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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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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Acknowledgements

We are grateful for the assistance from Gunnhild Jacobsen, Turid Nilsen, Trine Andreassen, and Kjell Aarstad for blood analyses, from Karin Tulluan for the randomisation process, and for valuable advice from Olav M.S. Fredheim and Line Oldervoll. We also thank the staff at the participating units and the patients for their participation. This study was supported by grants from the Norwegian Research Council and Norwegian Cancer Society.

Conflict of interest

The authors declare that they have no conflict of interest

Author information

Authors and Affiliations

  1. Pain and Palliation Research Group, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Kristin Moksnes, Stein Kaasa, Ørnulf Paulsen & Ola Dale

  2. Department of Oncology, St. Olav’s University Hospital, Trondheim, Norway

    Stein Kaasa

  3. Department of Medicine, Palliative Care Unit, Telemark Hospital, Skien, Norway

    Ørnulf Paulsen

  4. Sunniva Centre for Palliative Care, Haraldsplass Deaconess Hospital, Bergen, Norway

    Jan Henrik Rosland

  5. Department of Surgical Sciences, University of Bergen, Bergen, Norway

    Jan Henrik Rosland

  6. Department of Clinical Pharmacology, St. Olav’s University Hospital, Trondheim, Norway

    Olav Spigset

  7. Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway

    Olav Spigset

  8. Department of Anaesthesiology and Emergency Medicine, St. Olav’s University Hospital, Trondheim, Norway

    Ola Dale

  9. Department of Circulation and Medical Imaging, Pain and Palliation Research Group, St. Olav’s University Hospital, Bevegelsesbygget 3 etg, NO - 7006, Trondheim, Norway

    Kristin Moksnes

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  1. Kristin Moksnes
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Corresponding author

Correspondence to Kristin Moksnes.

Additional information

ClinicalTrials.gov id: NCT0014496

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Moksnes, K., Kaasa, S., Paulsen, Ø. et al. Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain. Eur J Clin Pharmacol 68, 1147–1156 (2012). https://doi.org/10.1007/s00228-012-1228-3

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  • DOI: https://doi.org/10.1007/s00228-012-1228-3

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