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Fast Fact and Concept #86:
Methadone: Starting dose information
Author: Charles F. von Gunten, MD
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Methadone is an effective opioid analgesic for
severe pain. Because of low cost
(a month 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 FF# 75. 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 inter-individual 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
Begin fixed dose methadone 5 or 10 mg orally bid or tid for 4-7 days.
If incomplete pain relief, increase the dose by 50% and continue for 4-7
days.
Continue increasing dose every 4-7 days until stable pain relief achieved.
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
Load: Start methadone at fixed oral dose (e.g. 5 or 10 mg) q 4h prn only.
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.
Day 1: Replace 1/3 of opioid dose with oral methadone on bid or tid
schedule
Day 2: Replace next 1/3 of opioid dose.
Day 3: Complete change to methadone.
Reference
Bruera E, Sweeney. Methadone use in cancer patients with pain: a review. J
Pall Med 2002; 5:127-138.
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.
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