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Azelastine (Astepro) Nasal Spray for Allergic

Rhinitis ................................................................. p 29

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TheOnMedical Letter
Drugs and Therapeutics
Published by The Medical Letter, Inc. • 1000 Main Street, New Rochelle, NY 10801 • A Nonprofit Publication
Volume 51 (Issue 1310)
April 20, 2009
Azelastine (Astepro) Nasal Spray for
Allergic Rhinitis
A new formulation of the H1-antihistamine azelastine
hydrochloride 0.1% nasal spray (Astepro – Meda) has
been approved by the FDA for treatment of seasonal
allergic rhinitis (SAR) in patients >12 years old and is
being heavily advertised to the public on radio, television
and the Internet. All azelastine products require a pre-
scription.
DRUGS FOR ALLERGIC RHINITIS — The first-line
treatment for mild to moderate allergic rhinitis is usually
an oral second-generation H1-antihistamine such as
loratadine (Claritin, and others), fexofenadine (Allegra,
and others) or cetirizine (Zyrtec, and others). These
drugs are generally non-sedating. Mild sedation can
occur with cetirizine in recommended doses and with
loratadine in higher-than-recommended doses; fexofe-
nadine is not sedating. Cetirizine is a more potent hista-
mine antagonist than the other two, and its safety in
young children is better established. Loratadine and cet-
irizine are available without a prescription. The
intranasal H1-antihistamines azelastine and olopata-
dine (Patanase) are alternatives to oral H1-antihista-
mines for treatment of allergic rhinitis; they have a more
rapid onset of action, but they may cause sedation.
Intranasal corticosteroids such as fluticasone
(Flonase, and others) are more effective than either oral
or intranasal antihistamines and are preferred for treat-
ment of moderate to severe disease.1,2
THE OLD AZELASTINE — The original 0.1% nasal
spray formulation of azelastine (Astelin) has been avail-
able since 1997. Its patent expires in 2010. Many
patients have complained about its bitter taste. A meta-
analysis of randomized controlled trials in patients with
seasonal and perennial allergic rhinitis (sponsored by
the manufacturer of Astelin and Astepro) found that
intranasal azelastine was more efficacious than
placebo and showed a trend toward being more effica-
cious than an oral second-generation antihistamine
such as loratadine or cetirizine.3
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THE NEW FORMULATION — In an effort to improve
on the taste of Astelin, Astepro was formulated in a
sorbitol-based solution with the artificial sweetener
sucralose added to mask the bitterness. Studies in
healthy volunteers have shown that systemic exposure
and other pharmacokinetic parameters are similar to
those of the old formulation.4
Table 1. Pharmacology of Azelastine
Drug class H1-antihistamine
Formulation Nasal spray: 137 mcg/spray
(200 sprays/bottle)
Onset of action 30 minutes
Tmax 3 hours
Metabolism Oxidatively metabolized to active metabolite
desmethylazelastine by CYP450 enzymes
Elimination 75% feces (<10% unchanged)
(oral dose)
Half-life 22 hrs (azelastine)
52 hrs (desmethylazelastine)
NEW VS. OLD FORMULATION — In an unpublished,
randomized, double-blind 2-week study in 834 patients
12 to 83 years old with SAR, those receiving Astepro
or Astelin, 2 sprays per nostril twice daily, had signifi-
cantly greater reductions in nasal symptom scores
than those treated with placebo (27.9% and 23.5% vs.
15.4%).5 One spray per nostril twice daily was not sig-
nificantly superior to placebo for either formulation in
this study, but that dose was approved for Astepro by
the FDA based on results of earlier studies with the
original formulation.
ADVERSE EFFECTS — Astelin – In clinical studies
with the original formulation, 19.7% of patients
reported bitter taste and 11.5% reported somnolence.
Astepro vs. Astelin – According to data from a poster
presentation provided by the manufacturer, a dose of 2
sprays per nostril of the new formulation tasted 71%
less bitter than the old formulation and caused less
nasal discomfort.6 According to Medical Letter consult-
ants, Astepro still tastes bitter and tastes cloyingly
sweet as well.
In the unpublished clinical trial that compared the 2 for-
mulations of azelastine in patients with SAR, adverse
effects with the 2-spray dose were similar with either
29
Table 2. H1-Antihistamines for Allergic Rhinitis
Drug Formulations Adult Dosage Pediatric Dosage Cost1
Nasal Sprays
Azelastine – Astelin (Meda) Metered-dose pump spray 1-2 sprays each 5-11 yrs: 1 spray each $96.30
(137 mcg/spray) nostril bid nostril bid
Astepro (Meda) Not approved 94.80
Olopatadine – Patanase (Alcon) Metered-dose pump spray 2 sprays each Not approved 95.77
(665 mcg/spray) nostril bid
Oral Second-Generation H1-Antihistamines
Cetirizine2 – generic 5, 10 mg tabs; 5, 10 mg 5 or 10 mg 1x/d 6-11 mos: 2.5 mg 1x/d 9.993
Zyrtec (Pfizer) chew tabs; 5 mg/5 mL syrup 12-23 mos: 2.5 mg 1x/d-bid 21.993
2-5 yrs: 2.5 or 5 mg 1x/d
or 2.5 mg bid
6-11 yrs: 5 or 10 mg 1x/d
Desloratadine – Clarinex 5 mg tabs; 0.5 mg/mL syrup 5 mg 1x/d 6-11 mos: 1 mg 1x/d 119.70
(Schering-Plough) 1-5 yrs: 1.25 mg 1x/d
Clarinex Reditabs 2.5, 5 mg disintegrating tabs 6-11 yrs: 2.5 mg 1x/d 87.00
>12 yrs: 5 mg 1x/d
Fexofenadine – generic 30, 60, 180 mg tabs; 60 mg bid or 6-23 mos: 15 mg bid4 79.20
Allegra (Sanofi-Aventis) 30 mg/5 mL susp 180 mg 1x/d 2-11 yrs: 30 mg bid 97.80
Levocetirizine – Xyzal 5 mg tabs; 2.5 mg/5 mL 5 mg 1x/d 6-11 yrs: 2.5 mg 1x/d 88.50
(UCB/Sanofi-Aventis) oral soln
Loratadine2 – generic 10 mg tabs; 10 mg dis- 10 mg 1x/d 2-5 yrs: 5 mg 1x/d 8.253,5
integrating tabs; 1 mg/mL >6 yrs: 10 mg 1x/d
syrup and susp
Claritin (Schering-Plough) 10 mg tabs; 1 mg/mL syrup 23.993
Claritin Reditabs 5, 10 mg disintegrating tabs 23.993

