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

Abstract

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 (PCA) 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 above 40 mg a day, we recommend routine blood glucose monitoring.

Safety and Tolerance of D,L-Methadone in Combination with Chemotherapy in Patients with Glioma

“…The risk of hypoglycemia due to D,L-methadone intake is reportedly increased compared to other opioids (24). With an average intake of 15-30 mg/day in our cohort, dosage was below the critical level of 40 mg/day associated with developing hypoglycemia and none of our patients showed clinical signs or proven hypoglycemia.…”

Metabolic and Addiction Indices in Patients on Opioid Agonist Medication-Assisted Treatment: A Comparison of Buprenorphine and Methadone

“…This assertion is however undermined by: (1) preponderance of studies reporting low body weight in short half-life opioid (e.g., heroin) abusers who are not on MAT agonist therapy [58][59][60][61] even in the face of glucoregulatory abnormalities [62][63][64] ; and (2) excessive BWG consistently noted in OUD patients following the initiation of methadone [65][66][67][68][69][70][71] and to a lesser degree buprenorphine 6,7,72 treatment. Nonetheless, the debate about the issue is still ongoing 73 with a number of reports on the opposite directionality of the metabolic responses 74,75 , including hemoglobin A1C level decreases in buprenorphine-maintained NIDDM patients 76 in conjunction with heightened insulin sensitivity in methadone-treated OUD patients 77 as well as hypoglycemia in patients receiving chronic analgesia with methadone 78 . Methadone-induced hypoglycemia was also noted in a rodent model 79 .…”

Methadone in the treatment of bone pain in a patient with disseminated breast cancer

“…However, owing to tissue accumulation, a slow elimination rate and prolonged QT interval, using the drug, especially on a long-term basis, is associated with the risk of ventricular arrhythmias, such as torsade de pointes and respiratory depression [18]. Reports on hypoglycaemia have been published in recent years, especially with higher doses of the drug used, hence monitoring glucose levels during methadone treatment, especially with doses above 40 mg per day, is recommended [19]. Recent reports suggest the possibility of prolonged delirium after administration of small doses of methadone added to another opioid [20].…”

“…Jednakże, ze względu na gromadzenie się leku w tkankach, wolne tempo usuwania leku i wydłużony odstęp QT, stosowanie leku -szczególnie długoterminowo -wiąże się z ryzykiem wystąpienia arytmii komorowych, takich jak torsade de pointes i depresji oddechowej [18]. Z uwagi na fakt, że w ostatnich latach pojawiły się doniesienia o hipoglikemii, szczególnie w przypadkach stosowania większych dawek leku, należy monitorować stężenie glukozy podczas leczenia metadonem, w szczególności w przypadku dawek przekraczających 40 mg/dobę [19]. Ostatnie doniesienia sugerują, że istnieje ryzyko wystąpienia przedłużającego się delirium po podaniu małych dawek metadonu dodanego do innego opioidu [20].…”