Ketorolac Tromethamine

Concomitant use is contraindicated due to increased risk of bleeding.

Probenecid component inhibits OAT1/3, increasing ketorolac tromethamine plasma concentrations and risk of adverse reactions.

Concomitant use increases risk of bleeding and GI adverse reactions. No additional therapeutic benefit compared to ketorolac alone.

Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine 7.6 Potent Inhalation Anesthetics Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Warnings and Precautions (5.13) ] .

NSAID that may enhance risk of hemorrhage. Discontinue prior to Lovenox initiation if possible, or conduct close clinical and laboratory monitoring if coadministration is essential.

May cause severe, persistent hypertension or cerebrovascular accidents. Avoid concurrent use.

Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine 7.6 Potent Inhalation Anesthetics Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Warnings and Precautions (5.13) ] .

Administration should be done extremely cautiously with close monitoring due to potential increased bleeding risk, although in vitro studies showed minimal effect on template bleeding time.

Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine 7.6 Potent Inhalation Anesthetics Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Warnings and Precautions (5.13) ] .

Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine 7.6 Potent Inhalation Anesthetics Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Warnings and Precautions (5.13) ] .

May produce severe, prolonged hypertension. Concurrent use should generally be avoided.

May cause severe hypertension and bradycardia. Concurrent use should generally be avoided.

Probenecid significantly decreases ketorolac clearance and volume of distribution, increasing total AUC approximately threefold and terminal half-life approximately twofold.

Serious dose-related cardiac arrhythmias may occur if preparations containing vasoconstrictor are used during or following potent inhalation anesthetic administration.

Synergistic risk of serious GI bleeding when used together. Although no significant pharmacokinetic interaction observed, NSAIDs and warfarin together carry higher GI bleeding risk than either drug alone.

Ketorolac can reduce the natriuretic effect of furosemide. Close observation for signs of renal failure and diuretic efficacy is needed during concomitant therapy.

NSAIDs may diminish antihypertensive effect. In elderly, volume-depleted, or renal impaired patients, may result in deterioration of renal function.

At therapeutic concentrations, salicylate reduces ketorolac protein binding from 99.2% to 97.5%, representing potential two-fold increase in unbound ketorolac plasma levels.

Ketorolac can reduce the natriuretic effect of thiazide diuretics. Close observation for signs of renal failure and diuretic efficacy is needed during concomitant therapy.

Psychoactive Drugs Hallucinations have been reported when ketorolac tromethamine was used in patients taking psychoactive drugs (fluoxetine, thiothixene, alprazolam).

Therapeutic concentrations of digoxin , warfarin , ibuprofen , naproxen , piroxicam , acetaminophen , phenytoin and tolbutamide did not alter ketorolac tromethamine protein binding.