Nitrofurantoin 100 mg
Reading File
Finding Sources
Searching PubMed
nitrofurantoin urinary tract infection
Reading File
Reading File
Reading File
I now have comprehensive information from multiple authoritative sources. Here is a complete drug profile for Nitrofurantoin 100 mg:
Nitrofurantoin 100 mg
Drug Class
Nitrofuran antibiotic / Urinary antiseptic
Mechanism of Action
Nitrofurantoin is reduced by bacterial reductases (nitrofuran reductases) to highly reactive intermediates. These intermediates nonspecifically damage bacterial DNA and inhibit protein, RNA, and DNA synthesis. Because bacteria reduce nitrofurantoin far more rapidly than mammalian cells, the compound has selective antimicrobial toxicity. Its exact primary bactericidal target is not fully established, but the action is concentration-dependent.
- Goodman & Gilman's, p. 1193 | Katzung's, 16th Ed., p. 1395 | Harrison's 22E, p. 1222
Antimicrobial Spectrum
Susceptible organisms:
- Gram-positive: S. aureus, S. epidermidis, S. saprophyticus, E. faecalis, streptococci (including S. agalactiae, viridans group), corynebacteria
- Gram-negative: E. coli (primary target), Enterobacter, Salmonella, Shigella spp.
- Activity against ESBL-producing E. coli strains is an area of growing clinical interest
Inherently resistant:
- Pseudomonas aeruginosa
- Most Proteus spp.
- Many Klebsiella and Enterobacter spp.
No cross-resistance with other antibiotic classes; resistance emerges slowly. As TMP-SMX and fluoroquinolone resistance in E. coli has grown, nitrofurantoin has become an important alternative for uncomplicated UTI.
Dosage Forms & Dosing
| Formulation | Description | Dosing |
|---|---|---|
| Microcrystalline (standard) | Faster absorption | 50-100 mg four times daily |
| Macrocrystalline (Macrodantin) | Slower dissolution, fewer GI side effects | 100 mg four times daily |
| Macrocrystalline / monohydrate (Macrobid) | 25% macrocrystals + 75% monohydrate gel matrix - extended release | 100 mg twice daily x 7 days |
Standard adult treatment dose: 100 mg orally four times daily (or 100 mg BD with Macrobid formulation). Should be taken with food to improve bioavailability and reduce GI side effects.
Prophylaxis for recurrent UTI: 50-100 mg once daily at bedtime.
Pediatric dose: 5-7 mg/kg/day in divided doses; as low as 1 mg/kg/day for long-term prophylaxis (not in infants < 1 month).
A course should not exceed 14 days; repeated courses should be separated by rest periods.
Pharmacokinetics
- Absorption: Rapidly and nearly completely absorbed orally; GI absorption is enhanced by food
- Distribution: Plasma concentrations are negligible at therapeutic doses - drug is eliminated too rapidly for systemic antibacterial effect
- t½: 0.3 to 1 hour
- Urine concentration: ~200 mcg/mL at average daily doses - well above MIC for susceptible organisms
- Excretion: ~40% excreted unchanged in urine via glomerular filtration + tubular secretion. Rate of excretion is linearly related to creatinine clearance
- Urine color: Turns urine brown (harmless)
- pH note: Acidic urine (pH < 5.5) greatly enhances antibacterial activity; alkalinization reduces efficacy
Indications
- First-line treatment for uncomplicated lower UTI / acute cystitis
- Preferred agent for UTI in pregnancy (with caution - see below)
- Prevention of recurrent cystitis
- Active against ESBL-producing E. coli in UTI
NOT appropriate for:
- Pyelonephritis (upper UTI) - inadequate tissue/blood levels
- Prostatitis
- Systemic infections
Contraindications & Cautions
| Condition | Notes |
|---|---|
| Renal insufficiency (CrCl < 30 mL/min) | Drug accumulates systemically (toxicity) + urine levels fall below therapeutic range. Traditional cut-off is CrCl < 60 mL/min; some evidence supports use down to CrCl > 30 mL/min for short courses |
| G6PD deficiency | High risk of hemolytic anemia |
| Pregnancy at term (38-42 weeks) | Risk of neonatal hemolytic anemia |
| Neonates (< 1 month) | Immature enzyme systems - hemolytic risk |
| Elderly patients | Increased risk of pulmonary, hepatic, and neurological adverse reactions |
Adverse Effects
Common (GI):
- Nausea, vomiting, diarrhea - the most frequent; macrocrystalline/Macrobid formulations are better tolerated
- Anorexia
Hematologic:
- Hemolytic anemia (G6PD-deficient patients, newborns)
- Leukopenia, granulocytopenia
Pulmonary (important - especially with long-term use):
- Acute: Pneumonitis with fever, chills, cough, dyspnea, chest pain, pulmonary infiltrates, eosinophilia - develops within hours to days; resolves on stopping the drug
- Chronic: Interstitial pulmonary fibrosis - particularly in elderly on long-term therapy
Neurological:
- Headache, vertigo, drowsiness, nystagmus, muscular aches
- Severe polyneuropathy with demyelination and degeneration of sensory and motor nerves - most likely in renal impairment or prolonged use
Hepatic:
- Cholestatic jaundice, hepatocellular damage (drug-induced hepatitis)
Hypersensitivity:
- Rashes, chills, fever, pulmonary infiltration
Drug Interactions
- Antacids containing magnesium - reduce absorption; avoid coadministration
- Nalidixic acid and some fluoroquinolones (norfloxacin, ciprofloxacin) - nitrofurantoin antagonizes their action; avoid combination
- Urine alkalinizing agents reduce antibacterial efficacy
Special Populations
| Population | Recommendation |
|---|---|
| Pregnancy | Preferred for UTI (especially over fluoroquinolones and TMP-SMX). Avoid at term (38-42 wk) due to neonatal hemolysis risk |
| Elderly | Use with caution or avoid; increased risk of pulmonary fibrosis, hepatotoxicity, and peripheral neuropathy |
| Renal impairment | Avoid if CrCl < 30 mL/min (traditional guidance: < 60 mL/min) |
| G6PD deficiency | Contraindicated |
Key Summary Points
- Urinary antiseptic only - useful only for lower UTI; not for systemic infections or pyelonephritis
- 100 mg BD (Macrobid) x 7 days is the standard regimen for uncomplicated cystitis
- Achieves very high urine concentrations (~200 mcg/mL) but negligible plasma levels
- Macrocrystalline/Macrobid formulation reduces GI side effects compared to microcrystalline
- Avoid in significant renal impairment (drug fails to reach therapeutic urine levels and toxic blood levels build up)
- Monitor for pulmonary reactions in patients on long-term prophylaxis
Sources: Katzung's Basic & Clinical Pharmacology 16th Ed. | Goodman & Gilman's Pharmacological Basis of Therapeutics | Harrison's Principles of Internal Medicine 22E (2025)
This is a shared conversation. Sign in to Orris to start your own chat.