Xevolac Drug Interactions

Ketorolac is highly bound to human plasma protein (mean 99.2%) and binding is concentration-independent.
The following medicinal products are NOT to be co-administered with Ketorolac: Ketorolac should not be used with other ASA or other NSAIDs including cyclooxygenase-2 selective inhibitors as the risk of inducing serious NSAID-related adverse events may be increased.
Ketorolac inhibits platelet aggregation, reduces thromboxane concentrations and prolongs bleeding time. Unlike the prolonged effects from aspirin, platelet function returns to normal within 24-48 hours after ketorolac is discontinued.
Ketorolac is contraindicated in combination with anti-coagulants, such as warfarin since co-administration of NSAIDs and anti-coagulants may cause an enhanced anti-coagulant effect.
Although studies do not indicate a significant interaction between ketorolac and warfarin or heparin the concurrent use of ketorolac and therapy that affects haemostasis, including therapeutic doses of anti-coagulation therapy (warfarin) prophylactic low-dose heparin (2500-5000 units 12-hourly) and dextrans may be associated with an increased risk of bleeding.
Inhibition of renal lithium clearance, leading to an increase in plasma lithium concentration, has been reported with some prostaglandin synthesis-inhibiting drugs. Cases of increased lithium plasma concentrations during ketorolac therapy have been reported.
Probenecid should not be administered concurrently with ketorolac because of increases in ketorolac plasma concentrations and half-life.
NSAIDs should not be used for eight to twelve days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.
When ketorolac is administered concurrently with oxpentifylline, there is an increased tendency to bleeding.
The following medicinal products in combination with Ketorolac, are to be co-administered with caution: As with all NSAIDs, caution should be taken when co-administering with corticosteroids because of the increased risk of gastrointestinal ulceration or bleeding.
There is an increased risk of gastrointestinal bleeding when anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs.
Some prostaglandin synthesis-inhibiting drugs have been reported to reduce the clearance of methotrexate, and thus possibly enhance its toxicity.
Ketorolac tromethamine does not alter digoxin protein binding. In vitro studies indicated that at therapeutic concentrations of salicylate (300μg/ml), the binding of ketorolac was reduced from approximately 99.2% to 97.5% representing a potential twofold increase in unbound ketorolac plasma concentrations. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin and tolbutamide did not alter ketorolac protein binding.
Ketorolac injection reduced the diuretic response to furosemide in normovolemic healthy subjects by approximately 20% so particular care should be taken in patients with cardiac decompensation.
Co-administration with diuretics can lead to a reduced diuretic effect, and increase the risk of nephrotoxicity of NSAIDs.
As with all NSAIDs caution is advised when ciclosporin is co-administered because of the increased risk of nephrotoxicity.
There is a possible risk of nephrotoxicity when NSAIDs are given with tacrolimus.
NSAIDs may reduce the effect of diuretics and anti-hypertensive medicinal products. The risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e.g. dehydrated patients or elderly patients) when ACE inhibitors and/or angiotensin II receptor antagonists are combined with NSAIDs. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately titrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.
Ketorolac has been shown to reduce the need for concomitant opioid analgesia when it is given for the relief of postoperative pain.
Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
NSAIDs given with zidovudine increase the risk of haematological toxicity. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
There is no evidence in animal or human studies that ketorolac trometamol induces or inhibits the hepatic enzymes capable of metabolising itself or other drugs. Hence ketorolac would not be expected to alter the pharmacokinetics of other drugs due to enzyme induction or inhibition mechanisms.