AHFS Class:

• Antiallergic Agents 52:02

Generic Name(s):

• Azelastine Hydrochloride

Azelastine is a histamine H₁-receptor antagonist.1,2

Seasonal Allergic Rhinitis

Azelastine hydrochloride spray is used intranasally to provide symptomatic relief of seasonal allergic rhinitis (e.g., hay fever).1,11 In controlled dose-ranging studies in patients with seasonal allergic rhinitis, symptomatic relief was evident in some patients within 1 hour, and substantial relief of symptoms usually was apparent within 3 hours after intranasal administration;1,11,13 symptomatic relief reached peak effect between 4-6 hours and persisted throughout the 12-hour dosage interval.1,11,13 In addition to relief of nasal symptoms, improvement in ocular manifestations also may occur, possibly secondary to systemic absorption of the drug.16,19,21,22,24,27 In comparative studies, intranasal azelastine was more effective than placebo and at least as effective as oral antihistamines (e.g., cetirizine, terfenadine [no longer commercially available in the US]) or intranasal corticosteroids in relieving allergic rhinitis.16,17,18,19,20,21,22,23,24,27,28 However, unlike intranasal corticosteroids, azelastine does not appear to exhibit local histologic anti-inflammatory activity;16,17 therefore, beneficial effects on nasal obstruction appear to result principally from antihistaminic and/or other activity.17,18,22 Antihistamines are not curative and merely provide palliative relief; since seasonal allergic rhinitis may be a chronic, recurrent condition, successful therapy often may require long-term intermittent use of these drugs.3,4,5,6,25

The manufacturer states that results of clinical studies of patients with asthma receiving oral azelastine (in daily dosages up to 8 times the recommended daily dosage of azelastine hydrochloride nasal spray) indicate that the nasal spray may be used safely in patients with asthma and seasonal allergic rhinitis.1,26 In general, antihistamines may provide some benefit, and may be used with caution, in certain asthmatic patients to treat seasonal allergic rhinitis or other airway disease with a histamine-mediated component.10 Although some clinicians believe that the anticholinergic effects of some antihistamines may cause thickening of bronchial secretions resulting in further airway obstruction in asthmatics, especially those with status asthmaticus, most experts consider complete avoidance of currently available antihistamines in asthmatics unjustified.7,8,9,10,12 (See Cautions: Precautions and Contraindications, in the Antihistamines General Statement 4:00.)

The principal adverse effects of intranasal azelastine are local (e.g., bitter taste, nasal burning, pharyngitis, paroxysmal sneezing), but adverse systemic effects (e.g., somnolence, headache) also can occur.1,16,19,22,24,26,28 Anaphylactoid reactions,1 application site reaction,1 chest pain,1 aggravated condition,1 confusion,1 diarrhea,1 dyspnea,1 facial edema,1 involuntary muscle contractions,1 paresthesia,1 parosmia,1 pruritus,1 rash,1 tolerance,1 urinary retention,1 vision abnormality,1 and xerophthalmia1 have occurred in patients receiving azelastine nasal spray; a causal relationship between these events and the drug have not been established.1 The manufacturer states that there was no evidence of an effect on cardiac repolarization in patients who received azelastine hydrochloride nasal spray (548 mcg twice daily for 56 days) in a placebo-controlled study.1 Although 3- to 7-millisecond increases in mean QT_c intervals were observed with higher oral dosages of the drug, such increases were not considered to be clinically important.1 The manufacturer of azelastine hydrochloride nasal spray also states that no clinically important drug interactions were reported in a study of individuals receiving azelastine orally with erythromycin or ketoconazole.1,16 Erythromycin did not affect azelastine plasma concentrations or QT_c intervals, and while ketoconazole interfered with measurement of azelastine plasma concentrations, QT_c intervals were not affected.1,16

Allergic Conjunctivitis

Azelastine is used for the symptomatic treatment of ocular itching associated with allergic conjunctivitis.2,30,31 This indication is based on environmental studies (duration 2-8 weeks) in which therapy with azelastine ophthalmic solution was more effective than vehicle in providing relief of ocular itching in children and adults with allergic conjunctivitis.2 In a conjunctival antigen challenge study in adults, azelastine ophthalmic solution was more effective than vehicle in preventing ocular itching associated with allergic conjunctivitis.2 For the prevention of ocular itching, ophthalmic azelastine has a rapid onset of action (3 minutes) and a duration of effect of about 8 hours.2

