title: Ziconotide adverse events in patients with cancer pain: a multicenter observational study of a slow titration, multidrug protocol.
abstract: BACKGROUND
  Ziconotide is a new analgesic agent administered intrathecally. It is challenging to use and can induce several and sometimes serious adverse events. A low initial dosage followed by slow titration may reduce serious adverse events.
  
  
  OBJECTIVE
  To determine whether a low starting dosage of ziconotide, followed by slow titration, decreases the incidence of major adverse events associated with ziconotide when used for intractable cancer pain.
  
  
  METHODS
  Observational cohort study.
  
  
  METHODS
  Three French cancer centers.
  
  
  METHODS
  Patients with incurable cancer causing chronic pain rated above 6/10 on a numerical scale while receiving high-dose opioid therapy  (more than 200 mg/d of oral morphine equivalent) and/or exhibiting severe opioid-related adverse events received intrathecal infusions of ziconotide combined with morphine, ropivacaine, and clonidine.
  
  
  RESULTS
  Seventy-seven patients were included. Adverse events were recorded in 57% of them; moderate adverse events occurred in 51%. Adverse events required treatment discontinuation in 7  (9%) including 5  (6%) for whom a causal role for ziconotide was highly likely; among them 4  (5%) were serious. All patients experienced a significant and lasting decrease in pain intensity  (by 48%) in response to intrathecal analgesic therapy that included ziconotide.
  
  
  CONCLUSIONS
  Limitations include the nonrandomized, observational nature of the study. Determining the relative contributions of each drug to adverse events was difficult, and some of the adverse events manifested as clinical symptoms of a subjective nature.
  
  
  CONCLUSIONS
  The rates of minor and moderate adverse events were consistent with previous reports. However, the rate of serious adverse events was substantially lower. Our study confirms the efficacy of intrathecal analgesia with ziconotide for relieving refractory cancer pain. These results indicate that multimodal intrathecal analgesia in patients with cancer pain should include ziconotide from the outset in order to provide time for subsequent slow titration.
authors.affiliation: Department of Anesthesia and Pain, Lille, France. denis.dupoiron@ico.unicancer.fr
authors.forename: Denis
authors.initials: D
authors.lastname: Dupoiron
authors.forename: Francois
authors.initials: F
authors.lastname: Bore
authors.forename: Daniele
authors.initials: D
authors.lastname: Lefebvre-Kuntz
authors.forename: Olivier
authors.initials: O
authors.lastname: Brenet
authors.forename: Sabine
authors.initials: S
authors.lastname: Debourmont
authors.forename: Florence
authors.initials: F
authors.lastname: Dixmerias
authors.forename: Nadia
authors.initials: N
authors.lastname: Buisset
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lebrec
authors.forename: Dominique
authors.initials: D
authors.lastname: Monnin
mesh_terms: D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000145:classification / Q000150:complications*; D019370:Observation; D010147:Pain Measurement; D020960:omega-Conotoxins / Q000009:adverse effects*
chemical_list: D018712:Analgesics, Non-Narcotic; D020960:omega-Conotoxins; C078452:ziconotide