BNF Prescribing in Palliative Care

Types of patient (pharmacological context)

1. Opiate naive

2. Pain inadequately controlled on step two of the WHO pain ladder

WHO Pain Ladder

• 1st step: Paracetamol/NSAIDs

• 2nd step: Mild opioids e.g. Codeine or dihydrocodeine 30mg-60mg every four to six hours
  Tramadol dose: 50mg-100mg four to six hourly, maximum dose 400mg per 24 hours

• 3rd step: Strong opioid e.g. morphine

Basic Principles

Initiating treatment

starting dose for opioid-naïve patients: 20–30 mg morphine daily in divided doses
starting dose for patients being switched from a regular weak opioid: 40–60 mg morphine daily in divided doses

Regular immediate-release 4-hourly opioid PLUS rescue dose
5mg immediate-release morphine (4-hourly) —> 30mg immediate-release morphine (4-hourly)
5mg immediate-release oxycodone (4-hourly)

Once pain is controlled by 4-hourly immediate-release morphine, transfer to same total 24-hour dose using modified-release preparation for 12-hourly (or 24-hourly) administration.

Regular modified-release 12-hourly opioid PLUS rescue dose
10mg to 15mg modified-release morphine BD (12-hourly) —> 100mg modified-release morphine BD (12-hourly)
10mg modified-release oxycodone BD (12 hourly)

Rescue dose immediate-release opioid for breakthrough pain
5mg immediate-release morphine (every 2-4 hours)
5mg immediate-release oxycodone (every 2-4 hours)
The standard oral dose of a strong opioid for breakthrough pain is usually one-sixth (1/6) of the regular 24-hour dose

Review pain management if rescue analgesic is required frequently (twice daily or more)

Equivalent doses of opioid analgesics

Assume we wish to provide analgesia that equates to 10mg oral morphine:

Oral route of administration (reference 10mg oral morphine)
10mg Morphine
100mg Tramadol
6.6mg Oxycodone (oral oxycodone dose = 2/3 x oral morphine dose)
100mg Codeine
100mg Dihydrocodeine

Parenteral route of administration (reference 10mg oral morphine)
5mg Morphine IM, IV, SC
3mg Diamorphine IM, IV, SC
5mg Oxycodone SC

Optimise treatment of side effects before changing opioids

Managing opioid side-effects

1. Arrhythmias palpitations

2. Confusion, drowsiness, dizziness, euphoric mood; flushing; hallucination; headache, nausea, vomiting

3. Constipation

   first-line
   a faecal softener with a peristaltic stimulant (e.g. co-danthramer) or lactulose solution with a senna preparation should be used.

   second-line
   Peripherally acting opioid-receptor antagonists: blocks the gastro-intestinal (constipating) effects of opioids without altering their central analgesic effects

   Methylnaltrexone bromide (s.c injection)
   Naloxegol (Moventig®) (oral tablet)

4. Dry mouth

5. Paralytic ileus: vomiting, constipation, very little/absent abdominal pain, abdominal distension, no abdominal tenderness, bowel sounds absent

6. Hyperhidrosis

7. Hypotension

8. Miosis

9. Respiratory depression

10. Skin reactions

11. Urinary retention

12. Visual impairment

13. Withdrawal syndrome

Transdermal route

Do not routinely offer a transdermal patch as treatment if oral opioids are suitable

If oral opioids are unsuitable consider transdermal patches

1. Transdermal preparations of fentanyl (72-hourly) and buprenorphine (72-hourly, 4-day and 7-day patches) are available

2. Transdermal route is not suitable for acute pain or in patients whose analgesic requirements are changing rapidly changing

3. Immediate-release morphine can be given for breakthrough pain

buprenorphine ‘20’ [20 mcg/hr] equates to 48mg daily oral morphine
fentanyl ‘25’ patch [25 mcg/hr] equates to 60mg daily oral morphine

Additional notes

Diamorphine hydrochloride causes less nausea and hypotension than morphine.
In palliative care the greater solubility of diamorphine hydrochloride allows effective doses to be injected in smaller volumes

Tramadol hydrochloride produces analgesia by an opioid effect and enhancement of serotonergic/adrenergic pathways.
It has fewer of the typical opioid side-effects (notably, less respiratory depression, less constipation and less addiction potential); psychiatric and seizure reactions have been reported.
The effects of tramadol are only partially reversed by naloxone hydrochloride.

Buprenorphine has both opioid agonist and antagonist properties and may precipitate withdrawal symptoms, including pain, in patients dependent on other opioids.
It has abuse potential and may itself cause dependence.
It has a much longer duration of action than morphine and sublingually is an effective analgesic for 6 to 8 hours.
The effects of buprenorphine are only partially reversed by naloxone hydrochloride.

Renal impairment
Remifentanil, fentanyl, alfentanil are less likely to cause toxicity in patients with renal failure.
Oxycodone can be used in renal impairment provided the eGFR>10 mL/minute/1.73 m2
Most other opiates (morphine, diamorphine, buprenorphine, fentanyl, tramadol) are dependent on renal excretion, hence their doses will need to be reduced and titrated carefully.