Choice of opioid in palliative care
Morphine is the opioid of choice in palliative care. (For detailed discussion about opioid choice for pain in palliative care, see Choice of opioid for pain in palliative care. Opioid therapy for chronic breathlessness is discussed in Principles and choice of opioid therapy for chronic breathlessness in palliative care).
Morphine has a significant amount of data to support its use for pain and breathlessness. It is generally well tolerated, is available in a range of formulations that are listed on the Pharmaceutical Benefits Scheme (PBS), and is suitable for subcutaneous administration (treatment can be changed to a subcutaneous injection or infusion if needed).
Situations when it may be appropriate to consider using another opioid instead of morphine include:
- moderate to severe kidney impairment
- a history of allergy—true allergy to an individual opioid is rare; reported allergies to morphine are often pharmacologically predictable adverse effects (eg nausea and vomiting, constipation, hallucinations)
- unacceptable dose-related adverse effects
- patient preference
- refractory pain
- if an alternative opioid is already providing effective symptom management1
- if an alternative route of administration is required (eg difficulty swallowing, impaired gastrointestinal absorption, poor adherence to therapy) but parenteral administration is not appropriate; in this situation, a transdermal patch may be preferable.
Choosing an opioid and its route of delivery can be complex. Clinicians who are not experienced in palliative care may find they are more effective in their role if they are familiar with a limited range of opioids they can use with confidence.
Use the same opioid for regular and as-required therapy, unless:
- a suitable immediate-release formulation of the regular opioid is not available
- combination therapy solves practical difficulties (eg in the last days of life, it is common to continue a transdermal fentanyl patch and provide additional analgesia with a different opioid through continuous subcutaneous infusion and as an as-required option for breakthrough pain2)
- the patient is under specialist palliative care direction (eg for refractory pain).
See Prescribing considerations for opioids commonly used in palliative care for prescribing considerations for commonly used opioids in palliative care, and Prescribing considerations for opioids less commonly used in palliative care for prescribing considerations for less commonly used opioids in palliative care. Codeine is not included in these tables because it is not recommended for symptom management in palliative care; it has no efficacy or tolerability advantage over an equianalgesic dose of morphine. Codeine is converted to morphine via cytochrome P450 2D6—rapid metabolisers may experience significant morphine-related adverse effects and poor metabolisers may have inadequate symptom relief.
Hydromorphone and methadone are used in palliative care, but their prescription is limited to healthcare professionals experienced in their use because of safety concerns. Hydromorphone is easily confused with morphine but is approximately 5 times as potent. High-dose preparations of hydromorphone are available, further increasing the risk of serious harm if mistaken for morphine. Methadone has complex pharmacokinetic properties. It has a long and variable half-life; the potency and half-life of methadone differs between patients, causing variable interpatient analgesic effect. The time to reach steady-state concentration can be unpredictable and dose adjustment is extremely difficult.
Opioid | Prescribing considerations |
|---|---|
|
morphine | |
|
route of administration |
oral and parenteral |
|
pharmacokinetics |
full mu-receptor agonist metabolised in the liver—there are 2 main metabolites, one contributes significantly to morphine’s analgesic effect; the other has no analgesic effect, but may be responsible for some of the neurotoxic adverse effects sometimes seen with long-term, high-dose morphine treatment active metabolites are renally excreted—avoid or reduce doses in patients with moderate or severe kidney impairment [NB1] |
|
comments |
- |
|
oxycodone | |
|
route of administration |
oral and parenteral |
|
pharmacokinetics |
full mu-receptor agonist metabolised in the liver—CYP 2D6 polymorphism may explain variation in analgesia between patients reduce doses in patients with severe kidney impairment [NB1] |
|
Comments |
at the time of writing, oxycodone parenteral formulations are not available on the PBS—for current information, see the PBS website an oral combination formulation of modified-release oxycodone+naloxone may be less constipating compared with modified-release oxycodone alone, but evidence is weak. The maximum dose of naloxone (combination oxycodone+naloxone 160+80 mg daily) limits the practical use of these formulations in palliative care. If a higher oxycodone dose is required, consider switching to modified-release oxycodone as a single drug—see Switching opioids for advice. Alternatively, add a modified-release oxycodone (single-drug) formulation to the combination oxycodone+naloxone formulation (ie give both together). Be aware that either of these options may affect the patient’s bowel control; monitor and treat as required. Seek specialist advice if needed. avoid oral naloxone-containing preparations in patients with liver impairment—the bioavailability of oral naloxone is increased and, when given in combination with an opioid, reduces opioid efficacy |
|
Note:
PBS = Pharmaceutical Benefits Scheme NB1: Opioid doses may need adjustment in patients who are on renal dialysis—seek expert advice. For information on palliative care for patients with chronic kidney disease, see Principles of palliative care for patients with chronic kidney disease. | |
Opioid [NB1] | Prescribing considerations |
|---|---|
|
buprenorphine | |
|
route of administration |
parenteral (specialist only), sublingual (specialist only) and transdermal |
|
pharmacokinetics |
mu-receptor agonist, with some activity at kappa and delta opioid receptors [NB2] dose adjustment is not required in patients with kidney impairment transdermal formulation has slow onset and offset of effect—rapid dose titration is not possible sublingual buprenorphine has a slower onset than transmucosal fentanyl and has a relatively long duration—seek specialist advice if considering using sublingual buprenorphine |
|
comments |
despite buprenorphine’s high affinity for mu-receptors, it does not block the effects of other opioids if administered concomitantly—do not withhold buprenorphine if additional opioids are required for analgesia opioid-induced hyperalgesia is less common than with other opioids due to buprenorphine’s antihyperalgesic effects |
|
fentanyl | |
|
route of administration |
intranasal, parenteral, transmucosal and transdermal |
|
pharmacokinetics |
full mu-receptor agonist no active metabolites—suitable for use in severe kidney impairment poorly absorbed orally, but well absorbed across mucous membranes rapid onset of effect when administered intravenously, subcutaneously, transmucosally or intranasally transdermal formulation has slow onset and offset of effect—rapid dose titration is not possible |
|
comments |
fentanyl has a fast onset of effect, which may increase its desirability among drug users to reduce the risk of inadvertent overdose with intravenous fentanyl, use lower than calculated equianalgesic doses transdermal fentanyl may be less likely to cause constipation than oral morphineHadley, 2013Tassinari, 2008 consider avoiding transdermal fentanyl in patients with cachexia as its absorption is variableHeiskanen, 2009 use by subcutaneous route (injection or syringe driver) may be limited by the volume of the injection transmucosal fentanyl formulations have different pharmacokinetics and are not interchangeable; if switching, start the new formulation at the starting dose and increase as directed in the product information |
|
tapentadol | |
|
route of administration |
oral |
|
pharmacokinetics |
analgesic effect results from a synergistic combination of mu-receptor agonist effect and noradrenaline reuptake inhibition; it has no relevant effect on serotonin reuptake more potent opioid effect than tramadol dosage adjustments required in patients with severe kidney impairment [NB3] |
|
comments |
the role of tapentadol for pain in palliative care is unclear at the time of writing, immediate-release tapentadol tablets are not available on the PBS for the treatment of acute pain—for current information, see the PBS website |
|
tramadol | |
|
route of administration |
oral and parenteral |
|
pharmacokinetics |
analgesic effect results from weak mu-receptor activity (mediated primarily by active metabolite), and inhibition of serotonin and noradrenaline reuptake converted to an active metabolite (via cytochrome P450 2D6 isoenzyme) that is a more potent mu-receptor agonist. Rapid metabolisers are at increased risk of mu-receptor-mediated adverse effects (especially opioid-induced ventilatory impairment) if excessive doses are administered, or the patient has risk factors for opioid-induced ventilatory impairment. Poor metabolisers may experience inadequate analgesia and increased serotonergic toxicity [NB4] metabolite is renally excreted—dose adjustments required in severe kidney impairment [NB3] |
|
comments |
tramadol has a very limited role in pain management in palliative care concurrent use of tramadol with other serotonergic drugs increases the risk of serotonin toxicity (see Drugs most commonly associated with serotonergic toxidrome in the Toxicology and Toxinology guidelines for drugs associated with serotonin toxicity) [NB4] rapid intravenous administration is associated with an increased incidence of nausea and vomiting compared with oral administration because peak blood concentration is reached more quickly although reported anecdotally, there is inconclusive evidence that tramadol increases the risk of confusion in older patients compared to other opioids when doses are appropriately adjusted for age and comorbidities |
|
Note:
PBS = Pharmaceutical Benefits Scheme NB1: For patients who are already taking opioids that are not routinely used in palliative care, a change in opioid is not required unless the patient has or is likely to experience inadequate symptom control. For advice on switching opioids, see Switching opioids in palliative care. NB2: Buprenorphine is classified as a partial mu-receptor agonist but appears to act as a full mu-receptor agonist for analgesia. NB3: Opioid doses may need adjustment in patients who are on renal dialysis—seek expert advice. See Principles of palliative care for patients with chronic kidney disease for information on palliative care for chronic kidney disease. NB4: Signs of serotonin toxicity include altered mental status (eg agitation, anxiety, restlessness, confusion), autonomic stimulation (eg increased heart rate, increased blood pressure, fever, sweating, dilated pupils), and neuromuscular excitation (eg tremor, clonus, hyperreflexia, myoclonus, rigidity). | |