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Seasonal Allergies are coming At-Choo Soon
Key Terms
- Anticholinergics: act locally on nasal mucosa to inhibit serous and seromucous gland secretions
- Antihistamines: selectively block peripheral histamine-1 receptors, to minimize response to triggers
- IgE: immunoglobulin E, antibodies produced by the immune system as part of the body’s
defense against specific triggers
- Leukotriene receptor antagonists: inhibits activation of receptors that are correlated with pathophysiology of asthma, airway edema, smooth muscle contraction, and inflammatory responses
- Mast cell stabilizers:act locally to reduce histamine degranulation from mast cells
- Rhinitis medicamentosa: chronic nasal congestion associated with overuse of vasoconstrictor nasal medications, sometimes referred to as “rebound” nasal congestion
Shifting Trends
Springtime brings with it warmer weather, baseball games, and budding trees. In the Fall, we enjoy Friday night football games and pumpkin-flavored everything. For many, these seasonal changes also bring unrelenting watery eyes, runny noses, and scratchy throats. And it is only getting worse.
In 2010, the Asthma and Allergy Foundation of America (jointly with the National Wildlife Federation) released a report on the effect of a warming climate on allergies and asthma.
1 Ragweed is the chief Fall trigger for many patients’ allergies. According to the report, it grows faster and produces more pollen in an environment with more carbon dioxide. Longer growing seasons as a result of warmer weather allow ragweed plants to grow larger, releasing more pollen. In the Spring, budding trees and flowers are the primary pollen producers. A warmer climate means their habitat will expand to previously inhospitable areas. Fungal allergens, too, could be more problematic as the planet warms.
Review of Allergic Pathophysiology
Allergic rhinitis is characterized by sneezing, runny nose, nasal obstruction, and often accompanied by itchy, watery eyes. The physiological response to seasonal allergens is an IgE antibody-mediated inflammatory response.
2 The severity of this response can be mild to severe and varies with trigger type, the extent of exposure, and patient-specific factors.
The Pharmacist’s Role in Treating Seasonal Allergies
Allergic rhinitis is likely a condition that affects many of your patients. Indeed, surveys indicate physician-diagnosed allergic rhinitis affects upwards of 20% of adults and 13% of children in the United States. The functional and economic toll of seasonal allergies is immense. Impaired physical and social functioning and daytime somnolence can lead to lost days of work and lower quality of life.
As patients reach for over-the-counter allergy medications, the incidence of potentially harmful drug interactions increases as well. It is in this capacity that pharmacists can play a key role in alleviating patients’ symptoms while helping them minimize the effects of medications.
Cornerstones of Treatment for Seasonal Allergies
The most common medications used to treat allergic conditions are antihistamines, decongestants, and glucocorticoids. Leukotriene inhibitors, mast cell stabilizers, and anticholinergics can be useful in some cases, too. In recommending a medication to a patient, we should maximize symptom reduction and improve patient productivity while minimizing adverse effects and drug-drug interactions. The latest treatment guidelines were published in 2020 by the American Academy of Allergy, Asthma, and Immunology (AAAAI).
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Antihistamines
Oral antihistamines have long been the standard for seasonal allergies. They can be used proactively to minimize symptoms prior to trigger exposure, or reactively post-exposure. First-generation agents tend to be more sedating and require multiple daily doses. Second-generation agents, conversely, tend to cause less sedation and are taken once daily. These second-generation agents are sometimes called “non-sedating” antihistamines, but a more accurate label is “less-sedating.” Medications in both generations are available without a prescription.
