Acular (Page 2 of 2)
ACULAR ® (ketorolac tromethamine ophthalmic solution) 0.5% is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use. Its chemical name is (±)-5-Benzoyl-2,3-dihydro-1H -pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1) and it has the following structure:
ACULAR ® ophthalmic solution is supplied as a sterile isotonic aqueous 0.5% solution, with a pH of 7.4. ACULAR ® ophthalmic solution contains a racemic mixture of R-(+) and S-(-)- ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal forms. All forms are equally soluble in water. The pKa of ketorolac is 3.5. This white to off-white crystalline substance discolors on prolonged exposure to light. The molecular weight of ketorolac tromethamine is 376.41. The osmolality of ACULAR ® ophthalmic solution is 290 mOsmol/kg.
Each mL of ACULAR ® ophthalmic solution contains: Active: ketorolac tromethamine 0.5%. Preservative : benzalkonium chloride 0.01%. Inactives : edetate disodium 0.1%; octoxynol 40; purified water; sodium chloride; hydrochloric acid and/or sodium hydroxide to adjust pH.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug which, when administered systemically, has demonstrated analgesic, anti-inflammatory, and anti-pyretic activity. The mechanism of its action is thought to be due to its ability to inhibit prostaglandin biosynthesis.
Two drops of 0.5% ketorolac tromethamine ophthalmic solution instilled into the eyes of patients 12 hours and 1 hour prior to cataract extraction achieved a mean ketorolac concentration of 95 ng/mL in the aqueous humor of 8 of 9 eyes tested (range 40 to 170 ng/mL).
One drop of 0.5% ketorolac tromethamine ophthalmic solution was instilled into 1 eye and 1 drop of vehicle into the other eye TID in 26 healthy subjects. Five (5) of 26 subjects had detectable concentrations of ketorolac in their plasma (range 11 to 23 ng/mL) at Day 10 during topical ocular treatment. The range of concentrations following TID dosing of 0.5% ketorolac tromethamine ophthalmic solution are approximately 4 to 8% of the steady state mean minimum plasma concentration observed following four times daily oral administration of 10 mg ketorolac in humans (290 ± 70 ng/mL).
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Ketorolac tromethamine was not carcinogenic in either rats given up to 5 mg/kg/day orally for 24 months or in mice given 2 mg/kg/day orally for 18 months. These doses are approximately 125 times and 50 times higher respectively than the maximum recommended human topical ophthalmic daily dose given as QID for itching to affected eyes on a mg/kg basis.
Ketorolac tromethamine was not mutagenic in vitro in the Ames assay or in forward mutation assays. Similarly, it did not result in an in vitro increase in unscheduled DNA synthesis or an in vivo increase in chromosome breakage in mice. However, ketorolac tromethamine did result in an increased incidence in chromosomal aberrations in Chinese hamster ovary cells.
Ketorolac tromethamine did not impair fertility when administered orally to male and female rats at doses up to 9 mg/kg/day and 16 mg/kg/day, respectively. These doses are respectively 225 and 400 times higher than the typical human topical ophthalmic daily dose.
14 CLINICAL STUDIES
Two controlled clinical studies showed that ketorolac tromethamine ophthalmic solution was significantly more effective than its vehicle in relieving ocular itching caused by seasonal allergic conjunctivitis.
Two controlled clinical studies showed that patients treated for two weeks with ketorolac tromethamine ophthalmic solution were less likely to have measurable signs of inflammation (cell and flare) than patients treated with its vehicle.
Results from clinical studies indicate that ketorolac tromethamine has no significant effect upon intraocular pressure; however, changes in intraocular pressure may occur following cataract surgery.
16 HOW SUPPLIED/STORAGE AND HANDLING
ACULAR ® (ketorolac tromethamine ophthalmic solution) 0.5% is supplied sterile, in white opaque plastic LDPE bottles with white droppers, with gray high impact polystyrene (HIPS) caps as follows:
5 mL in 10 mL bottle NDC 0023-2181-05
Storage: Store at 15°-25°C (59°-77°F). Protect from light.
17 PATIENT COUNSELING INFORMATIONAllerganLogo.jpg
17.1 Slow or Delayed Healing
Patients should be informed of the possibility that slow or delayed healing may occur while using nonsteroidal anti-inflammatory drugs (NSAIDs).
17.2 Avoiding Contamination of the Product
Patients should be instructed to avoid allowing the tip of the bottle to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Also, to avoid the potential for cross-contamination, the patient should be advised to use one bottle for each eye following bilateral ocular surgery. The use of the same bottle of topical eye drops for both eyes following bilateral ocular surgery is not recommended.
17.3 Contact Lens Wear
Patients should be advised that ACULAR ® solution should not be administered while wearing contact lenses.
17.4 Intercurrent Ocular Conditions
Patients should be advised that if they develop an intercurrent ocular condition (e.g., trauma or infection) or have ocular surgery, they should immediately seek their physician’s advice concerning the continued use of ACULAR ® .
17.5 Concomitant Topical Ocular Therapy
Patients should be advised that if more than one topical ophthalmic medication is being used, the medicines should be administered at least 5 minutes apart.
© 2012 Allergan, Inc., Irvine, CA 92612, U.S.A.
ACULAR ® is manufactured and distributed by Allergan, Inc. under license from its developer,
Roche Palo Alto LLC, Palo Alto, CA, U.S.A.
® marks owned by Allergan, Inc.
Made in the U.S.A.
Principal Display Panel
sterile Rx only
| ACULAR |
ketorolac tromethamine solution/ drops
|Labeler — Allergan, Inc. (144796497)|
Revised: 06/2012 Allergan, Inc.
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