MtM essentials for allergic rhinitis management

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1 CREDIT: 2.0 Continuing Education EARN CE CREDIT FOR THIS ACTIVITY AT AN ONGOING CE PROGRAM OF THE UNIVERSITY OF CONNECTICUT SCHOOL OF PHARMACY AND DRUG TOPICS educational objectives Goal: To discuss the pathophysiology and clinical presentation of allergic rhinitis and review nonpharmacologic and pharmacologic treatments for the symptoms of allergic rhinitis. After participating in this activity, pharmacists will be able to: Describe the pathophysiology of allergic rhinitis Describe the clinical presentation of allergic rhinitis Differentiate the clinical presentation of allergic rhinitis with that of the common cold Discuss nonpharmacologic and pharmacologic therapy for allergic rhinitis prevention and treatment The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Pharmacists are eligible to participate in the knowledge-based activity, and will receive up to 0.2 CEUs (2 contact hours) for completing the activity, passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the online system and your participation will be recorded with CPE Monitor within 72 hours of submission. ACPE# H01-P Grant Funding: This activity is supported by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. Supported by an educational grant from Genentech Novartis Pharmaceuticals Corporation Activity Fee: There is no fee for this activity. Initial release date: September 10, 2015 Expiration date: September 10, 2018 To obtain CPE credit, visit and click on the Take a Quiz link. This will direct you to the UConn/Drug Topics website, where you will click on the Online CE Center. Use your NABP E-Profile ID and the session code: 15DT34-XVK37 to access the online quiz and evaluation. First-time users must pre-register in the Online CE Center. Test results will be displayed immediately and your participation will be recorded with CPE Monitor within 72 hours of completing the requirements. MtM essentials for allergic rhinitis management Danielle Wojtaszek, PharmD PHARMACIST, YAlE-NEW HAVEN HOSPITAl, SAINT RAPHAEl CAMPUS, NEW HAVEN, CONN. Devra K. Dang, PharmD, BCPS, CDE, FNAP ASSOCIATE ClINICAl PROFESSOR, UNIVERSITY OF CONNECTICUT SCHOOl OF PHARMACY, STORRS, CONN. Abstract Allergic rhinitis is one of the most common conditions affecting U.S. adults. This chronic condition can lead to various negative effects on a patient s health and quality of life, including bothersome symptoms, increased risk for comorbidities, and decreased productivity. The approaches to management of allergic rhinitis includes both nonpharmacologic and pharmacologic treatments. With numerous overthe-counter and prescription medication options available for the management of allergic rhinitis, pharmacists are uniquely qualified to help patients and prescribers navigate the various treatment options choosing the most appropriate therapy based on patient-specific factors. This article will review the nonpharmacologic and pharmacologic treatment of allergic rhinitis for nonpregnant, adult patients. Faculty: danielle Wojtaszek, Pharmd, and devra K. dang, Pharmd, BcPS, cde, FnaP For questions concerning the online CPE activities, cpehelp@advanstar.com. Dr. Wojtaszek is a pharmacist at the Yale-New Haven Hosptal, Saint Raphael Campus, New Haven, Conn. Dr. Dang is an associate clinical professor at the University of Connecticut School of Pharmacy, Storrs, Conn. Faculty Disclosure: Dr. Wojtaszek and Dr. Dang have no actual or potential conflict of interest associated with this article. Disclosure of Discussions of Off-Label and Investigational Uses of Drugs: This activity may contain discussion of unlabeled/unapproved use of drugs in the United States and will be noted if it occurs. The content and views presented in this educational program are those of the faculty and do not necessarily represent those of Drug Topics or University of Connecticut School of Pharmacy. Please refer to the official information for each product for discussion of approved indications, contraindications, and warnings. IMAGE: GETTY IMAGES /BALLYSCANLON /DIGITALVISION 50 Drug topics Septemb er 2015 DrugTopics.c om

2 continuing education CPE SERIES: MTM FOR THE PATIENT WITH RESPIRATORY DISEASE Welcome to the CPE series, Medication Therapy Management for the Patient with Respiratory Disease, which was designed for pharmacists who take care of patients with respiratory disease. Beginning in April 2015 and continuing through December 2015, pharmacists can earn up to 18 hours of CPE credit with 9 monthly knowledge-based activities from the University of Connecticut School of Pharmacy and Drug Topics. This series kicked off in April and May with MTM essentials for asthma management Part 1 and Part 2. In June and July, the focus shifts to MTM essentials for chronic obstructive pulmonary disease (COPD) management. The August CE activity is a primer on inhalers and nebulizers. In September, pharmacists have the opportunity to learn about allergic rhinitis management. In October, the CE activity covers MTM essentials for cold, flu, and sinusitis management. The November CE activity includes druginduced pulmonary disease recognition and management and idiopathic pulmonary fibrosis. The series concludes in December with a focus on MTM essentials for cough management. The series also offers applicationbased and practice-based activities in Introduction Allergic rhinitis is the fifth most common chronic condition in the United States, and it is estimated that up to 30% of U.S. adults suffer from allergic rhinitis. 1,2 Although allergic rhinitis is often considered a benign condition, it can have a negative effect on a patient s health and quality of life. Patients with allergic rhinitis have an increased risk of developing comorbidities such as sinusitis, otitis media, or asthma. 1 Allergic rhinitis is also associated with high direct and indirect costs. This condition generated an estimated $11.2 billion in direct healthcare expenditures in Additionally, because symptoms of allergic rhinitis lead to missed attendance at work or school, this condition can lead to as much as $2 to $4 billion of lost productivity annually. 2 Pharmacists in the primary care setting can play an important role in the management of this common chronic condition, which can be treated with self-care and with prescription and nonprescription medications. Pathophysiology of allergic rhinitis Allergic rhinitis is an inflammatory condition of the lining of the nose and upper respiratory tract that occurs in response to immunoglobulin E (IgE)-mediated allergic pathways. The events that lead to allergic rhinitis can be divided into an early phase and a late phase response. 