Nitrofurantoin-Induced Hives: Highly Probable Correlation
Yes, the hive that developed one day after starting nitrofurantoin is very likely correlated with the medication and represents a hypersensitivity reaction that warrants immediate discontinuation of the drug. 1
Evidence for Correlation
FDA-Documented Hypersensitivity Reactions
The FDA drug label for nitrofurantoin explicitly lists urticaria (hives) as a documented allergic/hypersensitivity reaction to this medication. 1 The label specifically states that "urticaria; anaphylaxis; arthralgia; myalgia; drug fever; chills; and vasculitis" have been reported, and notably emphasizes that "hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with nitrofurantoin formulations." 1
Temporal Relationship
The one-day timeline between drug initiation and symptom onset is consistent with acute hypersensitivity reactions to nitrofurantoin. 1 Acute reactions to nitrofurantoin typically occur within the first week of treatment, with many manifesting within the first few days. 1, 2
Spectrum of Allergic Reactions
Beyond simple urticaria, nitrofurantoin can cause more severe dermatologic reactions including: 1
- Maculopapular, erythematous, or eczematous eruptions
- Pruritus
- Exfoliative dermatitis (rare)
- Erythema multiforme including Stevens-Johnson syndrome (rare)
- Angioedema
Clinical Management
Immediate Action Required
Discontinue nitrofurantoin immediately. 1 The drug should not be restarted, as repeated exposures can lead to more severe reactions. 2 One case report documented a patient who experienced two successive acute pulmonary reactions after restarting nitrofurantoin, with the second episode being more severe. 2
Alternative Antibiotic Selection
For continued UTI treatment, consider alternatives based on susceptibility patterns: 3
- Trimethoprim-sulfamethoxazole (TMP-SMX): 40/200 mg dosing
- Trimethoprim alone: 100 mg
- Cephalexin: appropriate dosing
- Fosfomycin: 3 g single dose
- Fluoroquinolones should be reserved due to stewardship concerns 3
Monitoring for Progression
While isolated urticaria is typically benign, monitor for signs of more serious systemic reactions: 1, 4, 5
- Systemic inflammatory response syndrome (SIRS): fever, leukocytosis, altered mental status 4, 5
- Respiratory symptoms: dyspnea, chest pain, cough (acute pulmonary hypersensitivity) 1, 2
- Angioedema: particularly concerning if involving airway 1
- Anaphylaxis: rare but documented 1
Important Clinical Pitfalls
Do Not Rechallenge
Never restart nitrofurantoin in a patient who has experienced a hypersensitivity reaction. 2 Case reports demonstrate that rechallenge can result in more severe reactions, including life-threatening pulmonary toxicity and systemic inflammatory responses. 2, 5
Document the Allergy
Clearly document this as a drug allergy in the patient's medical record to prevent future exposures. 1 Nitrofurantoin is commonly used for UTI prophylaxis, so preventing inadvertent re-exposure is critical. 3
Consider Broader Hypersensitivity
The FDA label notes that hypersensitivity reactions are the most frequently reported adverse events with nitrofurantoin globally. 1 This patient should be counseled that they have demonstrated a drug hypersensitivity and should report this allergy to all healthcare providers.
Distinguish from Other Reactions
While this presentation is consistent with simple urticaria, be aware that nitrofurantoin can cause severe systemic reactions that may initially present with seemingly minor symptoms. 4, 5 One case report described an 85-year-old woman who developed profound leukocytosis and altered mental status after a single dose. 5