Drug Interactions between articaine / epinephrine and morphine liposomal

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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