The Hospice Clinician Blog

Introduction

Methadone is a potent synthetic opioid with unique characteristics that offer some distinct advantages over other opioid drugs. It was developed as an analgesic in Germany in the late 1940s. Despite its advantages, the level of Methadone prescribing for chronic pain has remained relatively low until recently. Primary reasons for the lack of widespread use of Methadone for chronic pain include:

• The difficulty of titrating the dosage when initiating Methadone therapy
• The fact that Methadone may carry some negative stigma since it is best known as a treatment of opioid drug addiction
• Complex pharmacokinetics, potential drug interactions, and dynamic opioid conversion ratios

Methadone and Prescriptive Authority

Regulations restrict the prescribing of Methadone for treatment of addiction to FDA approved drug treatment programs. These restrictions do not apply when Methadone is prescribed to treat pain, however, some healthcare professionals have been reluctant to prescribe it due to fear of scrutiny by regulatory agencies (Baumrucker (2000). Amer. J. Hospice & Palliative Care; 17(3): 153-154). Methadone is a schedule II controlled substance that may be prescribed for treatment of pain by any physician with valid Drug Enforcement Agency registration.

Pharmacokinetics of Methadone

Methadone is a fat soluble drug which is widely distributed and bound to various tissues. The extensive distribution and tissue binding is responsible for the long half-life of the drug and extended duration of analgesic effect upon continuous chronic use. (Goodman and Gilman. The Pharmacological Basis of Therapeutics 11th Edition). The Methadone distribution phase is complete in 4 to 6 days at which time a "steady-state" condition is achieved between drug levels in the plasma and drug tissue levels. It is because of this extensive distribution phase that the drug may appear to have a shorter duration of analgesic action initially, then exhibit a longer half-life & extended duration of action once the distribution phase is complete. During the last few days of the distribution phase after Methadone therapy is initiated the clinician should be alert for signs of drug accumulation and possible adverse effects (somnolence, delirium, respiratory depression). Methadone is primarily eliminated by metabolism in the liver to inactive metabolites.(Eap, et al. (2002) Clin. Pharmacokinetics 41: 1153-93).

There is no need for dosage adjustment of Methadone in patients with renal impairment such as those often required with Morphine which has a potentially toxic metabolite that can accumulate and cause toxicity in these patients.

Methadone Dosage for Hospice Patients

For opioid na�ve patients, a starting dose of 2.5mg orally every Q8hr has been suggested (The College of Physicians and Surgeons of Ontario (Nov 2000)). In frail, elderly patients the starting dose may need to be reduced to 2.5mg Q12h. The duration of analgesic effect of a single dose may be in the range of 4 to 6 hours for many patients during the initial distribution phase when starting Methadone treatment, therefore, a need for PRN doses should be expected in order to titrate to the therapeutic dose during this period.

Breakthrough pain can be managed by using Methadone doses equal to 25-50% of the total daily routine dose at intervals of every 4 hours as needed during the distribution phase. At the end of the distribution phase on approximately Day 5, the total amount of PRN Methadone required for the previous 24 hours is added to the routine total daily dosage and administered in divided doses at 8 or 12 hour intervals. Alternatively, oral morphine solution may be used on a PRN basis for management of breakthrough pain.

For patients who will be converted from another opioid to Methadone, there are a variety of published methodologies available. Outcome Resources pharmacists use  the following guidelines for conversion which were derived from Ayonrinde and Bridge (Med J Aust 2000) and Ripamonti (Cancer Pain & Palliative Care 1999):

Methadone Conversion Guide for Hospice

• Convert current opioid dose to the total daily dose of oral Morphine
  equivalent (see Opioid Conversion Table below)
• Convert the oral Morphine equivalent to the total daily dose
  of oral Methadone (see Morphine to Methadone ratio Table below)
• Divide total daily Methadone dose into 3 or 2 doses and administer
  at 8 or 12 hour intervals

Morphine to Methadone Ratio Table

Sample Methadone Conversion for hospice: 

We have a patient on Fentanyl patch 300mcg/hr that we want to convert to Methadone. Fentanyl is converted to an oral Morphine equivalent of 600mg/day using the opioid conversion table. The oral morphine equivalent is then converted to oral Methadone 60mg/day using the Morphine to Methadone ratio table. This total daily dose is then given in divided doses at 20mg Q8hr. This may be further converted to a Q12h regimen at 30mg Q12h for many patients allowing for greater convenience and compliance.

All equi-analgesic ratios are approximations and are intended to be used as tools to guide the clinician in the determination of an equivalent dosage. Final decisions regarding the appropriate conversion doses should be tempered by individual patient clinical factors including current level of pain, history of compliance with the previous regimen, renal and/or hepatic function, and potential drug interactions.

TO BE CONTINUED... See Part 2 for Advantages of Methadone, Indications for Use, and Drug Interactions.

Outcome Resources is dedicated to supporting hospices in the utilization of methadone and provides consultations and education programs for hospices geared toward this and other palliative appropriate medications. Call today to learn more or contact us for a Free Hospice Pharmacy Consultation.