Concurrent Use of Ketorolac PO and Enoxaparin 40 mg Daily for DVT Prophylaxis
The concurrent use of oral ketorolac with enoxaparin 40 mg daily for DVT prophylaxis is contraindicated and should be avoided due to significantly increased bleeding risk. 1
FDA Contraindication and Warnings
The FDA drug label for ketorolac explicitly states that "patients on therapeutic doses of anticoagulants (e.g., heparin or dicumarol derivatives) have an increased risk of bleeding complications if given ketorolac tromethamine concurrently; therefore, physicians should administer such concomitant therapy only extremely cautiously." 1
More specifically, the FDA warns that "the concurrent use of ketorolac tromethamine and therapy that affects hemostasis, including prophylactic low-dose heparin (2500 to 5000 units q12h), warfarin and dextrans have not been studied extensively, but may also be associated with an increased risk of bleeding." 1
The label further emphasizes that "until data from such studies are available, physicians should carefully weigh the benefits against the risks and use such concomitant therapy in these patients only extremely cautiously." 1
Mechanism of Increased Bleeding Risk
Ketorolac inhibits platelet aggregation through prostaglandin synthesis inhibition, which affects hemostasis independently of anticoagulation. 1
Enoxaparin provides anticoagulation through antithrombin III-mediated inhibition of factor Xa and thrombin, preventing clot formation. 2
The combination creates additive bleeding risk through two separate mechanisms affecting different components of the coagulation cascade. 1
Clinical Evidence on Bleeding Complications
Ketorolac can cause serious gastrointestinal bleeding, ulceration, and perforation at any time, with or without warning symptoms, and only one in five patients who develop serious upper GI adverse events on NSAID therapy is symptomatic. 1
Postoperative hematomas and wound bleeding have been reported in association with ketorolac use in postmarketing surveillance. 1
The FDA specifically notes that "patients receiving therapy that affects hemostasis should be monitored closely" when ketorolac is used. 1
Alternative Analgesic Strategies
If pain control is needed in a patient requiring enoxaparin DVT prophylaxis, consider these safer alternatives:
Acetaminophen as first-line analgesic (no antiplatelet effect or bleeding risk increase)
Opioid analgesics (morphine, hydromorphone, oxycodone) for moderate to severe pain
Tramadol for moderate pain as an intermediate option
Topical or regional anesthesia techniques when anatomically appropriate
Critical Caveats
Ketorolac duration is limited to 5 days maximum regardless of route, which further argues against its use in patients requiring ongoing DVT prophylaxis. 1
Elderly and debilitated patients are at highest risk for fatal GI bleeding events with NSAIDs, and these same populations often require DVT prophylaxis. 1
The bleeding risk persists even with short-term ketorolac therapy, as the FDA notes that "even short-term therapy is not without risk." 1
If this combination is absolutely unavoidable in exceptional circumstances, patients must be monitored extremely closely for signs of bleeding, including serial hemoglobin checks, stool guaiac testing, and assessment for ecchymosis or hematoma formation. 1