Can Metronidazole Cause Angioedema?
Yes, metronidazole can cause angioedema, though this is a rare hypersensitivity reaction. 1
Evidence for Metronidazole-Associated Angioedema
The most direct evidence comes from a comprehensive 2022 review of hypersensitivity reactions to metronidazole, which documented rare cases of angioedema among a broad spectrum of allergic reactions to this antibiotic. 1 This same review also reported cases of anaphylaxis, fixed drug eruption, serum sickness-like reactions, and severe cutaneous adverse reactions including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and acute generalized exanthematous pustulosis (AGEP). 1
Clinical Context and Mechanism
Angioedema from metronidazole represents an IgE-mediated or delayed hypersensitivity reaction, distinct from the more common gastrointestinal side effects (nausea, abdominal pain, diarrhea) and neurological toxicity (peripheral neuropathy, encephalopathy) associated with this drug. 2, 1
The frequency is exceedingly rare compared to other antibiotics like beta-lactams and NSAIDs, which are the most common causes of drug-induced angioedema. 3
Published desensitization protocols exist for both oral and intravenous metronidazole, indicating that clinicians have encountered true IgE-mediated reactions requiring careful reintroduction when no alternative exists. 1
Common Pitfalls and Clinical Considerations
Do not confuse angioedema with the common gastrointestinal side effects that metronidazole frequently causes—these are pharmacologic effects, not allergic reactions. 4
If angioedema occurs with metronidazole, immediately discontinue the drug and provide emergency management including epinephrine if there is airway compromise. 5
Document the reaction thoroughly and provide the patient with an allergy pass, as cross-reactivity patterns with other nitroimidazoles (like tinidazole) are not well established. 3
Consider alternative diagnoses if angioedema occurs, particularly if the patient is on ACE inhibitors or angiotensin II receptor antagonists, which are far more common causes of isolated angioedema. 5, 3
Management Approach
For confirmed metronidazole-induced angioedema: Avoid all nitroimidazole antibiotics unless absolutely necessary. 1
If metronidazole is essential and no alternatives exist: Referral to an allergist for evaluation and potential desensitization protocol is warranted. 1
Emergency medication including epinephrine should be prescribed to any patient with documented drug-induced angioedema. 3