Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain

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Abstract
Our aim was to compare pharmacological aspects of two switching strategies from morphine/oxycodone to methadone; the stop and go (SAG) strategy in which methadone is started directly after the initial opioid has been stopped, and the 3-days switch (3DS), in which morphine/oxycodone is gradually changed to methadone by cross-tapering over 3 days. Forty-two cancer patients with pain and/or opioid side effects were assessed in this randomised trial. Trough serum concentrations of methadone, morphine, morphine-6-glucuronide (M6G), and oxycodone were measured on days 1, 2, 3, 4, 7, and 14. Primary outcome was number of patients with methadone concentrations in apparent CSS on day 4. Secondary outcomes were exposure to opioids during the first 3 days, interindividual variation of opioid concentrations, and correlation between methadone concentrations and pain intensity (PI) day 3. Thirty-five patients received methadone (16 in the SAG group, 19 in the 3DS group). The median preswitch morphine equivalent doses were 620 (range 350–2000) mg/day in the SAG group and 800 (range 90–3600) mg/day in the 3DS group (p = 0.43);42% reached CSS for methadone in the SAG group on day 4 compared with 22% in the 3DS group (p = 0.42). The SAG group was significantly less exposed to morphine/M6G/oxycodone and significantly more exposed to methadone in the first 3 days. Methadone showed a low correlation with PI. More patients dropped out after intervention in the SAG group than in the 3DS group (38% vs. 5%; p = 0.032). One SAG patient suffered from respiratory depression on day 5. The SAG group was initially more exposed to methadone and less to the replaced opioids but without observed clinical benefit and with a higher dropout rate. Patients switched to methadone should be followed closely for the first 5 days, regardless of switching strategy.

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