GlobalEfficacy and safety of fexofenadine in children with allergic rhinitis
Intranasal corticosteroids and oral antihistamines are first-line pharmacological treatments of AR, with the latter often preferred in children based on ease of administration [2]. First-generation antihistamines are effective against many AR symptoms but because of poor selectivity for H1 histamine receptors and penetration through the blood-brain-barrier (BBB) exhibit sedative, cardiovascular and/or anti-cholinergic side effects [3]. Particularly in children with AR, this often results in daytime fatigue, irritability, tiredness, inattention, reduced short-term memory and behavioral problems, significantly affecting learning and social activities. They are even not recommended to be administrated in the evening due to the hangover effect the following morning [4] as highlighted by Meltzer et al. in a recent review comparing the efficacy and safety of first and second-generation antihistamines in children with AR [5].
In the brain, histamine regulates sleep/wake behavior through binding to four distinct G protein-coupled histamine (H) receptors. Thus, histamine receptors blockers (antihistamines) used to treat AR symptoms may produce somnolence. Accordingly, excessive sleepiness is often an unwanted side effect of antihistamines [6], overall, from the first generation [5]. Fexofenadine is a second-generation non-sedating highly selective H1-receptor antagonist, which does not cross the BBB, therefore cannot bind to H1-receptors in the central nervous system [7]. The recommended doses of fexofenadine have demonstrated efficacy and safety in different clinical trials [5]. Moreover, it relieved ocular symptoms of allergic conjunctivitis that occur concomitantly with AR and mitigated the adverse impact of AR on quality of life.
The pharmacodynamic and pharmacokinetic profiles of fexofenadine translate into an absence of sedative effects and a lack of impaired concentration, memory, or performance across the approved dosage range (Tab. 1). Additionally, fexofenadine is not associated with any objective or subjective performance, or cognitive/academic impairments. Regarding drug-drug interactions, the coadministration of erythromycin or ketoconazole with fexofenadine results in increases in fexofenadine plasma concentrations; however, these increases remain within the safety margins provided by the wide therapeutic window of fexofenadine without any effects on the QT interval [8]. Moreover, fexofenadine has no dose-related effect on the corrected QT (QTc) interval with cardiovascular safety well established in children and adult patients even when used at higher than recommended doses. Overall, fexofenadine is well tolerated and displayed a good safety profile in children with AR, aged 6 months to 11 years and over.
Tab. 1. Side effects of first- and second-generation antihistamines. Adapted with permission from [5].
| Antihistamines Class | ||
| First-generation | Second-generation | |
| Central nervous system | Agitation, confusion, dystonia, dyskinesia, hallucinations, headache impairment in coordination, learning, memory, psychomotor and sensorimotor functions, and sedation | Variable (such as sedation with cetirizine) Minimal or no side effects with fexofenadine |
| Cardiovascular system | Dose-dependent sinus tachycardia, reflex tachycardia, atrial refractory period prolongation and supraventricular arrhythmias | No side effects |
| Toxic high dose | Severe CNS and cardiac side effects, may lead to death unless treated | No severe side effects or deaths reported |
Literature
- Zhang Y, Lan F, Zhang L. Advances and highlights in allergic rhinitis. Allergy 2021;76:3383–9.
- Dykewicz MS, Wallace DV, Amrol DJ, Baroody FM, et al. Rhinitis 2020: A practice parameter update. J Allergy Clin Immunol 2020;146:721–67.
- Ten Eick AP, Blumer JL, Reed MD. Safety of antihistamines in children. Drug Saf 2001;24:119–47.
- Jáuregui I, Mullol J, Dávila I, Ferrer M, et al. Allergic rhinitis and school performance. J Investig Allergol Clin Immunol 2009;19(1):32–9.
- Meltzer EO, Rosario NA, Van Bever H, Lucio L. Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis. Allergy Asthma Clin Immunol 2021;17:113.
- Miller DB, O’Callaghan JP. The pharmacology of wakefulness. Metabolism 2006;55:S13–S19.
- Tashiro M, et al. Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography. J Clin Pharmacol 2004;44(8):890–900. doi: 0.1177/0091270004267590.
- Mansfield LE. Fexofenadine in pediatrics: oral tablet and suspension formulations. Expert Opin Pharmacother 2008;9(2):329–37. https://doi. org/10.1517/14656566.9.2.329.
- Ferrer M, Morais-Almeida M, Guizova M, Khanferyan R. Evaluation of treatment satisfaction in children with allergic disease treated with an antihistamine: an international, non-interventional, retrospective study. Clin Drug Investig 2010;30:15–34.
Conflict of interest: All authors are employees of Sanofi.
Disclosures: Medical Writing and publication funded by Sanofi.
