Drug Interactions between diflunisal and enoxaparin

GENERALLY AVOID: In patients receiving neuraxial anesthesia or spinal puncture, the risk of developing an epidural or spinal hematoma during low molecular weight heparin (LMWH) or heparinoid therapy may be increased by the concomitant use of other drugs that affect coagulation, including nonsteroidal anti-inflammatory drugs (NSAIDs). The development of epidural and spinal hematoma can lead to long-term or permanent paralysis.

GENERALLY AVOID: Theoretically, NSAIDs may potentiate the risk of bleeding complications associated with LMWH or heparinoid therapy. NSAIDs interfere with platelet adhesion and aggregation and may prolong bleeding time in healthy individuals. While these effects are generally slight and of relatively short duration with most NSAIDs (except aspirin) at recommended dosages, they may be of pronounced clinical significance when combined with the inhibitory effects of LMWHs or heparinoids on the clotting cascade. However, little clinical data exist regarding an actual interaction. In a controlled, randomized prospective study, 60 patients undergoing total hip replacement received enoxaparin (40 mg subcutaneously 12 hours pre- and every 24 hours postoperatively for 10 days) and analgesia with either ketorolac (30 mg IM on induction of anesthesia and every 24 hours postoperatively for 4 days) or an opioid plus acetaminophen. The authors reported no significant differences between the two groups for intraoperative blood loss, postoperative drainage, transfusion requirements, bruising, wound oozing, and leg swelling. However, there have been anecdotal reports of hemorrhagic complications in surgical patients treated with NSAIDs alone and in combination with a LMWH. In addition, NSAIDs are known to cause dose-related gastrointestinal bleeding, which may be complicated by anticoagulant therapy.

MANAGEMENT: Products containing NSAIDs, especially if given chronically and in high dosages, should preferably be avoided in patients receiving LMWHs or heparinoids. Close clinical and laboratory observation for bleeding complications is recommended if concurrent therapy is necessary. In patients undergoing neuraxial intervention, coadministration of these agents should be approached with caution and only after thorough assessment of risks and benefits. Besides bleeding complications, patients should also be monitored frequently for signs and symptoms of neurologic impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), and bowel or bladder dysfunction.

Switch to consumer interaction data