What are the side effects of Nitrofurantoin (antibiotic)?

Side Effects of Nitrofurantoin

Nitrofurantoin causes a spectrum of adverse effects ranging from common gastrointestinal symptoms to rare but serious pulmonary, hepatic, and neurologic complications that can be life-threatening or irreversible. 1

Common Adverse Effects

Gastrointestinal (Most Frequent)

• Nausea, vomiting, and anorexia are the most commonly occurring side effects 1
• Abdominal pain and diarrhea occur less frequently 1
• These are dose-related reactions that can be minimized by reducing the dosage 1
• Sialadenitis and pancreatitis have been reported 1
• Pseudomembranous colitis can occur during or after treatment 1

Serious Adverse Effects

Pulmonary Toxicity

Pulmonary reactions represent one of the most serious complications and can manifest as either acute or chronic patterns. 2, 1

Acute Pulmonary Reactions

• Occur at extremely low rates (0.001%) according to the American Urological Association 3
• Commonly manifest within the first week of treatment with fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia 1
• Acute reactions are reversible with cessation of therapy, often with dramatic resolution 1
• Cyanosis has been reported rarely 1
• EKG changes (non-specific ST/T wave changes, bundle branch block) have been associated with pulmonary reactions 1

Chronic Pulmonary Reactions

• Can involve pulmonary fibrosis if not recognized early 2, 4
• If symptoms are not recognized as drug-related and therapy continues, symptoms may become more severe 1
• Despite severe symptoms and extensive radiological involvement, patients may return to baseline following drug cessation 4

Hepatotoxicity

Hepatic reactions are rare (0.0003%) but can be severe, ranging from acute hepatitis to chronic active hepatitis leading to cirrhosis or death. 3, 1

• Hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis occur rarely 1
• Can present as either acute or chronic hepatitis-like syndrome 5, 6
• Nitrofurantoin-induced immune-mediated liver injury can result in both acute hepatic failure and cirrhosis with continued use 7
• Mechanism is poorly understood but believed to involve immunologic processes or direct cytotoxic reactions 6
• Risk factors include prolonged exposure, female sex, advanced age, and reduced renal function 6
• Laboratory abnormalities include increased AST, increased ALT 1

Neurologic Complications

Peripheral neuropathy is particularly concerning as it may become severe or irreversible, with fatalities reported. 1

• Conditions that increase risk of peripheral neuropathy include: renal impairment (creatinine clearance <60 mL/min or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases 1
• Asthenia, vertigo, nystagmus, dizziness, headache, and drowsiness have been reported 1
• Rare neurologic effects include benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis, and psychotic reactions 1
• Bulging fontanels (sign of benign intracranial hypertension) reported rarely in infants 1

Hematologic Effects

• Cyanosis secondary to methemoglobinemia reported rarely 1
• Glucose-6-phosphate dehydrogenase deficiency anemia 1
• Eosinophilia, agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia 1
• Most hematologic abnormalities resolve following cessation of therapy 1
• Aplastic anemia reported rarely 1

Dermatologic and Allergic Reactions

• Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) reported rarely 1
• Transient alopecia 1
• A lupus-like syndrome associated with pulmonary reactions has been reported 1
• Angioedema, maculopapular/erythematous/eczematous eruptions, pruritus, urticaria, anaphylaxis 1
• Arthralgia, myalgia, drug fever, chills, and vasculitis (sometimes associated with pulmonary reactions) 1
• Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience 1

Systemic Inflammatory Response

• Severe systemic inflammatory response syndrome can occur, mimicking conditions such as ischemia and infection 8
• Can present with hypoxia, altered mental status, and profound leukocytosis even after a single dose 8

Clinical Monitoring Considerations

• Regular assessment for adverse effects is necessary during prophylactic use, which typically ranges from 6-12 months though some patients may require longer periods 3
• Clinicians must consider iatrogenic and medication-induced etiologies when patients present with altered mental status or systemic inflammatory responses 8
• Given the severity of hepatotoxicity and pulmonary toxicity, clinicians should weigh risks and benefits before initiating therapy, especially for long-term prophylaxis in high-risk patients 6