Although second-generation antihistamines are preferred, patient preference should drive selection of therapy.
Second-Generation Antihistamines Are Preferred
As spring progresses into summer, almost every weather report includes a brief discussion of the pollen count alongside the predictions of sun, wind (which exacerbates allergies), or rain (which lessens allergies). Although intranasal corticosteroids (INCS) are first-line agents for seasonal allergic rhinitis,1-3 many patients prefer antihistamines because they provide relief quickly and effectively, have few adverse effects, and are accessible at reasonable prices. Many patients consult with pharmacy staff when they need relief from symptoms that wax and wane.
Usually, patients will find relief in the OTC aisle. Occasionally, some patients may need to step up to prescription antihistamines, INCS, or leukotriene-receptor antagonists (LTRAs).1,2 Although the antihistamines are generally safe and effective, pharmacy staff still need to remember a few key points.
Behind the Sneezing and Sniffling: Histamine
Since the early 1900s, researchers have known that histamine, a biogenic monoamine and neurotransmitter, is the culprit in most seasonal allergies.4 Researchers have also identified the H1 receptor, which is considered ubiquitous throughout the body, as the most likely cause of allergy symptoms (sneezing, itching, watery eyes, fatigue, and sinus swelling).5
The H1-receptor antagonists are grouped into first-generation and sec-ond-generation drugs.6 The first-generation drugs (brompheniramine, chlorpheniramine, dimenhydrinate, diphenhydramine, doxylamine, and hydroxyzine) tend to have more profound anticholinergic effects and can create psychomotor impairment, whereas the second-generation H1-receptor antagonists are less anticholinergic. The second-generation antihistamines are more selective for peripheral H1 receptors; adverse effects such as drowsiness, dry mouth, constipation, blurred vision, and urinary retention are less likely, but still possible.6 Patients older than age 65 should generally avoid the first-generation antihistamines.7
Guidelines are Available
The most recently updated guideline is the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology 2020 Joint Task Force Practice Parameter (TFPP) recommendations for the treatment of allergic rhinitis and nonallergic rhinitis in adolescents aged 12 and older and adults. Table 12 summarizes their recommendations for allergic rhinitis. These guidelines recommend against LTRAs for initial treatment of allergic rhinitis.
The 2015 American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines address patients aged 2 and older who suffer from allergic rhinitis.1 They recommend intranasal steroids and oral antihistamines as first-line treatment. Similar to the TFPP recommendations, this guideline recommends against LTRAs as first-line treatment.1
Monotherapy is Good, But Sometimes Ineffective
Patients often use INCS, the recommended first-line treatment, for days before experiencing relief, but oral antihistamines usually suppress histamine within hours. INCS and antihistamines can be used concurrently if patients still have symptoms after taking antihistamines. Combining LTRAs with antihistamines may provide added benefit for patients with comorbid asthma.1,2
If patients’ main symptoms are sneezing and itching, a second-generation antihistamine is usually a good choice.2 Table 23,8-14 lists available options. All the second-generation antihistamines are similarly effective.15 Some patients prefer nasal antihistamines, and when that is the case, pharmacists should review the directions with the patient because many patients use these incorrectly.
Diminishing Response is Common
Many people adopt a favorite antihistamine and use it exclusively. Although little is written on the topic, many if not most patients experience “antihistamine tolerance,” or diminished effectiveness.16 It can occur after as few as 7 days of antihistamine use but is usually associated with prolonged use. Taking a break for 3 to 14 days or using a different antihistamine can restore response to the original antihistamine.
Recommending antihistamines for seasonal allergy usually boils down to recommending the second-generation nonsedating antihistamines over the first-generation antihistamines to start treatment. Because the antihistamines have similar efficacy and safety profiles, price, availability, and patient preference should drive selection. Patients whose symptoms are unresponsive or severe need to see a prescriber.
