Drug Interactions between bupivacaine / hydromorphone and DepoDur

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.

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ADJUST DOSING INTERVAL: Concomitant epidural administration of local anesthetics may affect the release of morphine sulfate from the liposomal formulation. The mechanism of interaction is unknown. According to the product labeling, epidural administration of a 15 mg dose of liposomal morphine three minutes and ten minutes after a 3-mL test dose of lidocaine 1.5%-epinephrine 1:200,000 resulted in an increase in the mean peak serum concentration (Cmax) of morphine by 163% and 36%, respectively, compared to administration without a test dose. No significant difference in morphine Cmax levels was observed when liposomal morphine was administered 15 minutes after the lidocaine test dose as opposed to administration without test dose. Similarly, increases in morphine Cmax levels were also observed when liposomal morphine was administered epidurally at various time intervals up to 30 minutes after an analgesic dose of bupivacaine 0.25% (20 mL). The interaction did not occur when liposomal morphine was administered more than 30 minutes after the bupivacaine dose. The use of liposomal morphine with anesthetics other than lidocaine with epinephrine (test dose) and bupivacaine (analgesic dose) has not been evaluated. In vitro studies suggest a similar interaction with other amide local anesthetics. No data are available for ester-type local anesthetics.

MANAGEMENT: To minimize the potential for interaction between liposomal morphine and lidocaine-epinephrine test dose (1.5%-1:200,000, 3 mL), flush the epidural catheter with 1 mL of preservative-free 0.9% normal saline and wait at least 15 minutes after the test dose before administering the morphine. Following administration of an analgesic dose of bupivacaine (0.25%, 20 mL), flush the epidural catheter with 1 mL of preservative-free 0.9% normal saline and wait at least 30 minutes before administering the morphine. Liposomal morphine should not be mixed with any other medications. Once it has been administered, no other medication should be administered into the epidural space for at least 48 hours.

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