Skip to main content
Download PDF

CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria

Allergy, Asthma & Clinical Immunology volume 15, Article number: 61 (2019) Cite this article

Abstract

Oral H1-antihistamines (AHs) are the most commonly used therapy to treat allergic rhinitis and chronic urticaria. Older, first-generation AHs (e.g. diphenhydramine, hydroxyzine) have significant and common side effects including sedation, impairment with decreased cognitive function, poor sleep quality, dry mouth, dizziness, and orthostatic hypotension. These drugs have also been found to result in death from accidents, intentional or unintentional overdoses, and sudden cardiac death. The unfavourable risk–benefit profile of first-generation AHs led to the development of newer, less-sedating second- and third-generation AHs, which first became available in Canada in the 1980s. High-quality trials have proven that newer generation AHs are superior in safety compared to older first-generation AHs. On average, they have improved potency and efficacy. Second- and third-generation AHs are the recommended first-line treatment for mild allergic rhinitis and acute and chronic urticaria. Despite this evidence, older first-generation AHs continue to be over-utilized because of their over-the-counter (OTC) status and long history of use. The Canadian Society of Allergy Clinical Immunology (CSACI) recommends that newer generation AHs should be preferred over first-generation AHs for the treatment of allergic rhino-conjunctivitis and urticaria. To promote this recommendation, education of health professionals and the public is necessary. Further, given the dangers of older first-generation AHs, we believe they should be used only as a last resort with eventual consideration given to having them only available behind the counter in pharmacies.

Background

Histamine is a biogenic amine whose release results in allergic rhino-conjunctival symptoms as well as the urticarial wheal and flare reaction with itch [1].

H1-antihistamines are the most utilized class of medications for the treatment of allergic rhino-conjunctivitis and urticaria [2]. The most well-known first-generation AH, diphenhydramine (Benadryl©) has been available since 1946. This drug was introduced before current licensing standards, and thus it did not pass the rigorous safety and efficacy standards required today [1]. Since their introduction, the association between first-generation AHs and dangerous side effects, including sedation, respiratory depression, coma, and death, has become clear. However, because of their longevity, name recognition, and OTC status, both patients and practitioners continue to select older more dangerous first-generation AHs over well-studied newer, safer and affordable alternatives [3]. Furthermore, adverse events associated with these medications often preclude patients from trying other treatment options.

The unfavourable risk–benefit profile of first-generation AHs has led to the creation of newer, less-sedating 2nd- and 3rd-generation AHs, which first became available in Canada in the 1980s. Third-generation antihistamines are defined as being metabolites or enantiomers of previously available drugs and can therefore lead to an increase in efficacy and/or safety. In Canada these include: fexofenadine and desloratidine [4]. High-quality trials have proven newer generation AHs are superior in safety, are faster in onset of action, and have improved efficacy, length of action and potency compared to older 1st generation AHs [2, 5, 6]. Newer generation AHs are first-line treatment for mild allergic rhino-conjunctivitis and acute and chronic urticaria [7,8,9]. The cost of newer generation antihistamines has come down significantly and several are now available OTC. Despite the decrease in price, the newer generation AHs are often still more expensive than first generation AHs and cost remains a barrier.

Outside of North America, 1st generation antihistamines are mainly used for the treatment of motion sickness and as sleep aids, and not for the routine treatment of allergic rhinitis and urticaria because of their sedative tendencies. However, in Canada, online surveys of physicians and pharmacists show that Benadryl©(diphenhydramine) remains the most recommended antihistamine for allergic symptoms in children in each of the last 7 years [10]. The aim of this position statement is to highlight the known and newly recognized risks associated with first-generation AHs, to review the evidence of superior safety of newer generation AHs, and to recommend against the routine use of first-generation AHs (Table 1).

