Astelin - General Information
Astelin is an antihistamine and mast cell stabilizer available as a nasal spray for hay fever and as eye drops for allergic conjunctivitis.
Pharmacology of Astelin
Astelin is a relatively selective histamine H1 antagonist and an inhibitor of the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. Based on in vitro studies using human cell lines, inhibition of other mediators involved in allergic reactions (e.g. leukotrienes and PAF) has been demonstrated with azelastine. Decreased chemotaxis and activation of eosinophils has also been demonstrated.
Astelin for patients
To prevent contaminating the dropper tip and solution, care should be taken 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.
Patients should be advised not to wear a contact lens if their eye is red. OPTIVAR™ should not be used to treat contact lens related irritation. The preservative in OPTIVAR™, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling OPTIVAR™ before they insert their contact lenses.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Azelastine hydrochloride administered orally for 24 months was not carcinogenic in rats and mice at doses up to 30 mg/kg/day and 25 mg/kg/day, respectively. Based on a 30 µl drop size, these doses were approximately 25,000 and 21,000 times higher than the maximum recommended ocular human use level of 0.001 mg/kg/day for a 50 kg adult.
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 of up to 25,000 times the maximum recommended ocular human use level. At 68.6 mg/kg/day (57,000 times the maximum recommended ocular human use level), the duration of the estrous cycle was prolonged and copulatory activity and the number of pregnancies were decreased. The numbers of corpora lutea and implantations were decreased; however, the implantation ratio was not affected.
Teratogenic Effects: Pregnancy Category C. Azelastine hydrochloride has been shown to be embryotoxic, fetotoxic, and teratogenic (external and skeletal abnormalities) in mice at an oral dose of 68.6 mg/kg/day (57,000 times the recommended ocular human use level). At an oral dose of 30 mg/kg/day (25,000 times the recommended ocular human use level), delayed ossification (undeveloped metacarpus), and the incidence of 14th rib were increased in rats. At 68.6 mg/kg/day (57,000 times the maximum recommended ocular human use level) azelastine hydrochloride caused resorption and fetotoxic effects in rats. The relevance to humans of these skeletal findings noted at only high drug exposure levels is unknown.
There are no adequate and well-controlled studies in pregnant women. OPTIVAR™ should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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 OPTIVAR™ is administered to a nursing woman.
Safety and effectiveness in pediatric patients below the age of 3 have not been established.
No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.
OPTIVAR™ is contraindicated in persons with known or suspected hypersensitivity to any of its components.
Additional information about Astelin
Astelin Indication: For the treatment of itching of the eye associated with allergic conjunctivitis.
Mechanism Of Action: Antihistamines such as azelastine appear to compete with histamine for histamine H1- receptor sites on effector cells (mast cells). The antihistamines antagonize those pharmacological effects of histamine which are mediated through activation of H1- receptor sites and thereby reduce the intensity of allergic reactions and tissue injury response involving histamine release.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Azelastine
Synonyms: Azelastina [INN-Spanish]; Azelastinum [INN-Latin]
Drug Category: Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Bronchodilator Agents; Histamine H1 Antagonists; Lipoxygenase Inhibitors; Platelet Aggregation Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Azelastine: Astelin; Optivar;
Absorption: Absorption of azelastine following ocular administration was relatively low. Systemic bioavailability is approximately 40% after nasal administration.
Toxicity (Overdose): Not Available
Protein Binding: In-vitro studies in human plasma indicate that the plasma protein binding of azelastine and N-desmethylazelastine are approximately 88% and 97%, respectively.
Biotransformation: Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system, however the exact cytochrome P450 isoenzyme involved has not been determined. The major metabolite, desmethylazelastine, also has H1-receptor antagonist activity.
Half Life: Elimination half-life (based on intravenous and oral administration) is 22 hours. Elimination half-life of the active metabolite, desmethylazelastine, is 54 hours (after oral administration of azelastine).
Dosage Forms of Astelin: Solution / drops Ophthalmic
Chemical IUPAC Name: 4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)phthalazin-1-one
Chemical Formula: C22H24ClN3O
Azelastine on Wikipedia: http://en.wikipedia.org/wiki/Azelastine
Organisms Affected: Humans and other mammals