1 During the early phase, sensitization occurs in the nose when inhaled allergens are presented to CD4+ T lymphocytes, leading to the release of interleukins and cytokines. The release of cytokines and the interaction of T cells with B cells cause B cells to differentiate into plasma cells. These plasma cells secrete allergen-specific IgE, which binds to mast cells and basophils. On re-exposure to the allergen, the IgE recognizes the allergen and triggers degranulation of the mast cells. This leads to the release of preformed mediators, including histamine, cytokines, and proteases. 4 The mediators bind to nasal receptors, causing symptoms of nasal congestion, rhinorrhea, sneezing, and nasal itching. 1 The late phase occurs in up to 50% of patients with allergic rhinitis approximately four to eight hours after the initial allergen exposure. 1,5 During this phase, additional inflammatory mediators are released, which once again cause symptoms related to the early phase but with more significant nasal congestion. The inflammatory mediators released during the late phase can cause nasal epithelial damage in patients with chronic allergic rhinitis. 5 Contact of an allergen with the surface of the eye can cause allergic symptoms of the eye, known as allergic conjunctivitis. As in allergic rhinitis, allergic conjunctivitis is caused when mast cell degranulation occurs, leading to the release of mediators that cause symptoms of ocular pruritus, redness, swelling, and increased mucus secretion. 6 A phenomenon known as priming also can occur with repeated exposure to allergens. When priming occurs, a smaller amount of antigen is required to stimulate an immediate phase response. This becomes troublesome for the patient, as symptoms can occur despite decreased allergen exposure. 1,5 Classification of allergic rhinitis There are two classification systems of allergic rhinitis, differing based on major practice guidelines. Traditionally, allergic rhinitis is categorized as either seasonal or perennial, according to the classification system proposed by the American Academy of Allergy, Asthma, and Immunology; the American College of Allergy, Asthma, and Immunology; and the Joint Council of Allergy, Asthma, and Immunology 2008 guideline (hereafter referred to as the AAAAI 2008 guideline). 7 Seasonal allergic rhinitis is caused by outdoor allergens that are prominent during certain seasons, such as plant pollen during spring, whereas perennial allergic rhinitis is caused by allergens that are present in the environment throughout the year. Typically, allergens that cause perennial allergic rhinitis are found indoors and include dust mites, molds, insects, and pet dander. Some patients experience episodic rhinitis, in which the patient is only intermittently exposed to the allergen that causes symptoms. 1 Alternatively, allergic rhinitis can be categorized by symptom frequency and severity, according to the classification system proposed by the international Allergic Rhinitis and its Impact on Asthma 2008 guideline (hereafter referred to as the ARIA 2008 guideline). According to this classification, allergic rhinitis frequency can be defined as either intermittent (symptoms present less than four days per week or for less than four consecutive weeks) or persistent (symptoms present more than four days per week or for more than four consecutive weeks). Severity can be mild, meaning that the patient does not experience sleep disturbance, im- DrugTopics.com September 2015 Drug topics 51

3 Continuing Education MtM essentials FoR allergic RHinitiS ManageMent pairment of daily activities, or impairment at school or work and that symptoms are not bothersome; moderate/severe allergic rhinitis is defined as the patient experiencing at least one of the following: sleep disturbance, impairment of daily activities, impairment at school or work, or bothersome symptoms. 8 symptoms and complications of allergic rhinitis Allergic rhinitis typically presents with symptoms of rhinorrhea, sneezing, nasal congestion, and pruritus of the nose, eyes, ears, and throat. Patients suffering from allergic rhinitis may also experience sleep disturbances, headache, fatigue, or ocular manifestations. Cough can also occur, especially in patients with concomitant asthma. 1 Ocular symptoms can occur in 70% of patients with seasonal allergic rhinitis and approximately 50% of those with perennial allergic rhinitis. These symptoms are known collectively as allergic conjunctivitis and present as ocular itching, swelling, and discharge. 9 The symptoms associated with allergic rhinitis share some similarity to the presentation of the common cold and may be confused by patients. Both conditions cause symptoms of nasal congestion, rhinorrhea, and sneezing. However, allergic rhinitis is unlikely to present with accompanying sore throat, which is one sign that may indicate that the patient is in fact suffering from a cold. 10,11 Additionally, it is rare for a patient suffering from the common cold to experience itchy eyes; therefore, patients who are presenting with ocular pruritus are likely experiencing allergic rhinitis. 11 Allergic rhinitis is associated with a higher risk of certain complications and comorbidities. Allergic rhinitis can lead to the development of sinusitis, otitis media, and nasal polyposis. In addition, the bothersome symptoms of allergic rhinitis can cause sleep disturbances and cognitive impairment, which may interfere with a patient s work or daily activities. Allergic rhinitis is particularly problematic for patients with comorbid asthma, as allergic rhinitis has been associated with both the development and worsening of asthma symptoms. 8 goals of therapy As there is not currently a cure for allergic rhinitis, goals of treatment focus on improving symptoms and quality of life. Specifi - cally, the goals of treatment are to minimize the frequency and severity of symptoms, prevent associated complications, improve quality of life, prevent missed work days or reduced productivity, and minimize adverse effects of pharmacologic treatment. 1 Intranasal corticosteroids are the most effective class of medications available for the treatment of allergic rhinitis. Allergic rhinitis guidelines Three guidelines are available for the treatment of allergic rhinitis: the AAAAI 2008 guideline, the ARIA 2008 guideline, and the 2015 American Academy of Otolaryngology Head and Neck Surgery Foundation Clinical Practice Guideline for Allergic Rhinitis (hereafter referred to as the 2015 AAO-HNSF guideline). Each of these guidelines makes recommendations for the management of allergic rhinitis, which can include allergen avoidance, pharmacotherapy, and/or allergen immunotherapy. 2,7,8 Nonpharmacologic therapy Allergen avoidance should always be incorporated in allergic rhinitis treatment. 