Pharmacology Update

Azelastine HCl and Fluticasone Propionate Nasal Spray (Dymista™)

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 of study.

A combination histamine-1 receptor antagonist and a corticosteroid nasal spray has been approved by the FDA for the treatment of seasonal allergic rhinitis. The product contains azelastine (AZE) and fluticasone propionate (FP). It is manufactured by Cipla in India and will be distributed by Meda Pharmaceuticals as Dymista.

Indications

Azelastine and fluticasone (AZE/FP) is indicated for the relief of symptoms of seasonal allergic rhinitis in adolescent and adult patients (≥ 12 years of age) who require the use of both agents.1

Dosage

The recommended dose is 1 spray per nostril twice daily.1 Each spray contains 137 mcg of AZE HCl and 50 mcg of FP.

Potential Advantages

AZE/FP provides agents with different mechanisms of action and measurable improved effectiveness compared to either agent used alone.1,2

Potential Disadvantages

There is potential for additive adverse events with both agents. There may be a 50% increase in the systemic bioavailability of fluticasone with AZE/FP compared to FP alone, which is generally less than 2%.1

Comments

Safety and efficacy of AZE/FP were evaluated in three randomized, multicenter, double-blind, placebo-controlled 2-week clinical trials. Subjects (≥ 12 years; n = 3398) with moderate-to-severe allergic rhinitis were randomized to AZE/FP, AZE, FP, or vehicle placebo.1,2 The dose was one spray in each nostril twice daily (every 12 hours) for 14 days. Efficacy was based on the reflective total nasal symptom score (rTNSS) and instantaneous total nasal symptoms (iTNSS). rTNSS is the sum of the patient's assessment of four nasal symptoms — rhinorrhea, nasal congestion, sneezing, and nasal itching — on a 4-point categorical severity scale (0-3) ranging from absent to mild-to-moderate to severe. Primary efficacy was the sum of morning and evening change from baseline in rTNSS over 2 weeks. The iTNSS was based on scores recorded immediately prior to the next dose. Secondary efficacy endpoints were changes in total reflective ocular symptom score (rTOSS) and change from baseline assessed by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). This health-related quality-of-life questionnaire includes activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotion assessed on day 14. A meta-analysis of the three studies showed a reduced mean rTNSS of -5.7 (SD, 5.3) for AZE/FP, -5.1 (SD, 4.9) for FP, -4.4 (SD, 4.8) for AZE, and -3.0 (SD, 4.2) for placebo.2 The effect of AZE/FP was statistically different from monotherapy with either agent and placebo. These represent a relative reduction of about 30%, 27%, 23%, and 16%, respectively.2 Onset of action was observed at 30 minutes after the initial dose of AZE/FP. Time to 50% improvement was faster for AZE/FP over AZE but not FP. Similar results were observed for iTNSS. AZE/FP showed a clinically meaningful decrease in overall RQLQ compared to placebo but not over the active monotherapy arms.1 Ocular symptoms based on rTOSS were improved with all active treatments compared to placebo. AZE/FP was not statistically different from AZE monotherpy. AZE/FP is well tolerated. The incidence of common adverse events (dysgeusia, headache, epistaxis) was less than 5%.1

Clinical Implications

AZE/FP is first intranasal combination of a corticosteroid (fluticasone) and H-1 receptor antagonist (azelastine). It appears to provide a modest increase in effectiveness over monotherapy with fluticasone or azelastine in patients with moderate-to-severe allergic rihinitis. A small percentage of patients showed complete or near-complete symptom relief, 12.4%, 9.3%, and 7.1%, for AZE/FP, FP, and AZE, respectively. The number needed to treat to gain an additional patient with complete symptom relief over FP is 32 and 19 over AZE. n

References

1. Dymista™ Prescribing Information. Somerset, NJ: Meda Pharmaceuticals; May 2012.

2. Carr W, et al. A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis. J Allergy Clin Immunol 2012;129:1282-1289.