Table 1 H1 Antihistamines: pharmacokinetics and pharmacodynamics in healthy adults.
Full size table

Risks of first generation H1-antihistamines

Shortly after their introduction in the 1940s, the potential for severe adverse effects associated with their use was reported [11,12,13]. These older AHs have poor receptor selectivity and non-specifically bind muscarinic, serotonin, and α-adrenergic receptors, as well as cardiac potassium ion channels, leading to several intolerable and potentially life-threatening adverse effects [2]. They also cross the blood–brain barrier and may lead to significant CNS suppression and toxicity resulting in psychomotor impairment, coma, and even death [14]. Because of safety concerns, in 2009 Health Canada recommended that 1st Generation antihistamines not be sold in combination with other drugs to children under 6 for coughs and colds [15].

CNS suppression: sedation, poor sleep quality and decreased cognitive performance

Older, first-generation AHs are commonly used as sleep aids because of their strong sedative qualities. Surprisingly, the dose utilized for sleep induction is the same dose used for rhinitis symptoms. Despite their sedative effects, these older medications do not result in quality sleep [16, 17]. After a night-time dose of chlorpheniramine (1st generation), next-day “hang-over” effects like impaired vigilance, divided attention, working memory, sensory-motor performance, and reduced latency to daytime sleep has been observed [17].

In addition to poor sleep quality and increased sedation, older AHs have also been associated with decreased school performance measures [17]. Walker et al. found that students with symptoms of allergic rhinitis were 40% more likely to drop a grade from practice tests to final examinations and 70% more likely to drop a grade if they reported taking older sedating AHs [3].

CNS impairment and accidents

First-generation AHs have been associated with injuries and fatalities due to car, plane, and boating accidents [14]. A randomized controlled trial comparing fexofenadine 60 mg, diphenhydramine 50 mg, alcohol (0.1% blood alcohol concentration), and placebo found that driving performance was the poorest after diphenhydramine use and that drowsiness ratings were not predictive of the level of impairment [18]. Despite warnings that diphenhydramine may cause drowsiness and should not be taken when operating machinery it is not specified that this includes driving [19].

In a review of 484 fatalities in Ontario, drivers who were killed in car accidents and found to be at fault were 1.5 times more likely to have been under the influence of first-generation AHs [20]. The European Union has labelled diphenhydramine a Category III drug indicating that it is likely to produce severe effects on fitness to drive [21]. This carries their highest warning level and the recommendation: “Do not drive. Seek medical advice before driving again.” [21].

In a recent review of toxicology testing profiles from 6677 fatally injured civil aviation pilots in the United States from 1990 to 2012, diphenhydramine was the drug most commonly found on autopsy that was capable of causing impairment (7.3%) [22]. Due to the increased risk, first-generation AHs are banned for use by commercial and military airline pilots before or during flights [2, 5].

Overdose and toxicity

Diphenhydramine and other first-generation AHs are documented drugs of abuse, and overdose can result in significant anti-cholinergic effects including fever, flushing, pupillary dilatation, urinary retention, tachycardia, hypotension and coma [23]. Infants and children who experience accidental or intentional overdose may present with paradoxical excitation including irritability, hallucinations, and seizures followed by drowsiness, delirium, respiratory depression and coma [14, 23, 24]. In 2003, 28,092 exposures to diphenhydramine were reported to poison control centres in the United States—11,355 (40.4%) of these cases were in children under the age of six, resulting in at least six fatalities [23].

Risk of QT prolongation and torsade de pointes

Cardiac toxicity is an increasing concern with use of first-generation AHs, especially amongst older patients with significant comorbidities and polypharmacy via drug interactions.

The cardiac safety of first generation antihistamines was never studied as this was an unknown risk when introduced. In June 2016, Health Canada released a safety recall regarding hydroxyzine and issued a “black box” warning hydroxyzine can increase the risk of QT prolongation and torsade de pointes. Hydroxyzine has the potential to cause dizziness, palpitations, syncope, seizures, or sudden cardiac death [25, 26]. Furthermore, the new maximum daily dose has been reduced to 100 mg in adults and 50 mg in the elderly, if the medication cannot be entirely avoided.

