Activities Requiring Mental Alertness: In clinical trials, the occurrence of somnolence has been reported in some patients taking Astelin® Nasal Spray; due caution should therefore be exercised when driving a car or operating potentially dangerous machinery while using Astelin® Nasal Spray. 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.

Information for Patients: Patients should be instructed to use Astelin® Nasal Spray only as prescribed. For the proper use of the nasal spray and to attain maximum improvement, the patient should read and follow carefully the accompanying patient instructions. Patients should be instructed to prime the delivery system before initial use and after storage for 3 or more days (see PATIENT INSTRUCTIONS FOR USE). Patients should also be instructed to store the bottle upright at room temperature with the pump tightly closed and out of the reach of children. In case of accidental ingestion by a young child, seek professional assistance or contact a poison control center immediately.

Patients should be advised against the concurrent use of Astelin® Nasal Spray with other antihistamines without consulting a physician. 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. Patients should be advised to assess their individual responses to Astelin® Nasal Spray before engaging in any activity requiring mental alertness, such as driving a car or operating machinery. Patients should be advised that the concurrent use of Astelin® Nasal Spray with alcohol or other CNS depressants may lead to additional reductions in alertness and impairment of CNS performance and should be avoided (see Drug Interactions).

Drug Interactions: 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 (400 mg twice daily) increased the mean Cmax and AUC of orally administered azelastine hydrochloride (4 mg twice daily) by approximately 65%. Ranitidine hydrochloride (150 mg twice daily) 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 (500 mg three times daily for seven days) had no effect on azelastine pharmacokinetics or QTc based on analyses of serial electrocardiograms. Ketoconazole (200 mg twice daily for seven days) interfered with the measurement of azelastine plasma concentrations; however, no effects on QTc were observed.

No significant pharmacokinetic interaction was observed with the coadministration of an oral 4 mg dose of azelastine hydrochloride twice daily and theophylline 300 mg or 400 mg twice daily.

Carcinogenesis, Mutagenesis, Impairment of Fertility: 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/m2 basis).

Azelastine hydrochloride showed no genotoxic effects in the Ames test, DNA repair test, mouse lymphoma forward mutation assay, mouse micronucleus test, or chromosomal aberration test in rat bone marrow.

Reproduction and fertility studies in rats showed no effects on male or female fertility at oral doses up to 30 mg/kg (approximately 240 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis). At 68.6 mg/kg (approximately 560 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis), the duration of estrous cycles was prolonged and copulatory activity and the number of pregnancies were decreased. The numbers of corpora lutea and implantations were decreased; however, pre-implantation loss was not increased.

Pregnancy Category C: Azelastine hydrochloride has been shown to cause developmental toxicity. Treatment of mice with an oral dose of 68.6 mg/kg (approximately 280 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis) caused embryo-fetal death, malformations (cleft palate; short or absent tail; fused, absent or branched ribs), delayed ossification and decreased fetal weight. This dose also caused maternal toxicity as evidenced by decreased body weight. Neither fetal nor maternal effects occurred at a dose of 3 mg/kg (approximately 10 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis).

In rats, an oral dose of 30 mg/kg (approximately 240 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis) caused malformations (oligo-and brachydactylia), delayed ossification and skeletal variations, in the absence of maternal toxicity. At 68.6 mg/kg (approximately 560 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis) azelastine hydrochloride also caused embryo-fetal death and decreased fetal weight; however, the 68.6 mg/kg dose caused severe maternal toxicity. Neither fetal nor maternal effects occurred at a dose of 3 mg/kg (approximately 25 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis).

In rabbits, oral doses of 30 mg/kg and greater (approximately 500 times the maximum recommended daily intranasal dose in adults on a mg/m2 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/m2 basis).

There are no adequate and well-controlled clinical studies in pregnant women. Astelin® Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether azelastine hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Astelin® Nasal Spray is administered to a nursing woman.

Pediatric Use: The safety and effectiveness of Astelin® Nasal Spray at a dose of 1 spray per nostril twice daily has been established for patients 5 through 11 years of age for the treatment of symptoms of seasonal allergic rhinitis. The safety of this dosage of Astelin® Nasal Spray was established in well-controlled studies of this dose in 176 patients 5 to 12 years of age treated for up to 6 weeks. The efficacy of Astelin® Nasal Spray at this dose is based on an extrapolation of the finding of efficacy in adults, on the likelihood that the disease course, pathophysiology and response to treatment are substantially similar in children compared to adults, and on supportive data from controlled clinical trials in patients 5 to 12 years of age at the dose of 1 spray per nostril twice daily. The safety and effectiveness of Astelin® Nasal Spray in patients below the age of 5 years have not been established.

Geriatric Use: Clinical studies of Astelin® Nasal Spray did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.