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)

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. Seventy-one 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).