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Itching to Improve Allergic Rhinitis Management? Tips for Patient Care

INTRODUCTION

Disorders of the eyes, ears, nose, and throat are among the most common complaints of people seeking self-care remedies in community and ambulatory pharmacies. Allergic rhinitis and related conditions are often the source of some or all of these characteristic symptoms: nasal congestion, clear rhinorrhea (runny nose), nasal itching, or sneezing, sometimes accompanied by allergic conjunctivitis (red and watery eyes without signs of infection). Many of these symptoms can be managed empirically with nonprescription agents, including several agents previously available by prescription. For patients who do not respond to these drugs and for those with severe symptoms, new therapeutic approaches have emerged from medical research and are now available through physicians specializing in allergy/immunology.

This article reviews allergic rhinitis; special attention is paid to the epidemiology and etiology of allergic rhinitis, reasons the condition has increased in incidence in recent decades, advances in therapeutic management and how the pharmacist can best help patients with allergic rhinitis, and medication categories used to manage its symptoms and treat its causes.

EPIDEMIOLOGY AND ETIOLOGY OF ALLERGIC RHINITIS

Allergic rhinitis, also known by the lay term hay fever, has many different manifestations and permutations that affect the presenting clinical symptoms and scenarios. These differing clues provide valuable insights into the optimal ways to manage a specific patient’s condition and minimize its effects on his or her health-related quality of life. They also point to genetic, environmental, and other risk factors.

Epidemiologic studies show that allergic rhinitis is the sixth most common disease of adults and children in the United States (U.S.), affecting 60 million Americans; it is the most common chronic condition affecting children. Direct health care costs total $2 to $5 billion annually.1,2 Adults and children with allergic rhinitis have an increased risk of several associated conditions, including asthma, chronic rhinosinusitis, otitis media, nasal polyposis (polyps), atopic dermatitis, sleep-disordered breathing, conjunctivitis, respiratory infections, and orthodontic malocclusions (Table 1).

Table 1. Conditions Frequently Occurring Concomitantly in Patients with Allergic Rhinitis
Condition Description
Asthma Respiratory condition marked by spasms in the bronchi of the lungs, causing difficulty in breathing
Chronic rhinosinusitis Sinuses become inflamed and swollen, which interferes with drainage, leading to mucous buildup
Otitis media Inflammation of the middle ear characterized by an accumulation of infected fluid
Nasal polyposis Soft, painless, benign growths on the nasal passage lining or sinuses
Atopic dermatitis Also known as eczema; a skin condition characterized by red, itchy outbreaks
Sleep-disordered breathing Sleep disturbance characterized by abnormal breathing patterns that may result from obstructed nasal passages
Conjunctivitis Inflammation of the transparent membrane that lines the eyelid and covers the eye
Respiratory infections Acute infections involving the nose, sinuses, pharynx, larynx, trachea, bronchi, or lungs
Orthodontic malocclusions Misalignment between the upper and lower teeth as a result of mouth breathing secondary to nasal stuffiness

Allergic rhinitis may be seasonal (occurring in spring or fall when causative allergens are present in the environment) or persistent (formerly called perennial; caused by allergens present in a patient’s environment throughout the year). Seasonal allergens are often produced by trees, grasses, or weeds. Year-round allergens include those occurring indoors, such as those produced by house dust mites (fecal proteins), pets (dander, saliva), molds, and cockroaches. Some patients react to multiple allergens, leading to complex presentations of year-round symptoms exacerbated by seasonal allergens.

Family history is important in allergic rhinitis, as risks are increased when one parent is atopic and even greater when both parents are affected.3 Allergic rhinitis is mediated through immunoglobulin E (IgE) reactions to allergens; these can occur in the mast cells of the nasal passages or in circulating basophils. Once sensitized to an allergen, a patient re-exposed to the causative factor experiences marked histamine release and a complex cascade of immunologic factors that produce the characteristic symptoms of allergic rhinitis. Many different factors are involved in this cascade, providing numerous targets for therapeutic intervention aimed at reducing symptoms.

