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.
Bruera
Eduardo
E
Palliative Care Program, Edmonton General Hospital, Division of Palliative Care Medicine and Health Care Quality and Outcome Research Center, University of Alberta, Edmonton, Alberta, Canada Department of Pharmacology, Cornell University Medical College, New York, NY, USA.
Watanabe
Sharon
S
Fainsinger
Robin L
RL
Spachynski
Kathy
K
Suarez-Almazor
Maria
M
Inturrisi
Charles
C
D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002214:Capsules; D003362:Cost-Benefit Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000627:therapeutic use*; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D011446:Prospective Studies; D013488:Suppositories
D000701:Analgesics, Opioid; D002214:Capsules; D013488:Suppositories; D004091:Hydromorphone; D008691:Methadone