SEASONAL ALLERGIES – Choosing the right product for you

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What are the typical symptoms of allergic rhinitis?

Seasonal allergies (commonly referred to as Hay Fever) occur as a result of exposure to allergens at different times of the year. The most common presentation is allergic rhinitis (inflammation of the inner mucous membrane of the nose), with symptoms including itching, sneezing, rhinorrhea (runny nose), nasal congestion and itchy, watery eyes (allergic conjunctivitis). An individual may present with one or a variety of symptoms depending on the severity. Household allergens may also contribute to allergic rhinitis and typically occur year-round (termed perennial allergy).1

Could it be sinusitis (rhinosinusitis)? What makes it different from allergic rhinitis?

Rhinosinusitis or commonly referred to as “sinusitis” is defined as inflammation and/or mucosal thickening of 1 or more of the paranasal sinus cavities. It is classified as acute (occurring 4 weeks or less) that could be recurrent or chronic rhinosinusitis (lasting 12 weeks or more). As the paranasal sinus cavities are normally sterile, sinusitis usually occurs secondary to viral or bacterial respiratory infections. It is then possible that sinusitis may be mistaken for allergic rhinitis. The most common symptoms of sinusitis are characteristic of Upper Respiratory Tract Infection (URTI), including purulent nasal discharge and facial pain, headache, ear pain, fatigue and cough.

Treatment usually involves the use of analgesics/antipyretics and antibiotic therapy (if bacterial), and possibly decongestants.

When treating allergic rhinitis and symptoms don’t resolve with appropriate trial of medications (2-4 weeks), refer to a physician or a specialist for proper diagnosis.2,3,4

 

Are there any non-pharmacological treatments available?

Allergen avoidance is the first step in preventing symptoms but may not always be possible. Another non-pharmacological approach is the use of intranasal saline spray and irrigation which may provide some symptomatic relief through irrigation of allergen from the nasal mucosa. An allergy test (skin prick test) may help in identifying the allergen. Alternatively, an allergen-specific immunoglobulin (IgE) test, which requires a blood sample, is done when the skin test is inconclusive.5

 

What are some pharmacological options? 6, 7

When avoidance to environmental allergen is not possible, and nasal irrigation is not effective, there is a variety of pharmacotherapeutic options available:

  • antihistamines
  • decongestants
  • corticosteroid nasal sprays
  • allergen immunotherapy

Some of these medications are available in different preparations (oral, intranasal spray, eye drops) and are listed below.

Oral preparationsmost oral preparations are available over-the-counter (OTC) and most provide the ease of use of once daily dosing. Loratadine and desloratadine are also available as syrups, while cetirizine is also available as a chewable tablet – an option for children. As they are ingested, there is a higher risk of systemic adverse effects than when given locally, but each individual will respond differently. The following are available as oral preparations:

  • antihistamines: 1st and 2nd generation
  • combination antihistamine/decongestants
  • leukotriene receptor antagonist (LTRA)

Intranasal products – as applied locally, there is a lower risk of systemic adverse-effects when taken at usual dose (side-effects are localized). The onset of effect may also be faster than oral preparations:

  • corticosteroids
  • antihistamine
  • anticholinergics
  • decongestants

Combination Intranasal preparations – for treatment of resistant cases of allergic rhinitis (details below):

  • corticosteroid/antihistamine

Ophthalmic preparations (eye drops) – topical treatment for ophthalmic symptoms as stand-alone therapy or adjunct (additional therapy):

  • antihistamine/mast cell stabilizer
  • mast cell stabilizers

When choosing the appropriate pharmacotherapy, numerous factors are considered, such as your allergy symptoms, severity, duration, your past response to medications, cost, as well as other medication and/or conditions you have. Have a conversation with your doctor or pharmacist to see which product is right for you. This article will focus on the most common treatments available. Table 1 describes the efficacy and indications of different treatment modalities for allergic rhinitis.

