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Intrathecal Ziconotide: A Review of Its Use in Patients with Chronic Pain Refractory to Other Systemic or Intrathecal Analgesics

Abstract

Ziconotide (Prialt®) is a synthetic conopeptide analgesic that acts by selectively antagonizing N-type voltage-gated calcium channels. Intrathecal ziconotide is the only non-opioid intrathecal analgesic that is FDA-approved for use in patients with treatment-refractory, chronic pain. The efficacy of intrathecal ziconotide was demonstrated in randomized, double-blind, placebo-controlled trials in patients with treatment-refractory noncancer-related pain or cancer- or AIDS-related pain. Across trials, ziconotide recipients had significantly greater reductions in pain intensity during ziconotide treatment than those receiving placebo (primary endpoint). At the end of the titration period, approximately one-sixth to one-third of patients with noncancer chronic pain and one-half with cancer- or AIDS-related pain who received ziconotide reached a pain response threshold (≥30 % reduction in the pain intensity score). In ziconotide responders, analgesic effects were enduring, with some patients continuing treatment over extended periods. Across trials, the chief tolerability concerns in ziconotide recipients during the titration phase and during extended treatment were related to CNS adverse events. These were mostly of mild to moderate intensity, although serious adverse events were commonly attributed to ziconotide treatment, especially in trials with rapid ziconotide titration and that permitted higher dosages. In general, clinically important non-CNS adverse events were infrequent, and during the ziconotide titration phase, relatively few patients discontinued treatment because of adverse events. Ongoing research will assess various strategies for selecting patients for ziconotide treatment and for enhancing its efficacy and tolerability. At the present time, intrathecal ziconotide provides a treatment option for patients with severe, unremitting pain who have failed to respond to other intensive analgesic regimens.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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Correspondence to Mark Sanford.

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The manuscript was reviewed by: H. Breivik, Departments of Anaesthesiology and Pain Management and Research, Oslo University Hospital and University of Oslo, Oslo, Norway; A.A. van der Plas, Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; E. Viezi, Division of Pain Medicine, Department of Anesthesiology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio, USA; Y. Vorobeychik, Pain Medicine Division, Department of Anesthesiology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.

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Sanford, M. Intrathecal Ziconotide: A Review of Its Use in Patients with Chronic Pain Refractory to Other Systemic or Intrathecal Analgesics. CNS Drugs 27, 989–1002 (2013). https://doi.org/10.1007/s40263-013-0107-5

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Keywords

  • Placebo Recipient
  • Intrathecal Morphine
  • Titration Phase
  • Titration Period
  • Ziconotide