1. Seidman MD, Gurgel RK, Lin SY, Schwartz SR, Baroody FM, Bonner JR, et al; Guideline Otolaryngology Development Group. AAO-HNSF.. Clinical practice guideline: aAllergic rhinitis. Otolaryngol Head Neck Surg. 2015;152(s1 Suppl 1):S1-S43. doi:10.1177/0194599814561600
2. Dykewicz MS, Wallace DV, Amrol DJ, Baroody FM, Bernstein JA, Craig TJ, et al. Rhinitis 2020: aA practice parameter update. J Allergy Clin Immunol. 2020;146(4):721-767. doi:10.1016/j.jaci.2020.07.007
3. Benninger M, Farrar JR, Blaiss M, Chipps B, Ferguson B, Krouse J, et al. Evaluating approved medications to treat allergic rhinitis in the United States: an evidence-based review of efficacy for nasal symptoms by class. Ann Allergy Asthma Immunol. 2010;104(1):13-–29. doi:10.1016/j.anai.2009.11.020
4. Mahdy AM, Webster NR. Histamine and antihistamines. IAnaesth Intensive Care Med. 20174;185(45):210-21550–255. doi:10.1016/j.mpaic.2017.01.007
5. Wang XY, Lim-Jurado M, Prepageran N, Tantilipikorn P, Wang Dde Y. Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine. Ther Clin Risk Manag. 2016;12:585-–597. doi:10.2147/TCRM.S105189
6. Beck LA, Bernstein JA, Maurer M. A review of international recommendations for the diagnosis and management of chronic urticaria. Acta Derm Venereol. 2017;97(2):149-–158. doi:10.2340/00015555-2496
7. 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers cCriteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-–694. doi:10.1111/jgs.15767
8. Day JH, Briscoe MP, Rafeiro E, Ratz JD, Ellis AK, Frankish CW, et al. Comparative efficacy of cetirizine and fexofenadine for seasonal allergic rhinitis, 5-12 hours postdose, in the environmental exposure unit. Allergy Asthma Proc. 2005;26(4):275-282. PMID:16270720
9. Hampel F, Ratner P, Mansfield L, Meeves S, Liao Y, Georges G. Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy to cetirizine, 10 mg, with less drowsiness in patients with moderate-to-severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2003;91(4):354-361. doi:10.1016/S1081-1206(10)61682-1
10. Astepro Allergy. Healthcare professionalsAstepro Allergy. Accessed May 17, 2023. https://www.asteproallergy.com/healthcare-professionals
11. Patanase nasal spray. Prescribing information. Novartis Pharmaceuticals Corporation; 2021. Revised June 2023. Accessed May 17, 2023. https://www.novartis.com/us-en/sites/novartis_us/files/patanase.pdf
12. Allegra. Prescribing information. capsules and tablets. Aventis Pharmaceuticals Incsanofi-aventis US LLC; 2007.. Accessed May 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020872s018,021963s002lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20786se8-014,20872se8-011,20625se8-012_allegra_lbl.pdf
13. XYZAL Xyzal. Prescribing information. UCB, Inc; 2016. (levocetirizine dihydrochloride) tablets, for oral use XYZAL (levocetirizine dihydrochloride) oral solution. UCB, Inc. Revised June 2016. Accessed May 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022064s030,022157s013lbl.pdf
14. Claritin. Package insert. Schering Corporation; 2000. (loratadine) TABLETS, SYRUP, and RAPIDLY-DISINTEGRATING TABLETS. Accessed May 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20641s7lbl.pdf
15. Carson S, Lee N, Thakurta S. Drug class review: newer antihistamines.: Final Report Update 2. Drug Class Reviews.Scribd. May 2010. Accessed May 17, 2023. https://www.scribd.com/document/229484926/Drug-Class-Review-Antihistamine-Update-5-2010
16. Dannenberg TB, Feinberg SM. The development of tolerance to antihistamines; a study of the quantitative inhibiting capacity of antihistamines on the skin and mucous membrane reaction to histamine and antigens. J Allergy. 1951;22(4):330-339. doi:10.1016/0021-8707(51)90033-0
About the Author
Jeannette Y. Wick, MBA, RPh, FASCP, is the director of pharmacy professional development in the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy in Storrs.