Nitrofurantoin

# Nitrofurantoin ## Overview - **Classification**: Nitrofuran antibiotic - **Mechanism**: Metabolized by bacterial reductases to reactive intermediates that inactivate bacterial ribosomal proteins and other macromolecules, inhibiting synthesis of DNA, RNA, and protein. ## Primary Indications 1. **Acute Uncomplicated Cystitis (AUC)** - Treatment of lower urinary tract infections caused by susceptible organisms. 2. **Urinary Tract Infection Prophylaxis** - Prevention of recurrent UTIs. 3. **Asymptomatic Bacteriuria** - Only in select cases (e.g., pregnancy), per guidelines. ## Adult Dosing ### Standard Dosing **Acute Uncomplicated Cystitis (AUC)** - **Nitrofurantoin Macrocrystals (Macrodantin)**: - **Dose**: **50-100 mg** - **Frequency**: Every 6 hours (QID) - **Route**: Oral - **Duration**: 7 days - **Nitrofurantoin Monohydrate/Macrocrystals (Macrobid)**: - **Dose**: **100 mg** - **Frequency**: Every 12 hours (BID) - **Route**: Oral - **Duration**: 5 days **Urinary Tract Infection Prophylaxis** - **Dose**: **50-100 mg** (macrocrystals or monohydrate/macrocrystals) - **Frequency**: Once daily (HS - at bedtime) - **Route**: Oral - **Duration**: Up to 6-12 months (or as clinically indicated) ### Dose Adjustments - **Renal Impairment**: **Contraindicated** if **CrCl < 60 mL/min** (due to reduced efficacy and increased systemic toxicity, e.g., pulmonary, hepatic, peripheral neuropathy). Some sources state <30 mL/min for prophylaxis. - **Hepatic Impairment**: No specific dose adjustments. Use with caution; monitor LFTs with prolonged use. - **Elderly Patients**: Higher risk of adverse effects (e.g., pulmonary, hepatic, peripheral neuropathy) due to age-related decline in renal function. **Avoid if CrCl < 60 mL/min.** ## Pediatric Dosing ### Neonates (0-28 days) - **Contraindicated**: Risk of hemolytic anemia due to immature erythrocyte enzyme systems (e.g., G6PD deficiency not yet identified). - **Special Notes**: Also contraindicated for term pregnancy at 38-42 weeks and during labor/delivery. ### Infants (1-12 months) **Acute Uncomplicated Cystitis (AUC)** - **Dose**: **5-7 mg/kg/day** - **Frequency**: Divided every 6 hours (QID) - **Maximum**: **100 mg/dose** - **Special Notes**: Available as oral suspension (**25 mg/5 mL**). ### Children (1-12 years) **Acute Uncomplicated Cystitis (AUC)** - **Dose**: **5-7 mg/kg/day** - **Frequency**: Divided every 6 hours (QID) - **Maximum**: **400 mg/day** (or **100 mg/dose**) **Urinary Tract Infection Prophylaxis** - **Dose**: **1-2 mg/kg/day** - **Frequency**: Once daily (HS) or divided every 12 hours (BID) - **Maximum**: **100 mg/day** ### Adolescents (13-18 years) - **Dose**: Generally follows **adult dosing** for indication. - **Maximum**: **Adult maximum doses** (e.g., 100 mg BID for Macrobid). ## Safety Information ### Contraindications - **Absolute**: CrCl < 60 mL/min (or <30 mL/min for prophylaxis, or end-stage renal disease). - **Absolute**: History of cholestatic jaundice/hepatic dysfunction associated with prior nitrofurantoin use. - **Absolute**: Pregnancy at term (38-42 weeks), during labor and delivery, or when onset of labor is imminent. - **Absolute**: Infants younger than 1 month of age. - **Absolute**: G6PD deficiency (risk of hemolytic anemia). - **Absolute**: Hypersensitivity to nitrofurantoin. ### Common Adverse Effects - **Very Common (>10%)**: Nausea, headache, flatulence, abdominal pain. - **Common (1-10%)**: Vomiting, diarrhea, anorexia, rash, dizziness. - **Serious but Rare**: Pulmonary fibrosis, acute/chronic pneumonitis, hepatotoxicity (cholestatic jaundice, hepatitis), peripheral neuropathy, hemolytic anemia, C. difficile-associated diarrhea. ### Key Drug Interactions - **Antacids (containing magnesium trisilicate)**: Reduce nitrofurantoin absorption. Separate administration. - **Probenecid/Sulfinpyrazone**: Reduce renal excretion of nitrofurantoin, increasing serum levels and risk of toxicity; decrease efficacy in UTI. Avoid concomitant use. - **Oral Contraceptives**: Potential for reduced efficacy, though not consistently demonstrated. Advise backup contraception. ## Monitoring & Follow-up - **Before Treatment**: Assess renal function (CrCl). - **During Treatment**: - Monitor for signs of pulmonary toxicity (cough, dyspnea, fever). - Monitor for signs of peripheral neuropathy (numbness, tingling). - Monitor for signs of hepatic injury (jaundice, dark urine, fatigue). - **Clinical Signs**: Resolution of UTI symptoms. If prolonged use, consider CBC, LFTs, and pulmonary function tests at baseline and periodically. ## Clinical Pearls - 💡 **Take with food**: Enhances absorption and improves gastrointestinal tolerability. - 💡 **Urine discoloration**: May cause urine to turn dark yellow or brown, which is harmless. - 💡 **Not for pyelonephritis**: Achieves poor tissue concentrations outside the bladder; not effective for upper UTIs. - 💡 **Compliance**: Counsel patients on the full course to prevent recurrence and resistance. - 💡 **Formulation matters**: Macrobid (BID) is generally preferred over Macrodantin (QID) for convenience. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.