title: Patterns of dosage changes with transdermal buprenorphine and transdermal fentanyl for the treatment of noncancer and cancer pain: a retrospective data analysis in Germany.
abstract: BACKGROUND
  Previous studies have suggested that buprenorphine may have a low association with tolerance development compared with other strong opioids. In a previous study by our group, mean cohort and intraindividual dosage increases over an entire course of treatment and on a per-day basis were significantly lower with transdermal (TD) buprenorphine than with TD fentanyl. However, no information concerning the relationship between qualitative and quantitative dose changes is available.
  
  
  OBJECTIVE
  The aim of this study was to compare TD buprenorphine and TD fentanyl with respect to dosage increases, dosage stability, and the nature of dosage changes.
  
  
  METHODS
  This retrospective analysis used data from the IMS Disease Analyzer-Mediplus database, which contains patient-related data documented by 400 medical practices in Germany. Data from patients with noncancer or cancer pain treated with TD buprenorphine or TD fentanyl for at least 3 months between May 2002 and April 2005 were analyzed. Daily dosages were directly determined from the prescribed patch strength, taking into account the possibility of multiple patches applied simultaneously. To determine dosage stability, patients were classified based on the type of dosage change (stable, increase, alternating, or decrease) of the prescribed dosages. From the prescribed daily dosages, mean percentage increases were calculated on a per-patient basis for the entire treatment period and per day, and these were assessed in relation to the type of dosage change.
  
  
  RESULTS
  In total, 631 patients with noncancer pain and 605 patients with cancer pain were included in the analysis (782 women, 454 men; mean age, 76.3 years [range, 29-100 years]). Treatment indications included osteoarthritis, low back pain, osteoporosis (noncancer groups), and neoplasm (cancer groups). Patients had similar analgesic premedication requirements based on steps 1 to 3 of the World Health Organization analgesic ladder. Comedication requirements for breakthrough pain were also similar between the TD buprenorphine and TD fentanyl groups. The mean percentage increases per day were 0.10% (TD buprenorphine) and 0.25% (TD fentanyl) in the noncancer groups and 0.19% (TD buprenorphine) and 0.47% (TD fentanyl) in the cancer groups (both, P < 0.05). A significantly larger proportion of patients receiving TD buprenorphine had stable dosages over the entire treatment period compared with patients receiving TD fentanyl (noncancer groups: 56.9% vs 41.6%; cancer groups: 50.0% vs 26.2% [both, P < 0.05]). Compared with TD buprenorphine, the proportion of patients with alternating dosage changes was significantly greater in patients receiving TD fentanyl (noncancer groups: 22.7% vs 13.1%; cancer groups: 30.6% vs 11.8% [both, P < 0.05]).
  
  
  CONCLUSIONS
  In this retrospective data analysis, compared with TD buprenorphine, the increase in mean daily dosage was significantly greater in patients treated with TD fentanyl. Also, compared with TD buprenorphine, alternating dosage changes were seen in a significantly greater proportion of patients receiving TD fentanyl. On the other hand, a significantly greater proportion of patients treated with TD buprenorphine had stable dosages over their entire treatment periods.
authors.affiliation: Pain Clinic, University of Erlangen, Erlangen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sittl
authors.affiliation: Erasmus University, Rotterdam, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Nuijten
authors.affiliation: Grünenthal GmbH, Aachen, Germany. Electronic address: barbara.poulsen-nautrup@grunenthal.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Poulsen Nautrup
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002047:Buprenorphine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy*; D010148:Intractable Pain / Q000188:drug therapy*; D012189:Retrospective Studies
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D005283:Fentanyl