Oral Antihistamines | Generation | Recommended Adult Dose (≥12 years) | Recommended Pediatric Dose (6≥11 years) |
---|
Chlorpheniramine | 1 | 4mg every 4-6 hours | 2mg every 4-6 hours |
Clemastine fumarate | 1 | 1.34mg BID, or 2.68mg daily | 0.67mg BID, or 1.34mg daily |
Diphenhydramine | 1 | 25mg every 4-6 hours | Not recommended3 |
Hydroxyzine | 1 | 10-25mg at bedtime | 12.5-25mg at bedtime |
Triprolidine | 1 | 2.5mg every 4-6 hours | 1.25mg every 4-6 hours |
| | | |
Cetirizine (Zyrtec®) | 2 | 10mg daily | 5-10mg daily |
Desloratadine (Clarinex®) | 2 | 5mg daily | 2.5mg daily |
Fexofenadine (Allegra®) | 2 | 60mg BID, or 180mg daily | 30mg BID, or 60mg daily |
Levocetirizine (Xyzal®) | 2 | 5mg daily | 2.5mg daily |
Loratadine (Claritin®) | 2 | 5mg BID, or 10mg daily | 5-10mg daily |
Many of the agents listed above (and several other medications) are also available in ophthalmic and nasal dosage forms. The topical formulations generally cause little to no sedation. With all antihistamines, it is important that the patient use caution when drug-induced sedation would interfere with activities.
Glucocorticoids
Nasal steroids are now the gold standard for allergic rhinitis. They are the single most effective maintenance therapy and cause very few adverse effects. They can successfully treat both nasal and ophthalmic symptoms of seasonal allergies. Antihistamines often do little to relieve allergic nasal congestion; nasal steroids are particularly effective in these cases. Many of nasal steroids are available over the counter. The choice of agent is generally patient preference. Dose and frequency of these agents is product specific. Generally, though, the recommended dose for most products is 1 or 2 inhalations in both nostrils once or twice daily.
It is important that patients be counseled on correct dosing technique with nasal steroids. Proper positioning of the head will ensure the medication is distributed to the nasal tissues rather than draining down the throat. The patient should tilt the head slightly downward, while pointing the spray upward, away from the septum.
Older, first-generation agents are associated with higher systemic bioavailability. Second-generation agents are typically undetectable at the systemic level, which is preferable especially for children and when using year-round. The maximum effect of nasal steroids usually arrives after one to two weeks of daily use. In the interim, oral antihistamines can be used concurrently to treat allergy symptoms.
Nasal Steroid | Generation | OTC/Rx |
---|
Beclomethasone (Beconase®, Qnasl®) | 1 | Rx |
Budesonide (Rhinocort®) | 1 | OTC |
Flunisolide (Nasarel®) | 1 | Rx |
Triamcinolone (Nasacort®) | 1 | Rx and OTC |
| | |
Ciclesonide (Omnaris®, Zetonna®) | 2 | Rx |
Fluticasone furoate (Flonase Sensimist®) | 2 | OTC |
Fluticasone propionate (Flonase®) | 2 | Rx and OTC |
Mometasone (Nasonex®) | 2 | Rx |
Two of the above products – beclomethasone and ciclesonide – are delivered via dry aerosol. This delivery form may be preferable for patients put off by the scent or taste effects of the other aqueous solutions.
Anticholinergics and Mast Cell Stabilizers
The anticholinergic ipratropium bromide, in nasal spray form, can be useful for treating rhinorrhea (runny nose), but it is still less effective than the nasal glucocorticoids for sneezing, itching, and nasal obstruction.
4 If runny nose is still not well controlled on nasal steroids, it can be used concurrently. Ipratropium requires frequent dosing. Because of its inferiority to nasal steroids, ipratropium is not considered first-line treatment for seasonal allergies.
Cromolyn sodium, a mast cell stabilizer, is particularly useful for people who have episodic symptoms that can be anticipated. For example, a patient who is allergic to cats can use cromolyn nasal spray about 30 minutes prior to visiting a friend who has a cat to minimize nasal allergen triggering. In the same way, cromolyn can be initiated 1-2 weeks prior to environmental pollen peaks as a prophylactic measure. This agent does require frequent daily dosing when used for seasonal allergies. Cromolyn is also considered second-line treatment to nasal steroids but can be useful when other agents are not- well tolerated.
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Second-Line Agents | OTC/Rx | Typical Dose and Frequency |
---|
Ipratropium (Atrovent Nasal®) | Rx | 2 sprays in each nostril 2-3 times daily |
Cromolyn (NasalCrom®) | OTC | 1 spray in each nostril 3-4 times daily |
Nasal Decongestants
Nasal decongestants work by causing local vasoconstriction. Phenylephrine, oxymetazoline, xylometazoline, and naphazoline are the agents in this class. While they are very effective for nasal congestion, they are not recommended for allergic rhinitis monotherapy. Chronic use of nasal decongestants can give rise to rhinitis medicamentosa or “rebound” congestion. Downregulation of alpha-adrenergic receptors in the nasal tissues can occur in as little as 3 days of use. Patients who use nasal decongestants frequently often find themselves in a cycle of nasal congestion both caused by and relieved by the medication. Therefore, patients should be warned against using any of these singly agents for more than 72 hours.