Avoidance of allergen and other triggering factors (e.g., irritants) and application of cold compresses and lubricating eye drops are the initial means of managing allergic conjunctivitis.32,33,34,35,36,37 Drug therapy generally is reserved for use when such avoidance is not possible or is ineffective, and can include both prophylactic (e.g., topical mast-cell stabilizers) and symptomatic (e.g., topical and/or systemic antihistamines, topical vasoconstrictors, topical steroidal and nonsteroidal anti-inflammatory agents [NSAIAs]) therapy.32,33,34,35,36,37 The specific therapy(ies) employed will depend on the characteristics and severity of the allergic conjunctivitis.32,33,34,35,36,37 For patients with seasonal allergic conjunctivitis, prophylaxis with a mast-cell stabilizer often is initiated before and maintained throughout the pollen season, and symptomatic therapy with other agents (e.g., topical antihistamines, topical NSAIAs) generally is initiated as necessary to provide acute relief.32,33,34,35,36 Topical corticosteroids usually are reserved for short-term use in patients with moderate to severe symptoms of allergic conjunctivitis.32,33,34,35

The principal adverse effects of ocular azelastine are local (e.g., transient ocular burning/stinging, bitter taste), but adverse systemic effects (e.g., headache) also can occur 2,30,31 Asthma,2 dyspnea,2 fatigue,2 influenza-like symptoms,2 pruritus,2 rhinitis,2 pharyngitis,2 temporary blurring of vision,2 conjunctivitis,2 and ocular pain2 have been reported in 1-10% of patients receiving azelastine ophthalmic solution.2

For additional information on this and other uses of antihistamines, see Uses in the Antihistamines General Statement 4:00.

Administration

Intranasal Administration

Azelastine hydrochloride nasal spray is administered intranasally, using a spray pump.1,11 Patients should be instructed carefully in the assembly and use of the spray pump and the bottle containing azelastine solution.1 To obtain optimum results, patients also should be given a copy of the patient instructions provided by the manufacturer.1,11,14 Three months after initial insertion of the spray pump into the first of the 2 bottles provided in the dispensing package patients should discard both bottles of the drug, and usage of the bottles should not exceed the printed expiration date on the label.14 If the spray nozzle becomes clogged, the spray pump unit should be soaked in warm water, actuating the pump several times while holding it under the water;14 cleaning by inserting a sharp object into the spray pump nozzle is not recommended.14 The spray pump should be dried thoroughly before reassembly and repriming.14

Before initial use of azelastine hydrochloride nasal spray, patients should prime the pump until a fine mist appears, using up to 4 actuations of the pump.1,11,14 To actuate the spray pump and bottle assembly for priming and for intranasal use, the bottle is held in one hand, with 2 fingers on the shoulders of the pump unit and the thumb on the bottom of the bottle.14 A fine mist is produced by pressing the bottom firmly and rapidly upward with the thumb.14 If the nasal inhaler has not been used for 3 or more days, the pump should be reprimed with 2 actuations or until a fine mist appears.14 When the spray pump is inserted into the second bottle provided in the dispensing package, the pump should again be primed.14 After priming, the spray pump delivers a 137-mcg metered dose of azelastine hydrochloride aqueous nasal solution (equivalent to about 125 mcg of azelastine base).1 Caution should be exercised to avoid spraying azelastine hydrochloride nasal spray into the eyes.1,11,14

Prior to administration of azelastine hydrochloride nasal spray, patients should clear their nasal passages by gently blowing their nose.14 Patients should insert the nasal spray tip ¼ to ½ inch into a nostril and, tilting the head slightly forward while holding the bottle vertically upright, aim the spray tip toward the back of the nose.14 The pump then should be rapidly and firmly pressed and actuated into the nostril while holding the other nostril closed, gently sniffing at the same time;14 a burning or stinging sensation may be felt briefly after actuation.14 This procedure then is repeated for the other nostril,14 and then again, beginning with the first nostril, to provide a second spray into each nostril.14 Patients should be instructed not to administer the entire dose (i.e., 4 sprays) into a single nostril.2,14 The patient should not tilt the head back after dosing.14 If azelastine hydrochloride solution is delivered in a stream of liquid rather than as a mist, it may fail to provide maximum benefit and may cause some discomfort.14 Therefore, patients should be instructed that a fine mist, produced only by rapid and firm pumping action, is required with each actuation.14 The patient instructions provided by the manufacturer should be consulted for additional information on use of the spray pump containing azelastine hydrochloride.1,2,11,14

