Methadone Use and the Risk of Hypoglycemia for Inpatients With Cancer Pain

J Pain Symptom Manage. 2016 Jan;51(1):79-87.e1. doi: 10.1016/j.jpainsymman.2015.08.003. Epub 2015 Sep 3.


Context: Methadone is an important drug in the management of both cancer-related and non-cancer-related pain and is the main pharmacologic agent used in the treatment of opioid addiction. Unexpected hypoglycemia has been observed in patients receiving methadone, prompting a more detailed investigation.

Objectives: To evaluate the incidence of hypoglycemia in a cohort of inpatients receiving methadone versus other opioids including fentanyl, hydromorphone, and morphine.

Methods: Retrospective observational cohort of inpatients in a tertiary cancer center admitted for more than 48 hours from November 1, 2011 to October 30, 2013. The main outcomes were lowest measured daily blood glucose (in mg/dL) and incidence of hypoglycemia (defined as blood glucose < 70 mg/dL, equivalent to 3.9 mmol/L) with variable methadone doses compared with other non-methadone opioids.

Results: Of the 641 eligible patients admitted during the study period who received at least one dose of methadone during admission, multivariable logistic regression showed significant associations between methadone and hypoglycemia at doses greater than 40 mg oral equivalents per day or with patient-controlled analgesia use. A dose-response relationship was observed, with an odds ratio of 3.1 (95% confidence interval 2.5, 3.6) when doses greater than 80 mg/day were used. No evidence of increased risk of hypoglycemia or of a dose-response curve was seen for the other opioids.

Conclusion: The risk of hypoglycemia is increased for patients taking more than 40 mg oral methadone equivalents per day. When starting methadone at or more than 40 mg/day, we recommend blood glucose monitoring.

Keywords: Methadone; adverse event; cohort study; hypoglycemia; opioid.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Blood Glucose / drug effects
  • Cancer Pain / blood
  • Cancer Pain / drug therapy*
  • Cancer Pain / epidemiology*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydromorphone / administration & dosage
  • Hydromorphone / adverse effects
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology*
  • Incidence
  • Inpatients
  • Male
  • Methadone / administration & dosage*
  • Methadone / adverse effects
  • Middle Aged
  • Retrospective Studies
  • Risk
  • Time Factors


  • Analgesics, Opioid
  • Blood Glucose
  • Hydromorphone
  • Methadone