Side Effects of Nitrofurantoin
The most common side effects of nitrofurantoin are nausea and headache, while rare but serious adverse effects include pulmonary toxicity and hepatotoxicity that require immediate discontinuation of the medication. 1, 2
Common Side Effects
- Gastrointestinal effects: Nausea, vomiting, anorexia, abdominal pain, and diarrhea are the most frequently reported side effects and are dose-related (can be minimized by reducing dosage) 1, 2
- Neurological effects: Headache, dizziness, drowsiness, and vertigo 1
- Dermatological effects: Rash and urticaria 1
Serious Adverse Effects
Pulmonary Reactions
- Acute pulmonary reactions: Occur within the first week of treatment and present with fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia 1
- Chronic pulmonary reactions: Include pulmonary fibrosis and interstitial pneumonitis with prolonged use 1
- Warning signs: If respiratory symptoms are not recognized as drug-related and nitrofurantoin therapy is not stopped, symptoms may become more severe 1
- Risk: Extremely low rates of serious pulmonary adverse events (0.001%) 2
Hepatic Reactions
- Hepatotoxicity: Includes hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis (rare) 1
- Risk: Extremely low rates of serious hepatic adverse events (0.0003%) 2
- Case reports: Combined pulmonary and hepatic toxicity has been reported but is rare 3
Neurological Reactions
- Peripheral neuropathy: May become severe or irreversible; fatalities have been reported 1
- Risk factors: Renal impairment (creatinine clearance under 60 mL/minute), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases increase risk 1
- Rare neurological effects: Benign intracranial hypertension, confusion, depression, optic neuritis, and psychotic reactions 1
Hematologic Reactions
- Blood disorders: Agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia 1
- Rare effects: Aplastic anemia and cyanosis secondary to methemoglobinemia 1
Allergic Reactions
- Hypersensitivity: Most frequent spontaneously reported adverse events in worldwide postmarketing experience 1
- Manifestations: Lupus-like syndrome, angioedema, maculopapular/erythematous/eczematous eruptions, pruritus, urticaria, anaphylaxis, arthralgia, myalgia, drug fever, chills, and vasculitis 1
Dosing Considerations and Safety
Dosing Impact on Side Effects
- Lower dose recommendation: 50 mg daily prophylaxis shows equivalent efficacy to 100 mg with fewer adverse effects (particularly respiratory symptoms like cough and dyspnea) 4
- Standard treatment dosing: 100 mg twice daily for 5-7 days for acute uncomplicated cystitis 2
Contraindications
- Renal impairment: Contraindicated in patients with creatinine clearance under 60 mL/minute 1, 5
- Pregnancy considerations: While not specifically contraindicated, benefits and risks should be carefully weighed 5
Monitoring and Management
When to Discontinue
- Immediate discontinuation: If pulmonary symptoms (cough, chest pain, dyspnea), hepatic symptoms (jaundice), or signs of peripheral neuropathy develop 1
- Resolution: Many adverse effects, particularly pulmonary reactions, are reversible with prompt cessation of therapy 1
Long-term Prophylaxis Considerations
- Duration: Prophylactic use typically ranges from 6-12 months, though some patients may require longer periods 2
- Monitoring: Regular assessment for adverse effects is necessary during prophylactic use 2
Comparison to Other UTI Treatments
- Side effect profile: Nitrofurantoin has similar efficacy but a greater risk of adverse events compared to other prophylactic treatments 6
- Gastrointestinal effects: More common with nitrofurantoin than with other UTI treatments, leading to higher withdrawal rates 6
- Benefit consideration: Despite higher side effect risk, nitrofurantoin may be preferred due to lower risk of promoting antimicrobial resistance 6