Drug Interactions between aspirin / carisoprodol / codeine and dalteparin

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

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.