Azelastine

Astelin, Astepro

Abnormalities in bones of the skeleton have been noted in animals receiving more than 240 times the human dose of azelastine. There are no adequate studies in pregnant women. Azelastine should be used during pregnancy only if the physician feels that the benefit justifies the potential risk to the fetus.

It is not known whether azelastine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azelastine is used by a nursing woman.

Azelastine is a prescription medication used to treat allergy symptoms of the eyes or nose such as runny or stuffy nose, sneezing, itching. This medication belongs to a group of drugs called antihistamines. It works by preventing histamine release and by blocking histamine at receptors. Histamine is a chemical of the immune system that causes allergy symptoms.

Azelastine comes in nasal spray form to be sprayed into your nose, usually twice a day.

Azelastine also comes in eye drop form to be applied into the affected eye(s) twice a day.

Common side effects of azelastine nasal spray include unusual taste, nose or eye irritation, and headache. Do not operate machinery or drive until you know azelastine will affect you. 

Common side effects of azelastine eye drops include eye irritation and stinging.

Azelastine is a prescription medication used to treat allergy symptoms of the eyes or nose such as runny or stuffy nose, sneezing, itching.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Azelastine is part of the drug class:

• Other antiallergics

• Azelastine nasal spray is to be sprayed into your nose, usually twice a day. Do not spray it into your eyes or mouth.
  • The azelastine bottle will need to be primed before you use it for the first time. You should see a fine mist after you do six priming sprays. This will indicate it is ready for use. (You will need to prime azelastine nasal spray if you have not used the spray for 3 or more days.)
  • Blow your nose first. Then while spraying the medicine, gently breathe in (inhale). To avoid experiencing a bitter taste after taking azelastine, avoid tilting your head back right after taking azelastine.
  • After using 200 sprays, throw away the bottle.
• Azelastine eye drops is to be sprayed into the affected eye(s) twice a day.
  • To prevent contaminating the dropper tip and eye drop solution, do not to touch any surface, the eyelids, or surrounding areas with the dropper tip of the bottle.
  • Keep bottle tightly closed when not in use.
  • This product is sterile when packaged.
  • Do not to wear a contact lens if eyes are red.
  • Azelastine eye drops should not be used to treat contact lens related irritation.
  • If you wear soft contact lenses and if your eyes are not red, wait at least 10 minutes after using azelastine eye drops before re-inserting your contact lenses.

• Store azelastine nasal spray at 20°-25°C (68°-77°F).
• Store azelastine drops at 2° and 25°C (36° and 77°F).
• Keep this and all medicines out of the reach of children.

12.1 Mechanism of Action

Azelastine HCl, a phthalazinone derivative, exhibits histamine H1-receptor antagonist activity in isolated tissues, animal models, and humans. Azelastine HCl nasal spray, 0.1% is administered as a racemic mixture with no difference in pharmacologic activity noted between the enantiomers in in vitro studies. The major metabolite, desmethylAzelastine, also possesses H1-receptor antagonist activity.

12.2 Pharmacodynamics

Cardiac Electrophysiology:

In a placebo-controlled study (95 subjects with allergic rhinitis), there was no evidence of an effect of Azelastine HCl nasal spray, 0.1% (2 sprays per nostril twice daily for 56 days) on cardiac repolarization as represented by the corrected QT interval (QTc) of the electrocardiogram. Following multiple dose oral administration of Azelastine 4 mg or 8 mg twice daily, the mean change in QTc was 7.2 msec and 3.6 msec, respectively.

Interaction studies investigating the cardiac repolarization effects of concomitantly administered oral Azelastine HCl and erythromycin or ketoconazole were conducted. These drugs had no effect on QTc based on analysis of serial electrocardiograms. At a dose approximately 8 times the maximum recommended dose, Azelastine HCl does not prolong the QTc interval to any clinically relevant extent.