 

Table 1: Comparison of Symptom Relief in Allergic Rhinitis Therapies 7, 8, 9

 

Medication

Rhinorrhea

Congestion

Sneezing

Nasal Itch

Eye Symptoms

Oral antihistamines

+

+/-

+

+

+/-

Decongestants
(oral and topical)

+

Intranasal corticosteroids

++

++

++

++

+/-

Leukotriene receptor antagonists

+

+

+/-

+/-

+/-

Intranasal anticholinergics

++

Intranasal antihistamines

++

++

++

++

+/-

Abbreviations:

– = no effect;  +/- = modest or variable effect;  + = moderately effective;  ++ = effective

 

How to choose the right treatment for you

Treatment of mild and infrequent symptoms: 6, 7, 10

Typically, mild intermittent/infrequent symptoms are treated with oral antihistamines. They relieve most symptoms such as rhinorrhea, nasal itch, sneezing, and conjunctivitis, but may not be as effective for nasal congestion. Most of these medications are available over-the-counter (OTC), while some are available with a prescription. Most antihistamines are now available as “non-drowsy”, which are classified as 2nd generation antihistamines. The use of 1st-generation antihistamines (ex: diphenhydramine or Benadryl®; and chlorpheniramine or Chlor-Tripolon) for treatment of seasonal allergies is no longer recommended given their adverse effect profile as sedating and having anticholinergic side-effects ®. 10

Although not as common, certain individuals may still experience drowsiness with 2nd generation antihistamines, specially at higher doses. Among them, cetirizine, is more likely to cause sedation but not as much as 1st generation antihistamines. Newer antihistamines have come to market and are available by prescription only, but the data is still lacking, especially on their safety profile (Bilastine® and Rupall®).

Intranasal antihistamine levocabastine is also effective when used daily on an as-needed basis and provides the benefit of a more rapid onset with minimal systemic side-effects compared to oral antihistamines. Considering that cost may be a factor for certain individuals, oral preparation antihistamines are more readily available and less expensive than the nasal spray antihistamine.

As antihistamines are not effective for treatment of nasal congestion, decongestants can be added on an as-needed basis for breakthrough relief (discussed in the “Add-on” section below).

Antihistamine eye drops are also available. See “Adjunct treatments, specific symptoms and special population” section below.

 

Table 2: Common antihistamine preparations for treatment of mild and infrequent symptoms 6,7

2nd Generation antihistamines (oral):

  • cetirizine (Reactine® OTC, generics – also available by prescription)
  • loratadine (Claritin® and liquids OTC, generics – OTC)
  • desloratadine (Aerius®, Aerius Kids, generics – OTC)
  • fexofenadine (Allegra®, generics – OTC)
  • bilastine (Blexten® – by prescription only)
  • rupatadine (Rupall® – by prescription only)

Intranasal antihistamine:

  • levocabastine (Livostin Nasal Spray ® – by prescription only)

Combination intranasal (antihistamine/corticosteroid):

  • Azelastine/fluticasone propionate (Dymista® – by prescription) *see corticosteroid section

Indications and duration:

  • Mild and infrequent symptoms
  • Treatment – rhinorrhea, nasal itch, sneezing, and allergic conjunctivitis
  • INNEFECTIVE for nasal congestion (some benefit with desloratadine)
  • Onset: Effect within minutes to a few days (longer with oral preparations)
  • Duration: Taken daily as needed while allergy present
  • Prophylaxis preferred – most effective when taken before allergen exposure
  • Monitor: Improvement in 1 week and at 2 weeks

Possible Side-effects:

  • Oral (systemic side-effects more likely with higher dose): Somnolence (some at higher doses, more common with cetirizine), headache, dizziness, nausea, and possible anticholinergic effects: dry mouth, water retention, constipation, memory impairment, delirium (a concern for the elderly)
  • Nasal sprays (mostly local):  Irritation of the nasal mucosa (dryness or nosebleed)

Caution and Contraindications:

  • Caution advised in the elderly
  • Caution advised in patients with QT prolongation
  • Blexten®: contraindicated in patients with history of QT prolongation and pregnancy
  • Rupall: contraindicated in pregnancy

Additional Notes: 6, 11

Blexten®: newer prescription 2nd generation antihistamine for treatment of allergic rhinitis (patients ³ 12 y.o.). Also indicated for chronic spontaneous urticaria: pruritus (itching) and hives (³ 18 y.o.)

