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 ofconversion ratios.In thesepatients,administration of sublingualfentanyl atdoses determinedbya conversion ratio of 1/50 was effective and safe. Further studies are needed to validate the use of this conversion method.