Open Access Open Access  Restricted Access Subscription or Fee Access

Lack of correlation between the effective dose of fentanyl sublingual spray for breakthrough cancer pain and the around-the-clock opioid dose

Srinivas R. Nalamachu, MD, Neha Parikh, Larry Dillaha, MD, Richard Rauck, MD

Abstract


Objective: To examine the relationship between the dose of fentanyl sublingual spray needed to control breakthrough cancer pain (BTCP) and the dose of around-the-clock (ATC) opioid used to control background pain.

Design: Analysis was based on the open-label, dose-titration phase (up to 26 days) of a randomized, double-blind, placebo-controlled trial.

Patients: Opioid-tolerant cancer patients (aged 18 years) with chronic pain of moderate severity in the 24 hours before screening while receiving stable doses of scheduled ATC opioid therapy for 1 week and 1 to 4 episodes of BTCP per day.

Interventions: Fentanyl sublingual spray was initiated at 100 μg. Dose titration proceeded until a dose was reached that provided adequate pain relief for two consecutive BTCP episodes without intolerable adverse effects (AEs).

Results: Overall, 98/130 (75.4 percent) patients completed the dose-titration phase and achieved pain relief, and 73.5 percent of those who completed the titration period attained an effective dose of 600 μg (median effective dose, 800 μg). No clinically relevant correlation was found between effective doses of fentanyl sublingual spray for the treatment of BTCP and the ATC opioid doses used to control persistent pain (Spearman rank correlation [rs ] = 0.351, n = 98). Sixty percent of patients reported 1 AE during the dose-titration phase. The most common AEs considered related to study treatment were nausea (6.2 percent), somnolence (4.6 percent), dizziness (3.8 percent), and vomiting (3.8 percent).

Conclusions: These findings highlight the importance of titrating the dose of fentanyl sublingual spray to optimize dosing for individual patients. 


Keywords


breakthrough cancer pain, fentanyl, sublingual spray, transmucosal

Full Text:

PDF

References


Portenoy RK, Hagen NA: Breakthrough pain: Definition, prevalence and characteristics. Pain. 1990; 41(3): 273-281.

Jacox A, Carr DB, Payne R: New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med. 1994; 330(9): 651-655.

Portenoy RK, Payne D, Jacobsen P: Breakthrough pain: Characteristics and impact in patients with cancer pain. Pain. 1999; 81(1-2): 129-134.

Portenoy RK, Bruns D, Shoemaker B, et al.: Breakthrough pain in community-dwelling patients with cancer pain and noncancer pain, part 1: Prevalence and characteristics. J Opioid Manag. 2010; 6(2): 97-108.

Caraceni A, Martini C, Zecca E, et al.: IASP Task Force on Cancer Pain: Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliat Med. 2004; 18(3): 177-183.

Prommer E: The role of fentanyl in cancer-related pain. J Palliat Med. 2009; 12(10): 947-954.

Shojaei AH: Buccal mucosa as a route for systemic drug delivery: A review. J Pharm Pharm Sci. 1998; 1(1): 15-30.

Rauck R, Reynolds L, Geach J, et al.: Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: A randomized, double-blind, placebo-controlled study. Curr Med Res Opin. 2012; 28(5): 859-870.

INSYS Therapeutics, Inc: Subsys (fentanyl sublingual spray), CII [package insert]. Chandler, AZ: INSYS Therapeutics, Inc, 2013.

Shojaei AH, Khan M, Lim G, et al.: Transbuccal permeation of a nucleoside analog, dideoxycytidine: Effects of menthol as a permeation enhancer. Int J Pharm. 1999; 192(2): 139-146.

Malkawi AH, Al-Ghananeem AM, Crooks PA: Development of a GC-MS assay for the determination of fentanyl pharmacokinetics in rabbit plasma after sublingual spray delivery. AAPS J. 2008; 10(2): 261-267.

Christie JM, Simmonds M, Patt R, et al.: Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. J Clin Oncol. 1998; 16(10): 3238-3245.

Farrar JT, Cleary J, Rauck R, et al.: Oral transmucosal fentanyl citrate: Randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients. J Natl Cancer Inst. 1998; 90(8): 611-616.

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(2-3): 303-312.

Coluzzi PH, Schwartzberg L, Conroy JD, et al.: Breakthrough cancer pain: A randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR). Pain. 2001; 91(1-2): 123-130.

Mercadante S, Radbruch L, Davies A, et al.: A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: An open-label, randomised, crossover trial. Curr Med Res Opin. 2009; 25(11): 2805-2815.

Portenoy R, Messina J, Niebler G: Successful dose finding with fentanly effervescent bucccal tablets: Combined results of open-label titration. Presented at American Pain Society Annual Meeting, San Antonio, TX, May 3-6, 2006.

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(9): 805-811.

Weinstein SM, Messina J, Xie F: Fentanyl buccal tablet for the treatment of breakthrough pain in opioid-tolerant patients with chronic cancer pain: A long-term, open-label safety study. Cancer. 2009; 115(11): 2571-2579.

Nalamachu SR, Rauck RL, Wallace MS, et al.: Successful dose finding with sublingual fentanyl tablet: Combined results from 2 open-label titration studies. Pain Pract. 2012; 12(6): 449-456.

Hagen NA, Fisher K, Victorino C, et al.: A titration strategy is needed to manage breakthrough cancer pain effectively: Observations from data pooled from three clinical trials. J Palliat Med. 2007; 10(1): 47-55.

Mercadante S, Villari P, Ferrera P, et al.: Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain. Br J Cancer. 2007; 96(12): 1828-1833.

Mercadante S, Gatti A, Porzio G, et al.: Dosing fentanyl buccal tablet for breakthrough cancer pain: Dose titration versus proportional doses. Curr Med Res Opin. 2012; 28(6): 963-968.

Mercadante S, Porzio G, Aielli F, et al.: The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting. Support Care Cancer. 2013; 21: 2335-2339.

Taylor DR: Single-dose fentanyl sublingual sprayfor breakthrough cancer pain. Clin Pharmacol. 2013; 5: 131-141.




DOI: https://doi.org/10.5055/jom.2014.0212

Refbacks

  • There are currently no refbacks.