  • Less sedating than other prescription antihistamine cetirizine
  • Note:
  • Good alternative to Benadryl® for itching and hives – is non-drowsy and conveniently taken once daily (Benadryl® has to be taken numerous times a day) – an advantage if a patient has to maintain mental alertness following treatment
  • May be covered by third party insurance (if cost a concern for OTC products)
  • Taken on an empty stomach to improve absorption (1 hr before, or 2hrs after a meal)
  • Avoid combination medications such as antifungals (ketoconazole), antibiotic (erythromycin), anticonvulsants and grapefruit juice, as drug interactions may alter absorption and increase risk of side-effects or decrease efficacy
  • Avoid in pregnancy: limited safety data

Rupall®:  newer prescription 2nd generation antihistamine for treatment of allergic rhinitis (patients ³ 12 y.o.)

  • Less sedating than other prescription antihistamine cetirizine
  • May be covered by third party insurance (if cost a concern for OTC products)
  • Can be taken with or without food
  • Avoid combination with certain medications and food: fluconazole, erythromycin, grapefruit juice as drug interactions may alter absorption and increase risk of side-effects or decrease efficacy
  • Avoid in pregnancy: limited safety data
  • Limited data for use

 

Treatment of moderate-severe rhinitis or persistent mild symptoms 6, 7

Intranasal corticosteroids are the 1st line treatment for moderate to severe allergic rhinitis. When compared to antihistamines and leukotriene antagonists, they are shown to be more effective in relieving symptoms, especially in relieving nasal congestion and ocular symptoms associated with allergic rhinitis. The onset of effect is within 6-8 hours of 1st dose but full effect could be experienced up to 2 weeks. Regular use of intranasal corticosteroid is more effective than intermittent use. 12

The combination antihistamine/corticosteroid, azelastine/fluticasone (Dymista®) is a viable option for persistent symptoms or in severe allergic rhinitis by taking advantage of the combination of two different mechanism of actions of the two medications. 13

As administered locally, systemic effects are less likely but local irritation of the nasal mucosa is common (dryness and nosebleed). To minimize the local side-effect with intranasal corticosteroids and with other intranasal products, they should be sprayed towards the turbinate (away from the nasal bridge, pointing upwards and aimed laterally toward the tip of the ear). The corticosteroid preparations have different systemic bioavailability (how much is transferred systemically from the local site) which translate to systemic adverse-effects (eg. Hypothalamix Pituitary Adrenal axis and small significant effect on child’s growth) – a factor that is considered when choosing the right intranasal medication. The table below describes their bioavailability and their effect. 14, 15

 

Table 3: Intranasal corticosteroid for treatment of moderate to severe rhinitis 6, 7

Intranasal corticosteroids (INCS):

  • beclomethasone (generics – by prescription) – usually 1-2 sprays each nostril twice daily
  • budesonide (Rhinocort®, generics – by prescription ) – usually 1-2 sprays each nostril daily
  • ciclesonide (Omnaris, generics – by prescription) – usually 2 sprays each nostril daily
  • fluticasone furoate (Avamys® – by prescription) – usually 2 sprays each nostril daily
  • mometasone (Nasonex® – by prescription) – usually 1-2 sprays each nostril daily
  • fluticasone propionate (Flonase®, generics – by prescription OTC) – usually 1-2 sprays each nostril daily
  • triamcinolone (Nasacort® – OTC) – usually 1-2 sprays each nostril daily

Combination product (antihistamine/corticosteroid):

  • Azelastine/fluticasone propionate (Dymista® – by prescription)

Indications and duration:

  • Moderate to severe symptoms of allergic rhinitis, or mild persistent symptoms resistant to antihistamines
  • Treatment – rhinorrhea, nasal itch, sneezing, nasal congestion, allergic conjunctivitis
  • Combination products: persistent symptoms despite adequate trials of INCS
  • Onset: effect within minutes to a few days-weeks
  • Duration: mostly regular daily use, or taken daily as needed while allergen present, once daily to twice daily dosing depending on severity and preparation
  • Prophylaxis – more effective when taken before allergen exposure
  • Monitor: Improvement in 1 week and at 2 weeks

Possible Side-effects:

  • Irritation of the nasal mucosa (dryness or nosebleed)

Additional Notes:

