title: Lack of correlation between the effective dose of fentanyl sublingual spray for breakthrough cancer pain and the around-the-clock opioid dose.
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.
  
  
  METHODS
  Analysis was based on the open-label, dose-titration phase (up to 26 days) of a randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: International Clinical Research Institute, Overland Park, Kansas.
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Nalamachu
authors.affiliation: INSYS Therapeutics, Inc., Chandler, Arizona.
authors.forename: Neha
authors.initials: N
authors.lastname: Parikh
authors.affiliation: NSYS Therapeutics, Inc., Chandler, Arizona.
authors.forename: Larry
authors.initials: L
authors.lastname: Dillaha
authors.affiliation: The Center for Clinical Research, Winston-Salem, North Carolina.
authors.forename: Richard
authors.initials: R
authors.lastname: Rauck
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000336:Aerosols; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D059390:Breakthrough Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010147:Pain Measurement; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000336:Aerosols; D000701:Analgesics, Opioid; D005283:Fentanyl