The allergenic response comprises both an immediate release of mast cell mediators and a late- phase reaction. The immediate reaction is an IgE-mediated response by mast cells to a specific allergen that involves the rapid release of preformed mediators such as histamine, neutrophil and eosinophil chemotactic factors, kinins, and N-alpha-tosyl L-arginine methyl esterase. The cells also generate and release other factors, including leukotrienes, thromboxanes, and platelet- activating factor. During this immediate reaction, symptoms include clear rhinorrhea (nasal drainage), nasal obstruction and itching, and sneezing.4-8

Approximately one-half of patients with allergic rhinitis also have a late-phase reaction 4 to 8 hours later that results from release of cytokines from mast cells and T-lymphocytes. These factors are responsible for the chronic symptoms of allergic rhinitis, including nasal congestion. Late-phase symptoms peak at 12 to 24 hours after acute allergen exposure.

Over time, nasal mucosa become chronically inflamed and hyperresponsive in patients with allergic rhinitis, leading to nonspecific irritability and reactions to lower amounts of allergens. Related conditions can develop, or patients can become sensitive to additional allergens.9,10

IMPROVING THE MANAGEMENT OF ALLERGIC RHINITIS

For allergy sufferers, daily or near-daily symptoms have a significant impact on quality of life.11,12 Still, some health professionals may view allergic rhinitis as a minor annoyance that is easily treatable. In fact, as many as 60% of people with allergies continue to have symptoms despite treatment.13

In a survey of 1001 allergy sufferers (500 adults and 501 children [survey completed by parents for the children]), 75% to 80% considered their symptoms to be moderate to severe.12 More than 50% of respondents reported impairment of daily activities and/or increased levels of distraction, irritability, and fatigue due to allergy symptoms, and 90% reported disruption of sleep (for 40%, sleep disruption was significant).12

In addition to its impact on quality of life, allergic rhinitis is commonly associated with serious comorbidities such as asthma and lower respiratory infection.14 Yet, it is still regarded by many as a “trivial” condition.15,16

In the U.S. and other developed countries, the incidence of allergic rhinitis has risen in recent decades. Allergic rhinitis of several human atopic disorders whose evolutionary origins are unclear; several theories have been put forth by medical anthropologists as to why people have evolved with the capacity to react to common substances in their everyday environments, even to the point of developing life-threatening responses such as anaphylaxis and asthma. In considering this reactivity, it is important to remember how much “cleaner” today’s world is than just a few centuries ago — remarkable progress has been made in sanitation and eradication of microorganisms and helminths and other internal parasites.

Helminths remain common in most of the developing world. Children in these areas frequently have internal parasites and, as a result, very high IgE levels — 100 times higher than levels considered normal in developed countries and also 10 times higher than an American child with levels elevated by allergen exposures. However, children in the developing world have far less atopic disease than is currently seen in developed countries, perhaps indicating that the ultrahigh IgE levels are countered by other factors in the immune system to prevent excessive responses to allergens in the person’s immediate environment.17,18

The hygiene hypothesis is another explanation for the increase in atopic disorders in the developed world. Studies have shown that children raised on farms where they are exposed to animals have less atopic disease. Others have proposed that increased use of vaccines and antibiotics has reduced children’s exposures to microorganisms that in the past might have muted atopic responses, but this idea has not been confirmed using epidemiologic and other data.19,20

Other ideas relate to changes in construction patterns, with more energy-efficient homes, schools, and offices; tighter construction conserves energy but also traps indoor allergens to a greater degree than in older homes with open windows and more ventilation. Increased use of wall-to-wall carpeting and cool-water laundering likely also contribute to the increase in allergens present in the indoor environment.21 Such developments might explain increases in allergic rhinitis secondary to indoor allergens, but it does not address the outdoor allergens from trees, grasses, and weeds.

