Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain.
OBJECTIVE
A randomized, crossover, double-blinded placebo-controlled and non-blinded active drug-controlled, comparative clinical trial was conducted to evaluate the efficacy and safety of sublingual fentanyl tablet.


METHODS
Subjects were patients treated with strong opioids at fixed intervals for chronic cancer pain and with oral morphine as rescue medication for breakthrough pain. Sublingual fentanyl was administered at doses that were 1/25th (high dose) and 1/50th (low dose) of the dose of rescue morphine and was compared with placebo and oral morphine. The primary endpoint was pain intensity difference at 30 min after administration. (Clinical Trials Government; NCT00684632).


RESULTS
Fifty-one patients were enrolled in the investigation. Their mean pain intensity in visual analog scale before rescue medication prior to the investigation was 60.96 (16.44, standard deviation) mm. Compared with placebo, the low and high doses of sublingual fentanyl showed significant analgesic effects (least squares mean difference, 4.54 and 8.49 mm; P = 0.014, P < 0.001, respectively). Adverse reactions were observed in 17.6%, the most common being constipation, nausea and somnolence. The incidence of adverse reactions during the high-dose administration period was higher than that during the low-dose and active control drug administration periods.


CONCLUSIONS
Patients treated with strong opioid analgesics at fixed intervals for chronic cancer pain and with oral morphine at doses up to 20 mg as rescue medication were investigated. The doses of sublingual fentanyl to treat breakthrough pain were determined from rescue morphine doses by use of conversion ratios. In these patients, administration of sublingual fentanyl at doses determined by a conversion ratio of 1/50 was effective and safe. Further studies are needed to validate the use of this conversion method.
Department of Palliative Medicine, Jikei University Graduate School of Medicine, Tokyo nshimoya@jikei.ac.jp.
Naohito
N
Shimoyama
Department of Palliative Medicine, Saito Yukoukai Hospital, Ibaraki Present address: Department of Palliative Medicine, Japanese Red Cross Kitami Hospital, Kitami, Japan.
Ikuo
I
Gomyo
Department of Surgery, Omigawa General Hospital, Katori.
Osamu
O
Teramoto
Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto.
Keisuke
K
Kojima
Department of Palliative Medicine, Showa University Hospital, Tokyo.
Hitomi
H
Higuchi
Clinical Development Department 2, Development Division, Kyowa Hakko Kirin Co., Ltd., Tokyo.
Nobuyuki
N
Yukitoshi
Clinical Data Evaluation Department, Development Division, Kyowa Hakko Kirin Co., Ltd., Tokyo.
Eri
E
Ohta
Department of Anesthesiology, Teikyo University Chiba Medical Center, Ichihara, Japan.
Megumi
M
Shimoyama
D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D059390:Breakthrough Pain / Q000188:drug therapy* / Q000209:etiology*; D059350:Chronic Pain / Q000188:drug therapy / Q000209:etiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D009369:Neoplasms / Q000150:complications*; D010147:Pain Measurement; D018579:Patient Selection; D012720:Severity of Illness Index; D013607:Tablets; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D013607:Tablets; D009020:Morphine; D005283:Fentanyl
breakthrough pain; cancer pain; conversion ratio; opioid; sublingual fentanyl tablet