Ketral Drug Interactions

Given 10 mg orally for 6 days prior to co-administration of a single dose of warfarin 25 mg, no significant changes in pharmacokinetics of the warfarin enantiomers were detected. Ketorolac is highly bound to plasma proteins (mean 99.2%) and binding is independent of concentration. The in vitro binding of warfarin to plasma proteins is only slightly reduced by ketorolac. Ketorolac does not alter digoxin, protein binding. In vitro at therapeutic concentrations of salicylate (300 mcg/mL). The binding of ketorolac was reduced from approximately 99.2%-97.5%. Therapeutic concentrations of digoxin, warfarin, acetaminophen, phenytoin and tolbutamide did not alter ketorolac protein binding. Because ketorolac is a highly potent drug and present in low concentrations in plasma, it would be expected to displace other protein-bound drugs significantly.
There is no evidence that ketorolac induces or inhibits the hepatic enzymes capable of metabolizing itself or other drugs. Hence ketorolac would not be expected to alter the pharmacokinetics of other drugs due to enzyme induction of inhibition mechanisms.
Concomitant administration of ketorolac tromethamine and probenecid results in the decreased clearance of ketorolac and a significant increase in ketorolac plasma levels and terminal half-life of ketorolac.
Ketorolac tromethamine reduces the diuretic response to furosemide in normo-volemic healthy subjects by approximately 20%. Inhibition of renal lithium clearance leading to an increase in plasma lithium concentrations and potential lithium toxicity has been reported with some prostaglandin synthesis inhibiting drugs. Concomitant administration of ketorolac tromethamine and methotrexate, and thus possibly enhance the toxicity of methotrexate. Ketorolac tromethamine has been administered concurrently with morphine in postoperative pain without evidence of adverse interactions. There are no clinical data available dealing with the safety or efficacy of concomitant use with other non-steroidal anti-inflammatory drugs. It is not recommended that ketorolac tromethamine be routinely used with other non-steroidal anti-inflammatory drugs because of potential for additive side effects.