By Vanessa Brown and Jane Vella-Brincat for the
Palliative Care Medications Working Group
In palliative care, pain is one of the most common and difficult
symptoms to manage While simple analgesics, such as paracetamol or
non-steroidal anti-inflammatory drugs (NSAIDs), may be useful early
on in the disease process, most palliative care patients require
stronger analgesics, eg, opioids.
The World Health Organization has developed an "analgesic
ladder" for cancer pain (see illustration).
Therapy begins at the first step of the ladder The top two
steps feature the opioid analgesics commonly used in palliative
care in New Zealand.
Points to note:
- There is some debate over the second step in this ladder:
Regular paracetamol may be useful in opioid-induced hyperalgesia,
although use should be continued only if effective, as eight
tablets per day add significantly to the tablet burden Most
palliative care practitioners go to step three, either after step
one or, initially, depending on the severity of the pain.
- Pain relief from codeine may be from the
active metabolite, morphine.
- The place of tramadol in palliative care
remains unclear - it can be extremely emetogenic.
Some pains may not respond completely to opioids - remember the
non-physical elements of pain. Co-analgesics are useful when
response to opioids is poor. Switching route can sometimes help,
eg, from oral to subcutaneous.
Once the patient's pain is no longer controlled by the
second-step analgesics, in combination with paracetamol and/or
NSAID/co-analgesics, it may be time to initiate one of the three
top-step opioids available in New Zealand: morpine, oxycodone or
Avoid morphine in renally impaired patients
Morphine is metabolised by glucuronidation to morphine-3 and
morphine-6 glucuronide Both are active metabolites and morphine-6
is renally excreted Morphine should therefore be avoided in renally
Initiating morphine or oxycodone
Start with small oral immediate release doses every four hours
"when required" Titrate the dose to the pain (see panel for
appropriate starting opioid dose).
Keep a record of the amount taken and once a stable dosing
regimen is achieved (two to three days), convert to a long-acting
preparation by calculating the total 24-hour dose of immediate
release required, divide by two and give twice daily together with
"when required" doses of one-sixth of the regular 24-hour dose
immediate release for pain between doses.
Smaller initial doses of oxycodone best
Oxycodone is metabolised by CYP2D6 to active metabolites, eg,
oxymorphone This too is renally excreted, but it is unknown how
much is produced when oxycodone is metabolised, and therefore how
toxic oxycodone might be in the renally impaired As oxycodone has
twice the oral availability of morphine and a slightly longer
half-life, use smaller initial doses every four to six hours "when
required" The long-acting preparation of oxycodone (OxyContinTM)
has a layer of immediate-acting drug Initiating fentanyl patches
complex as it is slow acting. Current recommendations are to avoid
this opioid in patients who are opioid naive.
Fentanyl is completely metabolised by CYP3A4 and is useful in the
renally impaired As fentanyl patches release drug over three days,
titration to pain is difficult.
When converting from another opioid, use available conversion
tables to choose an appropriate patch size The original opioid
should be continued for 12 hours as fentanyl takes effect, ie,
attach patch and give the last dose of slow-release opioid at the
same time Breakthrough pain doses are usually of the original
opioid, but may alternatively be treated with sublingual/intranasal
Adverse effects of opioids differ from drug to
- All opioids are associated with the following adverse effects,
but the incidence (incidences below are for morphine) and severity
vary from opioid to opioid.
- Tolerance to some of these adverse effects can develop, eg,
nausea/vomiting, but not to others, eg, constipation.
- Constipation - 95% of patients, less with fentanyl [50%] - a
laxative should be prescribed prophylactically.
- Nausea/vomiting - 30 to 50% of patients - usually in the first
10 days until tolerance develops.
- Drowsiness - 20% of patients - usually in the first three to
five days until tolerance develops.
- Confusion - 2% of patients - either reduce the dose, change to
a different opioid or consider haloperidol.
- Hallucinations/nightmares - 1% of patients -
give halo?peridol or change to a different opioid.
- Hyperalgesia - usually to touch - may
improve on dose reduction.
Large amount of variation in opioid dosages
Most palliative care patients require an opioid at some stage of
their treatment There is a large amount of inter-patient variation
with respect to the appropriate opioid and the dose required.
The WHO ladder and suggested opioid equivalent doses are useful
references to help appropriately treat palliative care patients
Published in Pharmacy Today February 2012