ACULAR® (ketorolac tromethamine ophthalmic solution) 0.5% is the only topical NSAID indicated for the temporary relief of ocular itching due to seasonal allergic conjunctivitis. ACULAR® is also indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction.
ACULAR® relieves the ocular itch associated with seasonal allergic conjunctivitis and inflammation following cataract surgery due in part to its ability to inhibit prostaglandin biosynthesis.
In two double-masked, paired studies (N=241), ACULAR® Solution was found to be significantly more effective than its vehicle in relieving the ocular itch of seasonal allergic conjunctivitis.
Two controlled clinical studies showed that patients treated for two weeks with ACULAR® ophthalmic solution were less likely to have measurable signs of inflammation (cell and flare) than patients treated with its vehicle.
ACULAR® Solution is also proven safe in clinical trials, and avoids steroid-like side effects (e.g., no significant effect upon IOP). 1 There is no significant ocular toxicity reported in clinical studies to date with ACULAR®.
The most frequently reported adverse events have been transient stinging and burning on instillation (approximately 40%). Caution should be used in patients with sensitivities to other NSAIDs.
ACULAR® Solution is available in 3 mL, 5 mL and 10 mL plastic bottles with a controlled-dropper tip.
Please see full prescribing information included.
ACULAR® , a registered trademark of Syntex (U.S.A.) Inc., is manufactured and distributed by Allergan, Inc. under license from its developer, Syntex (U.S.A.) Inc., Palo Alto, CA.
ACULAR® is marketed by Allergan, Inc.
ACULAR® (ketorolac tromethamine ophthalmic solution) 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-1 H -pyrrolizine-1-carboxylic acid compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1).
ACULAR® is supplied as a sterile isotonic aqueous 0.5% solution, with a pH of 7.4. ACULAR® is 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. Each mL of ACULAR® ophthalmic solution contains: Active: ketorolac tromethamine 0.5%. Preservative: benzalkonium chloride 0.01%. Inactives: edetate disodium 0.1%; octoxynol 40; sodium chloride; hydrochloric acid and/or sodium hydroxide to adjust the pH; and purified water. The osmolality of ACULAR® is 290 mOsmol/kg.
Ketorolac tromethamine prevented the development of increased intraocular pressure induced in rabbits with topically applied arachidonic acid. Ketorolac did not inhibit rabbit lens aldose reductase in vitro.
Ketorolac tromethamine ophthalmic solution did not enhance the spread of ocular infections induced in rabbits with Candida albicans, Herpes simplex virus type one, or Pseudomonas aeruginosa.
Ketorolac tromethamine is 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, in part, to its ability to inhibit prostaglandin biosynthesis. Ketorolac tromethamine given systemically does not cause pupil constriction.
Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure. Prostaglandins also appear to play a role in the miotic response produced during ocular surgery by constricting the iris sphincter independently of cholinergic mechanisms.
Two drops (0.1 mL) of 0.5% ACULAR® ophthalmic solution instilled into the eyes of patients 12 hours and 1 hour prior to cataract extraction achieved measurable levels in 8 of 9 patients' eyes (mean ketorolac concentration 95 ng/mL aqueous humor, range 40 to 170 ng/mL). Ocular administration of ketorolac tromethamine reduces prostaglandin E 2 (PGE 2 ) levels in aqueous humor. The mean concentration of PGE 2 was 80 pg/mL in the aqueous humor of eyes receiving vehicle and 28 pg/mL in the eyes receiving ACULAR® 0.5% ophthalmic solution.
One drop (0.05 mL) of 0.5% ACULAR® ophthalmic solution was instilled into one eye and one drop of vehicle into the other eye TID in 26 normal subjects. Only 5 of 26 subjects had a detectable amount of ketorolac in their plasma (range 10.7 to 22.5 ng/mL) at Day 10 during topical ocular treatment. When ketorolac tromethamine 10 mg is administered systemically every 6 hours, peak plasma levels at steady state are around 960 ng/mL.