1,12 Avoidance of allergen triggers should be considered as first-line therapy in the treatment of allergic rhinitis; however, this method is often insufficient as monotherapy because allergen avoidance strategies may be impractical or difficult for patients to implement. 1,2,8 Patients must be able to identify their allergen triggers before implementing allergen avoidance measures, as treatment strategies differ depending on the allergen that causes symptoms. Patients who are allergic to outdoor plant pollen should be advised to avoid outdoor air exposure during highpollen seasons. Patients who are allergic to mold or fungi should maintain humidity levels in their home below 50% and thoroughly and frequently clean their home to prevent growth of these allergens. Patients who are allergic to pet dander should be advised to remove pets from the home, but if this is not possible, then pets should at least be kept out of bedrooms. More detailed information on specific allergen avoidance strategies can be found in Table 1. 1,13 Other nonpharmacologic treatments that can be used to relieve the symptoms of allergic rhinitis include nasal saline sprays/drops and nasal dilator strips to relieve mild nasal congestion and cold compresses or artificial tears to relieve mild allergic conjunctivitis. pharmacologic therapy There are several nonprescription and prescription drug classes available to treat the symptoms of allergic rhinitis (Tables 2-4). 1,2,6,14 The medication classes vary in their efficacy, route of administration (including oral, intranasal, and ophthalmic), and adverse effect profile. Pharmacotherapy should be selected based on patient-specific factors and with the goal of minimizing potential adverse effects of therapy. Pharmacologic options to treat allergic rhinitis in non-pregnant, adult patients are discussed herein. corticosteroids Intranasal corticosteroids are the most effective class of medications available for the treatment of allergic rhinitis. 2,7,8 The efficacy of corticosteroids in treating allergic rhinitis symptoms likely stems from their anti-inflammatory mechanism of action. 1 Intranasal corticosteroids are effective for treating all of the symptoms of allergic rhinitis, including sneezing, itching, rhinorrhea, nasal congestion, and ocular symptoms, and are considered a first-line pharmacotherapy option for the treatment of allergic rhinitis, according to recommendations from the ARIA 2008 and the 2015 AAO-HNSF guidelines. 2,8 Intranasal corticosteroids are also a recommended pharmacologic therapy option in the AAAAI 2008 guideline, but it does not explicitly state whether it is considered a first-line option. 7 Some intranasal corticosteroids are available over-the-counter (OTC), creating convenient access for patients to a first-line pharmacotherapy option (Table 2). 1,2 Although oral corticosteroids are also effective in treating allergic rhinitis, they are considered a last-line therapy option in patients with severe allergic rhinitis because of the potential for systemic adverse effects Drug topics September 2015 DrugTopics.com

4 continuing education The adverse effect profile of intranasal corticosteroids is tolerable in most patients, as the most common adverse effects are a result of local nasal mucosa irritation. Adverse effects may include dryness, burning, stinging, blood-tinged secretions, and epistaxis. 1,2 Some patients may experience sore throat and headache. 1 Epistaxis occurs in 10% to 20% of patients who use intranasal corticosteroids. Often, epistaxis is the result of improper administration of the intranasal corticosteroid. A more serious adverse effect associated with improper intranasal corticosteroid administration is septal perforation. To avoid symptoms of epistaxis and septal perforation, patients should be counseled to direct the spray away from the nasal septum when administering intranasal corticosteroids. Systemic adverse effects do not commonly occur with intranasal corticosteroids because of limited bioavailability at recommended doses. Older intranasal corticosteroids such as beclomethasone, flunisolide, and budesonide have more significant systemic absorption than newer intranasal corticosteroids such as fluticasone and mometasone. Therefore, older intranasal corticosteroids may be associated with a higher risk of systemic adverse effects such as hypothalamic-pituitary-adrenal suppression and osteoporosis. 1 However, the benefit of intranasal corticosteroids generally outweighs the risk of systemic adverse effects. 8,12 The onset of action of intranasal corticosteroids can occur approximately 30 minutes to two hours after administration. However, the maximum peak effect may not occur until after two to four weeks of use. 8,14 It is important to educate patients about the onset of effect of these agents so that patients have a realistic expectation as to when they may experience relief from their symptoms. Patients who are looking for more immediate relief of symptoms may benefit from the use of antihistamines or decongestants. TABlE 1 nonpharmacologic allergen avoidance/ minimization methods For the management of allergic rhinitis Allergen type Avoidance/minimization methods Outdoor pollen Limit outdoor activities during seasons with high pollen counts Keep house and car windows closed Wear a face mask over the mouth and nose when outdoors Shower as soon as possible upon returning indoors (to avoid spreading pollen from clothing and hair onto household furnishings and bedding) Use air conditioning when possible Mold Dust mites Cockroaches Pet dander Control humidity to below 50% when possible Clean frequently and thoroughly with 5% ammonia solution or dilute bleach with detergent Replace carpets with hardwood fl oors and wallpaper with paint Repair indoor water damage immediately Wash bedding every 1-2 weeks at F Encase pillows and mattresses in protective coverings Vacuum carpets, mattresses, and upholstery regularly Clean carpets with acaricide Use insecticide in cockroach-infested areas Make sure that stored food is tightly sealed Ophthalmic corticosteroids are also available to treat allergic conjunctivitis symptoms. However, because of their risk of causing adverse effects such as increases in intraocular pressure, formation of cataracts, and ocular infections, their use is limited to a last-line option for the treatment of severe allergic conjunctivitis. 6,15 Antihistamines Antihistamines are considered a first-line pharmacologic therapy option for the treatment of mild to moderate symptoms of allergic rhinitis, according to recommendations from the ARIA 2008 and the 2015 AAO-HNSF guidelines. 