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Concurrent use of Astelin Nasal Spray with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur.

Cimetidine increased the mean Cmax and AUC of orally administered azelastine hydrochloride by approximately 65%. Ranitidine hydrochloride had no effect on azelastine pharmacokinetics.

Interaction studies investigating the cardiac effects, as measured by the corrected QT interval (QTc), of concomitantly administered oral azelastine hydrochloride and erythromycin or ketoconazole were conducted. Oral erythromycin had no effect on azelastine pharmacokinetics or QTc based on analyses of serial electrocardiograms. Ketoconazole interfered with the measurement of azelastine plasma concentrations; however, no effects on QTc were observed.

/HUMAN EXPOSURE STUDIES/ ... With three different doses of oral azelastine, /investigators/ have performed a dose-response study to determine its protective effect on the airways against histamine-induced bronchoconstriction in 12 patients with mild, atopic asthma. On 4 separate days, patients undertook standardized inhalation-challenge tests with increasing concentrations of histamine (0.03 to 32 mg/mL) 4 hours after placebo or azelastine, 4.4, 8.8, and 17.6 mg, administered double blind and in random order. On 2 additional days, patients underwent methacholine challenge tests after placebo or azelastine, 17.6 mg. Baseline FEV1 between treatment days and 4 hours after placebo and azelastine did not change significantly. The three doses of azelastine, 4.4, 8.8, and 17.6 mg, increased the concentration of histamine required to cause a 20% fall in FEV1 (PC20) from 0.16 mg/mL geometric mean (GM) after placebo to 1.98 (p less than 0.01), 8.8 (p less than 0.01), and 8.1 (p less than 0.01) mg/mL, respectively. GM potency ratios derived from the PC20 values obtained for each patient indicated that the three increasing doses of azelastine displaced the histamine dose-response curve to the right by factors of 12.8, 54.4, and 50.2. Azelastine had no effect on the airway response to methacholine with GM PC20 values of 0.16 and 0.19 after placebo and azelastine, 17.6 mg. Azelastine is a potent H1histamine-receptor antagonist on human airways in vivo without demonstrable anticholinergic effect.

/SIGNS AND SYMPTOMS/ There have been no reported overdosages with Astelin Nasal Spray. Acute overdosage by adults with this dosage form is unlikely to result in clinically significant adverse events, other than increased somnolence, since one bottle of Astelin Nasal Spray contains 30 mg of azelastine hydrochloride. Clinical studies in adults with single doses of the oral formulation of azelastine hydrochloride (up to 16 mg) have not resulted in increased incidence of serious adverse events.

/LABORATORY ANIMALS: Acute Exposure/ Oral doses of 120 mg/kg and greater (approximately 460 times the maximum recommended daily intranasal dose in adults and children on a mg/sq m basis) were lethal in mice. Responses seen prior to death were tremor, convulsions, decreased muscle tone, and salivation.

/LABORATORY ANIMALS: Acute Exposure/ In dogs, single oral doses as high as 10 mg/kg (approximately 260 times the maximum recommended daily intranasal dose in adults and children on a mg/sq m basis) were well tolerated, but single oral doses of 20 mg/kg were lethal.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In 2 year carcinogenicity studies in rats and mice azelastine hydrochloride did not show evidence of carcinogenicity at oral doses up to 30 mg/kg and 25 mg/kg, respectively (approximately 240 and 100 times the maximum recommended daily intranasal dose in adults and children on a mg/sq m basis).

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In rabbits, oral doses of 30 mg/kg and greater (approximately 500 times the maximum recommended daily intranasal dose in adults on a mg/sq m basis) caused abortion, delayed ossification and decreased fetal weight; however, these doses also resulted in severe maternal toxicity. Neither fetal nor maternal effects occurred at a dose of 0.3 mg/kg (approximately 5 times the maximum recommended daily intranasal dose in adults on a mg/sq m basis).

For more Non-Human Toxicity Excerpts (Complete) data for Azelastine (10 total), please visit the HSDB record page.

The manufacturer states that azelastine ophthalmic solution should not be used for the symptomatic management of contact lens-related irritation. Patients should be advised not to wear contact lenses if their eye(s) are red.

Patients who are, or may become, pregnant should be told that this product should be used in pregnancy or during lactation only if the potential benefit justifies the potential risks to the fetus or nursing infant.

There is no known antidote to azelastine hydrochloride nasal spray.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

◉ Summary of Use during Lactation

◈ What is azelastine?

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including azelastine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Azelastine hydrochloride/

MEDICATION

Use (kg; approx.) in Germany (2009): >25

For the symptomatic treatment of seasonal allergic rhinitis and non-allergic rhinitis, as well as symptomatic relief of ocular itching associated with allergic conjunctivitis.

Azelastine hydrochloride preparations: (AHFS, 2011)

Azelastine currently is commercially available in the US as azelastine hydrochloride nasal spray preparation, having a pH of approximately 6.8.

Azelastine also is commercially available as azelastine hydrochloride ophthalmic solution. 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. Azelastine hydrochloride ophthalmic solution has a pH of approximately 5-6.5 and an osmolarity of approximately 271-312 mOsmL/L.