Diagnosis

The diagnosis of allergic rhinitis is made through a combination of patient history and symptoms, allergy testing, and, in rare cases, imaging. Patients whose symptoms are well managed empirically do not generally need further testing. According to a clinical practice guideline approved by the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO/HNSF), allergic rhinitis is diagnosed when patients present with a history and physical examination consistent with an allergic etiology and at least 1 of the following symptoms is present: nasal congestion, runny nose, itchy nose, or sneezing. The guideline advises clinicians against imaging of the sinuses in patients who can be diagnosed on the basis of history and examination.1

Children with allergic rhinitis often present with the classic signs and symptoms. They may also have allergic “shiners,” lower eyelid discoloration and edema, and altered breathing patterns. Shiners are transverse creases of the nose caused by frequent rubbing of the nose, a gesture sometimes called the “allergic salute.” Related symptoms include darkening and puffiness of the lower eyelid caused by venous pooling. Inflammation of the adenoids can cause children to breathe through the mouth rather than the nose; postnasal drip can produce a nonspecific clearing of the throat.1

When patients with the above presenting symptoms do not respond to empiric treatment, they are generally referred to an allergist or other clinician who can perform and interpret allergy testing. The AAO/HNSF guideline also recommends testing of patients when the diagnosis is uncertain or when a causative allergen must be identified so that targeted therapy can be instituted.1

IgE-specific testing uses either direct exposure of the skin to common allergens using skin pricks or intradermal injections. Patients must discontinue oral and intranasal antihistamines and other interfering medications for various time periods before skin testing.22 Blood tests can be used for patients with eczema, severe asthma, or other conditions that require uninterrupted pharmacotherapy.

When specific allergens produce reactions in a patient, preventive strategies can be implemented. Immunotherapy can also be started to reduce the patient’s sensitivity to the causative allergen.

Prevention and immunotherapy

As with many conditions, prevention of symptoms of allergic rhinitis is preferable to life-long treatment with medications that are not universally effective. Patients have 2 options for prevention of allergic rhinitis: avoiding allergens and decreasing the body’s response to them.

Avoidance strategies are possible only when specific allergens that can be avoided or eliminated have been identified through IgE-specific testing. Guidelines and published literature vary considerably in their interpretations of the evidence supporting specific avoidance strategies. Several interventions based on causative allergens are frequently recommended: removal of pets, use of high-efficiency particulate air (HEPA) filtration systems, use of impermeable bed covers that contain allergens in the mattress, and application of chemical agents for killing house dust mites (acaricides) to fabrics and mattresses in the home. Combining such strategies produces the best results.1

Decreasing the body’s response to allergens that cannot be eliminated involves the process of hyposensitization through allergen-specific immunotherapy. Subcutaneous immunotherapy (SCIT) using many different allergens has been used for more than a century to reduce or eliminate symptoms of allergic rhinitis caused. By exposing a patient to gradually increasing amounts of the causative allergen, the body’s immune tolerance can be increased. Usually administered in clinics or physician offices, SCIT is safe and well tolerated, although local and systemic reactions are possible, including anaphylaxis.1

Contemporary research has yielded immunotherapy products that can be administered sublingually; availability of sublingual immunotherapy (SLIT) products greatly increases the utility of hyposensitization by eliminating the need for frequent physician office visits for subcutaneous allergen administration and/or self-injection of allergens at home.1

At the time this monograph was prepared, 4 SLIT products were approved by the U.S. Food and Drug Administration (FDA). The products are indicated for use by patients with documented, IgE-mediated reactions to house dust mite (Odactra), mixed grass pollens (Oralair), Timothy grass and cross-reactive grass pollens (Grastek), and ragweed (Ragwitek).

Evidence regarding the relative efficacy and safety of SCIT versus SLIT is inconclusive at this time.23 SCIT is generally continued for up to 5 years, creating a substantial time cost for a treatment that is often administered under medical supervision. The newer SLIT products, generally self-administered in patients’ homes following an initial dose in a medical setting, have been associated with local adverse effects such as mouth and ear pruritus, mouth edema, and throat irritation, as well as systemic problems such as nausea and mild abdominal pain. Patients using SLIT should have auto-injectable epinephrine available in the home.24,25

Nonpharmacologic treatments and complementary medicine

Generally used in combination with other therapies, nonpharmacologic products can be recommended to patients with allergic rhinitis, including nasal rinses and strips.

