Contents:
Guideline background
There are no NICE guidelines on the use of methadone for pain therefore the specialist palliative audit and guidelines group (SPAGG) have developed these guidelines to ensure safe and consistent practice in line with local expert opinion.
A small number of patients with cancer experience pain that cannot be controlled by using the analgesic ladder even when antiepileptics and antidepressant drugs are added to opioid drugs.
Methadone has pharmacological specificities described in General drug information about methadone. In particular a long half-life and titration to an effective dose is often complex, therefore dose titration and modification should be carried out under the care and supervision of a specialist palliative care or pain team (1).
Recent guidelines and consensus papers have been published. We recommend that specialists and those wishing to safely prescribe methadone read these excellent documents. We have attempted to take account of their recommendations and cited some of them. They cannot be fully replicated for local guidelines as they operate in different clinical and health care systems than our (1, 2).
General drug information about methadone
- Methadone has a long and very variable half-life of 30-110 hours. The effect of dose increases could be clinically noticeable up to five days after they are implemented.
- Further drug information is available from the summary of product characteristics.
Drug and food interactions with methadone
Methadone is metabolised by the group of enzymes known as cytochrome P450. This is a highly complex group of enzymes that is often induced or inhibited by a number of other conventional and herbal medications as well as some foods (see below). This enzyme induction
or inhibition may result in pain in previously stable patients, or accumulation and therefore toxicity in others. For a comprehensive list of interacting drugs, refer to: www.atforum.com/pdf/drug_interactions.pdf
(See reference 11)
- Maintain an accurate, updated profile for each patient that includes all prescribed drugs and OTC products (including herbal remedies and dietary supplements).
- Use alternative, non-interacting, drugs whenever possible.
Usually, there are differences in the interactive properties of at least some members of any drug class. For example, the macrolide antibiotic erythromycin is a strong CYP3A4 inhibitor, likely to possibly interact with methadone, whereas the macrolide azithromycin does not appear to have this effect. - If a potentially interacting drug is used with methadone, it is better to adjust the methadone dose based on patient response rather than in advance based on an expected interaction.
The magnitude of drug interactions varies dramatically from patient to patient, and it is unlikely that the elected methadone dosage adjustment would exactly offset the actual effect of the second drug. - Signs/symptoms of either opioid withdrawal or overmedication (e.g., sedation), and their severity, can help gauge serum methadone level (SML) adequacy in the presence of an interacting drug. Adjustments of methadone or concomitant drug(s) may be appropriate to overcome such adverse reactions.
- If there are concerns about adverse effects of increased methadone concentrations, patients should be advised in advance of physical signs/symptoms of overmedication that might occur and what to do. It may be desirable to temporarily monitor SMLs in certain cases.
- Whenever possible, avoid concurrent administration of drugs with overlapping adverse-effect profiles. Otherwise, signs/symptoms of major variations in methadone concentration may be confused with side effects of concomitantly administered drugs, and vice versa.
- Consider pre-existing disease states.
For example, conditions associated with impaired renal or hepatic function may significantly alter drug metabolism and excretion. Patients with pre-existing cardiovascular conditions – particularly those with congestive heart failure or left ventricular systolic dysfunction – may be more sensitive to potential arrhythmogenic effects of certain drugs (including methadone). - In some cases, adverse drug reactions can be resolved by prescribing a medication with or without food, by altering dosing schedules, or by splitting doses into smaller increments.
- Unreported or seemingly inconsequential factors may play a role in drug interactions. For example, grapefruit juice or smoking cessation can hinder metabolism and increase methadone serum levels.
- Patients may not adhere to prescribed medication regimens, which could affect adverse reactions, and the more complicated the regimen the less likely that the patient will adhere to it. This can be important in methadone-maintained patients prescribed multiple medications.
Disclaimer
These Guidelines are intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.
Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.
Whilst SPAGG takes every care to compile accurate information , we cannot guarantee its correctness and completeness, and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.