Nitrofurantoin Side Effects
Nitrofurantoin causes primarily gastrointestinal side effects (nausea, vomiting, anorexia) that are dose-related and common, while serious pulmonary and hepatic reactions are rare but potentially life-threatening and require immediate drug discontinuation. 1
Common Adverse Effects
Gastrointestinal (Most Frequent)
- Nausea, vomiting, and anorexia occur most often and are dose-related reactions that can be minimized by reducing dosage 1
- Abdominal pain and diarrhea are less common gastrointestinal reactions 1
- Metallic taste may occur 1
- These gastrointestinal effects occur in 5-16% of patients but are mild, reversible, and predominantly self-limited 2
Serious Adverse Effects (Rare but Critical)
Pulmonary Toxicity
- Acute pulmonary reactions occur at extremely low rates (0.001%) but are the most critical concern 3
- Acute reactions manifest with fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia 1
- Acute reactions usually occur within the first week of treatment (often by day 4-8) and are reversible with immediate cessation of therapy 1, 4
- Resolution is often dramatic once the drug is stopped 1
- Chronic pulmonary reactions can involve pulmonary fibrosis if not recognized early and therapy continues 3
- Symptoms may be misdiagnosed as pneumonia or other respiratory conditions, potentially delaying discontinuation 4
Hepatotoxicity
- Serious hepatic adverse events occur at extremely low rates (0.0003%) 3
- Hepatic reactions include hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis 1
- Can present with abdominal pain and elevated liver enzymes 5
- May cause either acute or chronic hepatitis-like syndrome that can lead to liver failure or cirrhosis 6, 5
- Risk factors include prolonged exposure, female sex, advanced age, and reduced renal function 6
Neurologic Toxicity
- Peripheral neuropathy may become severe or irreversible, with fatalities reported 1
- Risk increased with renal impairment (creatinine clearance under 60 mL/min), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases 1
- Other neurologic effects include asthenia, vertigo, nystagmus, dizziness, headache, and drowsiness 1
- Benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis, and psychotic reactions reported rarely 1
Less Common Adverse Effects
Dermatologic
- Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) reported rarely 1
- Transient alopecia has been reported 1
Allergic/Hypersensitivity
- Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience 1
- Lupus-like syndrome associated with pulmonary reactions 1
- Angioedema, maculopapular/erythematous/eczematous eruptions, pruritus, urticaria, anaphylaxis, arthralgia, myalgia, drug fever, chills, and vasculitis 1
- ANCA-associated vasculitis reported (extremely rare) 7
Hematologic
- Cyanosis secondary to methemoglobinemia reported rarely 1
- Eosinophilia, glucose-6-phosphate dehydrogenase deficiency anemia, agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia 1
- Most hematologic abnormalities resolve following cessation of therapy 1
- Aplastic anemia reported rarely 1
Laboratory Abnormalities
- Increased AST/ALT, decreased hemoglobin, increased serum phosphorus 1
Critical Clinical Pitfalls
Patients must be instructed to immediately report breathing difficulties, chest pain, or unusual symptoms, as acute pulmonary reactions are often misdiagnosed as pneumonia or other conditions, delaying drug discontinuation 4
Do not use in patients with creatinine clearance under 60 mL/min due to increased risk of peripheral neuropathy from drug accumulation 1
Recurrent acute reactions can occur upon rechallenge, even after previous resolution of symptoms 4