Generic Name

Macrobid

Mechanism

• Intracellular activation: Nitrofurantoin is reduced by bacterial nitroreductases to reactive intermediates.
• Multiple targets:
• Inhibit bacterial *DNA*, *RNA*, and *protein* synthesis.
• Interfere with cell wall and oxygen‑dependent enzymes.
• High urinary concentration: Achieves >80 % of the dose excreted unchanged, ensuring potent activity in urine while sparing systemic tissues.

Pharmacokinetics

• Absorption: ~60 % oral bioavailability; absorption enhanced by food.
• Distribution: Widely distributed; concentrates in renal tubular cells and urine.
• Metabolism: Minimal; metabolized to a small volume of nitrofuran metabolites.
• Elimination: Primarily renal excretion; dose‑adjusted by creatinine clearance (CrCl).
• Half‑life: ~3–4 h (short, but adequate urinary exposure).

Indications

• Uncomplicated lower UTI (cystitis) in adults and children ≥6 months.
• As a first‑line agent when susceptibility data are unavailable or when local resistance patterns are low for nitrofurantoin.
• Not indicated for:
• Pyelonephritis, prostatitis, or urosepsis.
• Patients with significant renal impairment (CrCl < 30 mL/min).

Contraindications

• Contraindications:
• CrCl 7 days.
• Hematologic: Rare hemolysis in patients with G6PD deficiency.
• Neuropathy: Chronic therapy (>30 days) may cause peripheral neuropathy.

Dosing

• Administer with food to improve absorption and reduce GI upset.
• Switch to q24h once adequate urinary concentrations are achieved (≈4 h after dose).
• For prophylaxis (e.g., recurrent UTI), use 250 mg q12h for 7–12 months; monitor renal function.

Adverse Effects

• Common (≤5 %): Nausea, vomiting, dyspepsia, abdominal pain, metallic taste.
• Serious (>2 %):
• Acute interstitial nephritis and pulmonary hypersensitivity reactions.
• Hepatic enzyme elevations (≈2 %).
• G6PD‑related hemolytic anemia (rare).
• Peripheral neuropathy with prolonged use (>30 days).

Monitoring

• Renal function: CrCl at baseline, then every 2–4 weeks during prolonged therapy.
• Liver enzymes: ALT/AST before therapy and periodically if >1 month of use.
• Pulmonary: Evaluate for dyspnea or cough; consider chest imaging if symptoms develop.
• Hematology: CBC if signs of hemolysis or anemia.
• Pregnancy & lactation: Avoid if contraindicated; counsel patients.

Clinical Pearls

• Rapid urinary clearance allows a once‑daily regimen for uncomplicated cystitis, improving adherence; however, q12h remains the standard for initial dosing until adequate urinary levels are confirmed.
• Avoid in pregnancy: Nitrofurantoin is a *contraindicated* drug after 34 weeks gestation and in lactation due to potential hemolysis in the infant if G6PD‑deficient.
• Combine with local antibiograms: In communities with >10 % resistance rates to nitrofurantoin, consider an alternative agent rather than empiric use.
• Use caution in elderly: Age correlates with decreased CrCl; re‑calculate dosing to prevent accumulation and adverse effects.
• If renal function improves during therapy, consider stepping down to q24h to reduce GI side effects and enhance compliance.
• Educate patients to take the medication with food and to finish the full course even if symptoms resolve; premature cessation can precipitate recurrence and resistance.

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• References: US FDA label, CDC UTI Treatment Guidelines (2024), KDIGO guidelines for drug monitoring, *Current Medical Therapy* 2025.