Abstract

H1-antihistamines are recognized to be effective for conditions such as allergic rhinitis and chronic spontaneous urticaria. However, management of such conditions in the real-world primary care setting may be challenging due to diverse patient-specific considerations, the wide range of antihistamines available, choice of other treatment modalities, and the complexity of interpreting specialist treatment algorithms. Despite regular updates to international guidelines, regional/national surveys of healthcare professionals show a clear gap between guidelines and real-world practice, particularly at the primary care level. This article thus presents the consensus opinion of experts from relevant specialties in Malaysia—allergology, pediatrics, otorhinolaryngology, and dermatology—on harmonizing the use and choice of antihistamines in primary care. Patient profiling is recommended as a tool to guide primary care practitioners in prescribing the appropriate antihistamine for each patient. Patient profiling is a three-step approach that involves 1) identifying the individual’s needs; 2) reviewing patient-specific considerations; and 3) monitoring treatment response and referral to specialists in more severe or difficult-to-treat cases. Concurrently, guidelines should be reviewed and updated periodically to include recommendations that are easily actionable for primary care practitioners.

1. Köberlein, J., Vent, J., & Mösges, R. (2010). On the sustainability of guideline implementation. World Allergy Organization Journal, 3(10), 258–261. https://doi.org/10.1097/WOX.0b013e3181fdfc7a
2. Kulthanan, K., Chusakul, S., Recto, M. T., Gabriel, M. T., Aw, D. C., & Meshkova, R. (2018). Economic burden of the inadequate management of allergic rhinitis and urticaria in Asian countries based on the GA²LEN model. Allergy, Asthma & Immunology Research, 10(4), 370–378. https://doi.org/10.4168/aair.2018.10.4.370
3. Simons, F. E., & Simons, K. J. (2011). Histamine and H1-antihistamines: Celebrating a century of progress. Journal of Allergy and Clinical Immunology, 128(6), 1139–1150.e4. https://doi.org/10.1016/j.jaci.2011.09.005
4. Dávila, I., Del Cuvillo, A., Mullol, J., Jáuregui, I., Bartra, J., Ferrer, M., ... & Valero, A. (2013). Use of second generation H1 antihistamines in special situations. Journal of Investigational Allergology and Clinical Immunology, 23(Suppl 1), 1–16.
5. Prepageran, N., Wang, D. Y., Nair, G., & Maurer, M. (2014). The status quo and unmet needs in the management of allergic rhinitis and chronic rhinosinusitis: A Malaysian perspective. Asia Pacific Allergy, 4(3), 142–148. https://doi.org/10.5415/apallergy.2014.4.3.142
6. Fitzsimons, R., van der Poel, L. A., Thornhill, W., du Toit, G., Shah, N., & Brough, H. B. (2015). Antihistamine use in children. Archives of Disease in Childhood - Education and Practice Edition, 100(3), 122–131. https://doi.org/10.1136/archdischild-2013-304446
7. Kar, S., Krishnan, A., Preetha, K., & Mohankar, A. (2012). A review of antihistamines used during pregnancy. Journal of Pharmacology & Pharmacotherapeutics, 3(2), 105–108. https://doi.org/10.4103/0976-500X.95503
8. Kay, G. G., & Quig, M. E. (2001). Impact of sedating antihistamines on safety and productivity. Allergy and Asthma Proceedings, 22(5), 281–283.
9. Kuna, P., Jurkiewicz, D., Czarnecka-Operacz, M. M., Doniec, Z., Emeryk, A., Fal, A. M., ... & Jutel, M. (2016). The role and choice criteria of antihistamines in allergy management – expert opinion. Postepy Dermatologii i Alergologii, 33(6), 397–410. https://doi.org/10.5114/pdia.2016.63942
10. McCue, J. D. (1996). Safety of antihistamines in the treatment of allergic rhinitis in elderly patients. Archives of Family Medicine, 5(8), 464–468.
