What are the potential side effects of Macrobid (Nitrofurantoin)?

Side Effects of Macrobid (Nitrofurantoin)

Nitrofurantoin (Macrobid) can cause serious pulmonary reactions including chronic, subacute, or acute pulmonary hypersensitivity reactions, which may lead to permanent lung damage if not recognized early and discontinued. 1

Common Side Effects

Gastrointestinal Effects

• Nausea, vomiting, and anorexia are the most common side effects 1
• Abdominal pain and diarrhea occur less frequently 1
• Sialadenitis and pancreatitis have been reported 1
• Pseudomembranous colitis can occur during or after treatment 1

Dermatologic Effects

• Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely 1
• Transient alopecia can occur 1
• Maculopapular, erythematous, or eczematous eruptions may develop 1

Serious Adverse Effects

Pulmonary Reactions

• Chronic pulmonary reactions typically occur in patients who have received continuous treatment for six months or longer, manifesting as malaise, dyspnea on exertion, cough, and altered pulmonary function 1
• Subacute pulmonary reactions present with fever and eosinophilia (less often than in acute form) and may require several months for recovery 1
• Acute pulmonary reactions usually 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, 2
• Cyanosis has been reported rarely 1

Hepatic Effects

• Hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis occur rarely 1
• Laboratory monitoring may show increased AST (SGOT) and ALT (SGPT) 1

Neurologic Effects

• Peripheral neuropathy, which may become severe or irreversible (fatalities have been reported) 1
• Risk factors for peripheral neuropathy include renal impairment, anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases 1
• Asthenia, vertigo, nystagmus, dizziness, headache, and drowsiness 1
• Benign intracranial hypertension, confusion, depression, optic neuritis, and psychotic reactions (rare) 1

Hematologic Effects

• Cyanosis secondary to methemoglobinemia (rare) 1
• Decreased hemoglobin, eosinophilia, glucose-6-phosphate dehydrogenase deficiency anemia 1
• Agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia 1
• Aplastic anemia (rare) 1

Allergic Reactions

• Hypersensitivity reactions are the most frequent spontaneously-reported adverse events worldwide 1
• Lupus-like syndrome associated with pulmonary reactions 1
• Angioedema, pruritus, urticaria, anaphylaxis, arthralgia, myalgia, drug fever, chills, and vasculitis 1

Monitoring and Precautions

Risk Factors for Adverse Effects

• Elderly patients and those with renal impairment are at higher risk for side effects, particularly peripheral neuropathy 1
• Long-term use (>6 months) increases risk of chronic pulmonary reactions 1
• Patients with G6PD deficiency may experience hemolytic anemia 1

Safety in Long-Term Use

• Long-term studies have shown that macrocrystalline nitrofurantoin at lower doses (50mg daily) may have a more favorable safety profile than higher doses for prophylaxis 3
• Nausea tends to be more common with microcrystalline formulations compared to macrocrystalline (Macrodantin) formulations 3

Clinical Pearls

• Pulmonary reactions can be mistaken for pneumonia or other respiratory conditions; consider nitrofurantoin toxicity in patients with respiratory symptoms who recently started the medication 2
• Prompt discontinuation of the drug is essential when pulmonary reactions are suspected, as continued use may lead to permanent lung damage 1
• The macrocrystalline formulation (Macrodantin) may cause less gastrointestinal intolerance but can still produce the same serious adverse effects as the conventional form 4
• Nitrofurantoin should not be used when bacteremia is suspected as it does not achieve therapeutic serum levels 5