Newer-generation antihistamines and the risk of adverse events in children: A systematic review.
adverse events
antihistamines
children
pediatrics
systematic review
Journal
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
ISSN: 1399-3038
Titre abrégé: Pediatr Allergy Immunol
Pays: England
ID NLM: 9106718
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
01
04
2021
received:
01
12
2020
accepted:
13
04
2021
pubmed:
25
4
2021
medline:
21
10
2021
entrez:
24
4
2021
Statut:
ppublish
Résumé
H1-antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in pediatrics. Newer-generation AHs are associated with fewer adverse effects compared with first-generation AHs. However, their relative harms in the pediatric population still need scrutiny. We performed a systematic review of randomized controlled trials (RCTs), which included comparisons of safety parameters between an orally administered newer-generation AH and another AH (first- or second-generation), montelukast, or placebo in children aged ≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs), and treatment discontinuations, and assessed the methodologic quality of the included RCTs using the Cochrane's risk of bias tool. Forty-five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school-aged children with allergic rhinitis and had a follow-up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer-generation AH, but only two patients experienced a possibly drug-related serious AE. The occurrence of AEs, drug-related AEs, and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer-generation AHs. Our findings confirm that newer-generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer-generation AHs due to the paucity of head-to-head RCTs, variation in definitions and reporting of AEs, and short follow-up duration.
Sections du résumé
BACKGROUND
H1-antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in pediatrics. Newer-generation AHs are associated with fewer adverse effects compared with first-generation AHs. However, their relative harms in the pediatric population still need scrutiny.
METHODS
We performed a systematic review of randomized controlled trials (RCTs), which included comparisons of safety parameters between an orally administered newer-generation AH and another AH (first- or second-generation), montelukast, or placebo in children aged ≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs), and treatment discontinuations, and assessed the methodologic quality of the included RCTs using the Cochrane's risk of bias tool.
RESULTS
Forty-five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school-aged children with allergic rhinitis and had a follow-up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer-generation AH, but only two patients experienced a possibly drug-related serious AE. The occurrence of AEs, drug-related AEs, and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer-generation AHs.
CONCLUSION
Our findings confirm that newer-generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer-generation AHs due to the paucity of head-to-head RCTs, variation in definitions and reporting of AEs, and short follow-up duration.
Substances chimiques
Histamine Antagonists
0
Histamine H1 Antagonists
0
Cetirizine
YO7261ME24
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1533-1558Informations de copyright
© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Références
Pawankar R, Holgate ST, Canonica GW, Lockey RF, Blaiss MS. WAO white book on allergy 2013 update. World Allergy Organization (WAO). 2013.
Yanai K, Rogala B, Chugh K, Paraskakis E, Pampura AN, Boev R. Safety considerations in the management of allergic diseases: focus on antihistamines. Curr Med Res Opin. 2012;28(4):623-642.
Del Cuvillo A, Sastre J, Montoro J, et al. Use of antihistamines in pediatrics. J Investig Allergol Clin Immunol. 2007;17(Suppl 2):28-40.
Fitzsimons R, van der Poel LA, Thornhill W, du Toit G, Shah N, Brough HA. Antihistamine use in children. Arch Dis Child Educ Pract Ed. 2015;100(3):122-131.
Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011;128(6):1139-1150.e4.
Church MK, Maurer M, Simons FE, et al. Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper. Allergy. 2010;65(4):459-466.
Shimamura T, Shiroishi M, Weyand S, et al. Structure of the human histamine H1 receptor complex with doxepin. Nature. 2011;475(7354):65-70.
Carson S, Lee N, Thakurta S. Drug Class Review: Newer Antihistamines: Final Report Update 2 [Internet]. 2010.
McDonald K, Trick L, Boyle J. Sedation and antihistamines: an update. Review of inter-drug differences using proportional impairment ratios. Hum Psychopharmacol. 2008;23(7):555-570.
Parisi GF, Leonardi S, Ciprandi G, et al. Antihistamines in children and adolescents: a practical update. Allergol Immunopathol (Madr). 2020;48:753-765.
Wallace BC, Small K, Brodley CE, Lau J, Trikalinos TA. Deploying an interactive machine learning system in an evidence-based practice center: abstrackr. Proc of the ACM International Health Informatics Symposium (IHI). 2012:819-824
Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
Wandalsen GF, Miranda C, Ensina LF, et al. Association between desloratadine and prednisolone in the treatment of children with acute symptoms of allergic rhinitis: a double-blind, randomized and controlled clinical trial. Braz J Otorhinolaryngol. 2017;83(6):633-639.
Nayak AS, Berger WE, LaForce CF, et al. Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis. Allergy Asthma Proc. 2017;38(3):222-230.
Novák Z, Yáñez A, Kiss I, Kuna P, Tortajada-Girbés M, Valiente R. Safety and tolerability of bilastine 10 mg administered for 12 weeks in children with allergic diseases. Pediatr Allergy Immunol. 2016;27(5):493-498.
