Fast Fact and Concept #86: Methadone: Starting dose information

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Title: Fast Fact and Concept #86: Methadone: Starting dose information

Author(s): Charles F. von Gunten, MD

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. Methods of dose conversion to methadone from other opioid analgesics that account for this dual action were discussed in Fast Fact #75: Methadone for Pain. 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.

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 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 maintained with twice a day (bid) 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 authors? clinical experiences.

Conservative Approach

  1. Begin fixed dose methadone 5 or 10 mg orally bid or tid for 4-7 days.
  2. If incomplete pain relief, increase the dose by 50% and continue for 4-7 days.
  3. Continue increasing dose every 4-7 days until stable pain relief achieved.
  4. 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.

Loading Dose Approach

  1. Load: Start methadone at fixed oral dose (e.g. 5 or 10 mg) q 4h prn only.
  2. Calculate Maintenance: On day 8, calculate the total methadone dosage taken over last 24 h period and give in 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.

Conversion to Methadone From Another Strong Opioid

Calculate Total Methadone Dose (for conversion information, see FF# 75). Convert step wise in order to detect if the patient demonstrates a therapeutic response to a much lower dose of methadone that you had expected.

  1. Day 1: Replace 1/3 of opioid dose with oral methadone on bid or tid schedule
  2. Day 2: Replace next 1/3 of opioid dose.
  3. Day 3: Complete change to methadone.


Bruera E, Sweeney. Methadone use in cancer patients with pain: a review. J Pall Med 2002; 5:127-138.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing. Fast Facts and Concepts #86 . Methadone: Starting dose information. Von Gunten, CF., March 2003. End-of-Life Physician 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: 3/2003

Format: Handouts

Purpose: Instructional Aid, Self-Study Guide, Teaching

Training: Fellows, 3rd/4th Year Medical Students, PGY1 (Interns), PGY2-6, Physicians in Practice
Specialty: Anesthesiology, Emergency Medicine, Family Medicine, General Internal Medicine, Geriatrics, Hematology/Oncology, Neurology, OB/GYN, Ophthalmology, Pulmonary/Critical Care, Pediatrics, Psychiatry, Surgery
Non-Physician: Nurses

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Addiction, Chronic non-malignant pain, Controlled substance regulations, Pain, Pain assessment, Pain treatment

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