1. Cost for one bottle of nasal spray or 30 days’ treatment with oral drugs at the lowest adult dosage, according to February 2009 data from retail pharmacies
nationwide available from Wolters Kluwer Health.
2. Available without a prescription.
3. OTC cost for 30 10-mg tabs at drugstore.com. Accessed April 13, 2009.
4. Only approved for treatment of chronic idiopathic urticaria.
5. Cost is $4 by prescription for 30 10-mg tablets at Walmart, Target and some other stores.

formulation. For the most frequently reported adverse
effects of unpleasant taste (includes both bitter and
unpleasantly sweet), epistaxis, headache and nasal
discomfort, the incidence was 7%, 3%, 3% and 1%
with the new formulation and 8%, 2%, 2% and 4% with
the old one. Somnolence was reported by only 2% of
patients taking Astepro and 1% of those taking Astelin.
A one-year randomized open-label safety study com-
paring the 2 formulations of azelastine in patients with
chronic allergic or nonallergic rhinitis, both given as 2
sprays per nostril twice daily, also found their adverse
effects to be similar. Nasal mucosal ulceration
occurred in about 10% of patients with either drug.4
CONCLUSION — The new intranasal formulation of
the H1-antihistamine azelastine (Astepro) appears to
be similar to the old one (Astelin), with a slightly dif-
ferent but still unpleasant taste. Over-the-counter
second-generation oral antihistamines cost much
less and may be less sedating. Intranasal cortico-
steroids are more effective than either oral or
intranasal antihistamines for treatment of allergic
rhinitis. 
1. Drugs for allergic disorders. Treat Guidel Med Lett 2007; 5:71.
2. Olopatadine (Patanase) nasal spray for allergic rhinitis. Med
Lett Drugs Ther 2008; 50:51.
3. TA Lee and AS Pickard. Meta-analysis of azelastine nasal
spray for the treatment of allergic rhinitis. Pharmacotherapy
2007; 27:852.
4. WE Berger. Pharmacokinetic characteristics and safety and
tolerability of a reformulated azelastine hydrochloride nasal
spray in patients with chronic rhinitis. Expert Opin Drug Metab
Toxicol 2009; 5:91.
5. B Prenner et al. Double-blind, placebo-controlled study of the
original formulation of azelastine nasal spray compared to a
new formulation in patients with SAR. Presented at 47th
annual Scientific Session of the Western Society of Allergy,
Asthma and Immunology, Maui, Hawaii, Jan. 25-29, 2009.
6. H Sacks. Sensory study of a new formulation of azelastine
nasal spray with reduced bitterness. Presented at 46th annual
Scientific Session of the Western Society of Allergy, Asthma
and Immunology, Kailua-Kona, Hawaii, Jan. 21-25, 2008.

30 The Medical Letter • Volume 51 • Issue 1310 • April 20, 2009

 The Medical Letter®
On Drugs and Therapeutics

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The Medical Letter • Volume 51 • Issue 1310 • April 20, 2009 31