Methadone

Not recommended for use without specialist supervision

Methadone has both opioid and non-opioid properties and a much longer half life than other opioids. There is therefore no single potency ratio for methadone and other opioids. The half life is 24-72 hours and therefore there is risk of accumulation. Because of this accumulation dose adjustments should be made infrequently. Patients should be closely monitored for signs of opiate toxicity

Indications for useMethadone is used in various situations including:
1. Preferred strong opioid of choice in some centres for patients with renal failure/on dialysis
2. Neuropathic cancer pain not responding to a typical regime of NSAID + morphine combined with a tricyclic antidepressant and an anticonvulsant.
3. Neurotoxicity with morphine at any dose (e.g. sedation, hallucinations, dysphoria, delirium, myoclonus, allodynia, hyperalgesia) which does not respond to a reduction in morphine dose.
4. As an alternative to spinal analgesia and non-drug treatments when pain is unrelieved despite increasing doses of morphine and adjuvant analgesics, together with features of neurotoxicity.

Formulations available
Tablets 5 mg
Syrup  2mg / 5mls
Mixture 1mg / 1ml
Injection 10, 25 and 50 mg/1ml

Dose titration
If the patient is already receiving oral morphine use one of the following methods:
Pharmacologically method 1 is preferable but if patient and staff are not comfortable with a wholly prn regime, method 2 can be used.

Method 1: Oral Morphine to oral Methadone, prn only ( Morley and Makin method 1998)

  • Calculate the dose of methadone required by firstly adding up the total 24 hour dose of oral morphine in milligrams. If the patient has been having parenteral morphine or diamorphine calculate the 24 hour equivalent of oral morphine and then proceed as follows:
    The initial dose of oral Methadone should be 1/10 th of the 24 hr oral morphine dose
    N.B.  Starting dose of Methadone should not exceed 30mg 
    e.g. MST 30mg bd ? 60 mg oral morphine / 24 hours
    : give 6 mg Methadone PO as starting dose
  • Stop normal release morphine at the same time as giving the first dose of Methadone PO. If switching from modified release morphine, give the first dose of methadone at least 6 hrs after the last dose of a 12 hrly preparation.

1. Allow the patient to take the prescribed dose q3hr prn. determined by the
patient’s pain requirements.
2. On day 6, the amount of Methadone taken over the previous two days is noted and divided by 4 to give a regular q12hr dose PO, with provision for a smaller dose q3h prn. (calculated as ¼ of the regular q12hr dose PO)
3. If  = 2 doses/day of prn Methadone continue to be needed, the dose of regular Methadone should be increased by about ¼ once a week, guided by prn. use.

Method 2: Oral Morphine to oral Methadone q12h and prn (Blackburn et al 2002)

  • Stop all other opioids
  • Give a loading dose of Methadone at bedtime 1/10th of the previous 24 hr PO morphine dose, up to a maximum of 30mg. In elderly and cachectic patients omit loading dose.
  • Prescribe ½ of the loading dose as a regular q12hr dose.
  • Prescribe ¼ of the regular q12hr dose as prn dose q3hrly.
  • In the event of severe uncontrolled pain, despite repeated prn doses, a second loading dose can be given.
  • The regular q12h dose should not be altered until day 5.
  • • If the patient complains of pain within 3hr of a regular dose, take the next regular dose early (but the dose after that at the normal time)
  • If the patient is very drowsy, omit one dose and then continue with a reduced regular dose
  • If = 2 doses/day of prn Methadone continue to be needed, the dose of regular Methadone should be increased by about ¼ once a week, guided by prn use.

MANAGING BREAKTHROUGH PAIN DURING METHADONE CONVERSION USING METHOD 1 or 2
For patients in severe pain, unable to wait  3hr before giving the next dose of methadone, options include:

  • Using non-opioids
  • Methadone 5-10mg q1hr prn (i.e. a small fixed dose)
  • The previously used opioid q1hr prn (at dose of 50% of the prn dose used prior to switching)
  • If the previous opioid caused neurotoxicity, use an alternative immediate release strong opioid

PO METHADONE TO METHADONE SC / CSCI

  • To convert from PO Methadone to Methadone SC, give half the PO dose.
  • Due to its long half life, Methadone can be given SC q12hr. or in CSCI /24h.
  • CSCI Methadone may cause skin reaction; this is reduced by using saline as diluent, using a more dilute solution, changing site daily and changing syringe q12h
  • Additional rescue doses of Methadone SC can be given for breakthrough pain using 1/10th of the 24hr CSCI dose q3hr prn
  • If = 2 doses/day of prn Methadone continue to be needed, the 24 hr dose of Methadone SC should be increased by about ¼ once a week, guided by prn use.

OTHER OPIOIDS CSCI TO METHADONE CSCI – SEEK SPECIALIST ADVICE
PRESCRIBING PO METHADONE AS FIRST CHOICE STRONG OPIOID
• Start on methadone 5mg q12hr and 5mg prn q3hr
• If pain relief remains minimal, consider increasing to 10mg q12hr after 1-2 days, but generally do not increase the regular dose for one week.
• If necessary titrate the regular dose up by about ¼ once a week guided by prn use
• With higher regular doses, remember to increase the prn dose to ¼ of the q12hr dose
This titration can be used for patients with renal impairment who have not previously been on strong opiates.

References
1. Morley JS, Makin MK. The use of methadone in cancer pain poorly responsive to other opioids. Pain reviews 1998;5:51-58
2. Fainsinger R et al. Methadone in the management of cancer pain: a review. Pain 1993;52:137-147
3. Palliative drugs formulary PCF2 p 194-6
4. Ripamonti C et al. An update on the clinical use of Methadone in cancer pain. Pain 1997;70:109-115
5. Mercadente S et al. Rapid switching from Morphine to Methadone in cancer patients with poor response to morphine. J. of Clinical Oncology 1999;17:3307-3312
6. Blackburn D et al Methadone:the analgesic. European Journal of Palliative Care. 2005;12(5)

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