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.

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. CONCLUSION: 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.