Newer generation H1-antihistamines

Second- and third-generation non-sedating AHs were developed with decreased ability to cross the blood–brain barrier and without anticholinergic effects. Initially available for clinical use since 1981, this growing class of medications has been extensively studied in high-quality, randomized controlled clinical trials [27,28,29,30]. These studies demonstrated safety even in off-label high-dose regimens [31]. They have also been found to have an equivalent or faster onset of action compared to first-generation AHs [2, 5, 32]. Jones et al. found that the time to induce a 50% reduction in histamine-induced flare response for oral diphenhydramine (50 mg) was 79.2 min [33]. In contrast, the same outcome took 50 min for cetirizine [34, 35].

Superior safety of newer generation H1-antihistamines

Although not without side effects, in contrast to older generation AHs, newer generation medications have minimal serious safety concerns [5, 36]. There have been no fatalities directly associated with the use of the newer generation AHs available in Canada. Accidental exposures of up to 30-fold ingestions of cetirizine, loratadine, and fexofenadine have not resulted in any serious adverse events [37,38,39].

Two second-generation AHs (astemizole and terfenadine) have been associated with cardiac toxicity, however, both were removed from the market over 20 years ago. Since this time there have been no new concerns regarding cardiac toxicity and second- and third- generation AHs [5, 37]. Since the discovery of the above-noted cardiac toxicity, all second- and third-generation AHs are required by regulatory agencies to undergo thorough cardiac safety testing at standard and high off-label doses [5].

The level of sedation experienced by patients taking newer generation AHs varies by specific medication and the dose. Loratadine, fexofenadine, desloratidine, rupatadine and bilastine are the least-sedating antihistamines and, presently, loratadine, fexofenadine and desloratidine are the sanctioned choices for pilots, truck drivers and others who perform complex tasks like operating heavy machinery vs. cetirizine which is a low-sedating antihistamine [6, 9, 40].

Efficacy of first generation antihistamines versus newer generation

Perceived quicker onset of action of older AHs is often cited as a reason why patients and practitioners choose first-generation medications, however this perception has been proven inaccurate in clinical studies [33, 41]. Indeed, in a double-blind placebo controlled trial, both cetirizine and loratadine were found to have significantly faster onset of action, potency, and duration of action when compared to chlorpheniramine [42]. The prolonged duration of action with newer generation antihistamines vs. 1st generation antihistamines is also a distinct advantage [6] Epinephrine is the drug of choice for anaphylaxis, but H1-antihistamines are also used in its treatment, with the route of treatment varying with severity of reaction. Only 1st generation antihistamines are available for IV use but they can potentially increase vasodilation and hypotension if given rapidly. If an oral antihistamine is to be given, a low sedating antihistamine like cetirizine, which is absorbed rapidly, is preferable to sedating antihistamines like diphenhydramine [43].

Conclusion

First-generation AHs have been used for the treatment of allergic disease for over 70 years. However, common and serious adverse effects associated with these medications have been reported. First-generation AHs are in the process of being restricted as new evidence of harm, contraindications and dose limitations become apparent. Older AHs have not passed current safety or efficacy standards, and should not be used in routine circumstances for allergic disease. Newer generation AHs have been extensively studied over the past 30 years, and are safer, feature faster or equivalent onset of action, and are superior in efficacy compared to first generation AHs. The CSACI, therefore, recommends in agreement with other international bodies, that only less-sedating newer generation AHs should be first-line and preferred over older AHs and that the use of first-generation AHs should be significantly curtailed [9, 14].

Key points

  1. 1.

    First-generation AHs are associated with significant and, at times, serious adverse effects including fatal outcomes, and they should not be used as first-line treatment in allergic disease.

  2. 2.

    Despite package warnings, the level of CNS impairment caused by first generation AHs is not fully appreciated both by health care professionals and the public, which has resulted in preventable fatal injuries.

  3. 3.

