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Fast Fact and Concept #086: Methadone: Starting Dosing Information, 2nd Edition

First Author: Charles F. von Gunten, MD

Background   Methadone is an effective opioid analgesic for severe pain.  Because of low cost (a month’s supply may be US$5-10) and apparent efficacy in complex pain syndromes, it is increasingly used as a first-line opioid.  It is, in effect, a combination drug – part opioid and part NMDA receptor antagonist – although there is yet to be any evidence from controlled trials that it is a superior first-line analgesic to other opioids.  Methods of dose conversion to methadone from other opioid analgesics that account for its dual action were discussed in Fast Fact # 75.  A future Fast Fact will discuss different protocols for switching to methadone from other opioids.  This Fast Fact will describe strategies for beginning methadone when the patient has not been taking a strong opioid.  Note: due to its complex pharmacology, physicians unfamiliar with methadone are advised to seek consultation prior to initiating therapy (see Fast Fact #171).

Pharmacology   Methadone is lipophilic, thus it takes time to develop tissue stores that maintain serum levels. Note: There is enormous interindividual variation.  After a single dose there is a short distribution phase (associated with acute pain relief) with a half-life of 2-3 hours and a slow elimination phase (half-life 15-60 hours). Dosing must account for the accumulation of drug over days.  It is this accumulation that accounts for most therapeutic misadventures.  Liver metabolites are inactive; therefore no dose reduction is required with renal failure.  After steady-state is reached, about two-thirds of patients will get adequate pain relief with twice a day dosing. Note: a number of drugs will alter methadone metabolism, there needs to be close follow-up and attention to the addition or subtraction of interacting medications.

There are several approaches to starting methadone for the treatment of pain. All take into account the long-half life of the drug that leads to drug accumulation over days.  The following discussion presents approaches based on the literature and the author’s clinical experiences.

I.  Conservative Approach
a) Begin fixed dose methadone 5 or 10 mg orally bid or tid for 4-7 days.

b) If incomplete pain relief, increase the dose by 50% and continue for 4-7 days.

c) Continue increasing dose every 4-7 days until stable pain relief achieved.

d) Breakthrough pain: use an alternative short acting oral opioid with short half-life (e.g. morphine 10 mg) every 1 h prn for breakthrough pain and to provide pain relief during titration phase.  This dose too may need to be titrated based on efficacy.

II.   Loading Dose Approach

a) Load: Start methadone at fixed oral dose (e.g. 5 or 10 mg) q 4h prn only.

b) Calculate Maintenance: On day 8, calculate the total methadone dosage taken over the last 24 hour period and give that in scheduled, divided doses bid or tid.  Give 10% of total daily methadone as prn drug q1h for breakthrough pain.  Instruct the patient to call you if they need to use more than 5 breakthrough doses per day.  Example:  if someone took a total of 45 mg methadone on day 7 they would be converted to 15 mg tid scheduled with 5 mg as the prn dose.

References: 
1. Bruera E, Sweeney C. Methadone use in cancer patients with pain: a review. J Pall Med. 2002; 5:127-138.
2. Bruera E, et al.  Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind Study.  J Clin Oncol.  2004; 22:185-92.

Fast Facts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only.  Von Gunten CF.  Fast Fact and Concept #86.  Methadone: Starting Dose Information.  2nd Edition.  October 2007.  End-of-Life/Palliative Education Resource Center (www.eperc.mcw.edu). 

Disclaimer: Fast Facts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: October 2007

Format: Self-Study Guide Books

Purpose: Instructional Aid, Self-Study Guide, Teaching

Educational Objective: <p>Fast Fact</p>

ACGME Competencies: Medical Knowledge, Patient Care

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