avoid if CrCl <60 mL/min. Monitor for pulmonary and hepatic adverse reactions. Standard dosing as per renal function. |
| 1st trimester | Contraindicated due to risk of hemolytic anemia in fetus with G6PD deficiency; no adequate studies in pregnant women. |
| 2nd trimester | Use only if clearly needed; potential for hemolytic anemia in fetus with G6PD deficiency. |
| 3rd trimester | Contraindicated near term (38-42 weeks) due to risk of hemolytic anemia in newborn with G6PD deficiency; avoid use. |
Clinical note
Antacids may decrease absorption Can cause pulmonary fibrosis and peripheral neuropathy with long-term use.
| FDA category | Positive |
| Placental transfer | Placental transfer occurs; achieves fetal serum concentrations approximately 25-50% of maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
Hypersensitivity reactions including pulmonary reactions, hepatic reactions, and blood dyscrasias have occurred; use caution and discontinue at first signs of reaction.
| Common Effects | Nausea |
| Serious Effects |
AnuriaOliguriaSignificant renal impairment (CrCl <60 mL/min or serum creatinine >1.5 mg/dL)Pregnancy at term (38-42 weeks)Hypersensitivity to nitrofurantoinGlucose-6-phosphate dehydrogenase (G6PD) deficiencyPeripheral neuropathyPorphyria
| Precautions | Pulmonary reactions (acute, subacute, chronic) may occur; consider pulmonary toxicity with prolonged therapy, Hepatotoxicity including hepatitis and hepatic necrosis, Peripheral neuropathy (may become severe and irreversible), Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, CNS effects including dizziness, headache, and drowsiness, Pseudomembranous colitis due to Clostridium difficile, Superinfection with resistant organisms, Renal impairment (CrCl <30 mL/min) increases risk of toxicity; avoid use |
Loading safety data…
| Small amounts excreted in breast milk; generally considered safe in short-term use, but caution in infants with G6PD deficiency or <1 month old due to immature enzyme systems. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; limited human data. Avoid in term pregnancy (38-42 weeks) due to risk of hemolytic anemia in newborn. Use only if clearly needed in first trimester; second and third trimester use considered relatively safe but avoid near delivery. |
| Fetal Monitoring | Monitor maternal CBC, renal function, hepatic function; assess for signs of hemolysis (especially in G6PD deficiency); fetal monitoring if used near term. |
| Fertility Effects | No significant adverse effects on fertility reported in animal or human studies. |
| Food/Dietary | Take with food or milk to improve absorption and reduce gastrointestinal adverse effects. Avoid concurrent use of antacids containing magnesium trisilicate, which can decrease nitrofurantoin absorption. |
| Clinical Pearls | Nitrofurantoin achieves high urinary concentration with minimal systemic levels, making it effective for uncomplicated UTIs. Avoid in CrCl <30 mL/min due to inadequate urine levels and risk of toxicity. Monitor for pulmonary reactions (acute, subacute, chronic) and peripheral neuropathy, especially with prolonged use. Contraindicated in pregnant patients at term (38-42 weeks) and in G6PD deficiency due to risk of hemolytic anemia. |
| Patient Advice | Take with food to enhance absorption and reduce stomach upset. · Complete the full course even if symptoms improve; do not skip doses. · Urine may turn brown or dark yellow; this is harmless. · Avoid antacids containing magnesium trisilicate as they reduce absorption. · Report symptoms of pulmonary toxicity: cough, chest pain, fever, or shortness of breath. · Report numbness, tingling, or muscle weakness (signs of peripheral neuropathy). |