Custom-made capsules and suppositories of methadone for patients on high-dose opioids for cancer pain

In a prospective, open study, 37 advanced cancer patients in poor pain control receiving high doses of subcutaneous hydromorphone (mean daily dose: 276 +/- 163 mg) were switched to methadone by use of custom-made capsules (21 patients) or suppositories (16 patients). The change in opioid took place over 6. 5 +/- 3. 6 days (oral) and 3. 2 +/- 2. 7 days (rectal). The methadone/hydromorphone dose ratios were 1. 2 +/- 1. 3 and 3 +/- 2 for the oral and rectal routes, respectively (P = 0. 03) as compared to an expected ratio of 5-7, based on single dose available data. Pain intensity (VAS 0-100 mm) and the number of extra doses of analgesic per day were 51 +/- 22 and 3. 2 +/- 2. 7 with hydromorphone, versus 34 +/- 21 (P < 0. 001) and 2. 1 +/- 1. 9 (P = 0. 03) with methadone, respectively. The total cost of treatment was Canadian 148 +/- 202 with methadone as compared to Canadian 2135 +/- 472 with hydromorphone (P < 0. 001). Toxicity was limited to mild sedation in all patients and proctitis in 2 patients on suppositories (one of whom required discontinuation of methadone). Plasma levels obtained in 6 patients on suppositories revealed large inter-individual variation in methadone level (ng/ml) to dose (mg/day) ratio (range: 0. 8-8. 5). Within individuals, the ratio remained constant over a range of doses. We conclude that a slow switch-over to methadone is a safe, effective and low cost alternative in selected cancer patients receiving high doses of opioids for poor prognostic pain syndromes.