Relestat, 0.5 mg/ml, eye drops, solution.

One ml of eye drops, solution, contains 0.5 mg of epinastine hydrochloride.

(equivalent to 0.436 mg epinastine)

Excipient: benzalkonium chloride 0.1 mg/ml

For a full list of excipients, see section 6.1.

Eye drops, solution.

A clear colourless sterile solution.

Treatment of the symptoms of seasonal allergic conjunctivitis.

The recommended dose for adults is one drop instilled in each affected eye twice daily, during the symptomatic period.

There is no experience in clinical studies with the use of Relestat for more than 8 weeks.

To avoid contamination of the eye or eye drops do not allow the dropper tip to come into contact with any surface.

If more than one topical ophthalmic medicinal product is being used, the different medicinal products should be administered at least 10 minutes apart.

Elderly patients

Relestat has not been studied in elderly patients. Post-marketing safety data from the tablet formulation of epinastine hydrochloride (up to 20 mg once daily) indicates that there are no particular safety issues for elderly patients compared with adult patients. As such, no dosage adjustment is considered to be necessary.

Paediatric population

Safety and efficacy in patients ≥ 12 years has been established in clinical trials. Relestat may be used in adolescents (12 years of age and older) at the same dosage as in adults.

The safety and efficacy of Relestat in children less than 3 years of age have not been established. There are limited data on the safety in children aged 3-12 years, see section 5.1.

Hepatic impairment

Relestat has not been studied in patients with hepatic impairment. Post-marketing safety data from the tablet formulation of epinastine hydrochloride (up to 20 mg once daily) indicates that the incidence of adverse reactions was higher in this group compared with adult patients without hepatic impairment. The daily dose of a 10 mg epinastine hydrochloride tablet is more than 100-fold higher than the daily dose following Relestat. In addition, the metabolism of epinastine in humans is minimal (<10%). Therefore, no dosage adjustment is considered to be necessary.

Renal impairment

Relestat has not been studied in patients with renal impairment. Post-marketing safety data from the tablet formulation of epinastine hydrochloride (up to 20 mg once daily) indicate that there are no particular safety issues for patients with renal impairment. As such, no dosage adjustment is considered to be necessary.

Hypersensitivity to epinastine or to any of the excipients.

Relestat is for topical ophthalmic use only and not for injection or oral use.

Benzalkonium chloride is commonly used as a preservative in ophthalmic products and has been reported rarely to cause punctate keratopathy and/or toxic ulcerative keratopathy.

Benzalkonium chloride may be absorbed by and discolour soft contact lenses and therefore patients should be instructed to wait until 10-15 minutes after instillation of Relestat before inserting contact lenses. Relestat should not be administered while wearing contact lenses.

No interaction studies have been performed.

No drug-drug interactions are anticipated in humans since systemic concentrations of epinastine are extremely low following ocular dosing. In addition, epinastine is mainly excreted unchanged in humans indicating a low level of metabolism.

Pregnancy

Data on a limited number (11) of exposed pregnancies indicate no adverse effects of epinastine on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3).

Caution should be exercised when prescribing to pregnant women.

Lactation

Epinastine is excreted in the breast milk of rats, but it is not known if epinastine is excreted in human milk. Due to the lack of experience, caution should be exercised when prescribing to breast-feeding women.

Fertility

There are no adequate data from the use of epinastine on fertility in humans.

Based on the pharmacodynamic profile, reported adverse reactions and specific psychometric studies, epinastine has no or negligible influence on the ability to drive and use machines.

If transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinery.

In clinical studies, the overall incidence of adverse drug reactions following Relestat was less than 10%. No serious adverse reactions occurred. Most were ocular and mild. The most common adverse reaction was burning sensation in eye (mostly mild); all other adverse reactions were uncommon.

Within each frequency grouping, adverse reactions are presented according to System Organ Class in order of decreased seriousness. The following terminologies have been used in order to classify the occurrence of undesirable effects: 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).

