Introduction of oral methadone to high-risk patients with prolonged QT interval: A retrospective study

Miho Takemura; Kazuyuki Niki; Yoshiaki Okamoto; Yoshinobu Matsuda; Takahito Omae; Makie Kohno; Ikeda Ikeda; Mikiko Ueda

doi:10.5055/jom.0828

Authors

Miho Takemura, BP https://orcid.org/0000-0002-7170-6938
Kazuyuki Niki, PhD https://orcid.org/0000-0001-9089-9387
Yoshiaki Okamoto, PhD
Yoshinobu Matsuda, MD
Takahito Omae, MD, PhD
Makie Kohno, MD
Kenji Ikeda, PhD
Mikiko Ueda, PhD

DOI:

https://doi.org/10.5055/jom.0828

Keywords:

QT interval, methadone, cancer, heart disease, opioids

Abstract

Objective: Methadone may cause detrimental side effects such as corrected QT (QTc) prolongation. However, methadone may be desirable in patients with advanced cancer and those with heart disease who have intractable pain. Therefore, we aimed to evaluate the safety and efficacy of initiating methadone for cancer pain in patients at high risk of methadone-induced QTc prolongation.

Design: A retrospective cohort study.

Setting: Single center.

Patients: Sixty-four patients with cancer who started oral methadone to relieve pain and underwent 12-lead electrocardiogram monitoring at baseline and 1-2 weeks after initiation of methadone therapy from January 1, 2013, to March 31, 2022, were enrolled.

Main outcome measures: The primary endpoints were the change in QTc from baseline after oral methadone therapy and the difference in methadone doses between the high- and low-risk groups for methadone-induced QTc prolongation.

Results: None of the patients developed clinically significant methadone-induced QTc prolongation or any adverse events attributable to cardiotoxicity, although 32 patients (50.0 percent) had heart disease or prolonged QTc before oral methadone initiation. Moreover, the high-risk group received a lower dose of opioid analgesics prior to methadone administration. For this reason, they started with a lower methadone dose than the low-risk group.

Conclusions: Even in patients with heart disease or prolonged QTc at baseline, methadone may be safely administered by initiating low-dose methadone when the dose of other opioids is low and by adjusting the concomitant medications that can interact with methadone.

Author Biographies

Miho Takemura, BP

Department of Clinical Pharmacy Research and Education, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka; Department of Pharmacy, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan

Kazuyuki Niki, PhD

Department of Clinical Pharmacy Research and Education, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka; Department of Pharmacy, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan

Yoshiaki Okamoto, PhD

Department of Pharmacy, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan

Yoshinobu Matsuda, MD

Department of Palliative Care, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan

Takahito Omae, MD, PhD

Department of Palliative Care, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan

Makie Kohno, MD

Department of Palliative Care, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan

Kenji Ikeda, PhD

Department of Clinical Pharmacy Research and Education, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka, Japan

Mikiko Ueda, PhD

Department of Clinical Pharmacy Research and Education, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka, Japan

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