  • Long-term use of any intranasal preparations, including corticosteroid is preferred due to more localized side-effects
  • Blowing nose or using decongestants prior to use may improve absorption and efficacy
  • Systemic effects may be more of a concern if a patient is on other corticosteroids (eg. for asthma, COPD)
  • The effect of INCS on a child’s growth may be a concern for parents – more likely in higher or twice-daily dosing and higher bioavailability. Refer to specialist for children <2 y.o.
  • mometasone (Nasonex ®) and fluticasone propionate (Flonase ®) are usually recommended for children due to low systemic bioavailability and absence of growth suppression
  • beclomethasone (generics) and triamcinolone (Nasacort AQ®) – has been known to affect growth

 

  • Systemic bioavailability / effect on the HPA axis / effect on growth retardation:
    • beclomethasone: High 44% / ¯ urinary cortisol at 800 mcg/day / small sig. effect in age 6-9 yrs over 1 yr
    • budesonide: Moderate 31% / none / none at 2 yr
    • ciclesonide: Very low <1% / no info / no info
    • fluticasone furoate: Very low <0.5% / none / none at 1 yr
    • mometasone: Very low <0.5% / none / none at 1 yr
    • fluticasone propionate: Very low <0.5% / none / none at 1 yr
    • triamcinolone: High 46% / none / maybe

 

Add-on Therapy 6, 7

Decongestants (available as oral or intranasal spray, as stand-alone product or combination) can also be also be added to antihistamines to relieve nasal congestion for a short period of time (breakthrough). Additionally, intranasal decongestants can used as an adjunct to intranasal corticosteroid to improve its efficacy, especially at the onset of symptoms. Additionally, inhaled decongestants appear to have a stronger effect on nasal obstruction than oral decongestants. 16, 17

Given their pharmacological properties, the risk of systemic adverse-effects should be considered, especially with oral preparations (see below). The oral form is likely to cause more systemic effects than the topical intranasal preparation. That said, topical/intranasal preparations have a potential to cause rhinitis medicamentosa (rebound congestion). As such, their use should be limited to 3-7 days. 6, 7

 

Table 4. Decongestants as adjunct and breakthrough therapy

Add-On Decongestants

Oral form in combination with 2nd Generation Antihistamines preferred

  • cetirizine/pseudophedrine (Reactine Complete® – OTC)
  • desloratadine/pseudophedrine (Aerius Dual Action 12 Hours® – OTC)
  • fexofenadine/pseudophedrine (Allegra-D® – OTC)
  • loratadine/pseudophedrine (Claritin Allergy + Sinus® – OTC)

Intranasal spray

  • oxymetazoline (Claritin Allergy Decongestant®, Dristan®, Drixoral®, generics – OTC)
  • xylometazoline (Otrivin®, Balminil®, generics – OTC)
  • antihistamine pheniramine/phenylephrine combination (Dristan Nasal Mist® – OTC)

Indications and properties:

  • As adjunctive (additional) therapy for nasal congestion when using with antihistamines or intranasal corticosteroid
  • As needed for breakthrough symptoms  
  • To improve efficacy of antihistamine or inhaled corticosteroid at onset of rhinitis

Onset: Within the day

Monitor: Improvement in congestion within the day up to 3-4 days

Common Possible Side-effects:

  • Oral (systemic side-effects more likely) – Stimulant effect: increased HR, palpitations, nervousness, insomnia, tremor, irritability, urinary retention
  • Local (mostly localized side-effects) – nasal irritation

Caution and Contraindications:

  • Contraindicated in patients taking MAOi
  • Contraindicated in patients with severe hypertension and cardiovascular disease
  • Caution in patients with hyperthyroidism, angle-closure glaucoma, and prostatic hypertrophy
  • Avoid use oral formulation during the 1st term pregnancy (prefer intranasal)

 

Adjunct treatments, specific symptoms and special population:

A person experiencing allergic rhinitis may present with some or all of the symptoms described above. Additionally, some patients may be contraindicated on certain medications. The following summarizes options available for these specific conditions.

 

Rhinorrhea (runny nose)18

Intranasal anticholinergic ipratropium (generics) is indicated when rhinorrhea is the only symptom present. It is a viable option for sneezing caused by the runny nose, and especially helpful with  “skier’s nose”.

 

Ocular symptoms and ophthalmic preparations 6, 7, 19

Ophthalmic preparations are indicated for treatment of ocular symptoms (conjunctivitis due to allergies – itchy, gritty, watery eyes), when either allergic conjunctivitis is the only set of symptoms present, or as an adjunct therapy when oral antihistamine, INCS and leukotriene receptor antagonists are ineffective in providing relief.

