Stability, compatibility, and safety of intrathecal bupivacaine administered chronically via an implantable delivery system

Objective: The only agent approved by the U.S. Food and Drug Administration for chronic intrathecal infusion for the treatment of chronic pain is morphine sulfate. In patients who do not experience adequate relief from intrathecal opioids, bupivacaine is frequently added to increase efficacy. The studies reported here were conducted to demonstrate the stability and compatibility of bupivacaine in a commonly used implantable infusion system and the long-term clinical safety of this therapy. Methods: A commercially available bupivacaine solution (7.5 mg/ml) was incubated at 37 degreesC for 12 weeks with intact delivery systems and with the individual materials that comprise the fluid pathway. Intermittent samples were collected and analyzed using liquid chromatography. Materials chronically exposed to bupivacaine were analyzed for mechanical integrity. One hundred eight patients treated with intrathecal bupivacaine (average dose: 10 mg/d, range: 2-25 mg/d) and opioids for an average duration of 86 weeks were monitored clinically (patient interviews and neurologic examinations) approximately every 4 weeks. Results: Bupivacaine concentrations remained greater than 96% of the starting material after chronic exposure to the delivery system materials or the intact pump-catheter systems, and the mechanical integrity of the delivery system and materials remained intact. When combined with intrathecal morphine or hydromorphone, no clinical evidence of drug-induced toxicity or complications was observed in any patient. Supplementing opioid therapy with bupivacaine allowed the pain patient to continue to be effectively managed using an implantable intrathecal delivery system. Conclusions: Bupivacaine is stable and compatible with a commonly used implantable drug infusion system. In this study. chronic supplementation of intrathecal opioids with bupivacaine was a safe method for providing continued management of chronic pain of cancer or noncancer origin.