Antihistamine use in children Roisin Fitzsimons, 1,2 Lauri-Ann van der Poel, 1 William Thornhill, 3 George du Toit, 1,2 Neil Shah, 4,5 Helen A Brough 1,2 1 Children’s Allergy Service, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK 2 Department of Asthma, Allergy and Respiratory Science, King’s College London, London, UK 3 Evelina Children’s Pharmacy, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK 4 Department of Gastroenterology, Great Ormond Street Hospital, London, UK 5 TARGID, Catholic University of Leuven, Leuven, The Netherlands Correspondence to Dr Helen A Brough, Children’s Allergy Service, Guy’s and St Thomas’ NHS Foundation Trust, 2nd Floor, Stairwell B, South Wing, Westminster Bridge Road, London SE1 7EH, UK; helen.brough@gstt.nhs.uk RF and L-AvdP have contributed equally. Received 28 February 2014 Revised 17 July 2014 Accepted 28 July 2014 Published Online First 21 August 2014 To cite: Fitzsimons R, van der Poel L-A, Thornhill W, et al. Arch Dis Child Educ Pract Ed 2015;100:122–131. ABSTRACT This review provides an overview of the use of antihistamines in children. We discuss types of histamine receptors and their mechanism of action, absorption, onset and duration of action of first-generation and second-generation H(1)-antihistamines, as well as elimination of H(1)-antihistamines which has important implications for dosing in children. The rationale for the use of H(1)-antihistamines is explored for the relief of histamine-mediated symptoms in a variety of allergic conditions including: non- anaphylactic allergic reactions, atopic eczema (AE), allergic rhinitis (AR) and conjunctivitis, chronic spontaneous urticaria (CSU) and whether they have a role in the management of intermittent and chronic cough, anaphylaxis, food protein-induced gastrointestinal allergy and asthma prevention. Second-generation H(1)- antihistamines are preferable to first-generation H(1)-antihistamines in the management of non- anaphylactic allergic reactions, AR, AE and CSU due to: their better safety profile, including minimal cognitive and antimuscarinic side effects and a longer duration of action. We offer some guidance as to the choices of H(1)-antihistamines available currently and their use in specific clinical settings. H(1)-antihistamine class, availability, licensing, age and dosing administration, recommended indications in allergic conditions and modalities of delivery for the 12 more commonly used H(1)-antihistamines in children are also tabulated. INTRODUCTION H(1)-antihistamines are among the most commonly prescribed medicines in chil- dren. 1 Indications include acute allergic reactions in food allergy, allergic rhinitis (AR) and chronic spontaneous urticaria (CSU); they are also used for relief of histamine-mediated symptoms, but are not the drug of first choice, in the context of atopic eczema (AE) and ana- phylaxis. The International Study for Asthma and Allergies in Childhood (ISAAC) has shown a world-wide trend for increasing symptoms of eczema and AR in childhood. 2 In the UK, the Phase 3 (2002–2003) ISAAC study found a 10.1% prevalence of AR symptoms and 16% eczema symptoms in 6-year-old to 7-year-old children. 2 Hospital admissions for food allergic reactions in the UK have increased by 500% between 1990 and 2003. 3 In the last decade, the body of knowledge of the safety and efficacy of H (1)-antihistamines has increased substan- tially. 4–6 HISTAMINE AND THE ALLERGIC RESPONSE Histamine is a fundamental mediator in the pathophysiology of allergic condition in the smooth muscle, mucosa and skin ( figure 1). On allergen exposure, an antigen cross-links specific immunoglobin E (IgE) bound to the surface of mast cells and basophils and leads to degranulation with release of histamine and other pro- inflammatory mediators. Once released, histamine binds to G-protein-coupled receptors on a wide variety of cells within the surrounding tissues and vasculature. TYPES OF HISTAMINE RECEPTORS Four types of histamine receptors have been identified, which have varying degrees of responsibility for mediating an allergic response. 4–6 H1 and H2 recep- tors are present on a wide range of cells (endothelial, epithelial, smooth muscle, neurons and cells of the innate and acquired immune system) and when in an active state, stimulate both the early phase of an allergic response (vasodilata- tion leading to erythema, swelling and hypotension) and the late-phase response, by upregulating cytokine production and cell-adhesion molecules, leading to a proinflammatory state. 4 5 H(2)-receptor antagonists, such as ranitidine, work pri- marily on gastric mucosa, inhibiting gastric secretion. H3 and H4 receptors are less widely expressed but are inducers of pruritus and proinflammatory immune PHARMACY UPDATE 122 Fitzsimons R, et al. Arch Dis Child Educ Pract Ed 2015;100:122–131. doi:10.1136/archdischild-2013-304446 group.bmj.com on April 9, 2017 - Published by http://ep.bmj.com/ Downloaded from