2,8 While the AAAAI 2008 guideline recommends antihistamines as an option to treat allergic rhinitis, pause&ponder With the wide variety of pharmacotherapy options available to treat allergic rhinitis, it may be challenging for patients or prescribers to choose the most appropriate therapy based on patient-specific factors. How can pharmacists play a role in interprofessional healthcare teams to ease any confusion involved in the treatment of patients with allergic rhinitis? Remove pets from the home, if possible Keep pets out of bedrooms Vacuum carpets, mattresses, and upholstery regularly Source: Ref 1,13 it does not specify whether the guideline considers this class as a first-line option. 7 These agents are available as oral, intranasal, and ophthalmic formulations. This medication class works to treat symptoms of allergic rhinitis by antagonizing the histamine-1 receptors. Histamine is responsible for several symptoms of allergic rhinitis, including sneezing, itching, rhinorrhea, nasal congestion, and ocular symptoms. This class of medications is most effective at treating the symptoms of sneezing, itching, and rhinorrhea associated with allergic rhinitis. Oral antihistamines also have some effect in treating ocular symptoms, but ophthalmic antihistamines are specifically effective in treating the ocular symptoms associated with allergic rhinitis. 1,8 Antihistamines also have some effect in treating nasal congestion, with better efficacy achieved with intranasal antihistamines than with oral antihistamines. 1,8 However, antihistamines are much less effective at treating nasal congestion compared to intranasal corticosteroids and decongestants. 2,14 The oral anthistamines are frequently co-formulated with a decongestant for this reason. One of the advantages of antihistamines is a rapid DrugTopics.com September 2015 Drug topics 53

5 Continuing Education MtM essentials FoR allergic RHinitiS ManageMent TABlE 2 FirSt-line Fda-approved pharmacotherapy options For the treatment of allergic rhinitis Drug class Drugs Availability Comments Intranasal corticosteroids Second-generation oral antihistamines Second-generation intranasal antihistamines Beclomethasone dipropionate Budesonide Ciclesonide Flunisolide Fluticasone furoate Fluticasone propionate Mometasone Triamcinolone acetonide Acrivastine Cetirizine Desloratadine Fexofenadine Levocetirizine Loratadine Azelastine Olopatadine onset of action, typically providing symptom relief within 1 to 2 hours of administration of oral formulations and within 15 to 30 minutes of administration of topical formulations. 1,2,14 Additionally, several medications are readily available OTC. Oral antihistamines are divided into firstand second-generation agents. First-generation antihistamines with an FDA-approved indication for allergic rhinitis include brompheniramine, carbinoxamine, chlorpheniramine, cyproheptadine, clemastine, diphenhydramine, doxylamine, and hydroxyzine among others. Brompheniramine, chlorpheniramine, clemastine, diphenhydramine, and doxylamine are available as OTC products; carbinoxamine and cyproheptadine are not commonly prescribed for allergic rhinitis. The second-generation antihistamines indicated to treat allergic rhinitis are listed in Table 2. 1,2 The two subclasses of antihistamines differ in their adverse effect profile. The central nervous system (CNS) and anticholinergic effects of antihistamines are more problematic with first-generation antihistamines, as these drugs are more lipid soluble and are able to cross the blood-brain barrier. 14 CNS effects of first-generation antihistamines present as sedation and impaired cognition, and anticholinergic effects present as blurred vision, worsening of narrow angle glaucoma, dry mouth, Prescription; fl uticasone propionate and triamcinolone acetonide available OTC. Fluticasone propionate available in combination with azelastine. Prescription; cetirizine, fexofenadine, and loratadine available OTC. Acrivastine only available as a combination capsule with pseudoephedrine. Prescription only. Azelastine available in combination with fl uticasone propionate. urinary retention, constipation, and tachycardia. Sedation is typically the most commonly reported adverse reaction, but many patients do not subjectively feel this symptom or only experience it upon initial administration. Effective in treating all symptoms of allergic rhinitis. Onset of effect may take 30 min to 2 hr.; maximum peak effect may not occur until after two to four weeks of use. Direct spray away from nasal septum during administration to avoid epistaxis and septal perforation. Second-generation antihistamines preferred over fi rstgeneration antihistamines for allergic rhinitis because of lower risk of adverse effects. Rapid onset of action within 1-2 hr. Azelastine may cause sedation because of some systemic absorption. Rapid onset of action within min. Olopatadine is a dual-action antihistamine-mast cell stabilizer and is also available in ophthalmic formulation. Abbreviations: OTC, over the counter. Source: Ref 1,2 All three of the allergic rhinitis guidelines recommend second-generation antihistamines as the preferred option over first-generation antihistamines because of the improved adverse effect profile and more convenient once-daily dosing of these secondgeneration agents. However, slowed cognition and psychomotor performance can still be present, and nextmorning effects on the CNS can still occur with bedtime administration because of the long half-lives of these drugs (because of the presence of active metabolites). 7 Although sedation is a common adverse effect of firstgeneration antihistamines, paradoxical CNS stimulation may occur in the pediatric and geriatric populations. Second-generation antihistamines have a more complex chemical structure that prevents the drug from crossing the blood-brain barrier; therefore, these agents have a more tolerable adverse effect profile. 14 They typically cause minimal to no anticholinergic adverse reactions in most patients if dosed appropriately. Another difference between the generations of antihistamines is the dosing regimen. First-generation antihistamines must be dosed three to four times daily, whereas most second-generation antihistamines can be administered once daily. 1 All three of the allergic rhinitis guidelines recommend second-generation antihistamines as the preferred option over first-generation antihistamines because of the improved adverse effect profile and more convenient once-daily dosing of these second-generation agents. 2,7,8 Additionally, because of the potential for CNS and anticholinergic adverse reac- 54 Drug topics September 2015 DrugTopics.com

