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.

[Retrospective evaluation of pregabalin for cancer-related neuropathic pain].

BACKGROUND: Evidence to support the use of pregabalin in combination with opioid analgesics for the treatment of cancer-related neuropathic pain is limited. METHODS: We carried out a retrospective investigation on patients hospitalized in our department with cancer-related neuropathic pain and under pregabalin treatment. Patients were divided into two groups: A group (= < 300 mg pregabalin daily) and B group (> 300 mg pregabalin daily). The two groups were compared in terms of a suite of factors (e. g., age starting and maimtenance dose of pregabaline, adverse effect). RESULTS: Patient's age was significantly lower in the B group (> 300 mg pregabalin daily). Of the total number of patients involved in the study, 67% experienced mild and moderate somnolence. CONCLUSIONS: In this retrospective investigation, we conclude that the younger cancer patients may need lager doses of pregabalin to relieve cancer-related neuropathic pain. In addition, the mild and moderate somnolence occurs frequently when pregabalin is administered with opioid analgesics for the treatment of cancer-related neuropathic pain.

[Case of non-cancer abdominal pain successfully treated by a large amount of oral morphine].

A 34-year-old woman, with intractable non-cancer abdominal pain was successfully treated with large amounts of oral morphine. Medical records showed that she had been suffering from severe upper right abdominal pain with nausea and vomiting for 11 years. The pain continued all day long and the breakthrough pain occurred sometimes accompanied by nausea and vomiting. Various medical examinations including psychosocial exploration had been done to explain her pain mechanism and vomiting but causes were unknown. Psychological examination revealed she had no mental problems. A year and 6 months, she felt severe pain never experienced at the same area and she was transferred and admitted to our clinic. We conducted the epidural morphine analgesia. Her pain responded to this treatment. The dose of morphine was gradually increased and she was free from pain at the dose of 30 mg x day(-1) epidural morphine. With decreasing pain, her nausea and vomiting also diminished. This epidural dose could be clinically converted into 1,440 mg oral morphine. She was seen at our clinic twice a month for her pain condition and for checking the blood morphine level. In spite of large amount of morphine intake, no accumulation of blood morphine, M-6-G, and M-3-G levels was recognized.