SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT ENFLUAT 0.4 % Sterile Eye Drops 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Drug substance: Ketorolac Tromethamine 0,4 % Each bottle (5 ml) contains 20 mg of ketorolac tromethamine. Excipient(s): Benzalkonium chloride 0.006 % For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Eye drops Clear solution 4. CLINICAL PARTICULARS 4.1. Therapeutic indications ENFLUAT is indicated for the reduction of ocular symptoms such as ocular pain and foreign object sensation, photophobia, burning/stinging and lachrymation following ocular surgery. 4.2. Posology and method of administration Posology / frequency and duration of applications: 1 drop of the solution into the operated eye(s) for pain and burning/stinging 4 times a day for up to 4 days following refractive surgery. Method of administration Wash your hands before using the eye drop. 1. Spin the cap and open it. 2. Take out the safety ring on the bottle. 1 / 7
3. Put the cap on the bottle again and spin it. Make sure you close it tight. The tooth inside the cap will pierce the tip of the dropper and ENFLUAT will be ready to be dropped. You don t need to repeat this in the following usages. 4. Tilt your head back and gently pull the lower eyelid down until there is a small pocket. 5. DO NOT LET THE DROPPER TOUCH YOUR EYE OR EYELİD. 6. Turn the bottle upside down and squeeze it to release one drop into each eye that needs treatment. 7. Let go of the lower lid, and close your eye for 30 seconds. 8. Close the bottle. Must be used in 4 weeks after opening. Additional information on special populations: Renal and hepatic disorder: There is no statement about topical ofthalmic usage in patients with renal or hepatic disorder. Pediatric population: Usage in children younger than 3 years old, safety and efficacy of the drug in this population group is not confirmed. Geriatric population: There is no need a special dosing for elderly. No difference has been observed between young and old patients in the way of safety and efficiency. 4.3. Contraindications ENFLUAT is contraindicated in patient with hypersensitivity to ketorolac tromethaminin or to any of the excipients. 4.4. Special warnings and precautions for use The potential exists for cross-sensitivity to acetylsalicylic acid, phenylacetic acid and its derivatives and other non-steroidal anti-inflammatory drugs. Caution should be exercised in individuals who have previously exhibited sensitivities to these drugs. With some nonsteroidal anti-inflammatory drugs there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery. All topical nonsteroidal anti-inflammatory drugs (NSAIDs) including ketorolac tromethamine ophthalmic solution may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. 2 / 7
Use of topical NSAIDs may result in keratitis. In some susceptible 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. The experience with topical NSAIDs suggests that 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 may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Use of NSAIDs 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. It is recommended to use that ENFLUAT with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time. ENFLUAT must not be used while wearing contact lenses Usage in children younger than 3 years old, safety and efficacy of the drug in this population group is not confirmed. ENFLUAT may cause eye irritation because it contains benzalkonium chloride as preservative. Ketorolac tromethamine should not be administered while wearing contact lenses. Contact with soft contact lenses must be avoided. Contact lenses must be removed prior to application, with at least a 15-minute wait before reinsertion. Benzalkonium chloride is known to discolor soft contact lenses. 4.5. Interaction with other medicinal products and other forms of interaction Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. If it is going to be used together with topical eye drops there must be 5 minutes of break between administrations. It is recommended to use that ENFLUAT with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time. Any drug interactions have been reported. ENFLUAT has been safely administered with ophthalmic medications such as antibiotics, beta blockers, carbonic anhydrase inhibitors, cycloplegics and mydriatics. 4.6. Pregnancy and lactation General advice Pregnancy Category: C Women with childbearing potential / Contraception There are no special warnings for women with childbearing potential. Pregnancy 3 / 7