Irrigation of the nasal passages with saline is useful for removing allergens and preparing the membranes for administration of intranasal medications. A variety of neti pots and other devices for facilitating nasal irrigation with saline are available. These should be used as instructed in product labeling, including use of distilled or boiled water as recommended, as tap water is not reliably safe for this purpose. Nasal sprays can also be used to loosen and eliminate mucus and allergens.

Nasal strips are useful when congestion is a primary symptom of allergic rhinitis. By physically opening the nares and permitting the patient to breathe more quietly and easily, nasal strips can be useful during exercise and while sleeping. Nasal strips also offer a nonsurgical option in patients with sleep-disordered breathing who have allergic rhinitis or anatomic abnormalities.26

Dietary supplements are not recommended in the AAO/HNSF guideline. Butterbur has been used by some patients; its active ingredient, petasin, has antileukotriene and antihistamine activity. On the basis of limited clinical evidence available in a systematic review and several later randomized controlled trials, the AAO/HNSF guideline states that acupuncture is an “option” (not as strong as a “recommendation”).1,27,28

Management of allergic rhinitis with over-the-counter products

Empiric, symptomatic treatment using the wide variety of medications available over-the-counter (OTC) or by prescription is the most common approach to treating allergic rhinitis. This section provides a general overview of therapy for patients according to demographic characteristics, limited clinical information likely to be available to the community and ambulatory pharmacist, and presenting symptoms. Specific agents in the pharmacologic categories are discussed in more detail in the next section of this program.

When patients present in the pharmacy with symptoms of nasal congestion, runny nose, itchy nose, sneezing, and/or red, watery eyes, the pharmacist should first take a brief history. Questions that pharmacists should ask patients include:

  • Do your symptoms occur throughout the year or in a particular season?
  • Are symptoms worse in particular locations or areas of your home or work/school, or when you are outdoors?
  • Is one of your symptoms worse than the others?
  • Would you describe your symptoms as mild, moderate, or severe? Do they interfere with your work or other daily activities such as exercise or studying?
  • Have you ever been tested by a physician for allergies (if so, what were the results?), or have you ever been told by a health professional that you were allergic to pets, pollen, or indoor pests such as cockroaches or house dust mites?
  • Do you have any food or drug allergies?
  • Do you have any of these conditions: high blood pressure, asthma, atopic dermatitis, sleep-disordered breathing, conjunctivitis (“red or pink eye”), rhinosinusitis (inflamed nasal or sinus passages), or otitis media?
  • Have you used medications to treat your symptoms in the past? If so, what were the results?

For young children, a specific age should be determined, as many products are not approved for use in certain pediatric age groups. For women of child-bearing age, ask if they are or might be pregnant, as this may be an important contraindication for some drugs.

Based on this information, a therapeutic plan can be designed empirically using OTC products and environmental interventions. Patients with any or several of the above symptoms with no other known cause can be presumed to have allergic rhinitis and managed as follows1,25:

  • If symptoms are seasonal, treatment can be limited to periods of likely exposure to known allergens (e.g., trees and grasses in the spring, weeds in late summer and fall).
  • If symptoms are persistent, treatment should continue throughout the year.
  • If the patient has a known sensitivity to a specific allergen, discuss whether avoidance measures (e.g., removing pets from homes, removal of carpeting) and environmental controls (e.g., HEPA filtration devices, bed covers, acaricides) have been considered or used.
  • Patients with a primary symptom of nasal congestion can be managed with intranasal steroids (INS) or oral decongestants if no contraindications (e.g., minimum age limitations, pregnancy, high blood pressure) are present. In those not responding to a product in the first category chosen, dosages can be adjusted within OTC ranges, an alternative agent in the same category can be tried, or an agent in the other category can be added. Those with severe congestion can try a trial of topical (intranasal) decongestants for 3 to 5 days, but longer use should be avoided because of rebound symptoms upon medication discontinuance. If control remains poor, the patient should be referred for medical evaluation (e.g., allergy testing) and prescription agents or immunotherapy.
  • If sneezing, nasal itching, and/or rhinorrhea are the primary symptoms, an oral second- generation (non-sedating) antihistamine or INS can be recommended as initial therapy. If the patient does not respond to the first category chosen, dosages can be adjusted, an alternative agent in the same category can be tried, or a trial of therapy with a product from the other category can be started. Using INS and oral antihistamines in combination has not been beneficial in clinical trials and is not recommended for children or adults.29-31 Patients not responding adequately to any of these approaches should be referred for medical care (e.g., allergy testing, prescription medications, immunotherapy).
  • Oral second-generation antihistamines remain first-line therapy for patients with mild symptoms because of their low cost and minimal adverse effects.
  • INS products and intranasal antihistamines are first-line agents for patients with moderate-to-severe symptoms.
  • Ocular antihistamines can be recommended for patients older than minimum ages on product labeling who have symptoms of allergic conjunctivitis that are not relieved by systemic therapy.

