Azelastine hydrochloride 0.5 mg/ml Eye drops solution

Treatment and prevention of the symptoms of seasonal allergic conjunctivitis in adults and children 4 years and older.

Treatment of the symptoms of non-seasonal (perennial) allergic conjunctivitis in adults and children 12 years and older.

Seasonal allergic conjunctivitis

The usual dosage in adults and children 4 years and older is one drop in each eye twice daily that can be increased, if necessary to four times daily. If allergen exposure is anticipated Azelastine hydrochloride Eye drops, solution should be administered prophylactically, prior to the exposure.

Non-seasonal (perennial) allergic conjunctivitis:

The usual dosage in adults and children 12 years and older is one drop in each eye twice daily that can be increased, if necessary to four times daily.

As safety and efficacy have been demonstrated in clinical trials for a period of up to 6 weeks, the duration of any course should be limited to a maximum of 6 weeks.

Patients should be advised to contact their doctor if symptoms worsen or do not improve after 48 hours.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Azelastine hydrochloride Eye drops, solution is not intended for treatment of eye infections. Further warnings see 4.5 and 4.6.

Azelastine hydrochloride Eye drops, solution contains the preservative benzalkonium chloride.Benzalkonium chloride may cause eye irritation, especially with dry eyes or disorders of the cornea. Contact with soft contact lenses should be avoided. Contact lenses should be removed prior to application and the patient should wait at least 15 minutes before reinsertion. Known to discolour soft contact lenses.

No specific interaction studies have been performed.

Interaction studies at high oral doses of Azelastine have been performed however they bear no relevance to Azelastine hydrochloride Eye drops, solution, as systemic levels, after administration of the eye drops, are in the picogram range.

Pregnancy

There is insufficient information available to establish the safety of azelastine in human pregnancy. At high oral doses azelastine has shown to induce adverse effects (foetal death, growth retardation and skeletal malformation) in experimental animals. Local ocular application will result in minimal systemic exposure (picogram range). However, caution should be exercised when using Azelastine hydrochloride Eye drops, solution during pregnancy.

Breast Feeding

Azelastine is excreted into the milk in low quantities. For that reason Azelastine hydrochloride Eye drops, solution is not recommended during lactation.

Fertility

Effects on human fertility have not been investigated.

The mild, transient irritation which can be experienced after application of Azelastine hydrochloride Eye drops, solution is unlikely to affect vision to any greater extent. However, if there are any transient effects on vision, the patient should be advised to wait until this clears before driving or operating machinery.

The assessment of undesirable effects is based on the following frequencies:

Very common (≥ 1/10)

Common (≥ 1/100 to <1/10)

Uncommon (≥ 1/1,000 to <1/100)

Rare (≥ 1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Immune system disorders

Very rare: Allergic reactions (such as rash and pruritus).

Nervous system disorders

Uncommon: Bitter taste.

Eye disorders

Common: Mild, transient irritation in the eye.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Symptoms

No specific reactions after ocular overdosage are known, and with the ocular route of administration, overdosage reactions are not anticipated.

There is no experience with the administration of toxic doses of azelastine hydrochloride in humans. In the case of overdose or intoxication, disturbances of the central nervous system are to be expected based on the results of animal experiments.

Management

Treatment of these disorders must be symptomatic. There is no known antidote.

Pharmacotherapeutic group: Antiallergic, ATC code : S01GX07

Azelastine, a phthalazinone derivative is classified as a potent long-acting anti-allergic compound with selective H1 antagonist properties. An additional anti-inflammatory effect could be detected after topical ocular administration. Data from in vivo (pre-clinical) and in vitro studies show that Azelastine inhibits the synthesis or release of the chemical mediators known to be involved in early and late stage allergic reactions e.g. leukotriene, histamine, PAF and serotonin.

To date, long term therapy ECG evaluations of patients treated with high oral doses of azelastine, have shown that in multiple dose studies, there is no clinically significant effect of azelastine on the corrected QT (QTc) interval.

No association of azelastine with ventricular arrhythmia or torsade de pointes was observed in over 3700 patients treated with oral azelastine.

Relief of symptoms of allergic conjunctivitis should be noticed after 15-30 minutes.

General characteristics (systemic pharmacokinetics)

Following oral administration azelastine is rapidly absorbed showing an absolute bioavailability of 81%. Food has no influence on absorption.

The volume of distribution is high indicating distribution predominantly into the periphery. The level of protein binding is relatively low (80 - 90%, a level too low to give concern over drug displacement reactions).

Plasma elimination half-lives after a single dose of azelastine are approximately 20 hours for azelastine and about 45 hours for the therapeutically active metabolite N-Desmethyl azelastine. Excretion occurs mainly via the faeces. The sustained excretion of small amounts of the dose in the faeces suggests that some entero-hepatic circulation may take place.

Characteristics in patients (ocular pharmacokinetics)

After repeated ocular application of Azelastine hydrochloride (up to one drop in each eye, four times daily), C_max steady state plasma levels of azelastine hydrochloride were very low and were detected at or below the limit of quantification.

Azelastine hydrochloride displayed no sensitising potential in the guinea pig. Azelastine demonstrated no genotoxic potential in a battery of in vitro and in vivo tests, nor any carcinogenic potential in rats or mice.

In male and female rats, azelastine at oral doses greater than 3.0 mg/kg/day caused a dose-related decrease in the fertility index; no substance-related alterations were found in the reproductive organs of males or females during chronic toxicity studies, however.

Embryotoxic and teratogenic effects in rats, mice and rabbits occurred only at maternal toxic doses (for example, skeletal malformations were observed in rats and rabbits at doses of 68.6 mg/kg/day).

Benzalkonium chloride

Hypromellose

Disodium edetate,

Liquid sorbitol (crystallising)

Sodium hydroxide (for pH adjuster)

Water for injections.

Not applicable.

Unopened: 2 years.

Once opened: Do not use for longer than 28 days

This medicinal product does not require any special storage conditions

10 ml LDPE Blow fill Seal (BFS) container with white polypropylene spiked cap having a tamper-proof base ring. One bottle contains either 6 ml, 8 ml or 10 ml solution.

Not all pack sizes may be marketed.

No special requirements.