Opioid analgesics in palliative care


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).
Opioid analgesics 1
 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 fentanyl.

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 impaired patients.

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).

Opioid analgesics 2

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 fentanyl.

Adverse effects of opioids differ from drug to drug

  • 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 requiring opioids?

Published in Pharmacy Today February 2012


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