6 continuing education table 3 Secondary FDA-approved pharmacotherapy options for the treatment of allergic rhinitis Drug class Drugs Availability Comments Oral decongestants Intranasal decongestants Oral leukotriene receptor antagonist Intranasal mast cell stabilizer Intranasal anticholinergic Phenylephrine Pseudoephedrine Levmetamfetamine Naphazoline Oxymetazoline Phenylephrine Propylhexedrine Tetrahydrozoline OTC (pseudoephedrine must be purchased behind the pharmacy counter) OTC. Levmetamfetamine and propylhexedrine available as intranasal inhalers. Limitations on daily and monthly quantities of pseudoephedrine that patients may purchase. Phenylephrine is less effective than pseudoephedrine. Use with caution in patients with hypertension, CVD, glaucoma, and benign prostatic hyperplasia. Rapid onset of effect within 30 min. Use is limited to no more than 3 consecutive days to prevent rhinitis medicamentosa. Rapid onset of effect within 15 min. Montelukast Prescription only May be beneficial in patients with concomitant allergic rhinitis and asthma. Cromolyn sodium OTC Frequent dosing (3 to 4 times daily). Onset of action after approximately four to seven days of use; maximum effect may not be realized until after up to two weeks of use. Also available in ophthalmic formulation. Ipratropium bromide Prescription only Frequent dosing 2-3 times daily. Minimal systemic anticholinergic adverse effects. Abbreviations: CVD, cardiovascular disease; OTC, over the counter. Source: Ref 1,2,14 tions, first-generation antihistamines should generally be avoided in elderly patients for the treatment of allergic rhinitis. Even though they are commonly referred to as nonsedating antihistamines, somnolence has been reported with second-generation antihistamines. Among the three most popular OTC second-generation antihistamines, sedation is most commonly reported with cetirizine, occurring even at recommended doses in some patients. Sedation occurs less commonly with loratadine, usually at higher-than-recommended doses, and least commonly with fexofenadine. 16 Patients treated with fexofenadine should be advised to take this medication only with water and to avoid coadministration with fruit juices. Fexofenadine is a substrate of organic anion-transporting peptide (OATP) 1A2, and fruit juices such as apple, grapefruit, and orange juice are OATP1A2 inhibitors. Because OATPs are membrane transport proteins that facilitate drug uptake into cells, coadministration of these fruit juices with fexofenadine can decrease the drug s concentration by up to 70%. 17 Therefore, ingestion of fruit juices should be avoided within the four hours before and one to two hours after fexofenadine administration. Antihistamines are also available in intranasal formulations (Table 2). 1,2 Both of the intranasal antihistamines on the market at the time of writing (azelastine and olopatadine) are second-generation antihistamines. Both intranasal formulations are dosed twice daily and are also available as ophthalmic solutions. Additionally, azelastine plus fluticasone propionate is available as a prescription-only intranasal spray that is FDA-approved for the treatment of seasonal allergic rhinitis. Olopatadine is considered a dual-action antihistamine-mast cell stabilizer. Intranasal antihistamines are effective in treating symptoms of nasal itching, congestion, sneezing, and runny nose and are more effective in relieving nasal congestion as compared to oral antihistamines. 1,2,8 The most common adverse effect associated with use of intranasal antihistamines is bitter taste, occurring in 2% to 18% of patients. Other common adverse effects of intranasal antihistamines include epistaxis, headache, and nasal burning. Sedation may also occur in some patients, as systemic absorption is possible with the intranasal antihistamines, with higher risk associated with azelastine. 1,2,8 Ophthalmic formulations of antihistamines are also available by prescription to treat symptoms of allergic conjunctivitis. Additionally, ophthalmic dual-action antihistamine-mast cell stabilizers are available by prescription or by one OTC option, ketotifen (Table 4). 1,6 The advantage of these drugs is a quick onset of action, usually within minutes of use. 16 Adverse effects associated with these medications include burning and stinging upon instillation into the eye, headache, and ocular dryness. 18 Decongestants Decongestant medications are effective only at treating the nasal congestion symptom of allergic rhinitis. This class of medications works through alpha-1 adrenergic agonist activity, which causes constriction of nasal mucosa vasculature, resulting in relief of congestion from nasal mucosa swelling. 1,12,14 Decongestants are available as oral and intranasal formulations, as well as ophthalmic formulations to treat allergic conjunctivitis (Table 3). 1,2,14 The oral decongestants currently available in the United States are pseudoephedrine and phenylephrine. Both of these medications are available as OTC products; DrugTopics.com September 2015 Drug topics 55

7 Continuing Education MtM essentials FoR allergic RHinitiS ManageMent however, the sale of pseudoephedrine is restricted because of its use in the manufacturing of methamphetamine. There is a limit on the daily and monthly quantities of pseudoephedrine that a patient may purchase, and the medication must be stored and sold from behind the pharmacy counter. Because of these restrictions, it is less convenient for a patient to purchase pseudoephedrine than phenylephrine, which is readily available in the OTC section of pharmacies and other retailers. However, research suggests that the efficacy of phenylephrine at recommended OTC doses is minimal in terms of relieving nasal congestion. 1 OTC phenylephrine must be dosed every four hours while the extendedrelease version of pseudoephedrine can be dosed twice daily or once daily. Adverse effects associated with oral decongestants are primarily caused by sympathetic stimulation affecting the cardiovascular system and CNS. 1 Adverse effects include increased blood pressure and heart rate, nervousness, irritability, insomnia, headache, increased intraocular pressure, and urinary retention. 1,12,14 Because of their adverse effect profile, oral decongestants should be used with caution in patients with hypertension, cardiovascular disease, glaucoma, and benign prostatic hyperplasia. 1,14 Because of their adverse effect profile, oral decongestants should be used with caution in patients with hypertension, cardiovascular disease, glaucoma, and benign prostatic hyperplasia. Intranasal decongestants provide effective and fast targeted relief of nasal congestion. However, the use of intranasal decongestants must be limited to no more than three consecutive days because of the risk of developing a rebound of persistent nasal congestion symptoms known as rhinitis medicamentosa. If rhinitis medicamentosa occurs, the intranasal decongestant should be discontinued or tapered down. Patients may use intranasal corticosteroids to help relieve symptoms of nasal congestion associated with rhinitis medicamentosa. 