SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Azelastine.

0.5 mg / ml, Eye Drops, solution.

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Azelastine hydrochloride 0.05% (0.5 mg/ml). Each drop contains 0.015 mg azelastine hydrochloride.

For excipients see section 6.1.

3    PHARMACEUTICAL FORM

Eye drops, solution.

Clear, colourless solution

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

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.

4.2 Posology and method of administration

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 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.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4    Special warnings and precautions for use

As with other ophthalmic solutions, Optilast is not recommended for use whilst wearing contact lenses.

Optilast is not intended for treatment of eye infections. Further warnings see 4.5 and 4.6.

4.5    Interaction with other medicinal products and other forms of interaction

No specific interaction studies with Azelastine have been performed.

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

4.6 Pregnancy and lactation

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 during pregnancy.

Azelastine is excreted into the milk in low quantities. For that reason Azelastine is not recommended during lactation.

4.7 Effects on ability to drive and use machines

The mild, transient irritation which can be experienced after application of Azelastine 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.

4.8 Undesirable effects

Occasionally, a mild, transient irritation in the eye after application of Optilast is experienced. Less frequently reported is a bitter taste. In very rare cases allergic reactions may occur.

4.9 Overdose

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

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Antiallergic, ATC code : SO1GX07

Azelastine, a phthalazinone derivative is classified as a potent long-acting antiallergic compound with selective H1 antagonist properties. An additional antiinflammatory 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.

5.2 Pharmacokinetic properties

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

5.3 Preclinical safety data

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 30 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 50 mg/kg/day).

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Benzalkonium chloride (preservative), disodium edetate, hypromellose, liquid sorbitol (crystallising), sodium hydroxide and water for injections.

6.2    Incompatibilities

None known.

6.3 Shelf life

Unopened: 3 years.

Once opened: do not use for longer than 4 weeks.

6.4 Special precautions for storage

No special precautions for storage.

6.5 Nature and contents of container

10 ml opaque HDPE bottle and LDPE dropper with white HDPE screw cap. One bottle contains either 6 ml, 8 ml or 10 ml solution.

Not all volume fill sizes are marketed in all Member States.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Meda Pharmaceuticals Ltd Skyway House Parsonage Road Takeley

Bishop’s Stortford CM22 6PU

8    MARKETING AUTHORISATION NUMBER(S)

PL 15142/0035

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/08/2009

10 DATE OF REVISION OF THE TEXT

04/07/2013