Adherence to therapy

Throughout therapy, adherence is very important in the management of allergic rhinitis. Patients should be educated on the need to use medications as directed. Therapeutic benefits of some agents — INS products in particular — are not evident immediately, and patients need to know to administer the product for an adequate time period to assess its effectiveness. Medication administration technique is also very important; correct use of intranasal and ocular formulations should be demonstrated for patients and their comprehension ensured.

Since many patients have both an early-phase and a late-phase reaction to allergens, medications need to be taken regularly during allergy season (or year round, in those with persistent allergic rhinitis). Patients with seasonal symptoms should understand when to start and stop therapy, and those with persistent symptoms must know to continue treatment even if they feel better.

Motivational interviewing techniques can be used during educational sessions to explore patient perceptions of therapeutic goals, comprehension of the importance of treatment and administration technique, efficacy of agents for allergic rhinitis, occurrence of adverse drug effects that are limiting use of medications, financial or other obstacles that are affecting adherence, and patient satisfaction with treatment.

MEDICATION CATEGORIES FOR ALLERGIC RHINITIS

Translating the general recommendations presented in the last section into selection of a suitable product in the OTC aisle can be a difficult chore, even for a knowledgeable, sophisticated consumer. Patients can also overlook the availability of nonprescription products containing the decongestant pseudoephedrine, since these are stocked behind the pharmacy counter because of their potential for conversion into methamphetamine, a drug of abuse. Add in the frustration of determining when to seek medical care for allergy testing, prescription medications, or immunotherapy, and it is easy to see why many consumers have improved outcomes when pharmacists are involved in initial decisions and product selection.

In this section, medications and products available OTC or by prescription are reviewed by pharmacologic category (Table 2).1,32-60

Medication classes and individual agents Symptom coveragea Comments
  Congestion Rhinorrhea Sneezing Nasal itching Brand name Generic available? Rx or OTC? Other notes
Intranasal steroids +++ +++ +++ +++ Best class for initial therapy of seasonal and perennial allergic rhinitis; less effective for episodic use, as drug must be present when allergen is presented
Triamcinolone acetonide         Nasacort Allergy 24HR Yes OTC  
Budesonide         Rhinocort Allergy Yes OTC  
Flunisolide           Yes Rx  
Fluticasone propionate         Flonase Allergy Relief Yes  OTC Also indicated for allergic ocular symptoms
Fluticasone furoate         Flonase Sensimist Allergy Relief No OTC Also indicated for allergic ocular symptoms
Mometasone furoate         Nasonex Yes Rx  
Beclometasone dipropionate         Qnasl (nasal aerosol) No Rx  
Ciclesonide         Omnaris (aqueous nasal spray) and Zetonna (HFA nasal aerosol) No Rx  
Oral antihistamines + ++ ++ ++ Moderately effective for seasonal, perennial, and episodic allergic rhinitis
Cetirizine         Zyrtec Allergy Yes OTC Prescription-only products also available
Levocetirizine         Xyzal Allergy 24 HR Yes, but Rx only OTC  
Fexofenadine         Allegra Allergy Yes OTC Prescription-only products also available
Loratadine         Claritin Yes OTC  
Desloratadine         Clarinex No Rx  
Intranasal antihistamines ++ ++ ++ ++ Similar efficacy to intranasal steroids for seasonal and episodic allergic rhinitis; products other than Astepro are not approved for perennial cases
Olopatadine         Patanase (intranasal); Pataday (ophthalmic) Yes Rx  
Azelastine         Astelin, Astepro (intranasal); Optivar (ophthalmic) Yes Rx  
Azelastine plus fluticasone         Dymista Yes Rx  
Oral decongestants +++       Useful additive therapy for those with unrelieved or moderate-to-severe congestion
Pseudoephedrine         Sudafed, others Yes Behind the counter Available as "behind the counter" product as single agent and in combination with oral antihistamines
Phenylephrine         Various products in combination with antihistamines Yes OTC Efficacy at OTC doses is questionable
Topical decongestants         Limit use to 3–5 days
Oxymetazoline (nasal) +++       Afrin, others Yes OTC Ophthalmic formulation also marketed for eye symptoms
Tetrahydrozoline (nasal) +++       Tyzine No Rx Ophthalmic formulation also marketed for eye symptoms
Other agents          
Montelukast (oral) + + + + Singulair Yes Rx Leukotriene receptor antagonists are useful primarily in patients who also have asthma
Ipratropium (intranasal)   +++     Atrovent Yes Rx Third-line therapy for runny nose in perennial rhinitis
Cromolyn (intranasal) + + + +   Yes OTC Mast cell stabilizer used as third-line agent; administration and dosing schedule present challenges
Abbreviations: HFA, hydrofluoroalkane; OTC, over the counter; Rx, prescription.
aPlus signs indicate relative effectiveness for each symptom.