11. Yang, H. J., Kim, Y. H., Lee, B., Jung, S. S., Ye, Y. M., Choi, B. W., ... & Lee, S. (2017). Unmet primary physicians’ needs for allergic rhinitis care in Korea. Allergy, Asthma & Immunology Research, 9(3), 265–271. https://doi.org/10.4168/aair.2017.9.3.265
12. Scadding, G. K., & Williams, A. (2008). The burden of allergic rhinitis as reported by UK patients compared with their doctors. Rhinology, 46(2), 99–106.
13. Recto, M. T., Gabriel, M. T., Kulthanan, K., Castor, A. S., Casis-Que, A. J., De Guia, T. S., ... & Meshkova, R. (2017). Selecting optimal second-generation antihistamines for allergic rhinitis and urticaria in Asia. Clinical and Molecular Allergy, 15(1), 19. https://doi.org/10.1186/s12948-017-0074-3
14. Bousquet, J., Khaltaev, N., Cruz, A. A., Denburg, J., Fokkens, W. J., Togias, A., ... & ARIA Workshop Group. (2008). Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy, 63(Suppl 86), 8–160. https://doi.org/10.1111/j.1398-9995.2007.01620.x
15. Zuberbier, T., Aberer, W., Asero, R., Abdul Latiff, A. H., Baker, D., Ballmer-Weber, B., ... & Zwiener, R. (2018). The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy, 73(7), 1393–1414. https://doi.org/10.1111/all.13397
16. Del Cuvillo, A., Sastre, J., Montoro, J., Jáuregui, I., Ferrer, M., Dávila, I., ... & Valero, A. (2007). Use of antihistamines in pediatrics. Journal of Investigational Allergology and Clinical Immunology, 17(Suppl 2), 28–40.
17. Bayer Healthcare. (2015). Clarityne® Tablet & Syrup [Package insert].
18. GlaxoSmithKline Pharmaceutical Sdn Bhd. (2018). Zyrtec film-coated tablet/oral solution/oral drops (Cetirizine dihydrochloride) [Package insert].
19. HOE Pharmaceuticals Sdn. Bhd. (2014). Zoralix 5 SF Elixir 5mg/5ml [Package insert].
20. Kotra Pharma (M) Sdn. Bhd. (n.d.). Axcel® Chlorpheniramine Syrup [Package insert].
21. Merck Sharp & Dohme (Malaysia) Sdn. Bhd. (2018). Aerius® Syrup (Desloratadine 0.5 mg/mL) [Package insert].
22. Sanofi-aventis (Malaysia) Sdn. Bhd. (2017). Telfast® Oral Suspension (Fexofenadine hydrochloride 30mg/5ml) [Package insert].
23. Sunward Pharmaceutical Sdn. Bhd. (2019). Polarax tablet/syrup [Amended draft package insert].
24. Upha Pharmaceutical Mfg. (M) Sdn. Bhd. (2016). Chloramine Syrup [Package insert].
25. Xepa-Soul Pattinson (Malaysia) Sdn Bhd. (2017). Antamin™ Syrup [Package insert].
26. Chainani, E., Godse, K., Agarwal, S., & Patil, S. (2015). Knowledge and attitude of medical resident doctors toward antihistamines. Indian Journal of Dermatology, 60(6), 635. https://doi.org/10.4103/0019-5154.169141
27. Simons, F. E., & Simons, K. J. (2008). H1 antihistamines: Current status and future directions. World Allergy Organization Journal, 1(9), 145–155. https://doi.org/10.1186/s40413-018-0188-1
28. Randall, K. L., & Hawkins, C. A. (2018). Antihistamines and allergy. Australian Prescriber, 41(2), 41–45. https://doi.org/10.18773/austprescr.2018.013
29. Vuurman, E. F., van Veggel, L. M., Uiterwijk, M. M., Leutner, D., & O'Hanlon, J. F. (1993). Seasonal allergic rhinitis and antihistamine effects on children's learning. Annals of Allergy, 71(2), 121–126.