Ophthalmic Administration

Azelastine ophthalmic solution is applied topically to the eye.2 The manufacturer states that commercially available azelastine hydrochloride ophthalmic solution is not for injection or oral use. 2 To avoid contaminating the dropper tip and solution, patients should be advised that they should avoid allowing the tip of the dispensing container to contact any surface, the eyelids, or surrounding structures.2

The manufacturer states that azelastine ophthalmic solution should not be used for the symptomatic management of contact lens-related irritation.2 Patients should be advised not to wear contact lenses if their eye(s) are red.2 In addition, patients should be advised to remove their soft contact lenses prior to administration of each dose of azelastine ophthalmic solution because the solution contains benzalkonium chloride, which may be absorbed by soft contact lenses.2 Patients whose eyes are not red may reinsert soft contact lenses after at least 10 minutes following administration of the ophthalmic solution.2

Dosage

The manufacturer preferentially labels the dosage and concentration of azelastine hydrochloride in terms of the hydrochloride salt.1,2,14

Seasonal Allergic Rhinitis

Each 137 mcg of azelastine hydrochloride nasal spray is equivalent to 125 mcg of the base.1 When properly primed, the nasal spray pump delivers approximately 100 metered doses per bottle.1,16

The manufacturer states that safety and efficacy of intranasal azelastine have not been established in children younger than 5 years of age.1

For the symptomatic treatment of seasonal allergic rhinitis, the usual dosage of intranasal azelastine hydrochloride solution as the intranasal spray for adults and children 12 years of age or older is 2 sprays (274 mcg) in each nostril twice daily (1096 mcg of azelastine hydrochloride total daily, equivalent to 1 mg of azelastine base daily).1,11,16 Patients should be instructed to alternate nostrils between each actuation of azelastine hydrochloride nasal spray.14

For the symptomatic treatment of seasonal allergic rhinitis, the usual dosage of intranasal azelastine hydrochloride solution as the intranasal spray for children 5-11 years of age is 1 spray (137 mcg) in each nostril twice daily (548 mcg of azelastine hydrochloride total daily, equivalent to 500 mcg of azelastine base daily).1

Allergic Conjunctivitis

For the symptomatic treatment of ocular itching associated with allergic conjunctivitis in adults and children 3 years of age or older, the usual dosage of azelastine expressed in terms of the hydrochloride is 1 drop of a 0.05% solution in the affected eye(s) twice daily.2 The manufacturer states that safety and efficacy of azelastine ophthalmic solution has not been established in children younger than 3 years of age.2

Description

Azelastine is a histamine H₁-receptor antagonist.1,2 Azelastine, a phthalazinone derivative, is structurally unrelated to other currently available antihistamines and has been characterized a selective H₁-receptor antagonist.1,2,11,13,21,24,25,27 Although azelastine has been referred to as a second generation (“nonsedating”) antihistamine,10,12 adverse CNS effects (e.g., drowsiness) may occur with the drug, particularly at relatively high doses or when administered with CNS depressants (e.g., alcohol).1,11,12,15,16,22 The desmethyl metabolite also possesses antihistaminic activity.1,10,11,16 In addition, azelastine inhibits other mediators (e.g., leukotrienes, platelet activating factor [PAF]) involved in allergic reactions.2,29 Azelastine may inhibit the accumulation of eosinophils at the site of allergic inflammation and prevent eosinophil degranulation.1,29

Azelastine currently is commercially available in the US as azelastine hydrochloride nasal spray preparation, having a pH of approximately 6.8.1 When administered intranasally, approximately 40% of a dose reaches systemic circulation.1,11,16

Azelastine also is commercially available as azelastine hydrochloride ophthalmic solution.2 Azelastine hydrochloride ophthalmic solution is a sterile solution of the drug in water for injection; the solution contains benzalkonium chloride as a preservative and also contains edetate disodium, hydroxypropyl methylcellulose, sorbitol, and sodium hydroxide.2 Azelastine hydrochloride ophthalmic solution has a pH of approximately 5-6.5 and an osmolarity of approximately 271-312 mOsml/L.2

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Wallace Laboratories. Astelin^® (azelastine hydrochloride) nasal spray prescribing information. Cranbury, NJ; 2000 Apr.

2. Muro Pharmaceuticals. Optivar^® (azelastine hydrochloride) ophthalmic solution prescribing information. Tewksbury, MA; 2000 May.

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