Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

It is contraindicated the association of ketorolac trometamol with other NSAIDs, oxpentifylline (pentoxifylline), probenecid and lithium salts (see section 4.3).

It is also contraindicated the association of ketorolac trometamol with anti-platelet agents, oral anticoagulants and heparin (see section 4.3).

Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
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.

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 anticoagulation therapy (warfarin), prophylactic low-dose heparin (2500-5000 units 12-hourly) and dextrans may be associated with an increased risk of bleeding.

In patients currently receiving acetylsalicylic acid or other NSAIDs the risk of inducing serious NSAID-related adverse events may be increased.

When ketorolac is administered concurrently with oxpentifylline (pentoxifylline), there is an increased tendency to bleeding.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Probenecid should not be co-administered with ketorolac due to increased ketorolac plasma concentrations and half-life.

Some prostaglandin synthesis-inhibiting drugs have been reported to reduce the clearance of methotrexate, and thus possibly enhance its toxicity.

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.

Ketorolac trometamol does not alter the digoxin protein binding. In vitro studies indicate that, at therapeutic concentrations of salicylate (300 μg/ml), the binding of ketorolac was reduced from approximately 99.2 to 97.5%, representing a potential two-fold increase in unbound ketorolac plasma concentrations. The therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, paracetamol, phenytoin and tolbutamide do not affect the protein binding of ketorolac trometamol.

Ketorolac solution for injection reduces the diuretic response to furosemide in normovolaemic healthy subjects by approximately 20%, therefore, particular care should be taken in patients with cardiac decompensation.

NSAIDs may reduce the effect of diuretics and antihypertensive 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 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 hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.

Caution is required for the concomitant administration with quinolones because of the risk of the occurrence of convulsions.

Ketorolac has been shown to reduce the need for concomitant opioid analgesia when it is given for the relief of postoperative pain.