Clinical Drug Investigation

, Volume 31, Issue 9, pp 605–618 | Cite as

Newer Generation Fentanyl Transmucosal Products for Breakthrough Pain in Opioid-Tolerant Cancer Patients

  • Frank Elsner
  • Giovambattista Zeppetella
  • Josep Porta-Sales
  • Ignacio TagarroEmail author
Review Article


Oral normal-release morphine has long been considered the gold-standard treatment for cancer breakthrough pain. However, its relatively long time to analgesic onset, delay in maximal analgesic effect and prolonged duration of action make it unsuitable for the management of breakthrough pain episodes.

These limitations led to the development of an oral transmucosal formulation of the fast-acting opioid fentanyl (oral transmucosal fentanyl citrate [OTFC] lozenge on a plastic handle; Actiq®), which has been shown to produce more rapid and effective pain relief than oral morphine. However, the formulation itself has some limitations. Consequently, investigators have continued to develop other, newer generation, transmucosal formulations of fentanyl to further improve the management of breakthrough pain.

Recently, five such compounds (Effentora®/Fentora®, Abstral®, Instanyl®, Breakyl®/Onsolis™ and PecFent®) have been concurrently approved in Europe and/or the US, and have documented efficacy in quickly relieving breakthrough pain episodes. All of the available pivotal efficacy trials of these agents are randomized, double-blind comparisons with placebo. There are no head-to-head trials comparing any of the newer transmucosal formulations with each other. Only one non-pivotal study of intranasal fentanyl spray used a transmucosal preparation as an active comparator. However, that comparator was OTFC, not one of the newer transmucosal products. Close examination of the existing trials assessing these newer transmucosal preparations reveals significant variation in many study parameters, such as patient selection criteria, severity of breakthrough pain episodes, proportions of patients with a neuropathic pain component, titration protocols, choice of the primary endpoints, protocols for repeat dosing and rescue medication, the separation of treated episodes and the extent of the placebo response, all of which may have affected efficacy results. It is therefore difficult to evaluate the relative efficacies of these treatments on the basis of the available trials. Furthermore, given the differences in design between studies, the value of any potential meta-analyses including these trials would likely be limited. Blinded head-to-head comparisons of new transmucosal fentanyl preparations would be the only way to conclusively determine comparative effectiveness, but given the impracticalities of conducting such studies, these are unlikely.


Fentanyl Breakthrough Pain Pain Intensity Difference Sublingual Tablet Oral Transmucosal Fentanyl Citrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Editorial assistance was provided by inScience Communications, a Wolters Kluwer business. This assistance was funded by Meda Pharmaceuticals, San Fernando de Henares, Madrid, Spain. Giovambattista Zeppetella has received honoraria for participation on advisory boards and/or at symposia from Archimedes, Cephalon, Dompè, Flynn, Janssen-Cilag, Meda, Napp, Nycomed, ProStrakan, Pfizer and Wyeth. Josep Porta-Sales has participated on an advisory board for Meda. Frank Elsner has received honoraria for participation on advisory boards and/or at symposia from Archimedes, Cephalon, Nycomed, ProStrakan, Janssen-Cilag, Meda, Wyeth, Shire, Grünenthal and Mundipharma. Ignacio Tagarro is an employee of Meda.


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Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Frank Elsner
    • 1
  • Giovambattista Zeppetella
    • 2
  • Josep Porta-Sales
    • 3
  • Ignacio Tagarro
    • 4
    Email author
  1. 1.Klinik für PalliativmedizinUniversitätsklinikum Aachen, RWTH Aachen UniversityAachenGermany
  2. 2.St Clare HospiceHastingwood, EssexUK
  3. 3.Servicio de Cuidados PaliativosInstitut Català d’Oncologia, L’Hospitalet de LlobregatBarcelonaSpain
  4. 4.Meda PharmaceuticalsSan Fernando de Henares, MadridSpain

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