title: Evaluation of dosing guidelines for use of controlled-release codeine in chronic noncancer pain.
abstract: OBJECTIVE
  The clinical utility of guidelines for conversion of patients from a combination analgesic preparation of acetaminophen 300 mg plus codeine 30 mg every 4h to 6h as needed to scheduled controlled-release (CR) codeine every 12h was evaluated.
  
  
  METHODS
  Adult patients with chronic noncancer pain underwent a two-week evaluation on acetaminophen plus codeine, followed by eight weeks of treatment with CR codeine. Patients taking four to six tablets of acetaminophen plus codeine per day were transferred to 50 mg CR codeine every 12 h; those on seven to nine tablets were transferred to 100 mg every 12 h; those on 10 to 12 tablets were transferred to 150 mg every 12 h; and those on greater than 12 tablets were transferred to 200 mg every 12 h. Subsequent dose adjustments were permitted. Acetaminophen (325 mg) was available for rescue. Pain intensity (five-point categorical and 100 mm visual analog scale), pain related disability, adverse events and acceptability were assessed.
  
  
  RESULTS
  Of the 140 patients enrolled, 95 completed eight weeks of treatment with CR codeine. During month 1 and month 2, the mean CR codeine daily doses were 295.7+/-119.1 mg and 390.3+/-163.4 mg, respectively. Pain scores during both CR codeine month 1 and 2 were significantly lower than on acetaminophen plus codeine (53.6+/-20.9 mm and 49.7+/-23.7 mm versus 59.6+/-17.5 mm; P=0.0003, P=0.0001, respectively). CR codeine treatment was rated as moderately or highly acceptable by 82% of patients compared with 50% for acetaminophen plus codeine (P=0.001). Only seven patients (5.9%) discontinued CR codeine treatment because of adverse events.
  
  
  CONCLUSIONS
  The results confirm the safety, efficacy and patient acceptability of the initial conversion and maintenance dosing recommendations for CR codeine from a combination opioid/nonopioid analgesic.
authors.affiliation: William Osler Health Centre, Brampton, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Russell
authors.forename: C Peter N
authors.initials: CP
authors.lastname: Watson
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Clark
authors.forename: William
authors.initials: W
authors.lastname: Arkinstall
authors.forename: Dwight
authors.initials: D
authors.lastname: Moulin
authors.forename: Helen
authors.initials: H
authors.lastname: Hays
authors.forename: John
authors.initials: J
authors.lastname: Eisenhoffer
authors.forename: Patricia
authors.initials: P
authors.lastname: Quigley
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Harsanyi
authors.forename: Andrew
authors.initials: A
authors.lastname: Darke
mesh_terms: D000328:Adult; D002908:Chronic Disease; D003061:Codeine / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D017410:Practice Guidelines as Topic / Q000592:standards
chemical_list: D003692:Delayed-Action Preparations; D003061:Codeine