Introduction
Macrobid (nitrofurantoin monohydrate/macrocrystals) is an antibacterial medication specifically formulated for the treatment of urinary tract infections (UTIs). As a nitrofuran antibiotic, it has been widely used for decades due to its targeted action in the urinary tract and distinctive mechanism of action that differs from other antibiotic classes.
Mechanism of Action
Nitrofurantoin undergoes enzymatic reduction by bacterial flavoproteins to reactive intermediates that attack ribosomal proteins and other cellular components. These activated compounds inhibit bacterial synthesis of DNA, RNA, proteins, and cell wall formation. The drug is bactericidal against susceptible organisms at therapeutic concentrations and achieves effective concentrations primarily in the urine.
Indications
- Treatment of acute uncomplicated cystitis caused by susceptible strains of Escherichia coli, Staphylococcus saprophyticus, Enterococcus faecalis, and certain strains of Klebsiella and Enterobacter species
- Prophylaxis of recurrent urinary tract infections (off-label use)
Dosage and Administration
Acute cystitis treatment:- Adults: 100 mg twice daily for 5 days
- Children ≥12 years: 100 mg twice daily for 5-7 days
- Contraindicated when creatinine clearance <60 mL/min
- Avoid use in patients with significant renal impairment due to inadequate drug concentration in urine and increased systemic exposure
- Use with caution due to potential decreased renal function
- Assess creatinine clearance before initiation
- Take with food or milk to enhance absorption and minimize gastrointestinal upset
- Complete full course of therapy even if symptoms improve
Pharmacokinetics
Absorption: Rapid but incomplete gastrointestinal absorption (approximately 90% of dose is unabsorbed) Distribution: Primarily concentrated in urine; low serum concentrations Metabolism: Partially metabolized in most body tissues Elimination: Renal elimination with half-life of 20-60 minutes Urine concentrations: Therapeutic concentrations achieved only in urine (50-250 mcg/mL)Contraindications
- Known hypersensitivity to nitrofurantoin or other nitrofuran derivatives
- Patients with creatinine clearance <60 mL/min
- Pregnant patients at term (38-42 weeks gestation)
- Infants <1 month old (risk of hemolytic anemia)
- History of cholestatic jaundice or hepatic dysfunction with previous nitrofurantoin use
Warnings and Precautions
Pulmonary reactions: Acute, subacute, or chronic pulmonary reactions may occur, including interstitial pneumonitis and pulmonary fibrosis Hepatic effects: Hepatic reactions, including hepatitis and cholestatic jaundice, may occur Hemolytic anemia: May occur in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Peripheral neuropathy: May occur, potentially becoming irreversible Clostridioides difficile-associated diarrhea: Reported with nearly all antibacterial agentsDrug Interactions
Antacids containing magnesium trisilicate: Reduced absorption and efficacy of nitrofurantoin Uricosuric agents (probenecid): May antagonize nitrofurantoin efficacy by inhibiting renal tubular secretion Drugs that reduce renal function: May decrease nitrofurantoin efficacy and increase toxicity riskAdverse Effects
Common (≥1%):- Gastrointestinal: nausea, vomiting, anorexia, abdominal pain
- Respiratory: cough, dyspnea
- Neurological: headache, dizziness
- Dermatological: rash
- Pulmonary fibrosis
- Hepatitis, hepatic necrosis
- Hemolytic anemia
- Peripheral neuropathy
- Stevens-Johnson syndrome
- Clostridioides difficile-associated diarrhea
Monitoring Parameters
- Symptom resolution (dysuria, frequency, urgency)
- Urinalysis and culture results when available
- Respiratory symptoms (cough, dyspnea)
- Hepatic function in prolonged therapy
- Neurological symptoms (numbness, tingling)
- Complete blood count in patients at risk for hemolytic anemia
Patient Education
- Take with food or milk to reduce stomach upset
- Complete entire course of therapy even if feeling better
- Report any breathing difficulties, cough, or chest pain immediately
- Report unusual tiredness, fever, or yellowing of skin/eyes
- Report numbness, tingling, or burning sensations in hands or feet
- Urine may turn dark yellow or brown (normal effect)
- Not for use in viral infections such as common cold or flu
- Contact healthcare provider if symptoms do not improve within 2-3 days
References
1. Macrobid® [package insert]. Cincinnati, OH: Procter & Gamble Pharmaceuticals; 2021 2. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120 3. Hooton TM. Uncomplicated urinary tract infection. N Engl J Med. 2012;366(11):1028-1037 4. Lexicomp Online. Nitrofurantoin monograph. Wolters Kluwer Clinical Drug Information, Inc.; 2023 5. American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694