    Newer generation AHs are proven to be much safer than first-generation AHs, have a faster onset of action, and have superior potency, selectivity and efficacy.

  4. 4.

    Despite the widespread availability of newer generation AHs, older AHs remain over-utilized.

  5. 5.

    To encourage the cessation of the routine use of older AHs including diphenhydramine (Benadryl©), this class of medications should have eventual consideration for availability on a behind the counter basis only.

  6. 6.

    Further efforts are needed to disseminate this information to healthcare providers and patients to help change practice and improve patient health and safety.

Availability of data and materials

Not applicable.

Abbreviations

AHs:

antihistamines

References

  1. Howarth P. Antihistamines in rhinoconjunctivitis. Clin Allergy Immunol. 2002;17:179–220.

    CAS  PubMed  Google Scholar 

  2. Simons FE, Simons KJ. Histamine and H1 antihistamines. In: Adkinson JN, et al., editors. Middleton’s allergy principles and practice. Elsevier Saunders: Philadelphia; 2014. p. 1503–33.

    Google Scholar 

  3. Walker S, et al. Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case-control study. J Allergy Clin Immunol. 2007;120(2):381–7.

    Article  Google Scholar 

  4. Handley DA, Magnetti A, Higgins AJ. Therapeutic advantages of third generation anthistamines. Expert Opin Investig Drugs. 1998;7(7):1045–54.

    Article  CAS  Google Scholar 

  5. Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011;128(6):1139–50.

    Article  CAS  Google Scholar 

  6. Nicholson AN, et al. Antihistamines and aircrew: usefulness of fexofenadine. Aviat Space Environ Med. 2000;71(1):2–6.

    CAS  PubMed  Google Scholar 

  7. Sussman G, et al. Insights and advances in chronic urticaria: a Canadian perspective. Allergy Asthma Clin Immunol. 2015;11(1):7.

    Article  Google Scholar 

  8. Brozek JL, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2016 revision. J Allergy Clin Immunol. 2017;140(4):950–8.

    Article  Google Scholar 

  9. Casale TB, et al. First do no harm: managing antihistamine impairment in patients with allergic rhinitis. J Allergy Clin Immunol. 2003;111(5):S835–42.

    Article  Google Scholar 

  10. The Medical Post OTC Survey: canadianhealthcarenetwork.ca, 2019. http://www.canadianhealthcarenetwork.ca/microsites/otc2019/pharmacists/product_06.php. Accessed 15 Sept 2019.

  11. Wyngaarden JB, Seevers MH. The toxic effects of antihistaminic drugs. J Am Med Assoc. 1951;145(5):277–82.

    Article  CAS  Google Scholar 

  12. Borman MC. Danger with benadryl of self medication and large dosage. J Am Med Assoc. 1947;133(6):394.

    Article  CAS  Google Scholar 

  13. Slater BJ, Francis N. Benadryl, a contributing cause of an accident. J Am Med Assoc. 1946;132:212.

    Article  CAS  Google Scholar 

  14. Church MK, et al. Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper. Allergy. 2010;65(4):459–66.

    Article  CAS  Google Scholar 

  15. Decision on the labelling of cough and cold products for children, H. Canada, Editor. 2008.

  16. Thakkar MM. Histamine in the regulation of wakefulness. Sleep Med Rev. 2011;15(1):65–74.

    Article  Google Scholar 

  17. Boyle J, et al. Allergy medication in Japanese volunteers: treatment effect of single doses on nocturnal sleep architecture and next day residual effects. Curr Med Res Opin. 2006;22(7):1343–51.

    Article  Google Scholar 

  18. Weiler JM, et al. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance. A randomized, placebo-controlled trial in the Iowa driving simulator. Ann Intern Med. 2000;132(5):354–63.

    Article  CAS  Google Scholar 

  19. Attitudes and beliefs about the use of over-the-countermedicines: a dose of reality. A national survey of consumers and health professionals. 2002, Harris Interactive.

