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Antihistamines and Allergy VOLUME 41 : NUMBER 2 : APRIL 2018 ARTICLE Antihistamines and allergy Katrina L Randall Staff specialist1 SUMMARY Senior lecturer2 There is now little role for sedating antihistamines in allergic conditions. Less sedating Carolyn A Hawkins Staff specialist1 antihistamines are equally efficacious. Lecturer2 The less sedating antihistamines can be taken long term with no loss of efficacy, and an ongoing good safety profile. 1 Department of Immunology Antihistamines have no role in the acute management of anaphylaxis. Canberra Hospital 2 Australian National University Medical School Introduction they can also signal constitutively without histamine Canberra Antihistamines are used in the management of allergic binding to the cell surface. There is a balance between 1 conditions. They are useful for treating the itching that the active and inactive forms of the receptor. The Keywords results from the release of histamine. presence of histamine stabilises the receptor in its acute allergic reactions, active form while antihistamines stabilise the inactive The early so-called ‘first generation’ antihistamines, allergic conjunctivitis, form of the receptor. The H antihistamine drugs such as promethazine, caused sedation. This is 1 allergic rhinitis, therefore act as inverse agonists.1 antihistamines, urticaria less of a problem with newer ‘second generation’ antihistamines, such as loratadine, and ‘third Loratadine is metabolised in the liver, while cetirizine, desloratadine and fexofenadine are not metabolised Aust Prescr 2018;41:42–5 generation’ antihistamines such as desloratadine. extensively. Cetirizine is eliminated in the urine, while The oral antihistamines available in Australia to https://doi.org/10.18773/ fexofenadine is excreted in the faeces. Dose reduction austprescr.2018.013 treat allergic conditions are listed in the Box. should be considered in patients with severe liver or Desloratadine and fexofenadine are registered for kidney dysfunction.1 use in infants six months and older, while loratadine and cetirizine can be used from 12 months of age. Avoid sedating antihistamines Some antihistamines are used for their antinausea or The sedating, first generation antihistamines now have sedative properties. little role in therapeutics. Their unfavourable adverse effect profile has prompted the Global Allergy and Pharmacology Asthma European Network to recommend making Antihistamines bind to histamine receptors on the these antihistamines prescription-only, rather than surface of cells. There are four types of histamine over-the-counter, drugs.3 The main concerns are their receptors in the body (H -H ), with H and H being 1 4 1 2 sedative properties and interference with rapid eye 1 most widely expressed. movement sleep.3,4 Studies have shown poorer school H1 histamine receptors are found on a variety of cells performance in children with allergic rhinitis treated including airway and vascular smooth muscle cells, with sedating antihistamines, compared to children endothelial cells, epithelial cells, eosinophils and treated with non-sedating antihistamines and healthy neutrophils.2 Although the receptors bind histamine, children.5 Sedating antihistamines have been found to be a cause of aviation accidents.3 An audit of media reports found a number of car accidents attributed to Box Oral antihistamines available in Australia sedating antihistamines, but none attributed to less sedating antihistamines.3 Sedating H1 antihistamines Less sedating H1 antihistamines There is also concern about the use of promethazine Cyproheptadine Cetirizine in children less than two years old as serious Dexchlorpheniramine Desloratadine behavioural and other adverse effects can occur.3 Pheniramine Fexofenadine This led to a black box warning by the US Food Promethazine Loratadine and Drug Administration (FDA) in 2004. Sedating Trimeprazine antihistamines can also have anticholinergic effects that can be particularly problematic in older patients Other sedating H1 antihistamines include doxylamine and diphenhydramine, used for sedation, and cyclizine, used mainly as an antiemetic. who are more susceptible to adverse effects such as dry mouth, urinary retention and delirium.6 42 Full text free online at nps.org.au/australianprescriber © 2018 NPS MedicineWise VOLUME 41 : NUMBER 2 : APRIL 2018 ARTICLE Sedating antihistamines are still favoured by some, Topical nasal antihistamines, such as azelastine, as parenteral formulations are available. However, for are also available and are recommended for nasal- promethazine there is a risk of severe tissue injury, limited mild disease and for on-demand treatment.10 including gangrene, with both intramuscular and To augment the efficacy of oral antihistamines intravenous administration.7 