Intranasal corticosteroids

For many patients with allergic rhinitis, INS products have replaced oral antihistamines as first- line treatment. Intranasal triamcinolone acetonide, fluticasone propionate, and fluticasone furoate are now available in OTC products indicated for use in pediatric and adult patients with allergic rhinitis. Any of these is suitable for first-line treatment of patients with allergic rhinitis in whom symptoms are moderate or severe or presenting symptoms are sneezing, nasal itching, or rhinorrhea. INS products are also a suitable alternative to decongestants in patients with nasal congestion as a primary symptom and in those with only mild symptoms.

Preference studies conducted among patients have demonstrated advantages of intranasal fluticasone furoate in those who find the taste and smell of fluticasone propionate formulations bothersome and in those who complain that the products drip into their throats or run out of their noses.61,62 A Japanese study reported similar findings in a comparison of fluticasone furoate with mometasone furoate intranasal sprays.63

In addition to the OTC products containing INS, numerous other intranasal corticosteroids indicated for allergic rhinitis are available by prescription (Table 2).1,32-41 Therapeutic effects of INS products are not immediate; patients with nasal congestion will not experience the immediate relief they might achieve with decongestants. Peak therapeutic benefits of INS therapy should be evident at 2 to 3 weeks after therapy begins.

INS products are contraindicated only in patients with a hypersensitivity to the medication or other components of specific formulations. Adverse effects of INS products are generally minor, such as sneezing, stinging, headache, and epistaxis. In the low doses used topically with INS, the major adverse effects observed with systemic corticosteroids, such as cataract formation, glaucoma, and bone mineral density changes, are uncommon. Suppression of growth by INS is a concern in pediatric patients whose epiphyseal plates have not closed. Growth should be monitored and the lowest effective doses should be used to minimize this effect.

Oral, intranasal, and ocular antihistamines

Antihistamines, long the mainstay of treatment of allergic rhinitis, are available in 3 useful formulations: oral, for patients needing systemic action; intranasal, for patients in whom topical application is effective for congestion, rhinorrhea, sneezing, and nasal itching; and ocular, for patients with allergic conjunctivitis. Because of major differences in use scenarios and adverse effects for these 3 routes of administration, they should be considered separately when developing a therapeutic plan.

Oral antihistamines have been available OTC for many years and are familiar agents to pharmacists and patients. They are effective agents for treating most symptoms of allergic rhinitis, but their effects on congestion are less than for rhinorrhea, sneezing, and nasal itching. However, INS products that are now available without a prescription provide greater relief for these symptoms than do oral antihistamines, and they do so without producing sedation and other anticholinergic effects that are especially noticeable with first-generation antihistamines.

