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.