Section Number

Subject

Change

3

Pharmaceutical Form

Text Added

Eye drops, solution.

A clear colourless sterile solution.

4.2

Posology and Method of Administration

Text Removed/Added

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

4.4

Special Warnings and Precautions for Use

Text Added

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.

4.6

Fertility, pregnancy and lactation

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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.

BreastfeedingLactation

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.

4.8

Undesirable Effects

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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 (≥1/100 to <1/10): burning sensation/ eye irritation

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

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): dysgeusia

Skin and subcutaneous tissue disorders

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

*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.

5.1

Pharmacodynamic Properties

Text Added

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 a₁-, a₂-, 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.

6.3

List of excipients

Text Added

Benzalkonium chloride,

Disodium edetate,

Sodium chloride,

Sodium dihydrogen phosphate dihydrate,

Sodium hydroxide/hydrochloric acid (pH adjustment),

Purified water.

.

10

Date of Revision of the Text

Text Removed/Added

            13^th July 2010 6^th October 2011

4.2

Posology and method of administration

Text added:

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

Text deleted:

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.

6.5

Nature and content of container

Text added:

10

Text deleted:

5

Text deleted:

10

Date of revision of the text

Date deleted:

2007-10-18

Replaced with:

13^th July 2010