Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial

Anesth Analg. 2008 Feb;106(2):628-37, table of contents. doi: 10.1213/ane.0b013e3181606fad.

Abstract

Background: Ziconotide is a non-opioid drug indicated for management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted and who are intolerant of or refractory to other treatments.

Methods: Six-hundred and forty-four patients with severe chronic pain participated in this open-label, multicenter study. Ziconotide titration was followed by long-term infusion. Efficacy assessments included the Visual Analog Scale of Pain Intensity. Safety was assessed via adverse events (AEs), vital signs, and routine laboratory values.

Results: One-hundred and nineteen patients received ziconotide for > or = 360 days; total exposure was 350.9 patient years. Median duration of ziconotide therapy was 67.5 days (range, 1.2-1215.5 days); mean dose at last infusion was 8.4 microg/d (range, 0.048-240.0 microg/d). Median Visual Analog Scale of Pain Intensity scores at baseline, month 1, and the last available observation up to month 2 were 76 mm (range, 4-100 mm), 68 mm (range, 0-100 mm), and 73 mm (range, 0-100 mm), respectively. Most patients (99.7%) experienced > or = 1 AE. Most AEs were of mild (43.5%) or moderate (42.3%) severity; 58.6% of AEs were considered unrelated to ziconotide. The most commonly reported AEs (> or = 25% of patients) included nausea, dizziness, headache, confusion, pain, somnolence, and memory impairment. Clinically significant abnormalities (> 3 times the upper limit of normal) in creatine kinase levels were reported in 0.9% of patients at baseline, 5.7% at month 1, and 3.4% at ziconotide discontinuation. No drug-related deaths, IT granulomas, or permanent adverse sequelae occurred with ziconotide therapy.

Conclusion: We conclude that long-term IT ziconotide is an option for patients with severe, refractory chronic pain.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Ambulatory Care / methods
  • Chronic Disease
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / epidemiology
  • Humans
  • Infusion Pumps
  • Male
  • Middle Aged
  • Pain / drug therapy*
  • Pain / epidemiology
  • Time
  • omega-Conotoxins / administration & dosage*
  • omega-Conotoxins / adverse effects*

Substances

  • omega-Conotoxins
  • ziconotide