30. Blaiss, M. S., & Allergic Rhinitis in Schoolchildren Consensus Group. (2004). Allergic rhinitis and impairment issues in schoolchildren: A consensus report. Current Medical Research and Opinion, 20(12), 1937–1952. https://doi.org/10.1185/030079904x13266
31. Kay, G. G. (2000). The effects of antihistamines on cognition and performance. Journal of Allergy and Clinical Immunology, 105(6), S622–S627. https://doi.org/10.1067/mai.2000.106153
32. Church, M. K., Maurer, M., Simons, F. E., Bindslev-Jensen, C., van Cauwenberge, P., Bousquet, J., ... & Zuberbier, T. (2010). Risk of first-generation H1-antihistamines: A GA²LEN position paper. Allergy, 65(4), 459–466. https://doi.org/10.1111/j.1398-9995.2009.02325.x
33. Yang, Y. H., Lin, Y. T., Lu, M. Y., Tsai, M. J., & Chiang, B. L. (2001). 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 Pacific Journal of Allergy and Immunology, 19(3), 171–175.
34. Garavello, W., Romagnoli, M., Sordo, L., Gaini, R. M., Di Berardino, C., & Angrisano, A. (2003). Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: A randomized study. Pediatric Allergy and Immunology, 14(2), 140–143.
35. Batchelor, H. K., & Marriott, J. F. (2015). Formulations for children: Problems and solutions. British Journal of Clinical Pharmacology, 79(3), 405–418. https://doi.org/10.1111/bcp.12268
36. Nunn, T., & Williams, J. (2005). Formulation of medicines for children. British Journal of Clinical Pharmacology, 59(6), 674–676. https://doi.org/10.1111/j.1365-2125.2005.02410.x
37. Banfield, C., Gupta, S., Marino, M., Lim, J., & Affrime, M. (2002). Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine. Clinical Pharmacokinetics, 41(4), 311–318. https://doi.org/10.2165/00003088-200241040-00004
38. Sádaba, B., Azanza, J. R., Gomez-Guiu, A., & Rodil, R. (2013). Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria. Therapeutics and Clinical Risk Management, 9, 197–205. https://doi.org/10.2147/TCRM.S16079
39. Bailey, D. G. (2010). Fruit juice inhibition of uptake transport: A new type of food–drug interaction. British Journal of Clinical Pharmacology, 70(5), 645–655. https://doi.org/10.1111/j.1365-2125.2010.03722.x
40. Meltzer, E. O., Blaiss, M. S., Naclerio, R. M., Stoloff, S. W., Derebery, M. J., Fogarty, C. P., ... & Williams, P. V. (2012). Burden of allergic rhinitis: Allergies in America, Latin America, and Asia-Pacific adult surveys. Allergy and Asthma Proceedings, 33(Suppl 1), S113–S141. https://doi.org/10.2500/aap.2012.33.3603
41. Yun, J., Katelaris, C. H., Weerasinghe, A., Adikari, D. B., & Ratnayake, C. (2011). Impact of chronic urticaria on the quality of life in Australian and Sri Lankan populations. Asia Pacific Allergy, 1(1), 25–29. https://doi.org/10.5415/apallergy.2011.1.1.25
42. Kay, G. G., Berman, B., Mockoviak, S. H., Vuurman, E. F., Magthari, A. H., & O'Hanlon, J. F. (1997). Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance. Archives of Internal Medicine, 157(20), 2350–2356.
43. Wilken, J. A., Berkowitz, R., & Kane, R. (2002). Decrements in vigilance and cognitive functioning associated with ragweed-induced allergic rhinitis. Annals of Allergy, Asthma & Immunology, 89(4), 372–380. https://doi.org/10.1016/S1081-1206(10)62038-8
44. Simons, F. E., Fraser, T. G., Reggin, J. D., & Simons, K. J. (1996). Comparison of the central nervous system effects produced by six H1-receptor antagonists. Clinical & Experimental Allergy, 26(9), 1092–1097.
