Acular

Acular

ketorolac

Manufacturer:

Allergan

Distributor:

DKSH
Full Prescribing Info
Contents
Ketorolac tromethamine.
Description
Each mL of ophthalmic solution also contains benzalkonium chloride 0.01% as preservative and the following inactive ingredients: Disodium edetate 0.1%, octoxynol 40, sodium chloride, hydrochloric acid and/or sodium hydroxide to adjust the pH and purified water.
Acular has a pH of 7.4 and osmolality of 290 mOsmol/kg. It is a racemic mixture of R-(+) and S-(-) ketorolac tromethamine.
Ketorolac tromethamine, a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs), is (±)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1). It has a molecular weight of 376.41. It may exist in 3 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.
Action
Pharmacology: Animal: 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 I or Pseudomonas aeruginosa.
Clinical: Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug which, when administered systemically, has demonstrated analgesic, anti-inflammatory and antipyretic 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 Acular instilled into the eyes of patients 12 hrs and 1 hr prior to cataract extraction achieved measurable levels in 8 of 9 patients' eyes (mean ketorolac concentration 95 ng/mL aqueous humor, range 40-170 ng/mL). Ocular administration of ketorolac tromethamine reduces prostaglandin E2 (PGE2) levels in aqueous humor. The mean concentration of PGE2 was 80 pg/mL in the aqueous humor of eyes receiving vehicle and 28 pg/mL in the eyes receiving Acular.
One drop (0.05 mL) of Acular was instilled into 1 eye and 1 drop of vehicle into the other eye 3 times daily in 26 normal subjects. Only 5 of 26 subjects had a detectable amount of ketorolac in their plasma (range: 10.7-22.5 ng/mL) at Day 10 during topical ocular treatment. When ketorolac tromethamine 10 mg is administered systemically every 6 hrs, peak plasma levels at steady state are around 960 ng/mL.
Two controlled clinical studies showed that Acular 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 2 weeks with Acular 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 eg, antibiotics, β-blockers, carbonic anhydrase inhibitors, cycloplegics and mydriatics.
Indications/Uses
For the temporary relief of ocular itching due to seasonal allergic conjunctivitis. Also for the treatment of postoperative inflammation in patients who have undergone cataract extraction.
Dosage/Direction for Use
For the Relief of Ocular Itching Due to Seasonal Allergic Conjunctivitis: Recommended Dose: 1 drop (0.25 mg) 4 times a day.
For the Prophylaxis and Reduction of Inflammation and associated symptoms following Ocular Surgery: Apply 1 drop to the affected eye(s) 3 times daily beginning 24 hrs before ocular surgery and continuing through the first 3 weeks of the postoperative period.
Contraindications
Patients who have previously demonstrated hypersensitivity to any of the ingredients of Acular.
Warnings
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.
Special Precautions
General: 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.
Information for Patients: Acular should not be administered while wearing contact lenses.
Carcinogenicity, Mutagenicity & Impairment of Fertility: An 18-month study in mice at oral doses of ketorolac tromethamine equal to the parenteral maximum recommended human dose (MRHD) 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 mcg/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 and 16 mg/kg, respectively.
Use in pregnancy: Teratogenic Effects: 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 during late pregnancy should be avoided.
Use in lactation: Caution should be exercised when Acular is administered to a nursing woman.
Use in children: Safety and efficacy in pediatric patients <12 years have not been established.
Use In Pregnancy & Lactation
Use in pregnancy: Teratogenic Effects: 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 during late pregnancy should be avoided.
Use in lactation: Caution should be exercised when Acular is administered to a nursing woman.
Adverse Reactions
In controlled clinical studies, the most frequent adverse events reported with the use of Acular have been transient stinging and burning on instillation. These events were reported by approximately 40% of patients treated with Acular. In all development studies conducted, other adverse events occurring <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 include eye dryness, corneal infiltrates, corneal ulcer and visual disturbance (blurry vision).
Storage
Store at controlled room temperature 15-30°C (59-86°F). Protect from light.
ATC Classification
S01BC05 - ketorolac ; Belongs to the class of non-steroidal antiinflammatory agents. Used in the treatment of inflammation of the eye.
Presentation/Packing
Ophthalmic drops 0.5% (sterile, isotonic, aqueous) x 5 mL.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in