Waikato DHB Palliative Care Guidelines

1. Management of persistent pain in the palliative setting

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This is a fundamental aspect of caring for palliative patients. Pain may be a patient’s greatest fear and adequate pain relief is essential for their comfort and dignity.

Several principles should be followed closely:

the characteristics and cause of each pain should be established (there is often more than one type of pain)
pain is most often due to tumour involvement but also can be related to its treatment (e.g. mucositis), to complications of general illness and debility (e.g. constipation, pressure areas, etc) and can also be completely unrelated to the cancer (e.g. arthritis, IHD, etc)
analgesics should be charted and given regularly
adequacy of pain relief and development of side effects should be monitored regularly
patients must be reviewed carefully for concurrent problems if analgesic requirements increase
oral regimens are the most acceptable and convenient
when using opioids, simple analgesics such as paracetamol should be continued and co–analgesics may also be necessary
the concept of ‘total pain’ is used widely in palliative care and acknowledges that cancer pain is caused by and influenced by many issues. Physical pain is only one component – attention must be given to psychological problems, social problems, intellectual, spiritual and cultural issues and other concurrent physical symptoms.

1.1 Mild to moderate pain

1.1.1 Paracetamol

500 – 1000mg PO qid (Maximum dose 4g/ 24 hours).

Paracetamol is safe to use if patient has liver metastases but the dose should be reduced in hepatic failure.

1.1.2 Codeine Phosphate

Note: Codeine is rarely indicated for pain management in palliative care.

15 – 60mg PO 4-6 hourly (Maximum dose 240mg/ 24hours).

1.1.3 Dihydrocodeine (DHC Continus™ )

Note: DHC Continus™ is rarely indicated for pain management in palliative care.

60-120mg bd. Anticipate and warn about constipation.

Morphine is the most commonly used as first line opioid. Codeine and Dihydrocodeine are only temporary strategies for analgesia given the limited potency, dosing limitations and the high incidence of side effects.

Codeine phosphate is about one tenth as potent as morphine i.e. 60mg codeine 6mg morphine.

10% of the caucasian population do not metabolise codeine phosphate to its active form which is morphine.

If the patient is taking selective serotonin re-uptake inhibitors (SSRI’s) concurrently, codeine phosphate may be ineffective.

1.1.4 Tramadol

Not recommended routinely for reasons of efficacy and side effects and has a significant part-charge for the patient.

The dose is 50-100mg, 4 hourly PO/IV/IM.

A slow release preparation is now available with 50mg, 100mg, 150mg and 200mg tabs for bd dosing. 50mg PO Tramadol ≅. 10mg PO Morphine.

It has high bio-availability so that the potency of IV and PO is roughly equivalent.

By injection, Tramadol is one tenth as potent as Morphine.

Tramadol is part opioid but it also inhibits the uptake of noradrenaline and serotonin – it is thought to act like a tricyclic antidepressant in neuropathic pain and the dual mode of action is probably synergistic.

The major side effect is NAUSEA but it is less sedating and less constipating than Codeine or Morphine – PRN laxatives must still be charted.

It must NOT be used concurrently with SSRIs e.g. Fluoxetine due to risk of serotonin syndrome and Monoamine Oxidase Inhibitors (MAOI) must be stopped 14 days before commencing Tramadol.

Not recommended in patients with epilepsy.

1.1.5 Non steroidal anti-inflammatory drugs (NSAIDs)

These are all ulcerogenic in the gastro-intestinal tract (even if given rectally or topically) – especially Aspirin and may precipitate acute renal failure.

All NSAIDS should be used with caution in palliative care.

A second NSAID from a different subclass (excluding Aspirin) may be effective if the first choice has failed – Naproxen and Diclofenac are from different subclasses.

The ulcerogenic potential of NSAIDs may be increased by concurrent use of corticosteroids – this combination is best avoided, particularly in the elderly.

If corticosteroids must be combined with an NSAID or there is a past history of peptic ulceration, proton pump inhibitors (e.g. Omeprazole or Pantoprazole) reduce the risk of duodenal and gastric ulceration. Misoprostol has been shown to reduce the incidence of gastric ulceration.

Diclofenac SR 75mg bd or 100mg daily PO/PR and Naproxen 250-500mg PO bd. are examples of commonly used NSAIDS.

Tenoxicam (Tilcotil™) can be used via subcut injection, 20mg daily – it has a long half-life and can be given once daily.

1.1.6 Digesic™ and Paradex™ (Dextropropoxyphene + Paracetamol)

These are generally not recommended. They are no more effective than the standard therapy and are known to be dangerous in overdose.