45. Federal Aviation Administration. (2019). Guide for aviation medical examiners: Pharmaceuticals (therapeutic medications) do not issue – do not fly. https://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/pharm/dni_dnf/
46. Staevska, M., Gugutkova, M., Lazarova, C., Hamelmann, E., Church, M. K., & Zuberbier, T. (2014). Night‐time sedating H1‐antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: A randomized controlled trial. British Journal of Dermatology, 171(1), 148–154. https://doi.org/10.1111/bjd.12846
47. Herman, D., Arnaud, A., Dry, J., Ferrandiz, J., Gervais, P., & Lhermitte, M. (1992). Efficacité clinique et tolérance de la loratadine versus cétirizine dans le traitement de la rhinite allergique saisonnière [Clinical effectiveness and tolerance of loratadine versus cetirizine in the treatment of seasonal allergic rhinitis]. Allergie et Immunologie, 24(7), 270–274.
48. Mann, R. D., Pearce, G. L., Dunn, N., & Shakir, S. (2000). Sedation with “non-sedating” antihistamines: Four prescription-event monitoring studies in general practice. BMJ, 320(7243), 1184–1186. https://doi.org/10.1136/bmj.320.7243.1184
49. Salmun, L. M., Gates, D., Scharf, M., Greiding, L., Ramon, F., & Heithoff, K. (2000). Loratadine versus cetirizine: Assessment of somnolence and motivation during the workday. Clinical Therapeutics, 22(5), 573–582. https://doi.org/10.1016/S0149-2918(00)80045-4
50. Ramaekers, J. G., Uiterwijk, M. M., & O'Hanlon, J. F. (1992). Effects of loratadine and cetirizine on actual driving and psychometric test performance, and EEG during driving. European Journal of Clinical Pharmacology, 42(4), 363–369. https://doi.org/10.1007/bf00280119
51. Georgitis, J. W., Meltzer, E. O., Kaliner, M., Weiler, J., & Berkowitz, R. (2000). Onset-of-action for antihistamine and decongestant combinations during an outdoor challenge. Annals of Allergy, Asthma & Immunology, 84(4), 451–459. https://doi.org/10.1016/S1081-1206(10)62280-6
52. Kaiser, H. B., Banov, C. H., Berkowitz, R. R., Campbell, E. W., Jr, Dockhorn, R. J., Finn, A. F., Jr, ... & Srebro, S. H. (1998). Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis. American Journal of Therapeutics, 5(4), 245–251.
53. Lockey, R. F. (2006). Rhinitis medicamentosa and the stuffy nose. Journal of Allergy and Clinical Immunology, 118(5), 1017–1018. https://doi.org/10.1016/j.jaci.2006.06.018
54. Mortuaire, G., de Gabory, L., François, M., Masse, G., Bloch, F., Brion, N., ... & Serrano, E. (2013). Rebound congestion and rhinitis medicamentosa: Nasal decongestants in clinical practice. Critical review of the literature by a medical panel. European Annals of Otorhinolaryngology, Head and Neck Diseases, 130(3), 137–144. https://doi.org/10.1016/j.anorl.2012.09.005
55. Aaronson, D. W. (1998). Side effects of rhinitis medications. Journal of Allergy and Clinical Immunology, 101(2), S379–S382. https://doi.org/10.1016/s0091-6749(98)70225-8
56. Deckx, L., De Sutter, A. I., Guo, L., Mir, N. A., & van Driel, M. L. (2016). Nasal decongestants in monotherapy for the common cold. Cochrane Database of Systematic Reviews, 10(10), CD009612. https://doi.org/10.1002/14651858.CD009612.pub2
57. Thomas, J., Pandhi, R. K., Oberoi, C., Khera, B., Sahu, P., & Kanwar, A. J. (1998). A multicentric trial of loratadine and cetirizine in urticaria. Indian Journal of Dermatology, Venereology and Leprology, 64(1), 12–16.