1 Intranasal decongestants have limited systemic absorption and therefore are not usually associated with the systemic symptoms seen with oral decongestants when used at recommended doses. Adverse effects associated with intranasal decongestants are usually local effects of nasal stinging, burning, dryness, and sneezing. 1 Patient education on the proper administration technique and emphasis on not exceeding the daily recommended dosing are important to minimize systemic exposure to these medications. One advantage of decongestants over some other classes of allergic rhinitis medications is their quick onset of action. The effect of oral decongestants begins within 30 minutes, and the effect of intranasal decongestants begins within 15 minutes. 1 Ophthalmic decongestants are available in combination with ophthalmic antihistamines to reduce ocular redness associated with allergic conjunctivitis. Adverse effects of ophthalmic decongestants include burning and stinging of the eye on administration and mydriasis. Similar to the intranasal decongestants, ophthalmic decongestants may lead to rebound symptoms if used continuously. Therefore, the use of ophthalmic decongestants should be limited to less than 10 days. 6 Leukotriene receptor antagonists Montelukast is the only leukotriene receptor antagonist that is FDA-approved for the treatment of allergic rhinitis symptoms. This medication is also indicated as adjunctive therapy for the treatment of asthma and is primarily prescribed for this condition. leukotrienes are released from the nasal mucosa on exposure to an allergen, causing symptoms of allergic rhinitis. Montelukast works by preventing leukotrienes from binding to their receptors. 19 The onset of action of montelukast is not immediate, but the effect can be realized after approximately one day of therapy. 1 Clinical studies have found that montelukast is less effective in treating symptoms of allergic rhinitis than intranasal corticosteroids and is either equally or slightly less effective than oral antihistamines. 1,2 The 2015 AAO-HNSF guideline recommends against the use of leukotriene receptor antagonists because of this inferior efficacy compared with other pharmacotherapy options and cost. However, the guideline does recognize that montelukast may be particularly benefi cial in patients with concomitant allergic rhinitis and asthma, as the drug has been shown to improve both conditions. 2 Montelukast is usually a well-tolerated medication with minimal adverse effects. However, it is associated with the rare but serious adverse effect of neuropsychiatric events, including aggression, depression, and suicidal ideation. 1,2 Mast cell stabilizers Intranasal cromolyn is the only mast cell stabilizer that is FDA-approved for the treatment of allergic rhinitis. This agent binds to mast cells, which prevents the release of mediators that cause the symptoms of allergic rhinitis. 1 Intranasal cromolyn is less effective than intranasal corticosteroids and oral or intranasal antihistamines and is therefore considered a second-line pharmacotherapy option for the treatment of allergic rhinitis. Its onset of action is relatively slow, not occurring until after approximately four to seven days of use. 1,7 Additionally, its maximum effect may not be realized until after up to two weeks of use. 1 This medication may also be used prophylactically to prevent the symptoms of allergic rhinitis. 12 If the onset of symptoms can be predicted (eg, seasonal allergic rhinitis), the medication should be initiated approximately two weeks before the expected start of symptoms. The advantage of intranasal cromolyn is its well-tolerated adverse effect profile and lack of clinically significant drug interactions. Common adverse effects associated with the medication include local effects such as nasal stinging and burning, sneezing, unpleasant taste, and epistaxis. The medication has an inconvenient dosing regimen, requiring administration four times daily Drug topics September 2015 DrugTopics.com

8 continuing education table 4 Ophthalmic medications for the treatment of allergic conjunctivitis Drug class Drugs Availability Comments Antihistamines Emedastine Prescription only Alcaftadine Mast cell stabilizers Cromolyn Lodoxamide Prescription only Full response may be delayed from up to 4 to 6 weeks of treatment. Nedocromil Best if used prophylactically when exposure to the offending Pemirolast allergen causing allergic conjunctivitis symptoms can be anticipated. Frequent dosing (4 times daily with lodoxamide and pemirolast, 4 to 6 times daily with cromolyn), except for nedocromil (twice daily). Antihistamine + mast cell stabilizer Azelastine Epinastine Ketotifen Olopatadine Bepotastine Prescription; ketotifen available OTC; olopatadine also available as intranasal spray Azelastine and olopatadine also available in intranasal formulation. Decongestants Naphazoline OTC Limit use to <10 days to avoid rebound symptoms. Antihistamine + decongestant Naphazoline + pheniramine OTC Limit use to <10 days to avoid rebound symptoms. NSAIDs Ketorolac tromethamine Prescription only May take up to 2 weeks for maximum effect. Corticosteroid Dexamethasone Prescription only Reserved as last-line pharmacotherapy option for treatment Loteprednol of severe allergic conjunctivitis because of risk of increased Prednisolone intraocular pressure, formation of cataracts, and increased risk of ocular infections. Abbreviations: NSAID, nonsteroidal anti-inflammatory drug; OTC, over the counter. Source: Ref 1,6 Several mast cell stabilizers are available in ophthalmic formulations for the treatment of allergic conjunctivitis (Table 4). 1,6 The full response to ophthalmic mast cell stabilizers may be delayed from up to four to six weeks of treatment, therefore these medications are not particularly useful in treating acute symptoms of allergic conjunctivitis. More often, ophthalmic mast cell stabilizers are used prophylactically when exposure to the offending allergen causing allergic conjunctivitis symptoms can be anticipated. 1,6 Intranasal anticholinergics Currently, ipratropium is the only intranasal anticholinergic agent that is indicated for the treatment of allergic rhinitis. The only symptom of allergic rhinitis that this agent effectively treats is rhinorrhea. 1 This medication does not cross the blood-brain barrier because of its chemical structure; therefore, it has minimal systemic anticholinergic effects. Adverse effects include nasal dryness, mild epistaxis, and headache. 