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). |
| Molecular Weight | 238.2 |
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 | Contraindicated at term (38-42 weeks) and during labor/delivery due to risk of hemolytic anemia in neonate. Avoid in first trimester unless no alternative; animal studies show fetal toxicity but human data limited. |
| 2nd trimester | Use only if clearly needed; caution due to possible fetal hemolytic anemia if G6PD deficiency. |
| 3rd trimester | Contraindicated at term (38-42 weeks) due to risk of hemolytic anemia in neonate. Avoid in pregnant patients with G6PD deficiency. |
Clinical note
Antacids may decrease absorption Can cause pulmonary fibrosis and peripheral neuropathy with long-term use.
| FDA category | Positive |
| Placental transfer | Nitrofurantoin crosses the placenta; fetal serum concentrations are about 25-50% of maternal levels. |
■ 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 |
AnuriaOliguriaSignificant renal impairment (CrCl <60 mL/min or serum creatinine >1.2 mg/dL)Pregnancy at term (38-42 weeks)Known hypersensitivity to nitrofurantoinG6PD deficiency (relative, but absolute in neonates and pregnant patients at term)
| 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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| Breastfeeding |
| Nitrofurantoin is excreted into breast milk in small amounts. Use with caution in nursing mothers of infants with G6PD deficiency. The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor infant for diarrhea, rash, or hemolysis. |
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
| Food/Dietary | Take with food or milk to increase absorption and reduce GI upset. Avoid alcohol during therapy and for 3 days after completing course. No specific food restrictions beyond taking with meals. |
| Clinical Pearls | Macrocrystalline formulation reduces GI side effects vs macrocrystalline; always check CrCl <30 mL/min contraindicated; give with food to improve absorption and reduce nausea; avoid in G6PD deficiency; urine may turn brown/yellow; consider susceptibility testing due to increasing resistance; ineffective for pyelonephritis; short-course therapy (3-7 days) for uncomplicated UTI. |
| Patient Advice | Take with food or milk to reduce stomach upset and improve absorption. · Complete full course even if symptoms improve; do not skip doses. · Do not take with antacids containing magnesium trisilicate. · Urine may become dark yellow or brownish; this is harmless. · Report any new symptoms like numbness, tingling, muscle weakness, or vision changes. · Avoid alcohol during therapy and for 3 days after stopping. · Inform your doctor if you have kidney disease, G6PD deficiency, or lung problems. · May cause dizziness; use caution when driving or operating machinery. |