| Summary of Changes to Acular® Summary of Product Characteristics (SPC)
The current Acular® SPC is dated 15th September 2011
This supersedes SPC dated 16th February 2010
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Section Number
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Subject
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Change
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2
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Qualitative and Quantitative Composition
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Text Removed/Added
Ketorolac trometamol 0.5%w/v 5 mg/mL.
Contains benzalkonium chloride 0.01%w/v 0.1 mg/mL.
For a full list of excipients, see section 6.1.
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3
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Pharmaceutical Form
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Text Added
Eye drops, solution.
Clear, colourless to pale yellow aqueous solution.
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4.1
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Therapeutic Indications
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Text Added
Acular® is indicated for the prophylaxis and reduction of inflammation and associated symptoms following ocular surgery.
Acular is indicated in adults.
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4.2
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Posology and Method of Administration
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Text Removed/Added
Route of administration: Ocular.
Posology
Post-operative inflammation:
One drop instilled into the eye three times daily starting 24 hours pre-operatively and continuing for up to three weeks post-operatively.
Paediatric population
There is no relevant use of Acular in the paediatric population in the indication: For the prophylaxis and reduction of inflammation following cataract surgery.
Method of administration
Ocular use.
Instil one drop of the solution into the inferior conjunctival sac of the eye to be treated, while pulling the lower eyelid gently downwards and looking upwards.
No special dosage for the elderly.
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4.3
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Contra-indications
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Text Added
Hypersensitivity to the active substance or to any of the excipients.
The potential exists for cross-sensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs. Acular is contra-indicated in individuals who have previously exhibited sensitivities to these drugs.
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4.4
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Special Warnings and Precautions for Use
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Text Removed/Added
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, or patients with a known history of peptic ulceration.
In common with other anti-inflammatory drugs, Acular may mask the usual signs of infection.
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.
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.
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).
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4.5
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Interactions with other medicinal products and other forms of Interaction
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Text Removed/Added
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.
AcularÒ 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 AcularÒ is used concomitantly with other topical eye medications there must be an interval of at least 5 minutes between the two medications.
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4.6
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Fertility, pregnancy and lactation
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Text Removed/Added
There was no evidence of teratogenicity in rats or rabbits studied at maternally-toxic doses of ketorolac. Prolongation of the gestation period and/or delayed parturition were seen in the rat. Ketorolac and its metabolites have been shown to pass into the foetus and milk of animals. Ketorolac has been detected in human milk at low levels. Safety in human pregnancy has not been established. Ketorolac is therefore contra-indicated during pregnancy, labour or delivery, or in mothers who are breast feeding.
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.
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4.7
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Effects on Ability to Drive and Use Machines
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Text Removed/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.
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4.8
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Undesirable Effects
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Text Removed/Added
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):
Ocular stinging or burning
Common (>1/100, <1/10):
Superficial (punctate) keratitis
Eye pain
Localised allergic reaction
Eye and/or eyelid oedema
Ocular irritation
Ocular pruritus
Conjunctival hyperaemia
Rare (>1/10,000, <1/1,000):
Corneal ulcer
Corneal infiltrates
Blurred and/or diminished vision
Headache
Eye dryness
Epiphora
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 use of systemic non-steroidal anti-inflammatory agents (including ketorolac trometamol) have been observed at the doses used in topical ophthalmic therapy.
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.
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4.9
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Overdose
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Text Added
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.
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5.1
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Pharmacodynamic Properties
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Text Removed
Pharmacotherapeutic group: Anti-inflammatory agents, non-steroids
ATC code: S01BC 05.
Acular (ketorolac trometamol) is a non-steroidal anti-inflammatory agent demonstrating analgesic and anti-inflammatory activity. Ketorolac trometamol inhibits the cyclo-oxygenase enzyme essential for biosynthesis of prostaglandins. Acular has been shown to reduce prostaglandin levels in the aqueous humour after topical ophthalmic administration.
Ketorolac trometamol given systemically does not cause pupil constriction. Results from clinical studies indicate that Acular has no significant effect on intra-ocular pressure.
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5.3
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Preclinical Safety Data
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Text Added/Removed
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.
Acute, sub-acute 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.
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6.3
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Shelf Life
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Text Removed/Added
24 months, unopened.
Discard any unused contents 28 days after opening the bottle.
Unopened: 2 years.
Use within 28 days of first opening.
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6.4
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Special Precautions for Storage
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Text Removed/Added
This medicinal product does not require any special storage conditions.
Store below 25o C
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6.5
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Nature and Contents of Container
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Text Removed/Added
Bottle with dropper applicator, containing clear, colourless to slightly yellow, sterile ophthalmic solution. Pack sizes: 3ml, 5ml and 10 ml.
Low density polyethylene dropper bottles (with LDPE dropper tips) containing 3ml, 5ml or 10ml of solution. The drop size is 35 microlitres. Each bottle has a medium impact polystyrene (MIPS) screw-cap.
Not all pack sizes may be marketed.
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10
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Date of Revision of the Text
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Text Removed/Added
16th February 2010 15th September 2011
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Key:
Unchanged text appears as follows: eg Paediatric population
Added text appears as follows: eg Uveitis
Deleted (Removed) text appears as follows: eg Not applicable
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