Long-term safety and tolerability of fentanyl buccal tablet for the treatment of breakthrough pain in opioid-tolerant patients with chronic pain: an 18-month study

J Pain Symptom Manage. 2010 Nov;40(5):747-60. doi: 10.1016/j.jpainsymman.2010.02.009. Epub 2010 Jul 1.


Context: Breakthrough pain (BTP) is highly prevalent in patients with chronic cancer and noncancer pain, commonly requiring treatment with short-acting or rapid-onset opioids. This is the first report of an analysis of long-term safety from combined clinical trials of a rapid-onset transmucosal formulation of fentanyl, the fentanyl buccal tablet (FBT).

Objectives: This long-term (18-month), open-label study assessed the safety and tolerability of FBT for the treatment of BTP in a large cohort (n=646) of opioid-tolerant patients receiving around-the-clock (ATC) opioids for persistant noncancer pain.

Methods: This was a long-term, multicenter, open-label safety study that accepted patients naïve to FBT (new patients) as well as rollover patients from one of two previous short-term, randomized, placebo-controlled studies involving opioid-tolerant adults with chronic noncancer pain. All patients gave written informed consent, and the study was conducted according to Good Clinical Practice and with Independent Ethics Committee or Institutional Review Board approval.

Results: During maintenance treatment, 70 of 646 patients (11%) discontinued because of adverse events (AEs), 69 of 646 (11%) because of withdrawn consent, and 57 of 646 (9%) because of noncompliance. A total of 571 of 646 patients (88%) had one or more AEs; most were mild to moderate in intensity and typical of AEs associated with opioid use in a noncancer chronic pain population. Serious AEs were seen in 118 of 646 patients (18%); most were considered by the investigators to be unrelated or unlikely to be related to FBT. There were six deaths (three myocardial infarction, two cardiac arrest, and one pneumonia) that were considered by investigators to be unrelated or unlikely to be related to FBT. There were two reports of accidental overdose contained within nine reports of nonfatal overdose (FBT and/or ATC and/or other medications). Four patients had AEs of abuse or drug dependence, two in association with FBT. Drug withdrawal syndrome occurred in 23 patients after discontinuation of FBT alone or in combination with other opioids. Secondary assessments showed that average pain ratings, as assessed by the Brief Pain Inventory, remained relatively stable throughout the study and that consistent improvements were noted in functional measures.

Conclusion: FBT was generally safe and well tolerated, with self-reported functional improvement observed in most of the opioid-tolerant patients with BTP in association with chronic noncancer pain.

Publication types

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

MeSH terms

  • Administration, Buccal
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects
  • Chronic Disease / drug therapy
  • Female
  • Fentanyl / administration & dosage
  • Fentanyl / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Pain / drug therapy*
  • Pain Measurement
  • Patient Satisfaction*
  • Surveys and Questionnaires
  • Treatment Outcome


  • Analgesics, Opioid
  • Fentanyl