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 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 with the use of Relestat for more than 8 weeks.

The contents of the bottle remain sterile until the original closure is broken by twisting the cap to pierce the dropper tip. To avoid contamination do not touch any surface with the dropper tip.

If more than one topical ophthalmic medicinal product is being used, the 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.

Children and Adolescents

Relestat may be used in adolescents (12 years of age and older) at the same dosage as in adults.

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.

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.

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.

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

Eye disorders

Common (1/100 to <1/10): burning sensation

Uncommon (1/1000 to <1/100): allergic conjunctivitis, blepharoptosis, conjunctival oedema, conjunctival hyperaemia, eye discharge, eye dryness, irritation, itching, increased sensitivity, photophobia, visual disturbance

Nervous system disorders

Uncommon (1/1000 to <1/100): headache

Respiratory, thoracic and mediastinal disorders

Uncommon (1/1000 to <1/100): asthma, nasal irritation, rhinitis

Gastrointestinal disorders

Uncommon (1/1000 to <1/100): oral dryness, taste alteration

Skin and subcutaneous tissue disorders

Uncommon (1/1000 to <1/100): pruritus

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.

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,

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.

5 ml polyethylene bottle with a white polystyrene screw cap with spike device for opening the bottle.

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 05179/0004

18/10/2007

18/10/2007