Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined by titration for the treatment of breakthrough pain in Japanese cancer patients: a multicenter, randomized, placebo-controlled, double-blind phase III trial.
BACKGROUND
Breakthrough cancer pain typically has a rapid onset and relatively short duration. Due to this temporal profile, it may not be adequately relieved by oral opioid analgesics. The sublingual fentanyl orally disintegrating tablet is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid-onset analgesia, and which may be effective for breakthrough pain treatment.


METHODS
A multicenter, randomized, placebo-controlled, double-blind comparative study was conducted to evaluate the efficacy and safety of the sublingual fentanyl tablet at optimized doses for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals. The optimal dose was determined by open-label dose titration. The efficacy and safety of a 12-week extended treatment were also evaluated.


RESULTS
Eleven of 42 subjects who received the sublingual fentanyl tablet experienced adverse drug reactions. Common reactions were somnolence, constipation, nausea, and vomiting. No serious adverse reactions occurred. Sublingual fentanyl tablets at optimal doses and placebo were administered to 37 subjects in a double-blinded manner. A significant analgesic effect of the sublingual fentanyl tablet was present compared to placebo at 30 min after administration. The sublingual fentanyl tablet was also effective and safe during extended treatment, in which changes in basal opioid doses as well as sublingual fentanyl tablet doses were made as needed.


CONCLUSIONS
Sublingual fentanyl tablets at doses determined by titration were effective and safe for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals. Extended treatment up to 12 weeks was also effective and safe.
Department of Palliative Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan, nshimoya@jikei.ac.jp.
Naohito
N
Shimoyama
Ikuo
I
Gomyo
Nobuyuki
N
Katakami
Masakuni
M
Okada
Nobuyuki
N
Yukitoshi
Eri
E
Ohta
Megumi
M
Shimoyama
D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D059390:Breakthrough Pain / Q000188:drug therapy* / Q000209:etiology*; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010147:Pain Measurement / Q000379:methods; D013607:Tablets / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D013607:Tablets; D005283:Fentanyl