Can chlorpheniramine cause anaphylaxis?

Chlorpheniramine as a Cause of Anaphylaxis

Yes, chlorpheniramine can paradoxically cause anaphylaxis, though this is extremely rare. This creates a particularly dangerous clinical scenario where an antihistamine intended to treat allergic reactions becomes the trigger itself, potentially leading to diagnostic confusion and treatment delays.

Evidence for Chlorpheniramine-Induced Anaphylaxis

Documented cases confirm that chlorpheniramine can trigger true IgE-mediated anaphylaxis:

• Multiple case reports have documented anaphylaxis following chlorpheniramine administration, confirmed by elevated serum tryptase levels and positive intradermal testing 1, 2
• A pharmacovigilance database review identified 17 cases (31.5%) of anaphylaxis among 54 patients reporting chlorpheniramine-induced adverse drug reactions 1
• Patients presented with classic anaphylactic symptoms including urticaria, abdominal pain, generalized itching, and cardiovascular collapse immediately following chlorpheniramine injection 1, 2

Clinical Presentation and Diagnostic Pitfalls

The irony of this reaction creates significant diagnostic challenges:

• Symptoms typically develop immediately after chlorpheniramine administration (oral, intramuscular, or intravenous routes) 1, 2
• Clinicians may mistakenly attribute worsening symptoms to progression of the original allergic condition rather than recognizing chlorpheniramine as the culprit 3
• One documented case showed urticaria actually worsening after intravenous chlorpheniramine administration for symptom control 3

Diagnostic Confirmation

When chlorpheniramine-induced anaphylaxis is suspected, specific testing can confirm the diagnosis:

• Skin prick testing may be negative, but intradermal testing is more sensitive and can confirm the diagnosis 2
• Serum tryptase levels drawn at appropriate intervals (1 hour and 2-4 hours after reaction onset, plus baseline) support the diagnosis of anaphylaxis 1
• Cross-reactivity testing is essential, as patients may react to other piperazine derivatives (cetirizine, levocetirizine) but tolerate piperidine derivatives (fexofenadine, loratadine, ebastine) 1

Management Implications

Recognition of this paradoxical reaction is critical for proper treatment:

• Epinephrine remains the first-line treatment and should never be delayed 4, 5
• Chlorpheniramine should be immediately discontinued if anaphylaxis worsens after its administration 1, 3
• The standard anaphylaxis treatment algorithm applies: intramuscular epinephrine 0.3-0.5 mg (adults) or 0.01 mg/kg (children), repeated every 5-15 minutes as needed, plus aggressive fluid resuscitation 5
• Corticosteroids (methylprednisolone 1-2 mg/kg IV) may be added after initial resuscitation to prevent biphasic reactions 5

Important Clinical Caveats

Several critical points warrant emphasis:

• Chlorpheniramine is listed in anaphylaxis treatment guidelines as a secondary medication (10 mg IV for adults) 4, creating potential for administering the causative agent during resuscitation
• Aspirin intolerance may coexist with chlorpheniramine hypersensitivity, though the relationship remains unclear 3
• Patients with confirmed chlorpheniramine anaphylaxis must receive explicit instructions to avoid this medication and potentially cross-reactive antihistamines 1
• Alternative H1-antihistamines from different chemical classes should be identified through careful testing before future use 1

Risk Context

While chlorpheniramine-induced anaphylaxis is rare, awareness is essential:

• The drug has been used safely since the 1950s with an extensive safety profile 6
• However, the potential for life-threatening reactions exists, particularly with parenteral administration 1, 2
• Physicians must maintain clinical suspicion when allergic symptoms worsen rather than improve after chlorpheniramine administration 3