Optilast.

0.5 mg / ml, Eye Drops, solution.

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

For excipients see section 6.1

Eye drops, solution.

Clear, colourless 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 Optilast 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.

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

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.

No specific interaction studies with Optilast have been performed.

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

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 Optilast during pregnancy.

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

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

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.

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.

Antiallergic, ATC code : SO1GX07

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.

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 Optilast (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.

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).

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

None known.

3 years.

Do not use for longer than 4 weeks after first opening.

No special precautions for storage.

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.

No special requirements.

Meda Pharmaceuticals Ltd

249 West George Street

Glasgow

G2 4RB

Trading as:

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop's Stortford

CM22 6PU

UK

PL 15142/0036

1^st August 2009

25^th June 2012