Nitrofurantoin
Nitrofurantoin
Generic Name
Nitrofurantoin
Mechanism
- Selective bacterial reduction: In bacterial cells, nitrofurantoin is reduced by nitroreductase enzymes to reactive intermediates that damage intracellular components.
- Targets:
- Inhibits protein synthesis by binding to ribosomes.
- Disrupts DNA synthesis via reactive metabolites that alkylate DNA.
- Interferes with cell‑wall formation, leading to bacterial cell death.
- Urea‑superior environment: The drug accumulates in the urine in concentrations 10–20× serum levels, making it highly effective for cystitis.
Pharmacokinetics
| Parameter | Detail |
| Absorption | Rapid oral absorption; peak plasma concentration (C_max) ~ 1 h post‑dose. Bioavailability ~60% when taken with food. |
| Distribution | Widely distributed, 65–70 % protein binding (primarily to albumin). Penetrates epithelial tissues of the urinary tract. |
| Metabolism | Minimal; primarily excreted unchanged. Small amount oxidized to inactive forms. |
| Elimination | Renal clearance; *t*½ ≈ 7–10 h. Elimination depends on glomerular filtration and tubular secretion; largely unavailable in patients with CrCl < 60 ml/min. |
| Special Populations | Avoid in patients with renal impairment (CrCl < 60 ml/min) and in pregnancy. No significant CYP450 interaction. |
Indications
- Acute uncomplicated cystitis in women.
- Recurring UTIs (prophylaxis in susceptible patients).
- Infection in patients with urinary tract stasis (post‑nephrectomy, catheterization).
*Not indicated for:*
• Acute pyelonephritis.
• Complicated UTIs (e.g., endophthalmitis, prostatitis).
• Influenza or other viral infections.
Contraindications
Contraindications
• Severe renal dysfunction (Creatinine clearance ≤ 60 ml/min).
• Known hypersensitivity to nitrofurantoin or sulfonamides.
Warnings
• Pulmonary toxicity (interstitial lung disease). Report any unexplained dyspnea, cough, or chest pain.
• Peripheral neuropathy in patients with diabetes or renal insufficiency.
• Hepatotoxicity: monitor liver enzymes if therapy > 2 months.
• Anemia: rare methemoglobinemia; consider in infants and young children.
Dosing
| Population | Dose | Frequency | Notes |
| Adults | 50 mg | QID (every 6 h) | Common regimen 400 mg/day in 5 days for uncomplicated cystitis. |
| Adults | 100 mg | BID | Often used for prophylaxis (5 days per month for recurrent UTIs). |
| Pregnancy (≥ 2nd trimester) | 50 mg | QID | Avoid in first trimester due to potential teratogenicity. |
| Children > 2 yrs | 0.625 mg/kg | QID | Up to 50 mg per dose (max 200 mg/day). |
| Infants < 2 yrs | 0.625 mg/kg | QID | Contraindicated in < 6 mo due to risk of hemolysis in G6PD deficiency. |
• Administer at least 1 h before or 2 h after meals to avoid reduced absorption with high‑fat foods.
• Duration: 5 days for treatment; prophylaxis may extend up to 3 months with intermittent dosing.
Adverse Effects
Common (≤ 10 %)
• Nausea, vomiting, mild dyspepsia.
• Metallic taste.
• Crampy abdominal pain.
Serious (≤ 1 %)
• Pulmonary fibrosis: interstitial pneumonitis, fibrosis, or respiratory failure.
• Peripheral neuropathy: pain, numbness, docile: risk in long‑term use.
• Anemia / Methemoglobinemia: develops > 2 months; manifest as dyspnea, cyanosis.
• Severe rash / hypersensitivity: treat with corticosteroids; consider drug withdrawal.
Monitoring
| Timepoint | Test | Threshold | Action |
| Baseline | CrCl (eGFR) | > 60 ml/min | Proceed with therapy. |
| Every 2–4 weeks (prophylaxis > 1 month) | CBC, LFTs | ↑ AST/ALT > 2× ULN | Reassess dose or duration. |
| Long‑term use (> 3 months) | Pulmonary symptoms (dyspnea, cough) | New onset → discontinue & evaluate. | |
| Children < 12 yrs | G6PD status | Negative before initiating | Avoid therapy or use alternative. |
Clinical Pearls
- Avoid high‑dose ferrous sulfate concurrently with nitrofurantoin; iron decreases absorption due to competition for disulfide bonds.
- Metabolic control: In patients on anti‑diabetic therapy, nitrofurantoin doesn’t alter glucose levels; still monitor stone risk.
- Prophylactic regimens: Pulse dosing (5 days per month) reduces the risk of pulmonary toxicity compared to daily therapy.
- Urine pH influence: Nitrofurantoin is more active in alkaline urine; ensure patient maintains adequate fluid intake to keep urine pH 6–8.
- Renal inactivation: In patients with CrCl ≈ 30 ml/min, consider a lower dose or switch to fosfomycin; using nitrofurantoin beyond 1–2 weeks carries the risk of drug relapse.
- Pregnancy counseling: Use Nitrofurantoin only after the first trimester; offer alternative agents (ciprofloxacin, cephalexin) if earlier exposure is needed.
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• *This drug card consolidates evidence‑based pharmacology for Nitrofurantoin, suitable for quick reference by medical students and clinicians.*