12.3 Pharmacokinetics

Absorption: After intranasal administration, the systemic bioavailability of Azelastine HCl is approximately 40%. Maximum plasma concentrations (Cmax) are achieved in 2 to 3 hours.

Azelastine HCl administered intranasally at doses above two sprays per nostril twice daily for 29 days resulted in greater than proportional increases in Cmax and area under the curve (AUC) for Azelastine.

Distribution: Based on intravenous and oral administration, the steady-state volume of distribution is 14.5 L/kg. In vitro studies with human plasma indicate that the plasma protein binding of Azelastine and its metabolite, desmethylAzelastine, are approximately 88% and 97%, respectively.

Metabolism: Azelastine is oxidatively metabolized to the principal active metabolite, desmethylAzelastine, by the cytochrome P450 enzyme system. The specific P450 isoforms responsible for the biotransformation of Azelastine have not been identified. After intranasal dosing of Azelastine HCl to steady-state, plasma concentrations of desmethylAzelastine range from 20% to 50% of Azelastine concentrations. Limited data indicate that the metabolite profile is similar when Azelastine HCl is administered via the intranasal or oral route.

Elimination: Based on intravenous and oral administration, the elimination half-life and plasma clearance are 22 hours and 0.5 L/h/kg, respectively. Approximately 75% of an oral dose of radiolabeled Azelastine HCl was excreted in the feces with less than 10% as unchanged Azelastine.

Special Populations:

Hepatic Impairment: Following oral administration, pharmacokinetic parameters were not influenced by hepatic impairment.

Renal Impairment: Based on oral, single-dose studies, renal insufficiency (creatinine clearance <50 mL/min) resulted in a 70% to 75% higher Cmax and AUC compared to normal subjects. Time to maximum concentration was unchanged.

Age: Following oral administration, pharmacokinetic parameters were not influenced by age.

Gender: Following oral administration, pharmacokinetic parameters were not influenced by gender.

Race: The effect of race has not been evaluated.

Drug-Drug Interactions:

Erythromycin: No significant pharmacokinetic interaction was observed with the co-administration of orally administered Azelastine (4 mg twice daily) with erythromycin (500 mg three times daily for 7 days). In this study, co-administration of orally administered Azelastine with erythromycin resulted in Cmax of 5.36 ± 2.6 ng/mL and AUC of 49.7 ± 24 ng•h/mL for Azelastine, whereas, administration of Azelastine alone resulted in Cmax of 5.57 ± 2.7 ng/mL and AUC of 48.4 ± 24 ng•h/mL for Azelastine.

Cimetidine and Ranitidine: In a multiple-dose, steady-state drug interaction trial in healthy subjects, cimetidine (400 mg twice daily) increased orally administered mean Azelastine (4 mg twice daily) concentrations by approximately 65%. No pharmacokinetic interaction was observed with co-administration of orally administered Azelastine (4 mg twice daily) with ranitidine hydrochloride (150 mg twice daily). Oral co-administration of Azelastine with ranitidine resulted in Cmax of 8.89 ±3.28 ng/mL and AUC of 88.22 ± 40.43 ng•h/mL for Azelastine, whereas, Azelastine when administered alone resulted in Cmax of 7.83 ± 4.06 ng/mL and AUC of 80.09 ± 43.55 ng•h/mL for Azelastine.

Theophylline: No significant pharmacokinetic interaction was observed with the co-administration of an oral 4 mg dose of Azelastine HCl twice daily and theophylline 300 mg or 400 mg twice daily.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In 2-year carcinogenicity studies in rats and mice, Azelastine HCl did not show evidence of carcinogenicity at oral doses up to 30 mg/kg and 25 mg/kg, respectively. These doses were approximately 150 and 60 times the maximum recommended human daily intranasal dose [MRHDID] on a mg/m2 basis.

Azelastine HCl 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 150 times the MRHDID in adults on a mg/m2 basis). At 68.6 mg/kg (approximately 340 times the MRHDID 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.