Antihistamines for Children and Adolescents

Published by: Diana Luai Awad, Dr Pharmacist on Thursday 8.September.2022

The prevalence of allergic diseases in children is constantly increasing, and these pathologies are the leading cause of morbidity in pediatric practice¹. When exposed to an allergen, the antigen binds specific immunoglobulin E (IgE) associated with the surface of mast cells and basophils, and leads to their degranulation with the release of histamine and other pro-inflammatory mediators. The released histamine binds to receptors on various cells of the surrounding tissues and vessels.

Histamine is the main mediator in the pathogenesis of allergic conditions in smooth muscles, mucous membranes and skin. Therefore, the use of antihistamines in this group of patients is very relevant.

H₁-histamine receptor blockers: mechanism of action and application

H₁-histamine receptor blockers are used to relieve histamine-mediated symptoms in various allergic conditions, including:

non-anaphylactic allergic reactions
atopic dermatitis
allergic rhinitis and conjunctivitis
chronic spontaneous urticarial
anaphylaxis
food allergies.

In addition, antihistamines are used to prevent asthma, in particular to prevent allergen-induced nonspecific airway hyperresponsiveness as well as intermittent and chronic cough.

Antihistamines are among the most commonly prescribed drugs for children². Antihistamines reduce the release of proinflammatory mediators from mast cells and basophils, the chemotaxis and activation of inflammatory cells (especially eosinophils), and the expression of adhesion molecules induced by immunological and nonimmunological stimuli in epithelial cell lines. They inhibit the contraction of respiratory, vascular, gastrointestinal smooth muscles and reduce histamine-activated secretion of the salivary and lacrimal glands.

Classification of antihistamines in short

There are two generations of antihistamines

The first generation of antihistamines:

have low selectivity for H₁-receptors
also block muscarinic, cholinergic, alpha-adrenergic receptors, serotonin receptors and ion channels^3,4
block the development of the early phase of allergic inflammation
are characterized by a rapid onset of action
are lipophilic and easily penetrate the blood-brain barrier affecting the central nervous system and causing a sedative effect
when taking high doses, a paradoxical excitatory effect may develop.

Drowsiness with this group of drugs ranges from 40% with chlorpheniramine to 80% with hydroxyzine⁵. Other manifestations of the action on the central nervous system of first generation antihistamines are:

impaired coordination
dizziness
lethargy
decreased attention.

It has been shown that the use of drugs of this group in allergic rhinitis in children aggravates the decrease in learning ability associated usually with an allergic reaction⁶.

The second generation of antihistamines:

penetrate the blood-brain barrier to a smaller extent
have a longer therapeutic effect (up to 24 hours) compared to representatives of the first generation
block the development of both the early and late phases of allergic inflammation
have a minimally pronounced sedative effect
act selectivity for peripheral H₁-histamine receptors
also have a rapid onset of action.

E.g.: Cetirizine has an onset of action comparable to chlorpheniramine, so it is advisable to use it for non-anaphylactic food reactions in children such as food allergies.

Only three antihistamines have been studied in long-term studies, and they are all second-generation drugs. These are cetirizine⁷, levocetirizine⁸ and loratadine⁹.