  20. Cimbura G, et al. Incidence and toxicological aspects of drugs detected in 484 fatally injured drivers and pedestrians in Ontario. J Forensic Sci. 1982;27(4):855–67.

    Article  CAS  Google Scholar 

  21. Ravera S, et al. A European approach to categorizing medicines for fitness to drive: outcomes of the DRUID project. Br J Clin Pharmacol. 2012;74(6):920–31.

    Article  CAS  Google Scholar 

  22. McKay MP, Groff L. 23 years of toxicology testing fatally injured pilots: implications for aviation and other modes of transportation. Accid Anal Prev. 2016;90:108–17.

    Article  Google Scholar 

  23. Scharman EJ, et al. Diphenhydramine and dimenhydrinate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2006;44(3):205–23.

    Article  CAS  Google Scholar 

  24. Palmer RB, et al. Adverse events associated with diphenhydramine use in children, 2008–2015. Clin Toxicol (Phila). 2019;7:1–8.

    Article  Google Scholar 

  25. Schlit AF, et al. Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug. Pharmacol Res Perspect. 2017;5(3):e00309.

    Article  Google Scholar 

  26. Vigne J, et al. QT prolongation induced by hydroxyzine: a pharmacovigilance case report. Eur J Clin Pharmacol. 2015;71(3):379–81.

    Article  Google Scholar 

  27. Salmun LM, Lorber R. 24-hour efficacy of once-daily desloratadine therapy in patients with seasonal allergic rhinitis [ISRCTN32042139]. BMC Fam Pract. 2002;3:14.

    Article  Google Scholar 

  28. Murray JJ, et al. Comprehensive evaluation of cetirizine in the management of seasonal allergic rhinitis: impact on symptoms, quality of life, productivity, and activity impairment. Allergy Asthma Proc. 2002;23(6):391–8.

    CAS  PubMed  Google Scholar 

  29. Sussman GL, et al. The efficacy and safety of fexofenadine HCl and pseudoephedrine, alone and in combination, in seasonal allergic rhinitis. J Allergy Clin Immunol. 1999;104(1):100–6.

    Article  CAS  Google Scholar 

  30. Druce HM, et al. Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial. J Clin Pharmacol. 1998;38(4):382–9.

    Article  CAS  Google Scholar 

  31. Donado E, et al. No cardiac effects of therapeutic and supratherapeutic doses of rupatadine: results from a ‘thorough QT/QTc study’ performed according to ICH guidelines. Br J Clin Pharmacol. 2010;69(4):401–10.

    Article  CAS  Google Scholar 

  32. Simons FE, Simons KJ. H1 antihistamines: current status and future directions. World Allergy Organ J. 2008;1(9):145–55.

    Article  Google Scholar 

  33. Jones DH, Romero FA, Casale TB. Time-dependent inhibition of histamine-induced cutaneous responses by oral and intramuscular diphenhydramine and oral fexofenadine. Ann Allergy Asthma Immunol. 2008;100(5):452–6.

    Article  Google Scholar 

  34. Meltzer EO, Grant JA. Impact of cetirizine on the burden of allergic rhinitis. Ann Allergy Asthma Immunol. 1999;83(5):455–63.

    Article  CAS  Google Scholar 

  35. Grant JA, et al. A double-blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine-induced wheal and flare response for 24 h in healthy male subjects. Allergy. 1999;54(7):700–7.

    Article  CAS  Google Scholar 

  36. Mario Sanchez-Borges, Ignacio Ansotguei. Second generation antihistamines: an update. Curr Opin Allergy Clin Immunol. 2019;19(4):358–64.

    Article  Google Scholar 

  37. Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004;351(21):2203–17.

    Article  CAS  Google Scholar 

  38. Spiller HA, et al. Retrospective evaluation of cetirizine (zyrtec) ingestion. J Toxicol Clin Toxicol. 2002;40(4):525–6.

    PubMed  Google Scholar 

  39. Cobb DB, Watson WA, Fernandez MC. High-dose loratadine exposure in a six-year-old child. Vet Hum Toxicol. 2001;43(3):163–4.

