Long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray for breakthrough cancer pain in opioid-tolerant patients
Keywords:fentanyl, breakthrough cancer pain, intranasal
AbstractObjective: To assess the long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray (FPNS) in patients with breakthrough cancer pain (BTCP).
Design: A multicenter, open-label study.
Patients: Patients with chronic cancer pain treated with ≥60 mg/d oral morphine or equivalent experiencing 1-4 episodes per day of BTCP.
Intervention: All patients entered into a 16-week treatment phase after undergoing a dose-titration phase with FPNS.
Main outcome measures: Safety and tolerability were assessed by adverse events (AEs) and by nasal tolerability assessments. Consistency of effect was monitored through additional rescue medication use and FPNS dose change.
Results: Four hundred three patients were included in the safety analyses. Of these, 356 patients entered the treatment phase and 110 patients completed the study. FPNS was self-administered for 42,227 episodes. During the treatment phase, 99 patients (24.6 percent) reported treatment-related AEs; most were mild or moderate and typical of opioids. Serious AEs were reported by 61 patients (15.1 percent), but only five were considered related to study drug. Of the 80 deaths that occurred during this study, one was assessed as possibly related to study drug. Nasal assessments revealed no significant local effects. No additional rescue medication was required after 94 percent of FPNS-treated episodes. More than 90 percent of patients required no increase in their initial dose of FPNS.
Conclusions: FPNS use for BTCP was associated with AEs, typical of opioids, with no evidence of nasal toxicity. A large proportion of BTCP episodes were treated with a single dose, and doses remained stable over the 4-month period.
Davies AN, Dickman A, Reid C, et al.: The management of cancer-related breakthrough pain: Recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain. 2009; 13: 331-338.
Svendsen KB, Andersen S, Arnason S: Breakthrough pain in malignant and non-malignant diseases: A review of prevalence, characteristics and mechanisms. Eur J Pain. 2005; 9: 195-206.
Portenoy R, Bruns D, Shoemaker B, et al.: Breakthrough pain in community-dwelling patients with cancer pain and non-cancer pain, Part 1: Prevalence and characteristics. J Opioid Manag. 2010; 6: 97-108.
Portenoy RK, Payne D, Jacobsen P: Breakthrough pain: Characteristics and impact in patients with cancer pain. Pain. 1999; 81: 129-134.
Caraceni A, Martini C, Zecca E, et al.: Breakthrough pain characteristics and syndromes in patients with cancer pain: An international survey. Palliat Med. 2004; 18: 177-183.
Portenoy R, Bruns D, Shoemaker B, et al.: Breakthrough pain in community-dwelling patients with cancer pain and non-cancer pain, Part 2: Impact on function, mood, and quality of life. J Opioid Manag. 2010; 6: 109-116.
Fortner BV, Demarco G, Irving G, et al.: Description and predictors of direct and indirect costs of pain reported by cancer patients. J Pain Symptom Manage. 2003; 25: 9-18.
Fortner BV, Okon TA, Portenoy RK: A survey of pain-related hospitalizations, emergency department visits, and physician office visits reported by cancer patients with and without history of breakthrough pain. J Pain. 2002; 3: 38-44.
Abernethy AP, Wheeler JL, Fortner BV: A health economic model of breakthrough pain. Am J Manag Care. 2008; 14 (Suppl 1): S129-S140.
Zeppetella G, Ribeiro MD: Opioids for the management of breakthrough (episodic) pain in cancer patients. Cochrane Database Syst Rev. 2006; (1): CD004311.
Portenoy RK, Payne R, Coluzzi P, et al.: Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: A controlled dose titration study. Pain. 1999; 79: 303-312.
Portenoy RK, Taylor D, Messina J, et al.: A randomized, placebo-controlled study of fentanyl buccal tablet for breakthrough pain in opioid-treated patients with cancer. Clin J Pain. 2006; 22: 805-811.
Slatkin NE, Xie F, Messina J, et al.: Fentanyl buccal tablet for relief of breakthrough pain in opioid-tolerant patients with cancer-related chronic pain. J Support Oncol. 2007; 5: 327-334.
Vasisht N, Gever LN, Tagarro I, et al.: Formulation selection and pharmacokinetic comparison of fentanyl buccal soluble film with oral transmucosal fentanyl citrate: A randomized, open-label, single-dose, crossover study. Clin Drug Investig. 2009; 29: 647-654.
Breivik H, Cherny N, Collett B, et al.: Cancer-related pain: A pan-European survey of prevalence, treatment, and patient attitudes. Ann Oncol. 2009; 20: 1420-1433.
Davies A, Broadley K, Beighton D: Xerostomia in patients with advanced cancer. J Pain Symptom Manage. 2001; 22: 820-825.
Davies A, Vriens J: Oral transmucosal fentanyl citrate and xerostomia. J Pain Symptom Manage. 2005; 30: 496-497.
Jacobsen R, Moldrup C, Christrup L: Clinical rationale for administering fentanyl to cancer pain patients: Two Delphi surveys of pain management experts in Denmark. J Opioid Manag. 2008; 4: 383-391.
Dale O, Hjortkjaer R, Kharasch ED: Nasal administration of opioids for pain management in adults. Acta Anaesthesiol Scand. 2002; 46: 759-770.
Illum L: Nasal drug delivery–Possibilities, problems and solutions. J Control Release. 2003; 87: 187-198.
Watts P, Smith A: PecSys: In situ gelling system for optimised nasal drug delivery. Expert Opin Drug Deliv. 2009; 6: 543-552.
Lennernäs B, Hedner T, Holmberg M, et al.: Pharmacokinetics and tolerability of different doses of fentanyl following sublingual administration of a rapidly dissolving tablet to cancer patients: A new approach to treatment of incident pain. Br J Clin Pharmacol. 2004; 59: 249-253.
Portenoy R, Burton AW, Gabrail N, et al.: A multicenter, placebo-controlled, double-blind, multiple-crossover study of fentanyl pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain. Pain. (in press).
Fallon M, Gatti A, Davies AN, et al.: Efficacy, safety and patient acceptability of fentanyl pectin nasal spray compared with immediate-release morphine sulphate tablets in the treatment of breakthrough cancer pain: A multicentre, double-blind, double-dummy, multiple-crossover study. Eur J Cancer Supp. 2009; 7: 15.
Bennett DS, Burton AW, Fishman S, et al.: Consensus panel recommendatios for the assessment and management of breakthrough pain, Part 2: Management. Pharm Ther. 2005; 30: 354-361.
Walker G, Wilcock A, Manderson C, et al.: The acceptability of different routes of administration of analgesia for breakthrough pain. Palliat Med. 2003; 17: 219-221.
How to Cite
Copyright 2005-2023, Weston Medical Publishing, LLC
All Rights Reserved