STEP 3: Strong Opioids

First line:  Morphine remains the drug of choice

1. Gain control of pain

  • ‘Immediate’ release morphine (oral solution or tablets) gives greatest flexibility for dose titration
  • Starting dose 2.5mg–10mg four-hourly. In the opioid naïve, elderly or those with renal impairment use smaller doses e.g. 2.5mg four-hourly, with close monitoring
  • Additional PRN doses at the same starting dose may be prescribed up to hourly
  • Review the total daily dose of morphine every 24 hours. Titrate the dose to achieve pain relief by increasing in 30–50% increments per day

In patients with less severe pain, or where circumstances dictate, morphine may be initiated as a modified release preparation at the appropriate dose.

Use conversion table later in this section to determine the appropriate starting dose.

2. Reassess pain regularly

A ‘log’ of treatment kept by patients and carers is helpful in titration.

There is no ‘maximum’ dose if pain is morphine responsive.

Specialist palliative care advice should be sought in the following circumstances:

  • Rapidly escalating dose of morphine
  • Morphine exceeds 300mg po in 24 hours

If the patient develops adverse effects e.g. opioid toxicity (signs are respiratory depression, increasing drowsiness, confusion, myoclonic jerks and hallucination).

Benzodiazepines and opioids: reminder of risk of potentially fatal respiratory depression.
Search for benzodiazepines on:
Gabapentin (Neurontin): risk of severe respiratory depression.
Search for gabapentin on:
Pregabalin (Lyrica): reports of severe respiratory depression.
Search for pregabalin on:

  • If an alternative opioid is being considered because of toxicity

Always prescribe a laxative when initiating opioid and continue to review bowel habit.

3. Maintenance

Once pain is controlled there is a choice of options for maintenance:

  • Continue regular immediate release morphine


  • Change to 12 hourly modified release morphine

To change from immediate release morphine to modified release morphine,  add up the amount of morphine used in 24h and divide
the 24h total dose of morphine by 2.

E.g. patient on 10mg immediate release morphine 6 times in 24 hours:
Total daily dose = 60mg/24h.

Therefore morphine sulfate modified release would be: 60÷2= 30mg 12 hourly.

  • Patients on modified release opioids should always have available immediate release opioid prescribed PRN for episodes of breakthrough pain
  • The recommended dose of immediate release opioid (usually morphine) prescribed PRN for breakthrough pain is the equivalent of up to 1/6th of the total 24-hour opioid dose

For example:

A patient taking morphine sulfate MR 30mg BD, the breakthrough dose of morphine sulfate IR is:

  • 30mg + 30mg = 60mg
  • 60mg ÷ 6 = 10mg

Therefore the breakthrough pain dose of morphine sulfate immediate release is 10mg PRN.

  • If the regular dose of opioid is increased, ensure that the PRN breakthrough dose is increased appropriately so that it remains 1/6th of the total daily dose of regular opioid
  • Incident pain (e.g. exacerbations of pain on movement) may require faster acting analgesia
  • Ensure patients and their carers understand the use of the opioids they are taking and that doses are reviewed regularly

A patient should never be prescribed more than one modified release opioid at a time.

4. If further pain develops

Reassess cause of pain and treat appropriately (see Pain Assessment).

If there is consistent need for frequent breakthrough analgesia, and the pain is opioid sensitive, increase the total daily opioid dose by 30–50% and reassess.

If the proposed dose increase is greater than 30–50% seek advice from specialist palliative care.

5. Incident pain

First line choice of analgesia for predictable breakthrough pain related to particular event e.g. pain related to movement with a pathological fracture where there is no fixation option, should be an immediate release opioid used in anticipation of the pain, usually the same opioid as that they have prescribed as a modified release preparation. Immediate release preparations are available as described previously.

They should be used in advance of the expected pain and it maybe that increasing the background analgesia may not improve pain control. Seek specialist palliative care advice if needed.

Use the links below for more steps:

Step 1:

Step 2:

Step 3:


This Guide is intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.

Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.

While WMPCPS takes every care to compile accurate information , we cannot guarantee its correctness and completeness and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.