Source: FDA, National Drug Code (US) Revision Year: 2019
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 three times daily 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 three times daily 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).
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 900 times and 300 times higher respectively than the typical human topical ophthalmic daily dose given as twice daily to an affected eye on a mg/kg basis.
Ketorolac tromethamine was not mutagenic in vitro in the Amesassay 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 1500 and 2700 times higher than the typical human topical ophthalmic daily dose.
Two multicenter, randomized, double-masked, parallel group comparison studies including approximately 500 patients were conducted to evaluate the effects of ACUVAIL on anterior chamber cell and flare, and ocular pain relief following cataract extraction with posterior chamber intraocular lens (IOL) implantation. Results of these studies indicated that patients receiving ACUVAIL had a significantly higher incidence of clearing of anterior chamber inflammation 53% (167/318) versus patients receiving vehicle 26% (41/155) at day 14.
ACUVAIL was also significantly superior to vehicle in resolving ocular pain. On Day 1 post cataract surgery, 72% (233/322) of patients in the ACUVAIL group were pain free compared to 40% (62/156) of patients in the vehicle group.
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.
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