58. Zuberbier, T., Munzberger, C., Haustein, U., Aberer, W., Burtin, B., Rihoux, J. P., & Czarnetzki, B. M. (1996). Double-blind crossover study of high-dose cetirizine in cholinergic urticaria. Dermatology, 193(4), 324–327. https://doi.org/10.1159/000246281
59. World Health Organization. (2006). Reproductive health indicators: Guidelines for their generation, interpretation and analysis for global monitoring. WHO Press.
60. Mehta, N., Chen, K., & Powrie, R. O. (2014). Prescribing for the pregnant patient. Cleveland Clinic Journal of Medicine, 81(6), 367–372. https://doi.org/10.3949/ccjm.81a.13124
61. Gonzalez-Estrada, A., & Geraci, S. A. (2016). Allergy medications during pregnancy. The American Journal of the Medical Sciences, 352(3), 326–331. https://doi.org/10.1016/j.amjms.2016.05.030
62. Ban, G. Y., Kim, M. Y., Yoo, H. S., Shin, Y. S., Ye, Y. M., & Park, H. S. (2014). Clinical features of elderly chronic urticaria. The Korean Journal of Internal Medicine, 29(6), 800–806. https://doi.org/10.3904/kjim.2014.29.6.800
63. Chuamanochan, M., Kulthanan, K., Tuchinda, P., Chularojanamontri, L., & Nuchkull, P. (2016). Clinical features of chronic urticaria in aging population. Asian Pacific Journal of Allergy and Immunology, 34(3), 201–205. https://doi.org/10.12932/AP0708
64. Song, W. J., & Chang, Y. S. (2017). Respiratory allergies in the elderly: Findings from the Korean Longitudinal Study on Health and Aging phase I study (2005–2006). Asia Pacific Allergy, 7(4), 185–192. https://doi.org/10.5415/apallergy.2017.7.4.185
65. Divo, M. J., Martinez, C. H., & Mannino, D. M. (2014). Ageing and the epidemiology of multimorbidity. European Respiratory Journal, 44(4), 1055–1068. https://doi.org/10.1183/09031936.00059814
66. Pinto, J. M., & Jeswani, S. (2010). Rhinitis in the geriatric population. Allergy, Asthma & Clinical Immunology, 6(1), 10. https://doi.org/10.1186/1710-1492-6-10
67. Slavin, R. G. (2009). Treating rhinitis in the older population: Special considerations. Allergy, Asthma & Clinical Immunology, 5(1), 9. https://doi.org/10.1186/1710-1492-5-9
68. Bowden, T., & Coiera, E. (2017). The role and benefits of accessing primary care patient records during unscheduled care: A systematic review. BMC Medical Informatics and Decision Making, 17(1), 138. https://doi.org/10.1186/s12911-017-0523-4
69. Nyenhuis, S. M., & Mathur, S. K. (2013). Rhinitis in older adults. Current Allergy and Asthma Reports, 13(2), 171–177. https://doi.org/10.1007/s11882-013-0342-3
70. Maeda, T., Babazono, A., & Nishi, T. (2018). Surveillance of first-generation H1-antihistamine use for older patients with dementia in Japan: A retrospective cohort study. Current Gerontology and Geriatrics Research, 2018, 3406210. https://doi.org/10.1155/2018/3406210
71. Olasińska-Wiśniewska, A., Olasiński, J., & Grajek, S. (2014). Cardiovascular safety of antihistamines. Postepy Dermatologii i Alergologii, 31(3), 182–186. https://doi.org/10.5114/pdia.2014.43191
72. Philpot, E. E. (2000). Safety of second generation antihistamines. Allergy and Asthma Proceedings, 21(1), 15–20. https://doi.org/10.2500/108854100778249033