Purpose：Methadone is an opioid used in Japan for the treatment of cancer pain. A thorough consideration of complex pharmacokinetics with individual differences and of serious adverse effects is necessary before switching to methadone; therefore, methadone is not yet widely used. We examined the analgesic and adverse effects of methadone through clinical cases and considered the clinical significance of methadone as an opioid analgesic for the treatment of cancer pain. Methods：The clinical course of 44 patients with cancer pain who were switched to methadone from other opioids was analyzed. Results：Out of the 44 cases investigated, 37 cases （84.1％） were successful. In the successful cases, pain intensity before and after methadone administration was reduced from an average of 7.5 to 2.8, respectively, on the numerical rating scale. Strong drowsiness （six cases） and nausea （three cases） were observed as adverse effects. However, no serious effects, such as QT prolongation and respiratory depression, were recognized. Conclusion：For patients with refractory cancer pain who require a high opioid dose, methadone is considered to be one of the alternatives in pain therapeutics.

Background: Methadone can only be administered orally in Japan. However, it is unclear how to treat pain when patients become unable to take methadone orally because of the progression of the disease. Aims: To assess retrospectively end-of-life pain control management after patients become unable to take methadone orally. Methods: Twenty-eight patients with cancer pain undergoing treatment with oral methadone died at a palliative care unit between April 2013 and September 2014. All patients died of cancer and were unable to swallow before death. We assessed pain control approaches after the patients became unable to take methadone orally. Results: Twenty-one patients survived 1 day or longer after becoming unable to swallow. Methadone was switched to another opioid because of pain. Of these 21 patients, 10 patients survived for 1 week or longer after being switched to another opioid. At this point, methadone would be mostly eliminated from the blood circulation. Among these 10 patients, seven patients were treated with subcutaneous morphine, and three patients were excluded because their pain could not be evaluated. The conversion ratio from final oral methadone dosage to oral morphine equivalent dose of opioids used on the seventh day was 6.1. Conclusion: Even when patients become unable to ingest methadone, switching to other opioids may not always be necessary because of the long half-life of methadone when pain is absent at the end of life. If necessary, pain could be managed by switching to other opioids with a conversion ratio of 6.1.

Introduction: Paroxysmal atrial fibrillation (Paf) occurred in an inpatient who has been prescribed methadone for cancer pain in our palliative care unit, but oral administration of aprindine (antiarrhythmic agent) succeeded in defibrillation and methadone administration could be continued. Case: A 75-year-old man had developed multiple bone metastases after resection of thyroid cancer. Due to refractory cancer pain, switching from oxycodone to methadone was performed. Pain relief was achieved with methadone 40 mg/day and without QT interval prolongation. After methadone administration about 9 months, there suddenly became loss of appetite in the morning of one day. ECG examination revealed Paf onset. Aprindine 20 mg was orally administered for the purpose of defibrillation. After about 2 hours sinus rhythm was gained and later without recurrence. Conclusion: This case was considered to have the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration. If administration of antiarrhythmic agents is performed in a patient whom has been prescribed methadone, it is feared to lead to result in QT interval prolongation due to drug interactions. It is important to carefully select an agent that rarely leads to QT prolongation.