NITROFURANTOIN MACROCRYSTALLINE
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 multiple bacterial enzymes involved in carbohydrate metabolism, including acetyl-CoA synthetase, and disrupt cell wall synthesis.
| Metabolism | Primarily metabolized in the liver and tissues by various reductases; the major metabolite is aminofurantoin. Metabolism is not dependent on cytochrome P450 enzymes. |
| Excretion | Renal: 30-40% excreted unchanged in urine. Biliary/fecal: minimal; remainder metabolized or eliminated via other routes. |
| Half-life | Terminal half-life: 20-60 minutes (short, requires q6h dosing for therapeutic efficacy). |
| Protein binding | 60-90% bound to albumin. |
| Volume of Distribution | 0.3-0.7 L/kg (low; indicates limited tissue distribution, primarily concentrated in urine). |
| Bioavailability | Oral (macrocrystalline): 90-100% (enhanced with food). |
| Onset of Action | Oral: 30-45 minutes for bacteriostatic effect in urine. |
| Duration of Action | 4-6 hours (bactericidal effect persists as long as urine concentration exceeds MIC). |
100 mg orally twice daily for 5-7 days (uncomplicated UTI); 100 mg orally every 12 hours for 10-14 days (pyelonephritis: not first-line).
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated if CrCl <30 mL/min (ineffective due to inadequate urine concentration and increased risk of toxicity). Avoid in CrCl 30-60 mL/min; use only if no alternative and monitor closely. |
| Liver impairment | No dose adjustment required in Child-Pugh A or B. Contraindicated in Child-Pugh C (hepatic impairment may increase risk of hepatotoxicity). |
| Pediatric use | Children >1 month: 5-7 mg/kg/day orally divided every 6 hours (max 400 mg/day). For UTI prophylaxis: 1-2 mg/kg/day orally once daily. |
| Geriatric use | Use with caution due to age-related renal impairment. Avoid if CrCl <30 mL/min. Monitor for pulmonary and hepatic adverse effects. No specific dose reduction; adjust based on renal function. |
| 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 low concentrations (<0.3% of maternal dose); M/P ratio approximately 0.25. Generally compatible with breastfeeding; monitor infant for diarrhea or rash. Caution in G6PD-deficient infants due to theoretical risk of hemolysis. |
| Teratogenic Risk | First trimester: Avoid due to potential association with neural tube defects and oral clefts. Second and third trimesters: Considered relatively safe; may cause hemolytic anemia in G6PD-deficient fetuses. Avoid near term (38-42 weeks) due to risk of neonatal hemolysis. |
■ FDA Black Box Warning
Nitrofurantoin is contraindicated in patients with impaired renal function (creatinine clearance <60 mL/min or clinically significant elevated serum creatinine) because of the risk of pulmonary toxicity and lack of efficacy due to inadequate urinary concentrations.
| Common Effects | Nausea |
| Serious Effects |
Anuria, oliguria, or significant renal impairment (creatinine clearance <60 mL/min or clinically significant elevated serum creatinine). Hypersensitivity to nitrofurantoin. Pregnant patients at term (38-42 weeks gestation) or during labor and delivery due to risk of hemolytic anemia in the neonate. Infants less than one month of age because of potential for hemolytic anemia.
| Precautions | Pulmonary reactions (acute, subacute, or chronic) may occur; discontinue if pulmonary symptoms develop. Hepatotoxicity, including hepatitis, cholestatic jaundice, and chronic active hepatitis, has been reported. Peripheral neuropathy, especially in patients with renal impairment, anemia, diabetes, electrolyte imbalance, or vitamin B deficiency. Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Superinfection with resistant organisms may occur. Use caution in patients with pulmonary disease, hepatic impairment, or neurologic disorders. |
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| Fetal Monitoring | Monitor complete blood count (CBC) and liver function tests periodically. Assess for signs of pulmonary or hepatic toxicity. In pregnancy, monitor for hemolysis in G6PD-deficient mothers and fetal growth if used long-term. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility at therapeutic doses. |