The risk is higher for in allergic rhinitis for those who continue to have intravenous use and led to an FDA warning.8 symptoms, the preferred topical therapy is a The main role for sedating antihistamines is in corticosteroid nasal spray. These sprays should pregnancy, where they can be used for any of the be considered first-line treatment in moderate to 10 common indications for antihistamines, as they severe allergic rhinitis. Combination treatments have the strongest evidence of safety. They have containing both corticosteroids and antihistamines been taken by a large number of pregnant women are also available. Adjunctive treatments such as and women of childbearing age without any proven intranasal ipratropium bromide may be useful in increase in malformations or harm to the fetus. An reducing rhinorrhoea in those with perennial allergic 11 exception is promethazine for which adverse events rhinitis while nasal irrigation using saline solution have been reported in animal studies (at very high may improve symptoms and reduce the need for 12 doses). However, pregnant women must be warned oral antihistamines. about the other aspects of safety such as sedation Allergic conjunctivitis and consider whether they should not drive while Like allergic rhinitis, allergic conjunctivitis is IgE- taking these drugs. The newer antihistamines are mediated. It can be seasonal due to pollens or likely to be as safe in pregnancy but have not been perennial due to allergens present all year.13 Seasonal used by as many women, so they do not have the allergic conjunctivitis is typically associated with some same evidence of safety. degree of allergic rhinitis so allergen avoidance is the Newer antihistamines first step in management. The newer H1 antihistamines are less sedating. While Oral antihistamines can be used for allergic all the newer drugs appear equally efficacious in conjunctivitis or, if the symptoms are only related limited studies, there are few long-term head-to- to the eye, topical antihistamines with or without head studies.9 The patient can therefore choose mast cell stabilisers are recommended.13 Some the particular drug that they find works best, or topical products such as ketotifen, azelastine and the formulation (tablet size) that suits them. For olopatadine have both antihistamine and mast paediatric suspensions, the choice may be determined cell stabilising effects. Mast cell stabilisers such as by a preferred flavour. sodium cromoglycate are also available. Topical antihistamines give immediate relief, while mast cell Allergic rhinitis stabilisers provide more long-term protection.13 Allergic rhinitis refers to nasal inflammation due to The current guidelines for ocular-limited disease are the release of histamine and other mediators from either topical antihistamines, mast cell stabilisers or IgE-mediated mast cell degranulation in the nose. dual action drugs.13 A Cochrane review has shown Other conditions may cause similar symptoms, but that both antihistamines and mast cell stabilisers they can be distinguished from allergic rhinitis by are more effective than placebo for seasonal and allergy testing to confirm positive allergen-specific perennial allergic conjunctivitis, however there have IgE to specific triggers. Allergic rhinitis may be been no good studies to compare mast cell stabilisers seasonal (usually due to grass, tree or weed pollens) to antihistamines.14 or perennial (due to triggers such as pet hair, house dust mite or mould). It is important to ask the Acute allergic reactions patient if they also have respiratory symptoms as a The newer H1 antihistamines are the mainstay worsening in allergic rhinitis can lead to increased treatment of mild to moderate allergic reactions asthma symptoms. giving rise to allergen-specific mast cell degranulation. Avoiding trigger factors is the first step in the Patients with a known food allergy are advised to management of allergic rhinitis but some triggers carry these less sedating H1 antihistamines as part can be difficult to avoid. Drugs can help and oral of their allergy action plan. The use of sedating antihistamines are one of the mainstays of treatment. antihistamines should be avoided, especially because They are particularly useful for nasal itchiness, their sedative effects may mask a deterioration in sneezing and rhinorrhoea, but are less effective for consciousness, caused by the underlying allergic nasal obstruction. Oral antihistamines also have the reaction, indicating the onset of anaphylaxis and the benefit of treating associated conjunctival symptoms. requirement for adrenaline (epinephrine). Full text free online at nps.org.au/australianprescriber 43 VOLUME 41 : NUMBER 2 : APRIL 2018 ARTICLE Antihistamines and allergy Antihistamines
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