Acular

Section Number

Subject

Change

1.0

Name of medicinal product

Text Removed:

Acular®

2.0

Qualitative and quantitative composition

Text Added/ Removed:

Ketorolac trometamol 0.5% w/v. 5 mg/mL

Contains Excipients: benzalkonium chloride 0.01% w/v. 0.1mg/mL

4.1

Therapeutic indications

For the prophylaxis and reduction of inflammation following cataract surgery.

Acular is indicated in adults.

4.2

Posology and method of administration

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Posology

4.3

Contraindications

Text Added/ Removed:

ACULAR^® is contraindicated in individuals hypersensitive Hypersensitivity to the active substance or to any of the excipients. any component of the medication.

The potential exists for cross-sensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs. ACULAR ® is contraindicated in individuals who have previously exhibited sensitivities to these drugs.

ACULAR^® is not recommended for use in children due to insufficient data on safety and efficacy.

4.4

Special warnings and precautions for use

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It is recommended that ACULAR be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

In common with other anti-inflammatory drugs, ACULAR may mask the usual signs of infection.

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All non-steroidal anti-inflammatory drugs (NSAIDs) may slow down or delay wound healing.  Concomitant use of NSAIDs and topical steroids can increase the potential for healing problems.  Concomitant use of ACULAR and topical corticosteroids should be exercised with caution in patients susceptible to corneal epithelial breakdown.

Use of topical NSAIDS may result in keratitis.  In some patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation.  These events may be sight threatening.  Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Topical NSAIDs should be used with caution in patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g. dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time, as they may be at increased risk for corneal adverse events which may become sight threatening.

Post marketing experience with topical NSAIDs also suggest that use more than 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events

The preservative in ACULAR, benzalkonium chloride, may cause eye irritation.  Contact lenses must be removed prior to application, with at least a 15-minute wait before reinsertion.  Benzalkonium chloride is known to discolour soft contact lenses.  Contact with soft contact lenses must be avoided.

There have been post-marketing reports of bronchospasm or exacerbation of asthma in patients, who have either a known hypersensitivity to aspirin/non-steroidal anti-inflammatory drugs or a past medical history of asthma associated with the use of ACULAR, which may be contributory.  Caution is recommended in the use of ACULAR in these individuals (see section 4.8).

Text Removed:

Concomitant use of ACULAR® and topical corticosteroids should be exercised with caution in patients susceptible to corneal epithelial breakdown.

Use of topical NSAIDS may result in keratitis. In some patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Topical NSAIDs should be used with caution in patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g. dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time, as they may be at increased risk for corneal adverse events which may become sight threatening.

Post marketing experience with topical NSAIDs also suggest that use more than 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events.

ACULAR® contains benzalkonium chloride as a preservative and should not be used in patients continuing to wear soft (hydrophilic) contact lenses (since benzalkonium chloride is known to discolour this lens-type). Contact lenses should not be worn during instillation of the drug. After instillation there should be an interval of at least 15 minutes before reinsertion.

4.5

Interactions with other medicinal products and other forms of interaction

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No interaction studies have been performed.

ACULAR^® has been safely administered with systemic and ophthalmic medications such as antibiotics, sedatives, beta blockers, carbonic anhydrase inhibitors, miotics, mydriatics local anaesthetics and cycloplegics.

ACULAR^® may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical corticosteroids may increase the potential for healing problems (see section 4.4).

If ACULAR^® is used concomitantly with other topical eye medications there must be an interval of at least 5 minutes between the two medications.

4.6

Pregnancy Fertility, pregnancy and lactation

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Pregnancy
There are no or a limited amount of data from the use of ketorolac trometamol in pregnant women.  Animal studies are insufficient with respect to reproductive toxicity .  ACULAR is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breastfeeding

ACULAR should not be used during breast-feeding.  Ketorolac trometamol is excreted in human milk after systemic administration.

Fertility:

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

Text Removed:

There are no adequate data from the use of ACULAR^® in pregnant women.

Lactation

ACULAR^® is not recommended for nursing mothers. Ketorolac trometamol is secreted in human milk after systemic administration.

4.7

Effects on ability to drive and use machinery

Text Added:

ACULAR has no or negligible influence on the ability to drive and use machines.

Transient blurring of vision may occur on instillation of eye drops.  Do not drive or use hazardous machinery unless vision is clear.

4.8

Undesirable effects

The most frequent adverse events reported with the use of ACULAR are transient stinging and burning on instillation.

The frequency of adverse reactions documented during clinical trials is given below and is defined as follows: 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 available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:

Immune system disorders

Common:                    Hypersensitivity including localised allergic reactions

Nervous system disorders

Uncommon:                Headache

Eye Disorders

Very Common:            Eye irritation (including burning sensation)

                                    Eye pain (including stinging)

Common:                    Superficial (punctate) keratitis

                                    Eye and/or eyelid oedema

                                    Ocular pruritus

                                    Conjunctival hyperaemia

                                    Eye infection

                                    Eye inflammation

Uncommon:                Corneal ulcer

Corneal infiltrates

Blurred and/or diminished vision

Eye dryness

Epiphora

Iritis

Not known:                  Corneal damage, e.g. thinning, erosion, epithelial breakdown and                                               perforation*

Respiratory, thoracic and mediastinal disorders

Not known:                  Bronchospasm or exacerbation of asthma**

*Occasional post marketing reports of corneal damage including corneal thinning, corneal erosion, epithelial breakdown and corneal perforation have been received.  These occurred mainly in patients using concomitant topical corticosteroids and/or with predisposing co-morbidity (see section 4.4).

**There have been post-marketing reports of bronchospasm or exacerbation of asthma, in patients, who have either a known hypersensitivity to aspirin/non-steroidal anti-inflammatory drugs or a past medical history of asthma, associated with the use of ACULAR which may be contributory.

None of the typical adverse reactions reported with the systemic non-steroidal anti-inflammatory agents (including ketorolac trometamol) have been observed at the doses used in topical ophthalmic therapy.

Text Deleted:

a) The most frequent adverse events reported with the use of ACULAR^® are transient stinging and burning on instillation. The events below are classified according to their incidence in clinical trials.

b) Very Common (>1/10):

Common (>1/100, <1/10):

Rare (>1/10,000, <1/1,000):

Since ACULAR^® has been marketed globally a few spontaneous reports of urticaria and rash have been received.

c) Occasional post marketing reports of corneal damage including corneal thinning, corneal erosion, epithelial breakdown and corneal perforation have been received. These occurred mainly in patients using concomitant topical corticosteroids and/or with predisposing co-morbidity. See warnings and precautions section 4.4.

d) None of the typical adverse reactions reported with the systemic non-steroidal anti-inflammatory agents (including ketorolac trometamol) have been observed at the doses used in topical ophthalmic therapy.

4.9

Overdose

No case of overdose has been reported.  Overdose is unlikely to occur via the recommended method of administration.

If accidentally ingested, drink fluids to dilute.

5.3

Preclinical safety

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

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Acute, subacute and chronic studies of ACULAR^® in experimental animals have established the safety of the drug. In addition, octoxinol 40 was separately evaluated for its ocular safety. ACULAR^® was found to be non-irritating, it did not demonstrate a local anaesthetic effect, it did not influence the healing of experimental corneal wounds in rabbits, it did not enhance the spread of experimental ocular infections of Candida albicans, Herpes simplex virus type one, or Pseudomonas aeruginosa in rabbits, and it did not increase the ocular pressure of normal rabbit eyes.

10

Date of the revision of the text

Text Added:

March 2011