1,14 The disadvantage of intranasal ipratropium is an inconvenient dosing regimen, requiring administration two to four times daily, and lack of efficacy for the other symptoms of allergic rhinitis. It is typically reserved for combination therapy with other medications such as antihistamines or for the management of nonallergic rhinitis when rhinorrhea is the primary symptom. Ophthalmic nonsteroidal anti-inflammatory drug Ophthalmic ketorolac is a topical nonsteroidal anti-inflammatory drug (NSAID) used to treat the ocular itching of allergic conjunctivitis. The advantage of using an ophthalmic NSAID as compared to some other ophthalmic agents used to treat allergic conjunctivitis is that ophthalmic ketorolac does not cause the formation of cataracts. However, ophthalmic ketorolac is not as effective as some ophthalmic antihistamines, and up to two weeks of treatment may be required before the full effect is realized. 6 Omalizumab Omalizumab is a monoclonal antibody that binds to IgE, blocking IgE interaction with mast cell and basophil receptors. This agent is FDA-indicated for the treatment of moderate to severe persistent asthma caused by an aeroallergen that is not effectively controlled by inhaled corticosteroids and other medications, but is not currently FDA-approved for the treatment of allergic rhinitis. 20 However, research has shown that omalizumab decreases all nasal symptoms in adult and adolescent patients with allergies to birch and ragweed pollens. 8 Omalizumab is administered by subcutaneous injection every two to four weeks. Because of a risk of anaphylaxis associated with the medication, administration of omalizumab is limited to healthcare settings with healthcare providers who are prepared to manage life-threatening anaphylaxis reactions. 20 Allergen immunotherapy Allergen immunotherapy involves administration of gradually increasing amounts of allergen in patients with a confirmed IgEmediated allergic rhinitis. 2,8 The goal of this process is to increase immune tolerance to the allergen that causes the symptoms of allergic rhinitis. Administration of allergen immunotherapy can be either through the subcutaneous or sublingual route. Subcutaneous administration of allergen immunotherapy must be performed at regular intervals in a physician s office, while DrugTopics.com September 2015 Drug topics 57

9 Continuing Education MtM essentials FoR allergic RHinitiS ManageMent sublingual allergen immunotherapy is administered daily at home. There are three FDA-approved sublingual tablets available for allergen immunotherapy at the time of writing (five-grass pollen [Oralair], Timothy grass pollen [Grastek], and ragweed pollen [Ragwitek]). 21 Allergen immunotherapy is a costly and lengthy process, as the typical duration of therapy lasts from 3 to 5 years. 2 The effect of therapy is delayed; therefore, patients will not experience immediate relief of symptoms. This therapy also carries the risk of rare but serious adverse effects, including anaphylaxis. Due to this risk of anaphylaxis, the first dose of sublingual immunotherapy and every dose of subcutaneous immunotherapy should be administered at a healthcare office so that the patient may be observed for reaction and can be treated in case of anaphylaxis. 2 Additionally, it is a manufacturer recommendation that patients who are prescribed sublingual allergen immunotherapy tablets should also be prescribed self-injectable epinephrine in case of anaphylaxis. 21 Due to the risk for systemic reactions, subcutaneous allergen immunotherapy should not be used in patients with uncontrolled asthma, and sublingual allergen immunotherapy is contraindicated in patients with severe, unstable, or uncontrolled asthma. 2 Allergen immunotherapy is reserved for patients with confirmed IgE-mediated allergic rhinitis who have had an inadequate response to pharmacologic therapy with or without nonpharmacologic allergen avoidance strategies. 2 conclusion Various methods for the management of allergic rhinitis in adults are available, including nonpharmacologic treatment and prescription and over-the-counter medications. Nonpharmacologic allergen avoidance methods should be incorporated in all treatment regimens; however, this approach is often not suffi cient as monotherapy and may need to be combined with pharmacologic treatment. The medication classes used to treat allergic rhinitis differ in efficacy, route of administration, and adverse effect profile. Pharmacists should be knowledgeable on the differences among the various medications to help patients and prescribers choose the most appropriate medication based on patient-specific factors. For immediate cpe credit, take the test now online at Once there, click on the link below Free CPE Activities test questions 1. Which of the following symptoms of allergic rhinitis is more significant during the late phase response? a. Sneezing b. Nasal pruritus c. Nasal congestion d. Rhinorrhea 2. Which of the following are typical allergens that cause seasonal allergic rhinitis? a. Dust mites b. Plant pollen c. Pet dander d. Both A and C 3. Which symptom may suggest that a patient is suffering from the common cold rather than allergic rhinitis? a. Sneezing b. Rhinorrhea c. Nasal congestion d. Sore throat 4. Allergic rhinitis is associated with which of the following complications? a. Otitis media b. Sinusitis c. Nasal polyposis d. All of the above 5. The goal(s) of allergic rhinitis treatment include which of the following? a. Minimize the frequency and severity of symptoms b. Use pharmacotherapy to cure allergic rhinitis c. Prevent reduced productivity or missed days at work d. Both A and C 6. What is an appropriate allergen avoidance method to suggest for a patient who is allergic to dust mites? a. Avoid outdoor activities in the spring. b. Keep house and car windows closed. c. Wash bedding every one to two weeks at 131 to 140 F. d. Tightly seal all stored foods. 7. Which of the following are considered firstline therapy options for the treatment of allergic rhinitis? a. Intranasal corticosteroids b. Oral antihistamines c. Allergen avoidance methods d. All of the above 8. Intranasal corticosteroids are effective in treating which symptoms of allergic rhinitis? a. Sneezing, itching, rhinorrhea, nasal congestion, and ocular symptoms b. Sneezing, itching, and rhinorrhea only c. Congestion only d. Intranasal corticosteroids are not effective in treating symptoms of allergic rhinitis 9. A 27-year-old man comes to your pharmacy asking for recommendations for an OTC medication to treat his allergic rhinitis. He states he has seasonal allergies during the spring and has tried allergen avoidance methods as much as possible, but he still experiences symptoms of sneezing, rhinorrhea, and nasal congestion. He states that he would prefer to take a pill instead of using a nasal spray and wants to use something that will work as soon as possible. The patient states that besides suffering from allergic rhinitis, he is otherwise healthy. Which of the following would be a suitable first-line medication to recommend for this patient? a. Loratadine b. Fluticasone propionate nasal spray c. Phenylephrine d. Diphenhydramine 10. Which of the following statements is true regarding first-generation antihistamines? a. They are lipid soluble and able to cross the blood-brain barrier, causing CNS and anticholinergic adverse effects. b. They are preferred over second-generation antihistamines for the treatment of allergic rhinitis. c. They are always dosed once daily. d. All of the above 11. Which symptom(s) of allergic rhinitis does pseudoephedrine effectively treat? a. Nasal pruritus b. Nasal congestion c. Sneezing d. Ocular itching 58 Drug topics September 2015 DrugTopics.com

