KETOWELL Eye Drops

 Ketorolac Tromethamine Eye Drops 0.4 % w/v

COMPOSITION

Each ml contains:

Ketorolac Tromethamine           IP         4 mg

Benzalkonium Chloride             BP        0.06 % w/v

(as preservative)

Water for Injections                   BP        q.s.

 DESCRIPTION

A clear, colorless to pale yellow colored solution.

PHARMACODYNAMIC

Pharmacotherapeutic group: Anti-inflammatory agents, non-steroids.

ATC code: S01BC 05.

Ketorolac Trometamol Ophthalmic Solution (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. Ketorolac Trometamol Ophthalmic Solution 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 Ketorolac Trometamol Ophthalmic Solution has no significant effect on intra-ocular pressure.

 PHARMACOKINETICS

Ketorolac tromethamine solutions (0.1% or 0.5%) or vehicle instilled into the eyes of patients approximately 12 hours and 1 hour prior to surgery. Concentrations of ketorolac in aqueous humor sampled at the time of surgery were at the lower limit of detection (40 ng/ml) in 1 patient and below the quantitation limit in 7 patients dosed with 0.1% ketorolac tromethamine. The average aqueous humor level of ketorolac in patients treated with 0.5% ketorolac tromethamine was 95 ng/ml. Concentrations of PGE2 in aqueous humor were 80 pg/ml, 40 pg/ml and 28 pg/ml in patients treated with vehicle, 0.1% ketorolac tromethamine and 0.5% ketorolac tromethamine, respectively.

In the 21-day multiple dose (TID) tolerance study in healthy subjects, only 1 of 13 subjects had a detectable plasma level pre-dose (0.021 μg/ml). In another group of 13 subjects, only 4 subjects showed very low plasma levels of ketorolac (0.011 to 0.023 μg/ml) 15 minutes after the ocular dose.

Thus, higher levels of ketorolac in the aqueous humor and very low or no detectable plasma levels after ophthalmic doses, suggest that the use of ketorolac tromethamine by the ophthalmic route in treatment of ocular disorders results in quite low systemic absorption in patients.

 THERAPEUTIC INDICATION

Ketorolac Trometamol Ophthalmic Solution is indicated for the prophylaxis and reduction of inflammation and associated symptoms following ocular surgery. Ketorolac Trometamol Ophthalmic Solution is indicated in adults.

DOSAGE AND ADMINISTRATION

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 Ketorolac trometamol 0.5% w/v eye drops, solution in the paediatric population in the indication: For the prophylaxis and reduction of inflammation following cataract surgery.

Method of administration

Ocular use

Instill 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.

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

INSTRUCTION FOR USE

Apply KETOWELL Eye Drops in the following way:

1. Wash your hands. Tilt your head back and look at the ceiling.
2. Gently pull the lower eyelid down until there is a small pocket.
3. Turn the bottle upside down and gently press the bottle to release drops into eyes that needs treatment.
4. Let go of the lower lid, and close your eye for 30 seconds.
5. To avoid contamination, do not let the tip of dropper touch your eye or anything else.
6. Replace and tighten the cap straight after use.

 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.

 CONTRAINDICATION

Hypersensitivity to the active substance(s) or to any of the excipients. The potential exists for cross-sensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs. Ketorolac Trometamol Ophthalmic Solution is contraindicated in individuals who have previously exhibited sensitivities to these drugs. sensitivities to these drugs.

WARNING AND PRECAUTIONS

• It is not for injection.
• Do not use the eye drop with contact lenses.
• It is recommended that Ketorolac trometamol 0.5% w/v eye drops, solution 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, Ketorolac trometamol 0.4% w/v eye drops, solution may mask the usual signs of infection.
• Concomitant use of Ketorolac trometamol 0.4% w/v eye drops, solution and topical corticosteroids should be exercised with caution in patients susceptible to corneal epithelial breakdown.
• 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 surgery 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.

PREGNANCY, LACTATION AND FERTILITY

Pregnancy

There are no adequate data from the use of eye drops containing ketorolac trometamol in pregnant women. Studies in animals have shown reproductive toxicity. Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonal/foetal development and/ or postnatal development. Although a very low systemic exposure is expected after the use of ketorolac eye drops, Ketorolac trometamol 0.4% w/v eye drops is not recommended during pregnancy.

Breast-feeding

Ketorolac trometamol 0.4% w/v eye drops, solution 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.

DRUG INTERACTION

No interaction studies have been performed.

Ketorolac trometamol 0.4% w/v eye drops, solution have been safely administered with systemic and ophthalmic medications such as antibiotics, sedatives, beta blockers, carbonic anhydrase inhibitors, miotics, mydriatics, local anaesthetics and cycloplegics.

Ketorolac trometamol 0.4% w/v eye drops, solution 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.

 ADVERSE EFFECTS

Objective and subjective symptoms of ocular irritation, including conjunctivitis, blepharitis, keratitis, blepharoptosis, decreased corneal sensitivity, visual disturbances including refractive changes (due to withdrawal of miotic therapy in some cases), diplopia, ptosis.

PRESENTATION

KETOWELL Eye Drops are supplied in 5 ml sterilized opaque plastic container with nozzle and cap

 STORAGE AND OTHER INFORMATION

Store at temperature below 30 °C. Keep this medicine out of the sight and reach of children. Do not touch the dropper tip or other dispensing tip to any surface since this may contaminate the solution. Use the solution within one month after opening the container.