Switching Ratio from Parenteral to Oral Methadone 1:1.2 Is Safer Compared with Ratio 1:2 in Patients with Controlled Cancer Pain: A Multicenter Randomized-Controlled Trial (RATIOMTD-010810)

Abstract

Background: The most commonly used switching ratio from parenteral to oral methadone is 1:2. Methadone is highly bioavailable and a lower ratio might result in similar analgesia with less toxicity. Objective: To compare success and side effects with two ratios from parenteral to oral methadone: 1:2 versus 1:1.2 in hospitalized patients with cancer pain. Design: A multicenter double-blind randomized clinical trial. Settings/Particiants: Inpatients with well-controlled cancer pain with parenteral methadone requiring rotation to the oral route. Measurements: Outcomes included pain intensity (Brief Inventory Pain), opioid toxicity (Common Toxicology Criteria for Adverse Events), and methadone dose. Success was defined as no toxicity with good pain control at 72 hours. Results: Thirty-nine of forty-four randomized patients were evaluable: 21 in ratio 1:2 and 18 in ratio 1:1.2. Seventyone percent male. Median age 65 years. No significant differences in basal clinical characteristics between both groups. Median methadone dose pre/post switching was 24.5 mg-13.5 and 49 mg-27.3 for ratio 1:2, versus 23.3 mg-9.4 (p: not significant) and 28 mg-11.3 (p < 0.01) for ratio 1:1.2. Pain was well controlled without differences between both ratios. Drowsiness at day +1 (p < 0.017) and myoclonus at day +3 (p < 0.019) were more prevalent in group 1:2. Success was observed in 12 patients in ratio 1:2 versus 18 in ratio 1:1.2 (p < 0.001). Methadone side effects were observed in 12 patients in ratio 1:2 (mainly neurotoxicity symptoms) versus 2 in ratio 1:1.2 (p < 0.005). Conclusion: Ratio 1:1.2 when changing from parenteral to oral methadone resulted in lower toxicity and no difference in analgesia. More conservative dose adjustment during methadone route change should be considered. European Clinical Trials Register (EudraCT No. 2010-024092-39).

Changes of Intestinal Flora and Its Relationship with Nutritional Status for Patients with Cancer Pain

“…Some research reports showed that [ 9 ], in treating tumor diseases, if patients had nutritional risk or malnutrition, it would seriously affect the prognosis of patients. In the progress of tumor diseases, patients' pain mainly included their actual feelings about the disease and potential tissue damage [ 10 ]. In the progress of the tumor, the body also faces the interference of negative emotions in addition to the body's pain.…”

Caring for Our Patients With Opioid Use Disorder in the Perioperative Period: A Guide for the Anesthesiologist

“…methadone. 85 Dose reduction when converting to intravenous methadone can be determined on a caseby-case basis. Equally important is to verify a recent (eg, 6-12 months or less if stable dosing) EKG and QTc interval.…”

“…If converting from oral to intravenous methadone, generally accepted practice is to give one-third to one-half the oral daily dose divided over 24 hours, though a palliative care study for cancer patients recommended a 1:1.2 ratio over a 50% reduction or 1:2 ratio of parenteral to oral methadone. 85 Dose reduction when converting to intravenous methadone can be determined on a case-by-case basis. Equally important is to verify a recent (eg, 6–12 months or less if stable dosing) EKG and QTc interval.…”

What we know and what we don't know about the perioperative use of methadone in children and adolescents

“…Historically, the conversion from enteral to intravenous methadone in adults was reported as 2:1; however, little evidence exists to support this recommendation. More recent studies have suggested that a more appropriate dosing ratio is 1.2–1.3:1 based on bioavailability studies in adult subjects 32 and clinical trials in patients with cancer pain 33 …”

“…More recent studies have suggested that a more appropriate dosing ratio is 1. studies in adult subjects 32 and clinical trials in patients with cancer pain. 33 Opioid rotation to methadone is complex, and dosing strategies remain controversial. The first step is to determine an equianalgesic dose which involves the conversion of the current opioid regimen to daily oral morphine milligram equivalents (MMEs).…”