Patients with congestion-dominant seasonal nasal symptoms may find benefit from a combination of once-daily nasal steroid plus the long-acting nasal decongestant agent oxymetazoline. A study that evaluated this combination found that nasal symptoms were less than in the placebo group, and even less in the group using a steroid alone.
6 Moreover, the study found that the once-daily dosing with the steroid did not bring on rhinitis medicamentosa. Still, it is still advisable to discontinue use of a nasal decongestant once symptoms are well-controlled.
Leukotriene Receptor Antagonists
One medication in this class, montelukast (Singulair®), was used for patients who could not tolerate nasal sprays. However, recent trials revealed troubling neuropsychiatric changes associated with the drug. As a result, the FDA issued a boxed warning for montelukast, citing its link to insomnia, anxiety, depression, and suicidal ideation.
7, 8 With this new information, the risk/benefit ratio of montelukast increased significantly. Given the number of other safer alternatives for treating seasonal allergies, montelukast (and other agents in its class) should be avoided.
When to Refer at Patient to a Specialist
If a patient fails multiple courses of the recommended agents, an evaluation for non-allergic etiologies is advisable. A specialist should rule out other conditions before initiating allergen immunotherapy. Adult and pediatric patients who have prolonged, severe symptoms, co-existing asthma or nasal polyps should also be referred for further evaluation.
Summary
Seasonal allergy symptoms and allergic rhinitis are very common conditions, affecting 10-30 percent of adults and children in industrialized countries. Prevalence is increasing. Medications to treat allergic nasal symptoms are numerous, many available without a prescription. As such, pharmacists play a key role in advising patients on safe use of these medications.
The treatment of choice for most patients is a nasal glucocorticoid. These agents offer safety, minimal systemic absorption, convenient once-daily dosing, and over-the-counter availability. Nasal steroids can also be combined with oral antihistamines when symptoms are most severe. For some patients, targeted therapy with ipratropium or cromolyn may be beneficial. Nasal decongestants offer some short-term relief but should be used very cautiously – and briefly – to avoid “rebound” vasoconstriction. Recent warnings about serious neuropsychiatric adverse effects of leukotriene receptor antagonists have taken montelukast off the recommended list of allergy treatments. If patients have other pulmonary conditions, or fail multiple trials of the standard agents, an immunologist or otolaryngologist consult is warranted.
References
- National Wildlife Federation. Extreme Allergies and Global Warming.; 2010. Accessed March 22, 2022. https://www.aafa.org/media/1634/extreme-allergies-global-warming-report-2010.pdf
- Dykewicz MS, Wallace DV, Baroody F, et al. Treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2017;119(6):489-511.e41. doi:10.1016/j.anai.2017.08.012
- Dykewicz MS, Wallace DV, Amrol DJ, et al. Rhinitis 2020: A practice parameter update. J Allergy Clin Immunol. 2020;146(4):721-767. doi:10.1016/j.jaci.2020.07.007
- Milgrom H, Biondi R, Georgitis JW, et al. Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 1999;83(2):105-111. doi:10.1016/S1081- 1206(10)62620-8
- Pitsios C, Papadopoulos D, Kompoti E, et al. Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic treatment for moderate/severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2006;96(5):673-678. doi:10.1016/S1081-1206(10)61064-2
- Baroody FM, Brown D, Gavanescu L, DeTineo M, Naclerio RM. Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol. 2011;127(4):927-934. doi:10.1016/j.jaci.2011.01.037
- Druss B, Pincus H. Suicidal ideation and suicide attempts in general medical illnesses. Arch Intern Med. 2000;160(10):1522-1526. doi:10.1001/archinte.160.10.1522
- Federal Drug Administration. FDA requires Boxed Warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. Drug Safety and Availability. Published March 4, 2020. Accessed April 10, 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-boxed-warning-about-serious- mental-health-side-effects-asthma-and-allergy-drug