10 continuing education References 1. Apgar DA. Allergic rhinitis. In: Chisholm-Burns MA, Wells BG, Schwinghammer TL, Malone PM, Kolesar JM, Dipiro JT, eds. Pharmacotherapy: Principles and Practice. 3rd ed. New York: McGraw-Hill; 2013: Seidman MD, Gurgel RK, Lin SY, et al; Guideline Otolaryngology Development Group; AAO-HNSF. Clinical practice guideline: allergic rhinitis. Otolarlaryngol Head Neck Surg. 2015;152(1 Suppl):S1-S Blaiss MS. Allergic rhinitis: direct and indirect costs. Allergy Asthma Proc. 2010;31: Rosenwasser LJ. Current understanding of the pathophysiology of allergic rhinitis. Immunol Allergy Clin N Am. 2011;31: Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol. 2001;108(1 Suppl):S2-S8. 6. Hunter ML, Hilaire ML. Ophthalmic disorders. In: Chisholm-Burns MA, Wells BG, Schwinghammer TL, Malone PM, Kolesar JM, Dipiro JT, eds. Pharmacotherapy: Principles and Practice. 3rd ed. New York: McGraw-Hill; 2013: Wallace DV, Dykewicz MS, Bernstein DI, et al; Joint Task Force on Practice; American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of rhinitis: an updated practice parameter [erratum in J Allergy Clin Immunol. 2008;122:1237]. J Allergy Clin Immunol. 2008;122(2 Suppl):S Bousquet J, Khaltaev N, Cruz AA, et al; World Health Organization; GA 2 LEN; AllerGen. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA 2 LEN and AllerGen). Allergy. 2008;63(Suppl 86): Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet. 2011;378: Allan GM, Arroll B. Prevention and treatment of the common cold: making sense of the evidence. CMAJ. 2014;186: Steckelberg JM. I seem to get a cold every spring and fall. I m wondering if these colds are really seasonal allergies. How can I tell? Mayo Clinic website. www. mayoclinic.org/diseases-conditions/common-cold/ expert-answers/common-cold/faq Published December 24, Accessed July 22, Mandhane SN, Shah JH, Thennati R. Allergic rhinitis: an update on disease, present treatments and future prospects. Int Immunopharmacol. 2011;11: Platts-Mills TAE. Allergen avoidance. World Allergy Organization website. Published December Accessed July 22, Sur DK, Scandale S. Treatment of allergic rhinitis. Am Fam Physician. 2010;81: Bielory BP, Perez VL, Bielory L. Treatment of seasonal allergic conjunctivitis with ophthalmic corticosteroids: in search of the perfect ocular corticosteroids in the treatment of allergic conjunctivitis. Curr Opin Allergy Clin Immunol. 2010;10: Drugs for allergic disorders. Treat Guidel Med Lett. 2010;8: Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol. 2010;70: Hamrah P, Dana R. Allergic conjunctivitis: management. In: Post T, ed. UpToDate. Waltham, Mass.: Up- ToDate; Accessed August 5, Singulair (montelukast) prescribing information. Whitehouse Station, NJ: Merck & Co., Inc.; Xolair (omalizumab) prescribing information. South San Francisco, CA: Genentech, Inc.; Creticos PS. Sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; Accessed August 5, test questions 12. What is the disadvantage of treating nasal congestion related to allergic rhinitis with phenylephrine instead of pseudoephedrine? a. Phenylephrine must be purchased from behind the pharmacy counter. b. Limit on the daily and monthly quantities that a patient may purchase c. The efficacy at recommended OTC doses is minimal in terms of relieving nasal congestion. d. Both A and C 13. Which of the following medications to treat allergic rhinitis should be avoided in a 56-year-old man with uncontrolled hypertension? a. Mometasone nasal spray b. Pseudoephedrine c. Intranasal cromolyn d. Montelukast 14. What counseling point should be made to a patient who is using mometasone nasal spray to treat allergic rhinitis? a. It is considered a last-line pharmacotherapy option to treat allergic rhinitis because of the risk of systemic adverse effects associated with corticosteroid use. b. The spray should be pointed away from the nasal septum when administering doses to prevent the adverse effects of epistaxis and septal perforation. c. Use must be limited to no more than three consecutive days because of the risk of developing rhinitis medicamentosa. d. It only treats the allergic rhinitis symptom of nasal congestion. 15. What is the advantage of using intranasal cromolyn to treat allergic rhinitis? a. Available OTC b. Convenient, once-daily dosing c. Tolerable adverse effect profile d. Both A and C 16. Which of the following ophthalmic medications to treat allergic conjunctivitis would be most appropriate to use in a patient with cataracts? a. Ophthalmic ketorolac b. Ophthalmic prednisolone acetate c. Ophthalmic dexamethasone sodium phosphate d. All of the above are appropriate to use in a patient with cataracts 17. Which ophthalmic medication to treat allergic conjunctivitis must be limited to less than 10 days of use to prevent rebound symptoms? a. Ophthalmic ketorolac b. Ophthalmic naphazoline + pheniramine c. Ophthalmic prednisolone acetate d. Ophthalmic dexamethasone sodium phosphate 18. Why is omalizumab required to be administered by a healthcare professional in a healthcare setting? a. Omalizumab must be administered intravenously. b. The medication can cause anaphylaxis. c. The medication can cause neuropsychiatric adverse effects. d. Both A and C 19. A patient is experiencing rhinitis medicamentosa due to overuse of oxymetazoline nasal spray. What method can be used to treat this rebound nasal congestion? a. Discontinue or taper down use of oxymetazoline nasal spray. b. Continue use of oxymetazoline nasal spray to treat the congestion. c. Use an intranasal corticosteroid to treat allergic rhinitis symptoms. d. Both A and C 20. What is the disadvantage of subcutaneous allergen immunotherapy to treat allergic rhinitis? a. Frequent healthcare visits b. Lengthy process c. Delayed effect of therapy d. All of the above DrugTopics.com September 2015 Drug topics 59