nitrofurantoin
Brand: Macrobid, Macrodantin
Beers Criteria Prototype Drug
Drug Class: nitrofuran antibiotic
Drug Family: antibiotic
Subclass: urinary tract-specific antibacterial
Organ Systems: infectious-disease
Mechanism of Action
Prodrug activated by bacterial nitroreductase enzymes to reactive intermediates; damages DNA, ribosomes, and various metabolic enzymes simultaneously — this multi-mechanism explains very low resistance rates. Only achieves therapeutic concentrations in urine.
multiple bacterial enzymes and DNA (multi-mechanism)
Indications
- uncomplicated urinary tract infections (UTI)
- UTI prophylaxis (chronic suppression)
Contraindications
- CrCl <30 mL/min (inadequate urinary concentrations + toxicity accumulation)
- near-term pregnancy (33–42 weeks — hemolytic anemia risk in neonate)
- G6PD deficiency
- anuria/oliguria
Adverse Effects
Common
- GI upset
- nausea
- pulmonary hypersensitivity (acute — eosinophilic pneumonitis)
Serious
- pulmonary toxicity (acute hypersensitivity or chronic fibrotic)
- hepatotoxicity
- peripheral neuropathy (especially with renal impairment)
- hemolytic anemia (G6PD deficiency)
- lupus-like syndrome
Pharmacokinetics (ADME)
| Absorption | high with food (macrocrystalline > microcrystalline); always administer with food |
| Distribution | concentrates in urine only; inadequate tissue concentrations for systemic infections |
| Metabolism | hepatic (partial) |
| Excretion | renal (40% unchanged in urine) — ONLY effective for UTI because therapeutic levels only in urine |
| Half-life | 0.3–1 hour (Macrodantin) or 1.5–2 hours (Macrobid monohydrate-macrocrystalline) |
| Onset | 1–2 hours |
| Peak | 1 hour (macrocrystalline) |
| Duration | 6–12 hours |
| Protein Binding | 20–40% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| antacids (magnesium trisilicate) | reduce nitrofurantoin absorption | moderate |
| probenecid | reduces renal excretion of nitrofurantoin, reducing urinary concentrations and efficacy | moderate |
Nursing Considerations
- Always administer with food or milk to increase absorption and reduce GI side effects; the macrocrystalline (Macrodantin) formulation has less GI upset.
- Do not use when CrCl is <30 mL/min — inadequate urinary drug concentrations make it ineffective, and accumulation causes peripheral neuropathy.
- Counsel patients that urine will turn brown or rust-colored — normal and harmless.
- Monitor for new respiratory symptoms (cough, dyspnea) during therapy; acute pulmonary reactions can mimic pneumonia and must be distinguished by stopping the drug.
Clinical Pearls
- Nitrofurantoin is the preferred treatment for uncomplicated cystitis in non-pregnant adults because its narrow urinary distribution preserves gut flora and minimizes selection pressure for resistance compared to fluoroquinolones or trimethoprim-sulfamethoxazole.
- Chronic suppressive therapy with nitrofurantoin for recurrent UTI is well-established, but patients must be monitored periodically for pulmonary toxicity (insidious chronic interstitial pneumonitis).
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.