The most commonly used antihistamines in pediatric practice

First generation antihistamines*	The most common side effect is central nervous system depression, the effects of which range from mild drowsiness to deep sleep. After a few days of therapy, the sedative effects decrease. Other side effects: headache, psychomotor disturbances, dry mouth, blurred vision, difficulty or retention of urination, constipation.
		Indications	Age	Dose
Chlorphenamine		Relief of allergy symptoms in hay fever, hives, food and drug allergies, relief of itching in chickenpox	Liquid form 1-18 years Tablets 6-18 years old	1 month-2 years 1 mg twice a day 2–6 years 1 mg every 4–6 hours 6–12 years 2 mg every 4–6 hours 12–18 years 4 mg every 4–6 hours
Hydroxyzine		Pruritus	6 month-18 years	6 months - 6 years 5-15 mg at night, if necessary, increase to 50 mg per day in 3-4 doses 6-12 years 15-25 mg at night, if necessary increase to 50-100 mg in 3-4 divided doses 12-18 years 25 mg at night, if necessary increase to 100 mg in 3-4 doses
Promethazine hydrochloride		Relief of allergy manifestations – allergic rhinitis, insomnia associated with urticaria and itching	2-18 years	2–5 years 5 mg twice daily or 5–15 mg at night 5-10 years 5-10 mg twice a day or 10-25 mg at night 10-18 years 10-20 mg 2-3 times a day or 25 mg at night, if necessary, increase the dose to 25 mg 2 times a day
Second generation antihistamines*		As a rule, second-generation drugs do not cause side effects in the form of drowsiness or antimuscarinic effects.
Cetirizine		Allergic rhinitis, chronic idiopathic urticaria, atopic dermatitis	1-18 years	1-2 years 250 mcg/kg twice a day 2-6 years 2.5 mg twice a day 6-12 years 5 mg twice a day 12-18 years 10 mg once a day
Loratadine		Symptomatic treatment of allergies - allergic rhinitis, chronic idiopathic urticaria	2-18 years	2-12 years old Up to 30 kg 5 mg 1 time per day More than 30 kg 10 mg 1 time per day 12-18 years 10 mg once a day
Fexofenadine		-«-	6-18 years	6-12 years 30 mg twice a day 12-18 years 120-180 mg once a day
Levocetirizine		-«-	Liquid form 2-18 years Tablets 6-18 years old	2-6 years 1.25 mg twice a day 6-18 years 5 mg once a day
Desloratadine		-«-	1-18 years	1-6 years 1.25 mg once a day 6-12 years 2.5 mg once a day 12-18 years 5 mg once a day
Olopatadin		Seasonal allergic conjunctivitis	3-18 years	3-18 years 2 times a day, the maximum duration of treatment is 4 months
Akrivastine		Allergic rhinitis, chronic idiopathic urticaria	12-18 years	8 mg 3 times a day
Azelastine		Allergic conjunctivitis, seasonal allergic conjunctivitis Perennial conjunctivitisSeasonal and perennial AR Moderate to severe seasonal and perennial AR, if monotherapy with antihistamine or corticosteroid is inadequate applied topically, in the form of nasal sprays and eye drops	4–18 years 5–18 years 12–18 years	Child 4–18 years apply twice daily, increased if necessary to 4 times daily Child 12–18 years apply twice daily, increased if necessary to 4 times daily; max. duration of treatment 6 weeks 1 spray into each nostril twice daily Child 12–18 years 1 spray into each nostril twice daily

*The table includes UK-registered prescription (POM) and over-the-counter drugs.

Bibliography

Chad Z. Allergies in children //Paediatrics & child health.2001; 6 (8): 555-566.
Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. [Erratum appears in Lancet 2007;370(9593):1128] //Lancet 2006; 368: 733–743.
Simons FE. Advances in H1-antihistamines. [Review] [120 refs] //N Engl J Med 2004; 351: 2203–17.
Church MK, Church DS. Pharmacology of antihistamines //Indian J Dermatology 2013; 58: 219–24.
Scadding G. Optimal management of nasal congestion caused by allergic rhinitis in children: safety and efficacy of medical treatments. Paediatr //Drugs. 2008; 10: 151-162.
Simons F.E.R. Prospective, long-term safety evaluation of the H1-receptor antagonist cetirizine in very young children with atopic dermatitis. ETAC Study Group. Early Treatment of the Atopic //Child. J. Allergy Clin. Immunol. 1999; 104: 433-440.
Simons F.E.R. Early Prevention of Asthma in Atopic Children (EPAAC) Study Group. //Pediatr. Allergy Immunol. 2007; 18: 535-542.
Grimfeld A., Holgate S.T., Canonica G.W. et al. Prophylactic management of children at risk for recurrent upper respiratory infections: the Preventia I Study //Clin. Exp. Allergy. 2004; 34: 1665-1672.

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