Mixed Pollen Extract Sublingual Tablets (Oralair)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor
of Medicine, University of California, San Francisco.
Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field
The fda has approved the first mixed pollen extract sublingual tablet as immunotherapy to treat hay fever. The extract contains common grasses in the United States (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass). The product is manufactured by Stallergenes S.A. in France and distributed by GREER Laboratories as Oralair.
The mixed allergen extract is indicated as immunotherapy for the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or pollen-specific IgE antibodies for any of the five grass species in patients 10-65 years of age.1
The recommended dose for ages 10-17 is 100 index of reactivity (IR) on day 1, 2 × 100 IR on day 2, and 300 IR thereafter. For ages 18-65, the dose is 300 IR daily. The tablet is given sublingually, starting at least 12 weeks before the expected onset of each grass pollen season, and continued throughout the season.1 The tablet should be placed under the tongue until completely dissolved for at least 1 minute, and then swallowed. The tablets should not be taken with food or beverage, and no food or beverage should be taken 5 minutes after dissolution. The first dose should be given under the supervision of a physician and the patient should be monitored for at least 30 minutes for possible severe systemic or local allergic reactions. The tablets are available as 100 IR and 300 IR. IR is based on skin reactivity and is tested for Bioequivalent Allergy Unit with Timothy grass pollen as the reference (Summary Basis).
The tablets provide a more convenient alternative to allergy shots and may have fewer systemic reactions.3
Sublingual administration may be less effective than subcutaneous injection.3-6 The allergen extract can cause systemic allergic reactions (anaphylaxis) or severe local reactions (laryngopharyngeal swelling).1 An epinephrine auto-injection should be prescribed to patients receiving these extracts. Patients taking medication that may counteract the effect of epinephrine (e.g., beta-blockers, alpha-adrenergic blockers) should not be prescribed the allergen extract. The extract is contraindicated in patients with severe, uncontrolled asthma or a history of any severe systemic reactions. Common adverse events (vs placebo) in adults are oral pruritus (25% vs 5%) and throat irritation (22% vs 4%).
The efficacy of mixed pollen extract was evaluated in five double-blind, placebo-controlled trials of which four were natural field studies and one an environmental exposure study.1 Three of the natural field studies were for one season and one was for three seasons. In the 1-year studies, subjects were randomized to the mixed allergen extract or placebo starting 4 months before the grass pollen season and throughout the season. The primary endpoints included the daily Rhinoconjunctivitis Total Symptom Score ([RTSS], range 0-18, sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular symptoms), daily Rescue Medication Score (RMS, range 0-3, antihistamines = 1, nasal steroids = 2, oral steroid = 3), and the daily Combined Score (CS) equally weighing symptom and rescue medications. In the U.S. adult study, daily CS was reduced by 28% (95% confidence interval [CI]; -43 to -13), RTSS, -23% (-38 to 7.5), and RMS - 47% (-74 to -19). For the European adult study, results were -30%, -29%, and -30%, respectively. For children and adolescents, results were -30%, -31%, and -30%. In the long-term study, reductions in the CS were -16% for year 1, and -38% in years 2 and 3. In the allergen environmental chamber study, subjects were challenged with four of the five allergens for 4 hours. Mixed pollen extracts showed a reduction of RTSS by 29% compared to placebo. The FDA criteria for efficacy of the extracts are reduction of CS at least 15% and the 95% CI upper limit of -10%.2
The mixed allergen extract tablets provide an effective and more convenient form of immunotherapy for hay fever. The relative effectiveness of sublingual vs subcutaneous immunotherapy is not completely clear. Some studies suggest that sublingual is less effective than subcutaneous, while a systematic review suggests that Oralair is at least non-inferior to subcutaneous administration.7 The wholesale cost for Oralair is $300 for a 30-day supply.
- Oralair Prescribing Information. Lenoir, NC: GREER Laboratories; April 2014.
- http://www.fda.gov/downloads/BiologicsBloodVaccines/Allergenics/UCM393021.pdf. Accessed on May 5, 2014.
- Chelladurai Y, Lin SY. Effectiveness of subcutaneous versus sublingual immunotherapy for allergic rhinitis: Current update. Curr Opin Otolaryngol Head Neck Surg 2014; Apr 12. [Epub ahead of print].
- Aasbjerg K, et al. Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy. Clin Exp Allergy 2014,44:417-428.
- Nelson HS. Subcutaneous immunotherapy versus sublingual immunotherapy: Which is more effective?
J Allergy Clin Immunol Pract 2014;2:144-149.
- Chelladurai Y, et al. Effectiveness of subcutaneous versus sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: A systematic review. J Allergy Clin Immunol Pract 2013;1:361-369.
- Dranitsaris G, Ellis AK. Sublingual or subcutaneous immunotherapy for seasonal allergic rhinitis: An indirect analysis of efficacy, safety and cost. J Eval Clin Pract 2014;20:225-238.