Article Item

Ziconotide Dosing and Trialing Strategies

Jan 25, 2021, 15:02 PM by Jason E. Pope, MD

By Jason E. Pope, MD
President, Summit Pain Alliance
Santa Rosa, CA



Ziconotide is a non-opioid agent that is delivered into the intrathecal space for the treatment of refractory chronic pain.1 It is the only non-opioid Food and Drug Administration (FDA) approved intrathecal agent to treat chronic pain. Further, it has been studied by three randomized, placebo-controlled trials,2-4 along with numerous prospective and retrospective studies.5-11 Despite these accolades, poor adoption of intrathecal therapy as a treatment modality offered to patients has plateaued, as is the sustainability of monotherapy ziconotide. In diving into the available data, with a keen eye on patient selection, a pathway can be forged.12,13

The pharmacokinetics of ziconotide have been extensively described, demonstrating linear kinetics with a half life of 4.5 hours.14,15 Many trialing options have been described for intrathecal therapy,16 with no clear superior strategy for predicting long-term success with long-term intrathecal delivery.17,18 Of these, single shot, intrathecal trialing has emerged as a viable option for ziconotide.19,20 It is recommended by the Polyanalgesic Consensus Conference (PACC) of 201221 to monitor these patients for at least 12 hours.

Further, introducing ziconotide as the initial intrathecal agent improves the sustainability of the medication.1,22 Because of the “penetration interval” needed for the ziconotide to reach its site of action, the recommended dosing interval of 1.2 or 2.4 mcg per 24 hours may be to fast, as we suggested a slower titration schedule.

As described,23 ziconotide is not an opioid. Therefore, patients on opioids need to slowly wean off their systemic medications. It is not recommended for patients with a history of psychosis.


Best Practice

Performing a trial of medication with ziconotide, placed intrathecally, via bolus injection, is recommended. Performing the injection under fluoroscopy, with a lateral projection with needle entry within the intrathecal space is crucial. Injection of contrast to observe any filling defects prior to injection suggested.

The trial concentration and the manner at which to perform the injection have already been described.19 Typically, bolus injection dosing begins between 2 or 2.5 mcg/cc and 1 cc of medication is injected with barbotage. The patient is then observed for at least 4 hours.

Once the pump is implanted, placement of the medication within the reservoir of the pump and initiation of the infusion strategy, may occur on the day of surgery or shortly thereafter, in either an inpatient or outpatient setting. The dose initiated should be similar to the successful trialing dose if bolus delivery is performed. If continuous infusion is chosen as the infusion strategy, 0.5 to 1.0 mcg/cc is recommended. In either case, titration should occur in terms of increases of 0.1 to 0.2 mcg/day per week.

If side effects are encountered, the clinician needs to gauge each situation individually. If the side effects are not severe reactions, decreasing the dose by 50% initially, with a slower titration of 0.5 (the previous titration schedule), is recommended.



  1. Hayek SM, Deer TR, Pope JE, et al. Intrathecal therapy for cancer and non-cancer pain. Pain Phys 2011;14:219–48.
  2. Rauck RL, Wallace MS, Leong MS et al. A randomized, double-blind, placebo controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage 2006;31:393–406.
  3. Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA 2004;291:63–70.
  4. Wallace MS, Charapata SG, Fisher R, et al. Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial. Neuromodulation 2006;9:75–86.
  5. Webster LR, Fisher R, Chrpata S, Wallace MS. Long-Term Intrathecal Ziconotide for Chronic Pain: An Open Labeled Study. Journal of Pain and Symptom Management. 2009 March Vol 37 No 3. 363-372.
  6. Wallace MS, Rauck R, Fisher R, et al. Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial. Anesth Analg 2008;106(2):628e637
  7. Ellis DJ, Dissanayake S, McGuire D, et al. Continuous Intrathecal Infusion of Ziconotide for Treatment of Chronic Malignant and Nonmalignant Pain Over 12 Months: A Prospective, Open-label Study. Neuromodulation 2008, 11(1):40-49
  8. Raffaeli W, Sarti D, Demartini L, et al. Italian Regisery on Long-Term Intrathecal Ziconotide Treatment. Pain Physician. 2011 (14):15-24.
  9. Dupoiron D, Bore F, Lefebvre-Kuntz D, et al. Ziconotide Adverse Events in Patients with Cancer Pain: A multicenter Observational Study of a Slow Titration, Multidrug Protocol. Pain Physician 2012;15:395-403
  10. Wallace MS, Rauck RL, Deer T. Ziconotide Combination Intrathecal Therapy: Rationale and Evidence. Clin J Pain 2010;26:635-644
  11. Deer T, Kim C, Bowman R, et al. Intrathecal Ziconotide and Opioid Combination Therapy for Noncancer Pain: An Observational Study. Pain Physician 2009;12E291-E296
  12. Deer TR, Caraway DL, Wallace MS. A Definition of Refractory Pain to Help Determine Suitability for Device Implantation. Neuromodulation. 2014. Vol 17(8): 711-715.
  13. Pope JE, Deer TR, McRoberts WP. Intrathecal Therapy: The Burdon of Being Positioned as a Salvage Therapy. Pain Medicine. Article first published online: 19 MAY 2015. DOI: 10.1111/pme.12782
  14. Yaksh TL,De Kater A,Dean R et al.Pharmacokinetic analysis of ziconotide (SNX-111), an intrathecal N-type calcium channel blocking analgesic, delivered by bolus and infusion in dog. Neuromodulation 2012;15:508–519.
  15. Wermeling DP. Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain. Pharmacology 2005;25: 1084–1094.
  16. Deer TR, Prager J, Levy R et al. Polyanalgesic consensus conference–2012: recommendations on trialing for intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation 2012;15:420–435.
  17. Burton AW, Deer T, Wallace MS et al. Considerations and methodology for trialing ziconotide. Pain Physician 2010;13:23–33.
  18. Backryd E, Sorensen J, Gerdle B. Ziconotide Trialing by Intrathecal Bolus Injections: An Open-Label Non-Randomized Clinical Trial in Postoperative/Posttraumatic Neuropathic Pain Patients Refractory to Conventional Treatment. Neuromodulation 2015; E-pub ahead of print. DOI: 1111/ner.12293
  19. Mohammed SI, Eldabe S, Simpson KH et al. Bolus intrathecal injection of ziconotide (prialt) to evaluate the option of continuous administration via an implanted intrathecal drug delivery system: a pilot study. Neuromodulation 2013;16:576–581; discussion 582.
  20. Pope JE, Deer TR. Intrathecal Pharmacology Update: Novel Dosing Strategy for Intrathecal Monotherapy Ziconotide on Efficacy and Sustainability. Neuromodulation. 2015 Feb 24. doi: 10.1111/ner.12274. [Epub ahead of print]. Neuromodulation 2015; E-pub ahead of print. DOI: 10.1111/ner.12270
  21. Deer TR, Prager J, Levy R, et al. Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel. Neuromodulation 2012;15(5):436–64; discussion 464–6.
  22. Hayek SM, Hanes MC, Wang C et al. Ziconotide Combination Intrathecal Therapy for Noncancer Pain Is Limited Secondary to Delayed Adverse Effects: A Case Series With a 24-Month Follow-Up. Neuromodulation. 2015 Jul;18(5):397-403. doi: 10.1111/ner.12270. Epub 2015 Feb 5.
  23. Pope JE, Deer TR. Ziconotide: a clinical update and pharmacologic review. Expert Opin Pharmacother. 2103 May 14(7):957-66.

Download PDF.

Load more comments
New code
Comment by from
Close Nav