The question of relative sedative effects of the first- and second-generation antihistamines and of agents within these classes has been controversial.64,65 Analyses are further complicated since allergic rhinitis can produce sedation as a symptom of the disease. First-generation agents such as diphenhydramine produce distinct anticholinergic effects, including dry mouth, which can compromise oral health,66,67 and antihistamines are, in fact, used as hypnotics in some OTC products and clinical situations. However, a meta-analysis showed an absence of a sedative effect of diphenhydramine in published studies, while demonstrating statistically significant mild sedation with the second-generation (the “non-sedating”) agents.65

Currently, cetirizine is generally viewed as the most potent second-generation antihistamine (i.e., having the greatest effect at the recommended dose) but also as more sedating than other agents in this class.1 Given concerns about long-term anticholinergic burden and the adverse effects of strongly anticholinergic drugs in older adults (e.g., falls, dry mouth), first-generation antihistamines should be avoided as treatments for allergic rhinitis, especially in older adults.66,68

Two second-generation antihistamines are currently marketed in the U.S. as intranasal, prescription-only products. Azelastine is approved for both seasonal and persistent allergic rhinitis in children aged 6 years or older and adults. It is also available in a combination formulation with fluticasone that is approved for seasonal allergic rhinitis in those aged 12 years or older. Olopatadine is indicated for use in children aged 6 years or older and adults with seasonal allergic rhinitis.1

Both of these intranasal antihistamines must be dosed twice daily and can cause a bitter taste, epistaxis, somnolence, and headache.1 These factors argue toward using these products in patients with seasonal allergic rhinitis and in situations where exposure to known allergens can be predicted.

Numerous antihistamines are available in ocular formulations for treatment of allergic conjunctivitis. Most are prescription agents, including azelastine, cetirizine, and olopatadine. Ketotifen is available in OTC products. These are useful for patients in approved age ranges (as young as 3 years) with ocular symptoms of allergic rhinitis that are not resolved by other therapies.

Systemic and topical decongestants

For patients with nasal congestion as a primary symptom of allergic rhinitis and in those with congestion unrelieved by INS or antihistamine products, decongestants are very effective. Since congestion is usually a late-phase reaction, occurring several hours after allergen exposure, decongestants are better used on a scheduled basis during allergy seasons or times of known allergen exposure. Because of rhinitis medicamentosa that occurs with topical decongestants and the need for scheduled therapy, oral agents are highly preferred when decongestant therapy is indicated.

The need to dispense pseudoephedrine from “behind the pharmacy counter” was necessitated by diversion of the drug to manufacture illegal methamphetamine. This led to substitution of the less-effective phenylephrine in some combination products so that these could be available to consumers in nonpharmacy retail settings and from the OTC aisles of mass-merchandise stores when pharmacies are closed. However, the effectiveness of oral phenylephrine is questionable. In a phase 2 trial, phenylephrine in doses of 10 mg to 40 mg every 4 hours was not significantly better than placebo in relief of nasal congestion in adults with seasonal allergic rhinitis, and authors have been critical of continued use of this drug in OTC products.69-71

Oral pseudoephedrine is an effective decongestant. At higher doses, it raises the heart rate and blood pressure, but these effects are minimal when the drug is used at recommended doses.72 Stroke is a concern with pseudoephedrine in patients with hypertension and/or vasospasm.73 The drug should not be used during the first trimester of pregnancy because of its association with birth defects, and use at later times in pregnancy and during breastfeeding should be discouraged.

Topical decongestants such as oxymetazoline should be used only episodically and never for more than 3 to 5 days. If rhinitis medicamentosa develops, use can be tapered or stopped abruptly. Rebound congestion in this situation is difficult to manage, sometimes taking several weeks to subside.

Other agents

Cromolyn sodium, ipratropium bromide, and montelukast are additional agents used selectively in patients with allergic rhinitis.