Potter P, Mitha E, Barkai L, et al. Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2-11 years. Pediatr Allergy Immunol. 2016;27(1):55-61.
Potter P, Maspero JF, Vermeulen J, et al. Rupatadine oral solution in children with persistent allergic rhinitis: a randomized, double-blind, placebo-controlled study. Pediatr Allergy Immunol. 2013;24(2):144-150.
Wu KG, Li TH, Wang TY, Hsu CL, Chen CJ. A comparative study of loratadine syrup and cyproheptadine HCL solution for treating perennial allergic rhinitis in Taiwanese children aged 2-12 years. Int J Immunopathol Pharmacol. 2012;25(1):231-237.
Marcucci F, Sensi LG, Abate P, et al. Anti-inflammatory activity and clinical efficacy of a 3-month levocetirizine therapy in mite-allergic children. Inflamm Allergy Drug Targets. 2011;10(1):32-38.
Hampel F, Ratner P, Haeusler JM. Safety and tolerability of levocetirizine dihydrochloride in infants and children with allergic rhinitis or chronic urticaria. Allergy Asthma Proc. 2010;31(4):290-295.
Lee CF, Sun HL, Lu KH, Ku MS, Lue KH. The comparison of cetirizine, levocetirizine and placebo for the treatment of childhood perennial allergic rhinitis. Pediatr Allergy Immunol. 2009;20(5):493-499.
Ngamphaiboon J, Wirawarn T, Thongkaew T. Prevention of recurrent wheezing in young children by loratadine compared with ketotifen. J Med Assoc Thai. 2009;92(3):351-355.
Hampel FC, Kittner B, van Bavel JH. Safety and tolerability of fexofenadine hydrochloride, 15 and 30 mg, twice daily in children aged 6 months to 2 years with allergic rhinitis. Ann Allergy Asthma Immunol. 2007;99(6):549-554.
Milgrom H, Kittner B, Lanier R, Hampel FC. Safety and tolerability of fexofenadine for the treatment of allergic rhinitis in children 2 to 5 years old. Ann Allergy Asthma Immunol. 2007;99(4):358-363.
Simons FE. Early prevention of asthma in atopic children (EPAAC) Study Group. Safety of levocetirizine treatment in young atopic children: an 18-month study. Pediatr Allergy Immunol. 2007;18(6):535-542.
Chen ST, Lu KH, Sun HL, Chang WT, Lue KH, Chou MC. Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2-6 yr. Pediatr Allergy Immunol. 2006;17(1):49-54.
Prenner B, Ballona R, Bueso A, et al. Safety of desloratadine syrup in children six months to younger than 2 years of age: a randomized, double-blinded, placebo-controlled study. Pediatr Asthma Allergy Immunol. 2006;19(2):91-99.
de Blic J, Wahn U, Billard E, Alt R, Pujazon MC. Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial. Pediatr Allergy Immunol. 2005;16(3):267-275.
Potter PC. Paediatric Levocetirizine Study Group. Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial. Ann Allergy Asthma Immunol. 2005;95(2):175-180.
Bloom M, Staudinger H, Herron J. Safety of desloratadine syrup in children. Curr Med Res Opin. 2004;20(12):1959-1965.
Grimfeld A, Holgate ST, Canonica GW, et al. Prophylactic management of children at risk for recurrent upper respiratory infections: the Preventia I Study. Clin Exp Allergy. 2004;34(11):1665-1672.
Hsieh J, Lue K, Lai D, Sun H, Lin Y. A comparison of cetirizine and montelukast for treating childhood perennial allergic rhinitis. Pediatr Asthma Allergy Immunol. 2004;17(1):59-69.
Wahn U, Meltzer EO, Finn AF Jr, et al. Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis. J Allergy Clin Immunol. 2003;111(4):763-769.
Segal AT, Meltzer EO, Lockey RF, et al. Once-daily cetirizine is safe and effective for children with allergic rhinitis with and without intermittent asthma. Pediatr Asthma, Allergy Immunol. 2003;16(4):265-274.
Simons FE, Silas P, Portnoy JM, et al. Safety of cetirizine in infants 6 to 11 months of age: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol. 2003;111(6):1244-1248.
Lai DS, Lue KH, Hsieh JC, Lin KL, Lee HS. The comparison of the efficacy and safety of cetirizine, oxatomide, ketotifen, and a placebo for the treatment of childhood perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2002;89(6):589-598.
Chunharas A, Wisuthsarewong W, Wananukul S, Viravan S. Therapeutic efficacy and safety of loratadine syrup in childhood atopic dermatitis treated with mometasone furoate 0.1 per cent cream. J Med Assoc Thai. 2002;85(4):482-487.
La Rosa M, Leonardi S, Marchese G, et al. Double-blind multicenter study on the efficacy and tolerability of cetirizine compared with oxatomide in chronic idiopathic urticaria in preschool children. Ann Allergy Asthma Immunol. 2001;87(1):48-53.