Two controlled clinical studies showed that ACULAR® 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 ACULAR® 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 ACULAR® has no significant effect upon intraocular pressure; however, changes in intraocular pressure may occur following cataract surgery.
ACULAR® ophthalmic solution has been safely administered in conjunction with other ophthalmic medications such as antibiotics, beta blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics.
ACULAR® ophthalmic solution is indicated for the temporary relief of ocular itching due to seasonal allergic conjunctivitis. ACULAR® is also indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction.
ACULAR® ophthalmic solution is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formulation.
There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory agents. Therefore, caution should be used when treating 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.
General: It is recommended that ACULAR® ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.
Information for Patients: ACULAR® should not be administered while wearing contact lenses.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: An 18-month study in mice at oral doses of ketorolac tromethamine equal to the parenteral MRHD (Maximum Recommended Human Dose) and a 24-month study in rats at oral doses 2.5 times the parenteral MRHD, showed no evidence of tumorigenicity.
Ketorolac tromethamine was not mutagenic in Ames test, unscheduled DNA synthesis and repair, and in forward mutation assays. Ketorolac did not cause chromosome breakage in the in vivo mouse micronucleus assay. At 1590 ug/mL (approximately 1000 times the average human plasma levels) and at higher concentrations, ketorolac tromethamine increased the incidence of chromosomal aberrations in Chinese hamster ovarian cells.
Impairment of fertility did not occur in male or female rats at oral doses of 9 mg/kg and 16 mg/kg respectively.
Pregnancy Category C. Reproduction studies have been performed in rabbits, using daily oral doses at 3.6 mg/kg and in rats at 10 mg/kg during organogenesis. Results of these studies did not reveal evidence of teratogenicity to the fetus. Oral doses of ketorolac tromethamine at 1.5 mg/kg, which was half of the human oral exposure, administered after gestation day 17 caused dystocia and higher pup mortality in rats. There are no adequate and well-controlled studies in pregnant women. Ketorolac tromethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects: Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ACULAR® ophthalmic solution during late pregnancy should be avoided.
Nursing Mothers: Caution should be exercised when ACULAR® is administered to a nursing woman.
Pediatric Use: Safety and efficacy in pediatric patients below the age of 12 have not been established.
In controlled clinical studies, the most frequent adverse events reported with the use of ACULAR® ophthalmic solution have been transient stinging and burning on instillation. These events were reported by up to 40% of patients treated with ACULAR® ophthalmic solution. In all development studies conducted, other adverse events occurring less than 5% of the time during treatment with ACULAR® included ocular irritation, allergic reactions, superficial ocular infections, and superficial keratitis.
Other adverse events reported rarely with the use of ACULAR® ophthalmic solution include: eye dryness, corneal infiltrates, corneal ulcer, and visual disturbance (blurry vision).
The recommended dose of ACULAR® ophthalmic solution is one drop (0.25 mg) four times a day for relief of ocular itching due to seasonal allergic conjunctivitis.
For the treatment of postoperative inflammation in patients who have undergone cataract extraction, one drop of ACULAR® ophthalmic solution should be applied to the affected eye(s) four times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period.
ACULAR® (ketorolac tromethamine ophthalmic solution) is available for topical ophthalmic administration as a 0.5% sterile solution, and is supplied in white opaque plastic bottles with a controlled dropper tip in the following sizes:
3 mL --NDC 0023-2181-03
5 mL --NDC 0023-2181-05
10 mL--NDC 0023-2181-10
Store at controlled room temperature 15-30°C (59-86°F) with protection from light.
Rx only
U.S. Patent Nos. 4,089,969; 4,454,151; 5,110,493
ACULAR®, a registered trademark of Syntex (U.S.A.) Inc., is manufactured and distributed by Allergan, Inc. under license from its developer, Syntex (U.S.A.) Inc., Palo Alto, California, U.S.A.
©2000 Allergan, Inc.
Irvine, CA 92612
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