Patient-controlled analgesia with oral methadone in cancer pain: Preliminary report

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Abstract
Methadone is a very useful drug in cancer pain because of its low cost, lack of active metabolites, high oral availability, and the rapid onset of its analgesic effect. It seems to be well tolerated in patients with difficult pain syndromes who are receiving high doses of opioids, and it may deter the development of tolerance, but a high individual variation in terminal elimination half-life can result in different rates and extents of drug accumulation. For this reason, oral patient-controlled analgesia with methadone was used in 24 advanced-disease patients with pain. A regimen of self-administered oral methadone at fixed doses and flexible patient-controlled dosage intervals to achieve adequate analgesia, while avoiding toxic effects of methadone accumulation, was used in 24 patients requiring opioid therapy. After a priming period of three days with fixed doses of 3–5 mg three times a day for naïve patients and 50% of the morphine equivalent of methadone in patients switched from morphine, patients and relatives were instructed to maintain the night-time dose and to administer a second dose when the pain recurred. When than four doses of methadone a day were used, an increase of the dosage was prescribed. Continuous pain assessment and monitoring of symptoms were offered. The majority of patients achieved good pain relief until death, and three were switched to very low doses of subcutaneous morphine in their final days. The methadone escalation index was about 2% a day, with a mean dosage increase of 0.3 mg a day for an average of 60 days of treatment at doses ranging from 9 to 80 rug. The plasma concentration in 14 patients ranged from 0.013 to 0.273 mcg/ml with dosages of 20–80 mg during chronic treatment. A mean of 2.4 doses a day was reported, including the fixed night-time dose. The extent of side effects was considered acceptable. Patient-administered analgesia with oral methadone appears to be a simple, cheap and relatively safe technique for controlling cancer pain, permitting individualization by the patient him- or herself and avoiding the risk of accumulation. Continuous assessment is necessary.