1.1.7 Nefopam Hydrochloride (Acupan™)

This drug has a high incidence of side effects including hallucinations and confusion and is not recommended

1.2 Opioid therapy for severe pain

Opioids may be required initially for severe pain or when milder analgesics have failed.
Morphine is the drug of choice – Panadeine/ Codeine/ Tramadol should be discontinued but Paracetamol +/- NSAID should be continued.
Morphine is available in two formulations – normal release (Morphine Elixir or Sevredol™) for dose titration and breakthrough pain and controlled release (m-Eslon™ or LA Morph™) for maintenance treatment.
Methadone, Oxycodone and Transdermal Fentanyl (Durogesic™) are alternative strong opioids that are available for use in palliative patients under specific circumstances. Further information on these drugs is found later in this chapter.
The funding status of these long acting preparations may alter and patients should be prescribed the one which is fully funded if possible. Check with a pharmacist if unsure.

1.2.1 Anticipate and warn against side effects

Opioids may cause drowsiness / sedation, urinary retention, confusion and rashes but the commonest side effects are constipation and nausea.
Warn against side effect of drowsiness – this generally diminishes over a few days.
If there is a past history of nausea and vomiting or if the patient is concerned about their symptoms, anti-emetics should be charted regularly – nausea usually subsides after 3-4 days and often the antiemetic can be discontinued.

Nausea and Vomiting
Avoid Ondansetron
Chart regular laxatives (softener AND stimulant) e.g.Laxsol™ - If ineffective, Movicol™ 2 sachets nocte. (caution: a special authority number is required for Movicol™ .)
Lactulose is usually not well tolerated.
Patients should be cautioned about driving during dose stabilisation especially if drowsy. Patients on stable doses are normally safe to drive.
Drug addiction is NOT a concern in acute, severe pain or in those with chronic /persistent cancer pain – patients who improve after anticancer treatment are often able to stop or reduce their Morphine.

Information regarding titration of Morphine follows.

Note: Please read ALL of this section prior to prescribing.

1.3 Morphine

1.3.1 Immediate release Morphine

The secret of opioid prescription is regular review. The starting dose of morphine can be small and titrated upwards rapidly. A reasonable starting dose is 5mg every 4 hours but in acute situations the initial dose can be repeated every hour for three more doses, then reviewed. Consider contacting the palliative care team for advice.

Morphine Elixir: varying concentrations 1mg/ml, 2mg/ml, 5mg/ml, 10mg/ml.
Sevredol™ (10mg and 20mg tabs only) is a useful alternative if the taste of Morphine Elixir prevents usage.
During dose titration, assess how effective each dose is and for how long analgesia lasts.
The elderly and those with renal impairment require CAUTION during dose titration, as Morphine metabolites will accumulate – 6-8hourly dosing may be necessary and dose increases must be made more slowly to avoid developing narcosis or confusion. In patients with renal impairment other analgesics should be considered.
If toxicity develops e.g. excessive sedation, delay the next dose and reduce the amount by 25-50% – do not stop and avoid Naloxone if possible.
Once analgesia is achieved, change to a controlled release preparation (total 24 hour dose divided by 2 e.g. 120mg Morphine over 24 = 60mg m-Eslon™ bd) with an appropriate dose of rapid release Morphine for breakthrough pain. When on controlled release Morphine, breakthrough dose of Morphine Elixir or Sevredol™ should be approximately 20% of the total daily dose. This can be repeated every hour for three more doses, then needs to be reviewed.
When using Morphine Elixir avoid volumes > 10ml if possible (increase strength instead).

1.3.2 Slow release Morphine Sulphate

M-Eslon™ long acting capsules

Available in the following strengths, 10mg, 30mg, 60mg, 100mg, 200mg.
Give 12 hourly PO. (This can be used 8 hourly if required.)
Capsules can be swallowed whole or the contents sprinkled on food. Do not chew/crush.
DO NOT use rectally.
Not useful for acute pain because of slow onset of action and should not be used for dose titration.

LA Morph™ long acting tablets
Available in the following strengths, 10mg, 30mg, 60mg, 100mg.

Give 12 hourly PO. (This can be used 8 hourly if required.)
Do not chew/crush.
DO NOT use rectally.
Not useful for acute pain because of slow onset of action and should not be used for dose titration.

1.3.3 Subcutaneous Morphine

Note: Subcutaneous Morphine is approximately twice as potent as oral.

For acute pain a subcut injection can be given.

Subcut Morphine injections are more comfortable and acceptable than intramuscular.

If a patient is intolerant of oral Morphine, titration is best achieved with regular 4hourly subcut Morphine.
The method of dose titration is identical to that outlined in the section on Morphine Elixir.
An adequate dose will usually last for 4 hours (like Morphine Elixir).
If analgesia is achieved on 15mg 4hourly of subcut Morphine (i.e. 90mg/24hours) this is equivalent to 180mg oral Morphine/24hours – the reverse must be taken into account when converting from oral to subcut Morphine.
Subcut Morphine is the route of choice in severe pain.