ENFLUAT should be used during pregnancy only after the doctor s risk/benefit evaluation. Studies in animals are insufficient in terms of pregnancy, embryonal/foetal development, labour and/or postnatal development (See. Section 5.3). The potential risk for humans is unknown. Because of the known effects of prostaglin inhibitor medicines on rats fetal cardiovascular system, ENFLUAT use must be avoided in the late periods of pregnancy. Breast-feeding Caution should be taken when ENFLUAT is administered to a nursing woman. Reproductive ability/fertility There are no statements for the use of ketorolac tromethamine on fertility in humans. 4.7. Effects on ability to drive and use machines No information about effects on the ability to drive and use machines have been reported. However, caution should be exercised. 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 frequency of adverse reactions 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). Very common: Stinging and/or burning in the eye, Common: Conjunctival hyperemia, cornea infiltrations, headache, ocular oedema, ocular pain, allergic reactions, cornea oedema, iritis, ocular inflammation, ocular irritation, superficial keratitis, superficial ocular infections The side effects below are determined during clinical practice usage after marketing of ketorolac trometaminine oftalmic solution. Frequency is not known because they have been stated by a volunteer population of unknown numbers. Adverse effects that are added because of their seriousness, stating frequency, possible causative relation to topical ketorolac trometamine ophthalmic solution or these factors combination includes: corneal erosion, corneal perforation, corneal slimming or epithelial destruction. (refer to Special warnings and precautions for use) Reporting of suspicious adverse side effects If you feel any side effects listed or not listed in this leaflet speak to a doctor, pharmacist or nurse. Furthermore report the side effects you feel by clicking Reporting Medicine Side Effect in www.titck.gov.tr or by calling 0 800 314 00 08 side effect report line Turkey Pharmacovigilance Center. By reporting side effects you can help provide more information on the safety of this medicine 4 / 7
4.9 Overdose There is no experience of overdose by the ophthalmic route. If accidentally ingested, symptomatic and supportive treatment should be applied and it should be diluted by applying plenty of fluids. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group : Ophthalmic, Non-steroidal Anti-inflammatory drugs, ATC code : S01BC05 Ketorolac tromethamine is a non-steroidal anti-inflammatory drug. The mechanism of its action is based on its ability to inhibit prostaglandin biosynthesis. Ketorolac tromethamine reduce prostaglandin levels in the aqueous humour after topical ophthalmic administration. Ketorolac tromethamine given systemically does not cause pupil constriction. 5.2 Pharmacokinetic properties General properties Stable state peak plasma levels are 960 ng/ml when administered 10mg ketorolac trometamine every 6 hours systematically. It has been shown that the medicine is metabolized in liver in systematical administration studies. Ocular pharmacokinetics: Information about the ocular pharmacokinetics of ketorolac trometaminine is below: Absorption: 14C-labeled ketorolac tromethamine were quickly absorbed into the eye after a single dose application to rabbits. Tmax has been found 1 hour for humor aqueous. Humor aqueous and half-life in cornea in rabbits are 7.1 and 8.2 hours. Distribution: Mainly cornea and sclera, it distributes to ocular tissues epidemically. Humor aqueous concentration is 0.22 g Eq/mL. Biotransformation: It has been shown that the medicine is metabolized in liver in systematical administration studies. Elimination: The way of disposing medicine from eye is thought to be intraocular blood flow. According to clinical studies, there is no significant effect of ketorolac trometaminin on intraocular pressure. 5.3 Preclinical safety data Acute, sub-acute and chronic studies of ENFLUAT in experimental animals have established the safety of the drug. In addition, octoxinol 40 was separately evaluated for its ocular safety. ENFLUAT was found to be non-irritating, it did not demonstrate a local anaesthetic effect, it 5 / 7
did not influence the healing of experimental corneal wounds in rabbits, it did not enhance the spread of experimental ocular infections and it did not increase the ocular pressure of normal rabbit eyes. 6. PHARMACEUTICAL PARTICULARS 6.1. List of excipients Benzalkonium chloride Sodium chloride Disodium edetate Octoxinol 40 Sodium hydroxide and/or Hydrochloric acid Pure water 6.2. Incompatibilities No reports 6.3 Shelf life 24 months. 6.4. Special precautions for storage Store at room temperature below 25 C 6.5. Nature and contents of container ENFLUAT is available in PP ringed BSF moplen screw-capped, 5 ml LDPE dropper bottles. 6.6. Special precautions for disposal Any unused medicinal product or waste material should be disposed of in accordance with Regulation on Control of Medical Waste and Regulation on Packaging and Packaging Waste. 7. MARKETING AUTHORISATION HOLDER Biem İlaç San. ve Tic. A.Ş. Anıttepe Mah. Turgut Reis Cad. No: 21 Tandoğan / Çankaya Ankara Tel: 0312 230 29 29 Faks: 0312 230 68 00 e-mail: biemilac@biemilac.com.tr 6 / 7
8. MARKETING AUTHORISATION NUMBER(S) 2014/849 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorization: 13.11.2014 Renewal of the authorization: 10. DATE OF REVISION OF THE SmPC 06.05.2015 7 / 7