Second-Generation Antihistamines for Allergic Reactions

Primary Recommendations

The American Academy of Allergy, Asthma, and Immunology recommends fexofenadine for its superior safety profile regarding sedation, with a complete lack of sedation at all doses 1
Fexofenadine 180 mg once daily should be the default choice for adults and adolescents ≥12 years with allergic reactions because it maintains non-sedating properties even at higher-than-recommended doses 1

Cetirizine 10 mg once daily is equally effective for symptom relief but carries a 13.7% sedation rate that can impair driving ability and occupational performance 2
Loratadine 10 mg once daily is non-sedating at recommended doses but demonstrates inferior efficacy compared to both fexofenadine and cetirizine in head-to-head trials 1

Fexofenadine is the safest choice for patients with renal impairment, but requires dose reduction to 60 mg once daily for adults with decreased renal function 2
Cetirizine requires more aggressive dose reduction, with a 50% dose reduction in moderate renal impairment and contraindication in severe renal impairment (CrCl <10 mL/min) 2
Loratadine should be used with caution in severe renal impairment (CrCl <10 mL/min) 5

The American Academy of Allergy, Asthma, and Immunology specifically recommends avoiding all antihistamines if possible, especially in the first trimester of pregnancy, and using loratadine as an alternative if treatment is necessary 5
Fexofenadine excretion in breast milk is unknown, and caution should be used in nursing mothers 5
Adding pseudoephedrine to fexofenadine may be beneficial for patients with prominent nasal congestion, as it has complementary activity 4
The Journal of Allergy and Clinical Immunology recommends avoiding OTC cough/cold combination products in children <6 years due to the risk of fatalities and lack of efficacy data 4