title: Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial.
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.
  
  
  CONCLUSIONS
  We conclude that long-term IT ziconotide is an option for patients with severe, refractory chronic pain.
authors.affiliation: Center for Pain Medicine, University of California, San Diego, La Jolla, California 92093, USA. mswallace@ucsd.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wallace
authors.forename: Richard
authors.initials: R
authors.lastname: Rauck
authors.forename: Robert
authors.initials: R
authors.lastname: Fisher
authors.forename: Steven G
authors.initials: SG
authors.lastname: Charapata
authors.forename: David
authors.initials: D
authors.lastname: Ellis
authors.forename: Sanjeeva
authors.initials: S
authors.lastname: Dissanayake
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care / Q000379:methods; D002908:Chronic Disease; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000453:epidemiology; D013995:Time; D020960:omega-Conotoxins / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D020960:omega-Conotoxins; C078452:ziconotide