1.3.4 Subcutaneous Morphine infusions

It is necessary to estimate the expected 24 hour dose of Morphine at the time of prescription when using an infusion – this is easiest and safest if the patient has previously been on oral Morphine or has been titrated on subcut Morphine.
Boluses of subcut Morphine are often more effective for acute severe pain than commencing an infusion– aim to change to an infusion as soon as the appropriate Morphine dose is known.
Infusions can be delivered via a battery operated syringe driver e.g. Graseby Pump (small size, portable, fixed rate of delivery).
Subcut bolus or oral Morphine must always be available for breakthrough pain.
If regular breakthrough doses are needed the infusion dose should be reviewed.
Seek advice from Palliative Care Physicians if unfamiliar with subcutaneous infusions or complex prescribing required.

1.3.5 IV Morphine Infusions

These are rarely indicated.
1IV Morphine is approximately 3 times more potent than oral – patients must be monitored closely on IV infusions.
When charting an infusion you must ensure that additional bolus doses are available for breakthrough pain.

1.3.6 Intraspinal Morphine (Epidural /Intrathecal)

This intervention is performed and co-ordinated by the Pain Service in consultation with the Palliative Care Service.

Morphine is often combined with a local anaesthetic +/- clonidine.

1.4 Other opioids

1.4.1 Methadone

This drug has a place in pain management in specific circumstances. Methadone is difficult to use due to its long and variable half-life and a referral to or discussion with the Palliative Care Service is strongly recommended.

Indications for use:

renal impairment
Morphine allergy (rare)
unacceptable side effects with Morphine
evidence of Morphine tolerance
pain management in patients already on Methadone for drug addiction.

See Methadone Guidelines

1.4.2 Fentanyl

This drug is available in New Zealand on special authority for stable pain in patients with ‘terminal illness’ in the transdermal form Durogesic™ patches). IV or subcut fentanyl may occasionally be used under supervision of the Acute Pain Team or Palliative Care Team. See Pharmac website or check with the hospital pharmacist (relevant specialist only).

If considering using fentanyl, a Palliative Care referral is required.

Indications for use include;

renal impairment
uncontrolled nausea/vomiting or inability to swallow
unacceptable side effects with Morphine
evidence of Morphine tolerance.

1.4.3 Oxycodone

This is available in four formulations: immediate release capsules (Oxynorm™), controlled release
tablets (Oxycontin™), Oxynorm™ Liquid and Oxynorm™ injection

Oxynorm™ Liquid is available in 5mg/5ml

Oxynorm™ (capsule) is available in the following strengths: 5mg, 10mg, 20mg

Oxycontin™ (tablet) is available in the following strengths: 5mg, 10mg, 20mg, 40mg, 80mg and is taken 12 hourly.

Oxycodone injection is available in 10mg/ml strength in either 1ml or 2ml ampoules and is between 1.5 and 2.0 times more potent than oral. 10mg oral oxycodone = 5 - 7.5mg subcut oxycodone

The dose should be titrated in the same way as Morphine.

Usual starting dose is 2.5 - 5mg 6hourly (Oxynorm™).

It should be used with caution in renal impairment.

Oxycodone is similar to morphine in its action and has a similar side effect profile.

Note: When taken orally, Oxycodone is more potent than morphine i.e. 20mg oral morphine = 10mg oral oxycodone

Oxycodone capsules MUST be swallowed whole and are not to be broken, chewed or crushed.

Not to be given rectally.

The main indications for use at present are:

Morphine allergy (rare).

Persistent hallucinations or other signs of morphine neurotoxicity

Evidence of Morphine tolerance.

This drug is considerably more expensive than morphine. Morphine therefore remains the drug of first choice.

1.4.4 Pethidine

Pethidine has a therapeutic ceiling related to CNS toxicity (e.g. agitation, tremors, myoclonus and seizures) and SHOULD NOT be used in chronic cancer-related pain.

1.4.5 Rarely-used Opioids

Pentazocine, and Buprenorphine (Temgesic™) are inferior to Morphine and should NOT be used.

Hydromorphone is not available in New Zealand.

1.5 Prescribing of opioids

Prescriptions for Morphine SR, Morphine Elixir, Sevredol and other opioids must be in triplicate on the Ministry of Health CONTROLLED DRUG PRESCRIPTION FORM (H572).
They must be written legibly and indelibly in the practitioner’s own handwriting. (DO NOT use hospital stickers)
They must be dated and include the full physical address (e.g. PO Box not acceptable).
The maximum supply available is 10 days with 2 repeats. (30 days).
Elixirs can be prescribed in varying strengths (e.g.1mg/ml, 5mg/ml etc). NB You must document the strength used.
The strength, dose and frequencies must be stated (PRN is inadequate).
The total quantity requested and the dose prescribed must be written in words and numbers.

Sample Script

Information last reviewed: June 2009	Please foward any enquiries about this document to haggars@waikatodhb.govt.nz
Next review date: July 2010	For Palliative Care advice, please call 8691 or the specialist on-call.

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