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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


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. 


breakthrough cancer pain, fentanyl, sublingual spray, transmucosal

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