METHADONE INFORMATION SHEET
Methadone 5mg tablets, Methadone 2mg/ml, 5mg/ml or 10mg/ml oral liquid and Methadone injection 10mg/1ml for subcut (or IM) use. This guide is for methadone when it is being used as an analgesic in palliative care or pain patients not when in use for opioid dependence. Methadone is a potent opioid analgesic that has complex pharmacology making it difficult to use safely. Methadone should not be initiated other than by an expert in palliative care or pain medicine. Pharmacology Methadone acts as an agonist on mu opioid receptors, an antagonist on N-methyl-D aspartate (NMDA) receptors and on serotonin /noradrenaline pathways in the spinal cord. It has no active metabolites and is excreted mainly by the faecal route. Unlike morphine, the half life of methadone exhibits marked inter and intra individual variability. The elderly are particularly susceptible. Methadone
Oral availability Plasma half life Metabolism Elimination 85% 13 - 80 hours CYP 3A4 (2D6, 1A2) to inactive metabolite Faecal and slight renal (depending on urine pH)
Morphine
20-40% 2-3 hours Glucuronidation to active metabolites Metabolite mainly renal
Interactions CYP enzyme inducers eg phenytoin, dexamethasone, may decrease efficacy of methadone CYP enzyme inhibitors eg fluconazole, fluoxetine, may increase efficacy and adverse effects The efficacy and adverse effects of drugs metabolised by CYP2D6 eg nortriptyline, haloperidol, tramadol may be increased by methadone Methadone will also interact with other CNS depressants such as alcohol and benzodiazepines. Indications Methadone is mainly used in the treatment of opioid addiction but it is being used increasingly internationally for the treatment of moderate to severe pain and particularly in patients who are experiencing adverse effects to morphine or those with moderate to severe renal impairment. Advantages of methadone • oral or parenteral administration • no active metabolites • not excreted renally therefore “safe” in renal failure • has NMDA antagonistic properties o possibly more useful in neuropathic pain than morphine or fentanyl o possibly less risk of developing tolerance • effective when given twice daily
Approved by Clinical Director Hospital Palliative Care June 2009 Review June 2010
Disadvantages of methadone • accumulation due to unpredictable and long half life • conversion from other opioids is complicated • carries some stigma because of association with drug addiction • local site reactions when given subcutaneously (see later) Oral administration Methadone is available in liquid and tablet form. Liquid formulations are 2mg/mL, 5mg/mL and 10mg/mL. Only 5mg tablets are available. We generally recommend using the liquid, both to reduce tablet numbers and aid compliance particularly in the terminal phase. Oral to subcutaneous conversion Although the bioavailability of methadone is 85%, in practice, when converting from oral to subcutaneous methadone a range of between 50-75% of the 24 hour oral dose is given over 24 hours. Discuss with an expert if needed. Methadone cannot be mixed with any other medications so must be given in a separate syringe driver. Subcutaneous administration Due to its irritant properties and the need for a separate syringe driver, the subcutaneous route is only used if unavoidable. Methadone injection is available as 10mg/mL in 1mL ampoules. Dilute with sodium chloride 0.9% rather than water. A more dilute solution in a 20mL or 30mL syringe can be helpful. The subcutaneous site may need to be changed daily. Dosing • Stabilisation onto regular methadone takes at least 7 to 10 days. • For breakthrough pain give methadone liquid at a dose of 1/8th of the total daily dose. • Frequent use of breakthrough doses may lead to accumulation so it is advisable to give no more often than 3 hourly, up to a maximum of 4 times a day. Patient should be advised to contact a Health Professional if needing more than 2 breakthrough doses per day. • If 2 or more breakthrough doses per 24 hours are consistently required, the regular dose may be increased by 1/4 to 1/3. Increase baseline no more often than once a week. • Calculate the subcutaneous bolus dose for breakthrough pain as above ie 1/8th of the total daily dose. Give no more often than 3 hourly up to 4 times a day. The subcutaneous bolus is limited by volume to a maximum of 20mg (2mL). • We encourage early consultation with a Specialist Palliative Care (or Pain Service) provider if problems or concerns arise. For more information and advice within working hours contact either the Nurse Maude Hospice on (03) 375 4274 or the Christchurch Hospital Palliative Care Service on (03) 3641 473. After hours contact the on call Hospice doctor on (03) 375 4274
Approved by Clinical Director Hospital Palliative Care June 2009
Review June 2010