    CAS  PubMed  Google Scholar 

  40. Mann RD, et al. Sedation with “non-sedating” antihistamines: four prescription-event monitoring studies in general practice. BMJ. 2000;320(7243):1184–6.

    Article  CAS  Google Scholar 

  41. Durham CG, et al. Cetirizine versus diphenhydramine in the prevention of chemotherapy-related hypersensitivity reactions. J Oncol Pharm Practice. 2019;25(6):1396–401.

    Article  CAS  Google Scholar 

  42. Simons FE, McMillan JL, Simons KJ. A double-blind, single-dose, crossover comparison of cetirizine, terfenadine, loratadine, astemizole, and chlorpheniramine versus placebo: suppressive effects on histamine-induced wheals and flares during 24 hours in normal subjects. J Allergy Clin Immunol. 1990;86(4 Pt 1):540–7.

    Article  CAS  Google Scholar 

  43. Simons FE, et al. World allergy organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13–37.

    Article  Google Scholar 

Download references

Acknowledgements

I would like to thank the CSACI Board of Directors for their support of this project and their review and comments on this Position Statement.

Funding

This Position Statement received no funding.

Author information

Authors and Affiliations

  1. Division of Clinical Immunology and Allergy, McGill University, Montreal, QC, Canada

    Michael N. Fein

  2. Division of Allergy and Clinical Immunology, Western University, London, ON, Canada

    David A. Fischer

  3. The Canadian Society of Allergy and Clinical Immunology, Ottawa, ON, Canada

    David A. Fischer

  4. Division of Pediatrics, Faculty of Medicine, Memorial University, St. John’s, NL, Canada

    Andrew W. O’Keefe

  5. Gordon Sussman Clinical Research, Toronto, ON, Canada

    Gord L. Sussman

Authors
  1. Michael N. Fein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David A. Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew W. O’Keefe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gord L. Sussman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the Position Statement. All authors read and approved the final manuscript.

Corresponding author

Correspondence to David A. Fischer.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Dr. Michael N Fein is an Assistant Professor, Division of Clinical Immunology and Allergy, McGill University. He has been a member of an Advisory Board or received grants or honoraria from: Novartis, ALK, Aralez, and Stallergenes. Dr. David A Fischer is an Adjunct Professor, Division of Allergy and Clinical Immunology, Western University and President of the Canadian Society of Allergy and Clinical Immunology. He has received consulting fees and honoraria from ALK, AstraZeneca, Aralez, Merck, Mylan, Pfizer, Novartis, Pediapharm, Sanofi and Teva. Dr. Andrew O’Keefe is a Clinical Assistant Professor, Faculty of Medicine, Memorial University. He has received consulting fees and honoraria from CSL Behring, Pediapharm, Novartis, and Shire. Dr. Gord Sussman has been a member of an Advisory board or received grants or honoraria from: Novartis, Aralez, CSL Behring, Pediapharm, Genentech, DBV Technologies, GSK, AImmune, AstraZeneca, Stallergenes, Merck, Pfizer, Dyax, Biocryst, Green Cross, Kendrion, Shire, Regeneron and Leo Pharma. He has participated in or is participating in a clinical trial: Novartis, CSL Behring, Genentech, DBV Technologies, GSK, AImmune, AstraZeneca, Stallergenes, Merck, Pfizer, Dyax, Biocryst, Green Cross, Kendrion, Shire, Regeneron and Leo Pharma.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fein, M.N., Fischer, D.A., O’Keefe, A.W. et al. CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria. Allergy Asthma Clin Immunol 15, 61 (2019). https://doi.org/10.1186/s13223-019-0375-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13223-019-0375-9

Keywords

  • Histamine
  • H1-antihistamines
  • Diphenhydramine
  • CSACI position statement

Allergy, Asthma & Clinical Immunology

ISSN: 1710-1492

Contact us