Cromolyn sodium nasal spray is a challenging treatment for most patients. It acts directly on mast cells lining the nasal passages and must be present when the allergen is encountered. It is difficult to administer correctly, its onset of action is 2 to 4 weeks after therapy begins, and the drug must be used every 6 hours. All of these factors make cromolyn a third-line agent useful primarily in seasonal allergic rhinitis in patients whose responses to INS and antihistamine products are insufficient.

Ipratropium bromide is an anticholinergic prescription agent available for intranasal administration. Since it has no antihistaminic or anti-inflammatory activity, ipratropium is useful only for symptomatic relief; it is generally used in patients with rhinorrhea that is insufficiently managed with other agents.

The oral leukotriene receptor montelukast is approved by the FDA for treatment of seasonal allergic rhinitis in patients 2 years of age or older and for persistent allergic rhinitis in those 6 months of age or older. However, in clinical practice, its main utility is in patients with concomitant asthma and allergic rhinitis, and the AAO/HNSF guideline recommends that clinicians should not prescribe montelukast as primary therapy for allergic rhinitis because of efficacy and cost limitations. Safety also factors into the guideline recommendation, as neuropsychiatric effects have been associated with montelukast therapy, including aggression, depression, and suicidal ideation.1

Combination therapy

As mentioned above, combinations of the available medications are often needed for adequate management of allergic rhinitis. Therapy should be initiated with a single agent so that medications and doses effective for individual patients and their varying sets of symptoms can be identified. When symptoms are incompletely relieved, the general therapeutic rules of adding 1 agent at a time and “starting doses low and going slow” are good to follow in patients with allergic rhinitis. For patients with seasonal cases, it is also important to note which medications should be initiated before allergen exposure and which can be used once symptoms develop.

Pharmaceutical companies have marketed combination products for treatment of patients with allergic rhinitis. When cost-effective or needed to enhance adherence to therapy, fixed-dose combinations can be useful. However, these should be used only after effective agents and doses are identified.

In addition to the many OTC products combining antihistamines and decongestants, prescription products with azelastine plus fluticasone are available. The AAO/HNSF guideline makes these recommendations applicable to combining drug classes (as individual products) and use of fixed- dose combinations in patients with allergic rhinitis1:

  • When patients do not respond to or cannot tolerate INS, the most effective agent for addition is an intranasal antihistamine (e.g., prescription products combining azelastine plus fluticasone).
  • While commonly used, the combination of oral antihistamines plus INS offers little clinical benefit over INS alone.
  • If severe nasal congestion develops, a topical decongestant such as oxymetazoline can be used for a limited time period (3–5 days).
  • When patients dislike or cannot tolerate intranasal products, combination therapy with OTC oral antihistamines plus decongestants are the next best option.
  • If asthma or allergic conjunctivitis is present in patients with allergic rhinitis, therapy can be adjusted in favor of agents and routes of administration effective for the concomitant conditions.

CONCLUSION

Allergic rhinitis is a common condition whose incidence has risen in recent decades and whose pathophysiology is related to other diseases mediated through overresponse by the body to allergens. For those with allergic rhinitis, identification of a causative allergen is preferable to empiric therapy, but many patients seek relief on their own using OTC products. When an allergen is known, patients should take steps to remove its source from their homes and/or avoid contact.

When pharmacotherapy is indicated, recommended agents as outlined in this article should be used. Treatment should be personalized to manage the specific symptoms of allergic rhinitis (rhinorrhea, congestion, sneezing, and itchy nose) and take into consideration the age and preferences of the patient. The ultimate goal of treatment is to improve patients’ health-related quality of life and prevent long-term complications of the disease and any drugs used in its management.

RESOURCES

Allergy UK: Consumer-facing website with particularly good information on childhood allergies, including a patient symptoms diary and downloadable documents on key things for patients to learn, why allergy is increasing, and the link between genetics and allergies. [https://www.allergyuk.org/information-and-advice/conditions-and-symptoms/47-about-allergy]

American Academy of Allergy, Asthma & Immunology: Offers patient education materials, as well as [http://www.aaaai.org/conditions-and-treatments] photographs and images of allergic conditions and common allergens. [http://www.aaaai.org/about-aaaai/newsroom/photo-gallery]

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