Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses
determined from oral morphine rescue doses in the treatment of breakthrough
cancer pain.
Author(s): Shimoyama N(1), Gomyo I(2), Teramoto O(3), Kojima K(4), Higuchi H(5), Yukitoshi
N(6), Ohta E(7), Shimoyama M(8).
Affiliation(s): Author information:
(1)Department of Palliative Medicine, Jikei University Graduate School of
Medicine, Tokyo nshimoya@jikei.ac.jp. (2)Department of Palliative Medicine, Saito
Yukoukai Hospital, Ibaraki Present address: Department of Palliative Medicine,
Japanese Red Cross Kitami Hospital, Kitami, Japan. (3)Department of Surgery,
Omigawa General Hospital, Katori. (4)Department of Respiratory Medicine, Kumamoto
University Hospital, Kumamoto. (5)Department of Palliative Medicine, Showa
University Hospital, Tokyo. (6)Clinical Development Department 2, Development
Division, Kyowa Hakko Kirin Co., Ltd., Tokyo. (7)Clinical Data Evaluation
Department, Development Division, Kyowa Hakko Kirin Co., Ltd., Tokyo.
(8)Department of Anesthesiology, Teikyo University Chiba Medical Center,
Ichihara, Japan.
Publication date & source: 2015, Jpn J Clin Oncol. , 45(2):189-96
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.
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