Seasonal Allergic Rhinitis
Azelastine hydrochloride spray is used intranasally to provide symptomatic relief of seasonal allergic rhinitis (e.g., hay fever). 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; symptomatic relief reached peak effect between 4-6 hours and persisted throughout the 12-hour dosage interval. In addition to relief of nasal symptoms, improvement in ocular manifestations also may occur, possibly secondary to systemic absorption of the drug. 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. However, unlike intranasal corticosteroids, azelastine does not appear to exhibit local histologic anti-inflammatory activity; therefore, beneficial effects on nasal obstruction appear to result principally from antihistaminic and/or other activity. 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.
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. 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. 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.
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. Anaphylactoid reactions, application site reaction, chest pain, aggravated condition, confusion, diarrhea, dyspnea, facial edema, involuntary muscle contractions, paresthesia, parosmia, pruritus, rash, tolerance, urinary retention, vision abnormality, and xerophthalmia have occurred in patients receiving azelastine nasal spray; a causal relationship between these events and the drug have not been established. 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. Although 3- to 7-millisecond increases in mean QTc intervals were observed with higher oral dosages of the drug, such increases were not considered to be clinically important. 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. Erythromycin did not affect azelastine plasma concentrations or QTc intervals, and while ketoconazole interfered with measurement of azelastine plasma concentrations, QTc intervals were not affected.
Azelastine is used for the symptomatic treatment of ocular itching associated with allergic conjunctivitis. 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. In a conjunctival antigen challenge study in adults, azelastine ophthalmic solution was more effective than vehicle in preventing ocular itching associated with allergic conjunctivitis. 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.
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. 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. The specific therapy(ies) employed will depend on the characteristics and severity of the allergic conjunctivitis. 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. Topical corticosteroids usually are reserved for short-term use in patients with moderate to severe symptoms of allergic conjunctivitis.
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 Asthma, dyspnea, fatigue, influenza-like symptoms, pruritus, rhinitis, pharyngitis, temporary blurring of vision, conjunctivitis, and ocular pain have been reported in 1-10% of patients receiving azelastine ophthalmic solution.
For additional information on this and other uses of antihistamines, see Uses in the Antihistamines General Statement 4:00.