1. Key points
This presentation is in line with the goals of the Fundamentals programme – complex symptom management and prescribing has not been addressed – consider a masterclass for this.
We acknowledge there may be local variance in prescribing, so make sure you follow and share local guidelines and practice.
Specifically refer to the New Zealand Palliative Care Handbook (8th Edition).
See final slide for a list of resources that support this presentation.
Check the repository.
Note:
Many medications (~25% from UK data) used in palliative care are used outside their normal approved use.

2. Simple analgesics Paracetamol regularly Codeine phosphate NSAIDS
- Diclofenac and naproxen – common examples
- Not well tolerated in the older person so must be used with caution

3. Morphine Mu-opioid receptor agonist Active metabolites
Renally excreted – therefore, not for use in renal impairment
Subcutaneous morphine
- approximately twice as potent as oral morphine
- i.e. 20 mg oral = 10 mg subcut
Codeine 60 mg = 5-8 mg morphine i.e. 60 mg codeine QID = approx. 5 mg Q4H

4. Methods of morphine administration
Normal Release
- Morphine elixir
4 strengths available – be careful to check before administration
- Sevredol™ (10 mg & 20 mg tablets only)
Controlled release morphine
- Note: NOT to be crushed
- m-Eslon™ (10 mg, 30 mg, 60 mg,100 mg) can be sprinkled
- Arrow-Morphine LA tablets (10 mg, 30 mg, 60 mg, 100 mg)
Intraspinal – Step 4 on WHO Ladder

5. Oxycodone Mu- and kappa- opioid receptor agonist (semi-synthetic)
Renally excreted
- 19% unchanged, 50% oxymorphone
Onset action: 20-30min orally
? Less active metabolites than morphine
Notes:
Side effects as per morphine ? less vomiting (anecdotally).
Use if there is mild-moderate renal impairment although dose reduction should be considered.

6. OxyNormTM and Oxycodone CR
In palliative care, OxyNormTM is generally considered to be twice as potent as morphine when taken orally
Subcutaneous oxycodone
approximately twice as potent as oral oxycodone
i.e. 20 mg oral = 10 mg subcut
All preparations are funded
cost not excessive
useful alternative to morphine when morphine not tolerated or in presence of mild to moderate renal impairment

7. OxyNormTM and Oxycodone CR contd
Normal release:
OxyNormTM capsules (5 mg, 10 mg, 20 mg)
OxyNormTM oral liquid (5 mg/5 mL)
Can be used for titration and breakthrough pain (1/5th – 1/10th of the 24hr dose)
Controlled release:
Oxycodone CR tablets (5 mg, 10 mg, 20 mg, 40 mg, 80 mg) have a biphasic response - therefore, no need to give immediate release at the same time as slow release dose

8. Methadone Indications: - Morphine toxicity / unacceptable side effects
- Inadequate pain relief with other opioids
- Renal failure
- Neuropathic pain
- Previous narcotic dependence – on maintenance methadone
Routes: oral or subcut
5 mg tablet
3 strengths of elixir available – 2 mg, 5 mg and 10 mg per mL - check carefully before administration

9. Methadone contd Less nausea, constipation and drowsiness than morphine
t ½ or half life – 8-75hrs
Difficult medication to use – needs medical specialist input

10. Transdermal Fentanyl Indications
- When the oral route is unavailable e.g. dysphagia or severe
nausea and/or vomiting
- Renal failure
- Social (convenience)
- Morphine “phobia”
- Side effect profile, e.g. less constipation and sedation
Pain unresponsive to morphine is unlikely to be responsive to fentanyl, due to also being a mu-opioid receptor agonist
Need to titrate with short acting morphine or oxycodone before starting patch - see example on next slide
Notes:
Point out risk of serotonin toxicity as a result of interaction between Fentanyl and SSRIs.
Don’t forget to mention need for breakthrough/prn medication.

11. Transdermal Fentanyl contd
Example of dose comparison when titrating:
A 12.5 microgram/hour patch is (approx.)
equivalent to 30 mg morphine in a 24hr period

12. Transdermal Fentanyl contd
t ½ or half life hrs
Steady state plasma concentrations after 36-48hrs
Onset of action 12hrs
Duration of action 72hrs
Contraindication – uncontrolled pain requiring rapid dose titration
Patches are 12.5, 25, 50, 75 and 100 mcg/hour – not daily
The depot of drug in skin will continue to provide some analgesia for approx.17hrs after a patch is removed

13. Co-analgesics Antidepressants e.g. nortriptyline
Anticonvulsants e.g. sodium valproate, gabapentin, clonazepam
Non steroidal anti-inflammatories e.g. diclofenac, naproxen
Steroids e.g. dexamethasone
Anti-spasmodics e.g hyoscine butylbromide (Buscopan)

