Azelastine
Topical H1 antihistamine for allergic rhinitis and conjunctivitis
Azelastine is a second generation antihistamine from the phthalazinone class. Asta Medica launched the substance in the 1980s, and in Germany Allergodil, Vividrin akut and numerous generics are available over the counter as nasal spray and eye drops. A fixed combination with the nasal glucocorticoid fluticasone propionate (Dymista) expands the portfolio for treatment of moderate to severe allergic rhinitis.
The special feature of azelastine is its rapid local action. As early as 15 minutes after application, sneezing, itching, rhinorrhea and watery eyes improve, which makes the substance the preferred option for acute allergic symptoms and as on demand therapy. In contrast to systemic antihistamines, topical application causes considerably fewer central side effects such as fatigue.
Mechanism of Action
Azelastine competitively blocks H1 histamine receptors on endothelial cells, smooth muscle and nociceptive nerve fibres. Histamine is the central mediator of type I allergy and is released on IgE mediated mast cell activation. Binding to H1 receptors causes vasodilation, increased capillary permeability, itching and bronchial hyperreactivity.
Besides pure H1 antagonism, azelastine acts as a mast cell stabiliser and inhibits the release of further inflammatory mediators such as leukotrienes, tryptase and platelet activating factor. This combination of receptor blockade and reduction in mediators explains the broad anti inflammatory action in allergic mucosal disorders. The effect begins within 15 minutes of local application and lasts 12 hours.
Systemic absorption after nasal or ocular application is low, with less than 40 percent absorbed. In blood, azelastine is partially converted to the active metabolite desmethylazelastine, which itself has antihistaminergic activity. The half life is 20 to 25 hours. Despite the long half life, systemic effects with topical use are modest.
Indications
- Seasonal allergic rhinitis (hay fever) for treatment and prevention
- Perennial allergic rhinitis with house dust mites, animal dander or mould
- Acute and chronic allergic conjunctivitis with itching, redness and tearing
- Vasomotor rhinitis off label in non allergic nasal hyperreactivity
- Moderate to severe rhinitis as a fixed combination with fluticasone propionate (Dymista)
Dosage and Use
Nasal spray adults and children from 6 years: 1 spray of 0.1 percent solution into each nostril twice daily. Eye drops adults and children from 4 years: 1 drop of 0.05 percent solution into each eye twice daily, up to four times daily if needed. Dymista (azelastine plus fluticasone): 1 spray into each nostril twice daily, adults and adolescents from 12 years.
Application technique is decisive. Before spraying, blow the nose gently, hold the spray bottle upright, tilt the head slightly forward, direct the nozzle upward and outward into the nostril, and inhale gently during the spray. For eye drops, pull the lower eyelid down slightly, instil the drop, keep the eye closed for 1 minute and, if useful, compress the inner corner of the eye to reduce tear duct drainage.
Children under 6 years (nasal spray) or under 4 years (eye drops): not to be used. Older patients: no dose adjustment. Renal and hepatic impairment: no dose adjustment required because of low systemic exposure.
Side Effects
Common: bitter taste (after nasal use from drainage into the throat), burning or tingling in the nose, sneezing immediately after application, nosebleed, transient local itching or burning in the eye.
Uncommon: headache, fatigue (far less frequent than with systemic antihistamines), dry nasal mucosa, conjunctivitis, blurred vision shortly after application, skin rash.
Rare: systemic hypersensitivity reactions, dyspnoea, dizziness, throat numbness, photophobia, tearing, foreign body sensation.
Bitter taste: the typical bitter taste after nasal application results from drainage of the spray into the nasopharynx. Correct spray technique with the head tilted slightly forward, not tilting the head back, and rinsing the mouth with a glass of water afterwards reduce the complaint. With severe discomfort a switch to intranasal antihistamines with less taste effect or to systemic antihistamines can be considered.
Interactions
- Other antihistamines (oral, topical): combination not useful, no added benefit
- Central depressants (alcohol, benzodiazepines, opioids): theoretically enhanced sedation; with topical use usually not clinically relevant
- Intranasal decongestants (xylometazoline): short term combination to improve spray distribution possible; limit duration of combination to a few days to avoid rebound congestion
- Nasal or ocular corticosteroids: combination possible and, in severe allergic rhinitis, established as a fixed combination (Dymista)
Special Notes
Contraindications: known hypersensitivity to azelastine or any of the excipients; for eye drops, known hypersensitivity to benzalkonium chloride (preservative in some formulations).
Contact lenses: benzalkonium chloride in eye drops can discolour soft contact lenses and irritate the cornea. Remove contact lenses before application and reinsert no earlier than 15 minutes afterwards. For long term therapy, a preservative free preparation or a switch to an alternative such as ketotifen or olopatadine may be useful.
Pregnancy and lactation: data on topical use during pregnancy are limited; with reasonable indication and low systemic exposure usually unconcerning. Non sedating systemic antihistamines (loratadine, cetirizine) have better data. Lactation: with topical use systemic exposure is low and breastfeeding is possible.
Use in asthma: azelastine can relieve the nasal component of an allergy; with concomitant bronchial asthma, basic bronchial therapy with an inhaled corticosteroid remains necessary. Rhinitis and asthma often occur together (united airway disease) and an integrated approach is reasonable.
Duration of therapy: in seasonal rhinitis, azelastine is often used continuously for several weeks; with perennial use a break is not mandatory. With daily need beyond 6 months a medical reassessment and review of diagnosis are advisable.
You Might Also Be Interested In
- Cetirizine, oral second generation antihistamine
- Levocetirizine, R enantiomer of cetirizine
- Desloratadine, non sedating antihistamine
- Fexofenadine, oral antihistamine
- Budesonide, nasal corticosteroid
- Ketotifen, antihistamine with mast cell stabilising effect
Frequently Asked Questions
How quickly does azelastine nasal spray work?
Onset of action begins as soon as 15 minutes after application and lasts about 12 hours. This makes azelastine one of the fastest acting topical antiallergics. With regular twice daily use a stable effect develops within a few days. For acute symptom relief, on demand use is also possible.
Why does the spray taste bitter?
The bitter taste arises when part of the spray solution runs off into the nasopharynx and stimulates the taste nerves. Correct spray technique with the head tilted slightly forward, avoiding tilting the head back, reduces the phenomenon. Drinking a glass of water after spraying also helps. The effect is harmless and usually diminishes after a few days.
Azelastine or cetirizine?
For isolated nasal or ocular symptoms, topical azelastine is ideal because of its fast onset and minimal systemic exposure. For generalised allergic symptoms (sneezing, itching, runny nose, skin, eyes, mild airway symptoms) an oral antihistamine such as cetirizine or levocetirizine is simpler and offers once daily dosing.
Can I use azelastine with contact lenses?
Benzalkonium chloride as a preservative can discolour soft contact lenses and irritate the cornea. Remove contact lenses before instillation and reinsert no earlier than 15 minutes afterwards. Alternatively, there are preservative free single dose containers that are better tolerated by contact lens wearers.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guideline Allergic Rhinoconjunctivitis
- Gelbe Liste, Azelastine active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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