What is the recommended treatment with antihistamines for a drug reaction?

Antihistamine Treatment for Drug Reactions

For drug reactions presenting with urticaria or mild-to-moderate symptoms, use second-generation antihistamines as first-line therapy: cetirizine 10 mg IV/PO or loratadine 10 mg PO, avoiding first-generation antihistamines like diphenhydramine which can worsen hypotension and mask serious reactions. 1

Immediate Management Based on Reaction Severity

Mild Drug Reactions (Pruritus, Urticaria, Flushing)

• Stop the infusion immediately and maintain IV access with normal saline to keep vein open 1
• Administer second-generation H1 antihistamine: loratadine 10 mg PO or cetirizine 10 mg IV/PO 1
• Monitor for 15 minutes; most reactions are self-limiting and resolve spontaneously 1
• Avoid first-generation antihistamines (diphenhydramine) as they can exacerbate hypotension, tachycardia, diaphoresis, sedation, and potentially convert minor reactions into hemodynamically significant events 1

Moderate Drug Reactions (Mild Hypotension, Transient Cough, Shortness of Breath)

• Stop infusion and maintain IV access 1
• Cetirizine 10 mg IV/PO or loratadine 10 mg PO for urticaria 1
• Hydrocortisone 200 mg IV if symptoms do not improve after 15 minutes 1
• Consider H2 antagonist: famotidine 20 mg IV for additional symptom control 1
• IV normal saline bolus 1000-2000 mL for hypotension 1

Severe/Life-Threatening Reactions (Anaphylaxis)

• Epinephrine is first-line treatment, NOT antihistamines 1
• Epinephrine 0.3 mg IM (1 mg/mL solution) into anterolateral mid-thigh; may repeat once 1
• Antihistamines are adjunctive only and do not relieve stridor, bronchospasm, or shock 1
• After epinephrine, consider cetirizine 10 mg IV/PO for urticaria 1
• H2 antihistamines (famotidine 20 mg IV) may be added but evidence is minimal 1

Critical Pitfalls to Avoid

Why First-Generation Antihistamines Are Contraindicated

First-generation H1 antihistamines (diphenhydramine, hydroxyzine) should be avoided in drug reactions because they: 1

• Cause sedation that masks worsening symptoms and decreases awareness of anaphylaxis progression 1
• Exacerbate hypotension through anticholinergic effects 1
• Worsen tachycardia and diaphoresis 1
• Can convert minor infusion reactions into serious adverse events including shock 1

Second-Generation Antihistamines Are Safer

Second-generation antihistamines (cetirizine, loratadine, fexofenadine) have: 1

• Minimal sedation (except cetirizine causes noticeable sedation in ~10% of patients) 2
• No significant anticholinergic effects 2
• Rare cardiovascular effects (though can occasionally cause flushing, palpitations, dizziness) 1
• Preferential peripheral H1 receptor binding with minimal CNS penetration 3, 4

Specific Drug Reaction Contexts

Infusion Reactions (Chemotherapy, Biologics, IV Iron)

• Premedication is controversial and should be limited to high-risk patients (multiple drug allergies, prior reactions, asthma) 1
• When premedication is used: oral or IV antihistamine (diphenhydramine 25-50 mg or equivalent) plus corticosteroid 1
• For active reactions: second-generation antihistamines preferred over first-generation 1

Rechallenge After Reaction Resolution

• Restart infusion at 50% of initial rate after complete symptom resolution 1
• Increase slowly after 15 minutes if well tolerated 1
• Stop immediately if symptoms recur 1

Antihistamine Selection Algorithm

First choice: Cetirizine 10 mg IV/PO 1

• Most potent H1 antihistamine available 2
• Shortest time to maximum concentration for rapid relief 5
• Available in both IV and oral formulations 1, 6
• Onset within 1 hour, duration 24 hours 6

Alternative: Loratadine 10 mg PO 1

• Equally effective with less sedation than cetirizine 7, 2
• Onset within 1 hour, duration at least 24 hours 7
• Once-daily dosing 7

For inadequate response: 5

• Increase dose up to 4 times standard dose (e.g., cetirizine 40 mg daily) 5
• Add H2 antagonist (famotidine 20 mg twice daily) for combination therapy 1, 5

What Antihistamines Cannot Treat

Antihistamines are ineffective for: 1

• Stridor or laryngeal edema
• Bronchospasm (use albuterol nebulizer)
• Hypotension (requires epinephrine and IV fluids)
• Gastrointestinal symptoms in anaphylaxis
• Shock

These require epinephrine as first-line treatment with antihistamines only as adjunctive therapy 1