MACRODANTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MACRODANTIN (MACRODANTIN).
Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates that inhibit bacterial acetyl-CoA carboxylase, interfere with bacterial cell wall synthesis, and damage bacterial DNA. It is bactericidal against a broad spectrum of gram-positive and gram-negative bacteria.
| Metabolism | Nitrofurantoin is primarily metabolized in the liver via reduction by aldehyde oxidase and xanthine oxidase, and conjugation with glutathione. The metabolites are excreted in urine and bile. |
| Excretion | Renal: 30-40% unchanged, Hepatic metabolism: 60-70% to inactive metabolites, Fecal: <1% |
| Half-life | 20-60 minutes (prolonged in renal impairment, up to 8 hours in anuria) |
| Protein binding | 60-90% (reversible binding to albumin, increased binding at lower concentrations) |
| Volume of Distribution | 0.5-0.8 L/kg (limited distribution, concentrated in urine; low Vd due to rapid elimination) |
| Bioavailability | Oral: 87% (well absorbed, food enhances absorption) |
| Onset of Action | Oral: Within 30 minutes (rapid antibacterial effect in urinary tract) |
| Duration of Action | 4-6 hours (maintained by frequent dosing, effective only in urinary tract due to rapid clearance) |
100 mg orally twice daily for 5 days; for uncomplicated UTI. Route: oral. Frequency: twice daily.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated if CrCl < 30 mL/min. For CrCl 30-50 mL/min: use with caution, consider alternative if prolonged therapy. No specific dose reduction defined. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment. Not studied in severe hepatic impairment; use with caution. |
| Pediatric use | For patients ≥1 month: 5-7 mg/kg/day divided every 6 hours (max 400 mg/day) for acute UTI. For prophylaxis: 1-2 mg/kg once daily. |
| Geriatric use | Use with caution due to increased risk of peripheral neuropathy and pulmonary toxicity. Monitor renal function; avoid if CrCl <30 mL/min. Consider lower end of dosing range. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MACRODANTIN (MACRODANTIN).
| Breastfeeding | Excreted in human milk in trace amounts; M/P ratio unknown. Considered compatible with breastfeeding. Potential for diarrhea or hemolysis in G6PD-deficient infants. Use with caution. |
| Teratogenic Risk | Pregnancy category B. Animal studies show no fetal harm. Limited human data; first trimester use not associated with major congenital malformations. Avoid at term (38-42 weeks) due to risk of hemolytic anemia in newborn. Use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
Pulmonary reactions, including acute, subacute, and chronic pulmonary hypersensitivity reactions (interstitial pneumonitis, pulmonary fibrosis), can occur in patients treated with nitrofurantoin. These reactions can be fatal. If pulmonary symptoms occur, discontinue nitrofurantoin immediately.
| Serious Effects |
["Anuria, oliguria, or significant renal impairment (creatinine clearance <60 mL/min or serum creatinine >1.2 mg/dL)","Patients with known hypersensitivity to nitrofurantoin","Pregnant patients at term (38-42 weeks gestation), during labor and delivery, or when the neonate is suspected of having G6PD deficiency","Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolytic anemia","Patients with peripheral neuropathy (unless considered a therapeutic benefit outweighs risk)"]
| Precautions | ["Pulmonary reactions (hypersensitivity pneumonitis, pulmonary fibrosis) may occur; monitor for dyspnea, cough, fever, and chest pain.","Hepatic toxicity including hepatitis, cholestatic jaundice, and hepatic necrosis may occur; monitor liver function.","Peripheral neuropathy (may become severe or irreversible) has been reported; caution in patients with renal impairment, diabetes, electrolyte imbalance, vitamin B deficiency, or debilitating disease.","Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; discontinue if hemolysis occurs.","Pseudomembranous colitis due to Clostridium difficile overgrowth; consider if diarrhea occurs.","Use caution in patients with renal impairment (creatinine clearance <60 mL/min) due to risk of toxicity and lack of efficacy.","Elderly patients may be at increased risk for adverse reactions."] |
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| Monitor maternal liver function (AST/ALT), renal function, and blood counts (CBC with differential). For prolonged therapy, monitor for peripheral neuropathy. Fetal monitoring includes ultrasound for growth and amniotic fluid volume if used in pregnancy. |
| Fertility Effects | No significant effects on fertility reported in animal studies. No human data on fertility impairment. |