The following adverse drug reactions were reported during clinical trials with Relestat:

Nervous system disorders

Uncommon: headache

Eye disorders

Common: burning sensation/ eye irritation

Uncommon: conjunctival/ ocular hyperaemia, eye discharge, eye dryness, eye prutius, visual disturbance, increased lacrimation*, eye pain*

Respiratory, thoracic and mediastinal disorders

Uncommon: asthma, nasal irritation, rhinitis

Gastrointestinal disorders

Uncommon: dysgeusia

*Increased lacrimation and eye pain have been identified during postmarketing use of Relestat in clinical practice.

Paediatric population

Frequency, type and severity of adverse reaction in adolescents ≥ 12 years of age are expected to be the same as in adults.

There is limited experience in children 3-12 years of age regarding frequency, type and severity of adverse reactions.

After instillation of 0.3% epinastine hydrochloride eye drops 3 times daily (corresponds to 9 times the recommended daily dose) reversible miosis, without influence on visual acuity or other ocular parameters, was observed.

The 5 ml bottle of Relestat contains 2.5 mg of epinastine hydrochloride. A tablet formulation is marketed at a once daily dose of up to 20 mg epinastine hydrochloride, as such, intoxication after oral ingestion of the ophthalmic formulation is not expected even if the whole content of the bottle is swallowed.

No case of overdose has been reported.

Pharmacotherapeutic group: Ophthalmologicals; Decongestants and Antiallergics; Other antiallergics

ATC code: S01G X10

Epinastine is a topically active, direct H₁-receptor antagonist. Epinastine has a high binding affinity for the histamine H₁-receptor and a 400 times lower affinity for the histamine H₂-receptor. Epinastine also possesses affinity for the α₁-, α₂-, and the 5-HT₂ –receptor. It has low affinity for cholinergic, dopaminergic and a variety of other receptor sites. Epinastine does not penetrate the blood/brain barrier and, therefore, does not induce side effects of the central nervous system, i.e., it is non-sedative.

Following topical eye application in animals, epinastine showed evidence for antihistaminic activity, a modulating effect on the accumulation of inflammatory cells, and mast cell stabilising activity.

In provocation studies with allergens in humans, epinastine was able to ameliorate ocular symptoms following ocular antigen challenge. The duration of the effect was at least 8 hours.

Paediatric population

A 6-week, randomised, double-masked, vehicle controlled study (2:1) involving 96 ocular-wise non-symptomatic, healthy children aged 3-12 years, indicated that Relestat was well tolerated and did not identify any significant differences between the groups for any safety variable. Treatment related reactions were conjunctival follicles (6.3% in both epinastine and vehicle-treated subjects) and conjunctival hyperaemia (1.6% of epinastine treated subjects and none in the vehicle group). Safety and efficacy in patients ≥ 12 years has been established in clinical trials.

Following administration of one drop of Relestat in each eye twice daily, an average maximum plasma concentration of 0.042 ng/ml is reached after about two hours. Epinastine has a volume of distribution of 417 litres and is 64% bound to plasma proteins. The clearance is 928 ml/min and the terminal plasma elimination half-life is about 8 hours. Less than 10% is metabolised. Epinastine is mainly excreted renally unchanged. The renal elimination is mainly via active tubular secretion.

Preclinical studies in vitro and in vivo show that epinastine binds to melanin and accumulates in the pigmented ocular tissues of rabbits and monkeys. In vitro data indicate that the binding to melanin is moderate and reversible.

Non clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.

Benzalkonium chloride,

Disodium edetate,

Sodium chloride,

Sodium dihydrogen phosphate dihydrate,

Sodium hydroxide/hydrochloric acid (pH adjustment),

Purified water.

Not applicable.

2 years.

After first opening: 4 weeks.

Keep the bottle in the outer carton in order to protect from light.

Do not store above 25°C.

10 ml polyethylene bottle with a white polystyrene screw cap.

The fill volume is 5 ml.

No special requirements

Any unused product or waste material should be disposed of in accordance with local requirements.

Allergan Pharmaceuticals Ireland

Castlebar Road

Westport

Co. Mayo

Ireland

PL 41443/0004

18^th October 2002 / 18^th October 2007

March 2013

Version 2