Contents:
Guideline statements
The use of methadone for analgesia requires the involvement of a specialist palliative care team at all stages, even once pain control seems satisfactory long after initial titration.
Patients with uncontrolled pain should be referred either to a specialist palliative care or pain team.
The use of methadone is specifically indicated for the management of pain in patients that:
- Gain inadequate analgesia with or without unacceptable side effects following appropriate dose escalation of morphine and/or other opioids
- Experience tolerance to the analgesic effects of other opioids leading to opioid dose escalation and loss of analgesic benefit over time
- Are already receiving methadone for an indication other than pain.
The type of pains which we found in our cases series to be particularly responsive to methadone include:
- Tumours affecting the chest wall and pleura such as peripheral lung cancer or mesotheliomas,
- Pelvic tumours such as cervical cancers, invasive prostate cancers, bladder cancer, ano-rectal cancer or pelvic bone tumours,
- Complex retro peritoneal and pancreatic cancer that may involve nerve plexuses.
- In those circumstances it may be wise to consider methadone earlier in the disease process as a second line opioid and before massive dose escalation has taken place.
Conversion to methadone requires careful monitoring and where possible should take place in a specialist palliative care inpatient unit. Under specific circumstances with the involvement of the specialist palliative care or pain team, the conversion may be undertaken at home or in another care environment, but the method used will be adapted to the environment with appropriate risk assessment and added safeguards.
Careful patient selection before prescribing methadone should take place according to an expert consensus white paper (2):
- Moderate to severe pain (especially as a second-line opioid choice).
- Pain refractory to other opioids.
- True phenanthrene (e.g., morphine) allergy.
- Significant renal impairment.
- Need for a long-acting opioid (particularly as an oral concentrate solution).
- High opioid tolerance.
- Poorly controlled opioid-induced adverse effects with other opioids.
- History of dysphagia, inability to swallow, or feeding tube placement (NB: convenience of liquid long-acting opioid).
- Patient lives alone, or poor cognitive functioning, without a responsible caregiver.
- Lack of knowledgeable practitioner on transfer.
- History of opioid/medication nonadherence.
- History of substance misuse or Substance Use Disorder (patient or family).
- Multiple risk factors for methadone toxicity (e.g. clinical instability, multiple transitions in care, history of transplant).
- History of QTc prolongation or at high risk for such (see below in 3.7).
- Prognosis less than projected time to methadone steady state (i.e. 5 to 7 days).
- Obstructive or central sleep apnoea.
- Determined to be medically inappropriate after risk assessment.
Consideration should be made of the risk of long QT syndrome (see below) in exceptional cases this recommendation can be waived. (See reference 2 table 3).
- Between 450ms and 500ms, the requirement for methadone and risk of cardiac arrhythmia should be re-evaluated. If a decision in favour of a trial of methadone is taken, monitoring of ECG should be part of the close clinical management of titration.
- If the QTc is above 500 milliseconds, methadone should not be started until this has been corrected (when possible).
- When the initial QT interval is deemed normal (QTc<450ms), it is not possible to state how often the ECG should be repeated due to lack of evidence. An emerging consensus is to repeat the ECG within a month of completing the titration. Other times that may be appropriate are when a drug known to prolong QT interval is introduced, once the daily dose of methadone is over 100mg or when a substantial (e.g. doubling) methadone dose increase occurs.
- Consideration of burden vs. benefit is crucial and, in those with life limiting illness the potential benefit of controlling otherwise refractory pain may far outweigh the risks, even when monitoring for arrhythmia is impractical. ECG monitoring is generally not required in the last days of life.
- Pre-treatment one off ECG monitoring is recommended for all patients even those without recognised risk factors for QT prolongation.
- ECG is mandatory in the presence of other risk factors for QT interval prolongation including:
-
- A history of cardiac conduction abnormalities
- Advanced heart disease or ischaemic heart disease
- Liver disease
- A family history of sudden death
- Electrolyte abnormalities that could alter cardiac conduction
- Concurrent treatment with drugs which:
- May cause electrolyte abnormalities
- Have a potential to prolong QT including anti-arrhythmic drugs such as Amiodarone, psychotropic drugs including haloperidol, macrolide antibiotics including clarithromycin and erythromycin, domperidone. A full list can be found at http://www.azcert.org or https://crediblemeds.org
- The ultimate decision on ECG monitoring for each patient should be made by the consultant responsible for the methadone initiation.
- Monitoring of serum electrolytes is generally recommended in patients taking diuretics or at risk of hypokalaemia e.g. vomiting or diarrhoea.
- If the QT interval is prolonged >500msec
- Other drugs known to be possibly involved should be withdrawn if possible
- Discussion with a local cardiologist should be sought to help assess risk of arrhythmia to aid weighing up or risk vs. burden of treatment.
When patients are given the opportunity of taking methadone, they must be given adequate information for a joint decision to start methadone to be taken. See section 9 of this guideline.
Methadone prescribing responsibilities should only be passed onto the primary care team when the patient has been stabilised and with support of shared care guidelines (Appendix 3)1,2 and in areas where shared care has been approved.
Conversion from other opioids to subcutaneous methadone.
- It is not normally advised to convert to subcutaneous methadone from any opioid other than oral methadone.
- Although it is not impossible to prescribe subcutaneous methadone alongside another opioid, this is not covered by this guideline.
- Conversion is a prolonged process requiring considerable input from the patient to achieve successful conversion to oral methadone, therefore changing a patient in the final few days of life to subcutaneous methadone from other opioids is not advised.
Patient information and counselling
The NICE guidance on Opioids in Palliative care (CG140)14 states that patients should be asked about any concerns of being prescribed strong opioids, that verbal and written information should be offered to patients and carers and that they are offered frequent review of their pain control and side effects.
Responsibility for the communication around the use of methadone for pain control in palliative care is with the specialist palliative care team.
All patients should be offered a copy of the patient information leaflet (Apppendix 6).
In March 2015 new legislation came into force which allows the police to perform roadside testing for strong opiates including methadone15. Patients should be counselled about this and advised to carry information of their medication for example a repeat prescription sheet. If the medication, including methadone is being taken in accordance with medical advice and the patient’s driving is not impaired no action will be taken by the police. It remains an offence if driving is impaired and patients should be counselled not to drive if their ability is impaired e.g. drowsiness by the medication.
Disclaimer (SPAGG - Rewrite)
This Guide is 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.
While WMPCPS 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.