Yang YH, Lin YT, Lu MY, Tsai MJ, Chiang BL. A double-blind, placebo-controlled, and randomized study of loratadine (Clarityne) syrup for the treatment of allergic rhinitis in children aged 3 to 12 years. Asian Pac J Allergy Immunol. 2001;19(3):171-175.
Ciprandi G, Tosca M, Passalacqua G, Canonica GW. Long-term cetirizine treatment reduces allergic symptoms and drug prescriptions in children with mite allergy. Ann Allergy Asthma Immunol. 2001;87(3):222-226.
Graft DF, Bernstein DI, Goldsobel A, Meltzer EO, Portnoy J, Long J. Safety of fexofenadine in children treated for seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2001;87(1):22-26.
Salmun LM, Herron JM, Banfield C, Padhi D, Lorber R, Affrime MB. The pharmacokinetics, electrocardiographic effects, and tolerability of loratadine syrup in children aged 2 to 5 years. Clin Ther. 2000;22(5):613-621.
Simons FE. 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(2 Pt 1):433-440.
Wahn PU. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child. Pediatr Allergy Immunol. 1998;9(3):116-124.
Sienra-Monge JJ, Gazca-Aguilar A, Del Rio-Navarro B. Double-blind comparison of cetirizine and loratadine in children ages 2 to 6 years with perennial allergic rhinitis. Am J Ther. 1999;6(3):149-155.
Serra HA, Alves O, Rizzo LF, Devoto FM, Ascierto H. Loratadine-pseudoephedrine in children with allergic rhinitis, a controlled double-blind trial. Br J Clin Pharmacol. 1998;45(2):147-150.
Delgado LF, Pferferman A, Sole D, Naspitz CK. Evaluation of the potential cardiotoxicity of the antihistamines terfenadine, astemizole, loratadine, and cetirizine in atopic children. Ann Allergy Asthma Immunol. 1998;80(4):333-337.
Pearlman DS, Lumry WR, Winder JA, Noonan MJ. Once-daily cetirizine effective in the treatment of seasonal allergic rhinitis in children aged 6 to 11 years: a randomized, double-blind, placebo-controlled study. Clin Pediatr (Phila). 1997;36(4):209-215.
Winder JA, Noonan MJ, Lumry WR, Pearlman DS. Absence of QTc Prolongation with Cetirizine in Children Aged 6 to 11 Years. Pediatr Asthma, Allergy Immunol. 1996;10(4):181-190.
Ciprandi G, Tosca M, Ricca V, et al. Cetirizine treatment of rhinitis in children with pollen allergy: evidence of its antiallergic activity. Clin Exp Allergy. 1997;27(10):1160-1166.
de Benedictis FM, Forenza N, Armenio L, et al. Efficacy and safety of cetirizine and oxatomide in young children with perennial allergic rhinitis: a 10-day, multicenter, double-blinded, randomized, parallel-group study. Pediatr Asthma, Allergy Immunol. 1997;11(2):119-128.
Tinkelman DG, Kemp J, Mitchell DQ, Galant SP. Treatment of seasonal allergic rhinitis in children with cetirizine or chlorpheniramine: a multicenter study. Pediatr Asthma, Allergy Immunol. 1996;10(1):9-17.
Fasce L, Ciprandi G, Pronzato C, et al. Cetirizine reduces ICAM-I on epithelial cells during nasal minimal persistent inflammation in asymptomatic children with mite-allergic asthma. Int Arch Allergy Immunol. 1996;109(3):272-276.
La Rosa M, Ranno C, Musarra I, Guglielmo F, Corrias A, Bellanti JA. Double-blind study of cetirizine in atopic eczema in children. Ann Allergy. 1994;73(2):117-122.
Jobst S, van den Wijngaart W, Schubert A, van de Venne H. Assessment of the efficacy and safety of three dose levels of cetirizine given once daily in children with perennial allergic rhinitis. Allergy. 1994;49(8):598-604.
Allegra L, Paupe J, Wieseman HG, Baelde Y. Cetirizine for seasonal allergic rhinitis in children aged 2-6 years. A double-blind comparison with placebo. Pediatr Allergy Immunol. 1993;4(3):157-161.
Masi M, Candiani R, van de Venne H. A placebo-controlled trial of cetirizine in seasonal allergic rhino-conjunctivitis in children aged 6 to 12 years. Pediatr Allergy Immunol. 1993;4(4 Suppl):47-52.
Baelde Y, Dupont P. Cetirizine in children with chronic allergic rhinitis. a multicentre double-blind study of two doses of cetirizine and placebo. Drug Invest. 1992;4(6):466-472.
Boner AL, Miglioranzi P, Richelli C, Marchesi E, Andreoli A. Efficacy and safety of loratadine suspension in the treatment of children with allergic rhinitis. Allergy. 1989;44(6):437-441.
Roberts G, Xatzipsalti M, Borrego LM, et al. Paediatric rhinitis: position paper of the European academy of allergy and clinical immunology. Allergy. 2013;68(9):1102-1116.
Brożek JL, Bousquet J, Agache I, et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140(4):950-958.