Two types of eye drops are available. Their different characteristics as described below are factors to be considered in deciding the appropriate treatment.

Antihistamines and Mast Cell Stabilizers (Dual effect):

  •    ketotifen (Zaditor ®, generics – by prescription only)
  •    olopatadine (Pataday®, Patanol®, generics – by prescription only)

Onset: symptomatic relief in minutes, with lasting effect up to 12 hours

Other considerations:

  •    Pataday® is available as once daily dosing, applied as 1 drop to affected eyes
  •    Patanol® is available as twice daily dosing, applied as 1-2 drops to affected eyes
  •    Available by prescription and therefore more expensive, but with more rapid effect than the products below

Mast Cell Stabilizers:

  •    sodium cromogylate (Opticrom, generics – OTC)
  •    nedocromil (Alomide® – by prescription)
  •    lodoxamide (Alocril – by prescription)

Onset: longer onset of symptomatic relief (a few days up to 4 weeks)

Other considerations:

  •    Frequent administration (four times daily) initially may be required for optimal benefit
  •    Opticrom® or its generics is a less expensive option that’s available over-the-counter

 

Special Population 6, 7, 16

Pregnancy/breastfeeding

In general, topical preparations (intranasal and ophthalmic) are preferred in pregnancy and breastfeeding as side-effects are mostly localized. Inhaled corticosteroids are favoured as 1st-line therapy during pregnancy given the minimal side-effects and its efficacy for treatment of allergic rhinitis compared to antithistamines (oral and topical). Inhaled decongestants and saline nasal spray are also viable options. Avoid use of oral decongestants during 1st trimester due to possible malformations. 2nd generation antihistamines are preferred due to lower risk of decreased milk production in the breastfeeding mother and infant somnolence.

Elderly and patients with comorbid conditions

The elderly population is more likely to have other medical conditions and are therefore more susceptible to adverse-effects. Considering their sensitivity to these medications, topical preparations are the preferred choice of treatment.  As described above, individuals with hypertension or other cardiac conditions, closed-angle glaucoma, enlarged prostate, hyperthyroidism should take extra precaution when taking products with decongestants, more importantly with oral preparations. Avoid decongestants when these conditions are uncontrolled.

 

Summary

A treatment algorithm for allergic rhinitis is provided below on Figure 1. Note that mild or infrequent is defined as symptoms lasting <4 days per week or <4 weeks. Persistent symptoms are defined as lasting more than 1-2 months and are considered moderate. The number of symptoms experienced and the effect on a patient’s quality of life is also factored in choosing the appropriate therapy.6,7

 

Figure 1.  Treatment algorithm for Allergic Rhinitis 6

 

 

Sources:

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  5. Allergic Rhinitis – Immunology; Allergic Disorders – MSD Manual Professional Edition”. 2019. MSD Manual Professional Edition. Accessed September 8 2019. https://www.merckmanuals.com/en-ca/professional/immunology-allergic-disorders/allergic,-autoimmune,-and-other-hypersensitivity-disorders/allergic-rhinitis.
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  7. Kendrick J.  Allergic Rhinitis. In: CTMA [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2019 [updated AUG 2018; cited 2019 Sept 06]. Available from: http://www.myrxtx.ca. Also available in paper copy from the publisher.
  8. Wilson AM, O’Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis. Am J Med2004;116:338-4.
  9. Scadding GK, Durham SR, Mirakian R et al. BSACI guidelines for the management of allergic and non-allergic rhinitis. Clin Exp Allergy 2008;38:19-42.
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  13. Carr W, Bernstein J, Lieberman P et al. A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis. J Allergy Clin Immunol 2012;129(5):1282-9.
  14. Bielory L, Chun Y, Bielory BP et al. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis. Allergy2011;66(5):686-93.
  15. Dykewicz MS, Wallace DV, Baroody F et al. Treatment of seasonal allergic rhinitis: an evidence-based focused 2017 guideline update. Ann Allergy Asthma Immunol2017;119:489-511.
  16. Wallace DV, Dykewicz MS, Bernstein DI et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol2008;122:S1-84.
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  18. Grossman J, Banov C, Boggs P et al. Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications. J Allergy Clin Immunol1995;95(5 Pt 2):1123-7.
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