14. Antiemetics Metoclopramide - Dopamine receptor antagonist
- Increases peristalsis in upper gut
- Contraindicated in complete bowel obstruction and those with Parkinson’s
disease
- Watch for agitation and akathisia in higher doses, with chronic use, and
with presence of renal disease
- Oral or subcut
Domperidone
- Similar to metoclopramide but less extrapyramidal effects
- Drug of choice in older person
- Oral route
Reference regarding metoclopramide caution – agitation/akathisia/tardive dyskinesia
Currow, D. C. et al. (2012). Pharmacovigilance in hospice/palliative care: Rapid report of net clinical effect of Metoclopramide. Journal of Palliative Medicine, 15 (10),

15. Antiemetics Haloperidol
Dopamine receptor antagonist, hence not for use in Parkinson’s disease
Potent centrally acting antiemetic – very useful for opioid induced nausea, hypercalcaemia and renal failure
Can be given subcutaneously
Note and reference:
Often used to treat delirium due to its ability to be given subcut and to treat multiple symptoms, however, need to be aware that recent studies have recommended against its use for delirium. See reference below:
Agar, M.R., et al. (2017). Efficacy of oral risperidone, haloperidol or placebo for symptoms of delirium amongst patients in palliative care: A randomised clinical trial. JAMA Intern Med. 177 (1), 34-42

16. Antiemetics Cyclizine
Oral and subcut routes available - although subcut can be painful
Antihistamine, antimuscarinic
Indicated for motion sickness, mechanical bowel obstruction, raised intracranial pressure
Drowsiness can be profound
Can cause confusion in elderly so best to dose reduce
Note:
Choice of first or second line anti-emetic is often the choice /preference of the doctor prescribing.

17. Antiemetics Dexamethasone Centrally acting antiemetic
Especially useful in liver metastases, raised intracranial pressure, and to reduce vomiting in bowel obstruction
Added to first line antiemetics in palliative care
Watch for signs of confusion in the older person
Can cause insomnia – given in the morning to reduce this effect
Can be given subcut - need to watch for volume if given as bolus dose – may need to be divided
Notes:
Need to consider and plan for reduction and stopping over time.
There are other indications for Dexamethasone, including:
appetite stimulant
Anti-inflammatory properties (adjuvant pain relief)
Relief of symptoms in spinal cord compression and superior vena cava obstruction
site protector for subcut line.

18. Antiemetics Levomepromazine
Low potency anti-psychotic, blocks a number of differing receptors including dopamine, histamine, adrenergic and serotonin
Offers analgesic, antipsychotic, hypnotic and anti-emetic properties in palliative care
Most commonly used for intractable nausea and vomiting and severe agitation or delirium in last days of life
Side effect – akathisia and significant sedation
Note:
Choice of anti-emetic is often the choice/preference of the physician.

19. Midazolam
Commonly used for agitation and anxiety associated with dyspnoea
Short acting benzodiazepine
It is more quickly eliminated from the body compared with clonazepam.
Preferred routes in palliative care are subcut, intranasal and buccal

20. Laxatives Start laxatives when starting opioids Laxsol™
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Laxatives
Start laxatives when starting opioids
Laxsol™
- daily or twice daily
- up to 3 tablets TDS sometimes necessary
- docusate softens and senna stimulates
If not effective, add in Lax-Sachets™ as an osmotic – needs to be introduced early (note: requires special authority funding)
Kiwi crush will not normally control opioid induced constipation

21. Suppositories and enemas
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Suppositories and enemas
These will not often be required if a good bowel regime has been started
- use glycerine suppositories to soften and bisacodyl
suppository to stimulate
- or use sodium citrate/sodium lauryl sulfoacetate/glycerol
(MicrolaxTM enema) – use with caution
- or if these are not effective, try an oil retention enema
- or use a Fleet™ enema with care
Reference:
Larkin, P. et al. (2008). The management of constipation in palliative care: clinical practice recommendations. Palliative Medicine, 22 (7),
Link:
Philip Larkin’s palliative care lecture in May 2017
“Palliative approaches to the management of constipation – evidence and clinical implications for practice”.
Available on the HNZ website:

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Precautions
Stimulants are contraindicated for people with complete bowel obstruction
Bulking agents and high fibre diets are poorly tolerated in the palliative person
Lactulose is an osmotic laxative which is poorly tolerated in people who are unable to maintain a high fluid intake

23. Reassess, reassess, reassess
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Remember to ask
Why are you using the medication?
What is the most appropriate route?
Can we reduce the burden of taking lots of tablets?
Are there any contraindications?
Have you considered non-pharmacological interventions?
Reassess, reassess, reassess

24. Useful resources and references
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Useful resources and references
New Zealand Palliative Care Handbook. (8th Edition). (2016) - care-handbook
New Zealand Formulary -
Palliative Care Drugs -
Medsafe -
The local hospice or community pharmacist
Local DHB prescribing guidelines e.g. local hospice or specialist hospital team