Previous changes

March 2023 — minor update. Hypertonia added as a symptom of withdrawal, and undesirable effects added in line with manufacturers updated SPC for baclofen.

March 2021 — reviewed. Literature searches were conducted in February 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic.

September 2020 — minor update. Stable analgesic requirements were updated to highlight that fentanyl patches and buprenorphine patches are contraindicated in opioid-naive patients.

July 2015 to October 2016 — reviewed. Literature searches were conducted in September 2016 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. There have been structural changes to the topic and changes to the recommendations have been updated in line with NICE guidance Care of dying adults in the last days of life [NICE, 2015a]. 

April 2015 — minor update. Update to the text to reflect a new law on drugs and impaired driving.

July 2014 — two minor updates:

• Update to the text to include advice from the MHRA regarding the safe use and disposal of fentanyl patches following reports of accidental exposures that have led to life-threatening adverse effects.
• Update to the text on the use of metoclopramide in palliative care. Although the European Medicines Agency has restricted the use of metoclopramide this does not apply to unlicensed uses of metoclopramide (for example palliative care).

June 2014 — minor update. Update to the text to reflect the fact that tramadol has been reclassified to a Schedule 3 controlled drug.

January 2014 — minor update. Update to the text to correct a minor typographical error.

July 2013 — minor update. Update to the text to reflect advice from the MHRA regarding diclofenac.

June 2013 — reviewed. A literature search was conducted in May 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. There are no major changes to the recommendations.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic. Issued in April 2012.

July 2011 — minor update. Text updated to include information on novel fentanyl products for breakthrough pain based on recommendations from the North East Treatment Advisory Group. Issued in September 2011.

May 2011 — minor update. The 2011/2012 QOF indicators have been added to this topic. Issued in June 2011.

February 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

September 2010 — minor update. The choice of drug treatment for neuropathic pain has been updated in line with the NICE clinical guideline, Neuropathic pain. The pharmacological management of neuropathic pain in adults in non-specialist settings. Issued in September 2010.

June 2010 to July 2010 — minor update. The advice on the management of breakthrough pain for people taking oral morphine has been updated. Issued in July 2010.

December 2008 to March 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There have been no major changes to the recommendations.

September 2008 — minor update to include advice from the Medicines and Healthcare products Regulatory Agency (MHRA) regarding the safety of fentanyl patches. Issued in September 2008.

June 2007 — minor update. Gabapentin is now licensed up to a maximum dose of 3600 mg per day for the treatment of peripheral neuropathic pain. Issued in June 2007.

January 2006 — minor update. Prescriptions for diamorphine updated to reflect the change in handwriting requirements for controlled drug prescriptions. Issued in February 2006.

October 2005 — minor technical update. Issued in November 2005.

April 2005 — minor update to include new advice from the Committee on Safety of Medicines (CSM) on the safety of COX-2 selective inhibitors. Issued in April 2005.

January 2004 — written. Validated in December 2004 and issued in February 2005.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 March 2021.

HTAs (Health Technology Assessments)

No new HTAs since 1 March 2021.

Economic appraisals

No new economic appraisals relevant to England since 1 March 2021.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 March 2021.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 March 2021.

New policies

No new national policies or guidelines since 1 March 2021.

New safety alerts

No new safety alerts since 1 March 2021.

Changes in product availability

• Actimorph is licensed for treatment of severe pain only adequately managed with opioids. Tablet disperses rapidly in mouth and then swallowed. Alternatively, tablet may be placed in a spoon with addition of small quantity of water until sufficient dispersion to allow ingestion. See more here.

How should I approach pain assessment?

• Discuss pain with the person directly if possible. The person, if competent and able to communicate, is the most reliable source of information about their pain. If it is not possible to ask them (because of cognitive impairment or communication deficits, for example), the family or healthcare professionals may be able to help with the assessment, bearing in mind that family members may overestimate and healthcare professionals underestimate the person's pain.
• Assess each pain a person has with a view to establishing an underlying cause, bearing in mind that there may be more than one cause and more than one pain. Seek specialist advice if assessment is difficult because of complex or multiple pains.
• Assess pain regularly, particularly if it is not adequately controlled.
• Review the medical history and medical records to determine the known site and extent of the cancer. Pain occurring distant from the previously known sites of cancer may indicate either a non-malignant cause or secondary spread of the cancer.
• Assess the influence of psychological, social, and spiritual factors on the person's experience of pain.

How should I assess pain severity?

• Use a validated structured pain assessment tool, for example:
  • Numerical rating scale — mark on a scale of 0 (no pain) to 10 (worst possible pain) how strong the pain is.
  • Visual analogue scale — mark on a 10-cm line (with 'no pain' at one end and 'worst possible pain' at the other end) how strong the pain is.
  • The score can be correlated to the severity of the pain:
    • Mild pain: less than 3 out of 10 on a visual analogue scale or numerical rating scale.
    • Mild to moderate pain: 3–6 out of 10 on a visual analogue scale or numerical rating scale.
    • Severe pain: more than 6 out of 10 on a visual analogue scale or numerical rating scale.
• Differentiate between the person's usual level of pain, breakthrough pain, incident pain, and 'end of dose' failure of regular around-the-clock analgesia.
  • End of dose failure usually occurs at the same time each day, usually just before the next dose is due.

How should I assess the characteristics of the pain?

• Enquire about:
  • Site and number of pains.
  • Intensity/severity of pains.
  • Radiation.
  • Quality and type of pain. 
  • Timing (onset, duration, breakthrough, or incident pain).
  • Exacerbating and relieving factors.
  • Sensory disturbance.
  • Power/functional loss and effect on activities of daily living. 
  • Effect on sleep. 
  • Associated symptoms and signs.
  • The person's thoughts about the likely cause.
  • Presence of depression and/or anxiety.
  • Person's understanding and beliefs about the origin and progress of the pain. 
• Pain that presents insidiously and progressively worsens suggests a malignant cause for the pain.
• Acute onset of pain may be of a non-cancer related cause (for example pulmonary embolism, myocardial infarction, perforation of a viscus). Cancer-related causes include pathological fracture, bleeding into hepatic metastases, or spinal cord compression.
• The quality of the pain and exacerbating features can also suggest a cause.
• For more information on features of pain that may suggest a mechanism, see Table 3.

Table 3. Features suggesting a mechanism of the pain.

What elements of physical examination might assist in assessing palliative cancer pain?

• Examine the patient to try and determine the cause of pain, for example tender hepatomegaly or abnormal sensation.
• Look particularly for specific points of tenderness (which may indicate the site of origin of the pain) and signs of neurological deficit, which may suggest spinal cord compression.
• A full examination is rarely appropriate in people who are very unwell and in the last stages of life.

How should I investigate pain in palliative care?

• Consider investigations that are appropriate to the person's condition.
  • Limit investigations to those likely to significantly affect treatment decisions.
  • If the person is near the end of life, investigations are rarely indicated. They may be performed if a reversible condition may be the cause of their deterioration, or if the person has acute (potentially reversible) deterioration.
• If investigations are appropriate, ensure that the person's pain is adequately treated before they undergo diagnostic procedures. For more information on how to prescribe for incident pain (such as pain on movement), see Management of breakthrough pain.

How should I manage acute severe pain?

• Immediately relieve pain using a subcutaneous or slow intravenous dose of a strong opioid.
• The dose depends on the person's comorbidities and their existing analgesia:
  • If the person is opioid naive, consider a subcutaneous or slow intravenous dose of 5 mg of morphine (2.5 mg if the person is elderly or frail).
  • If the person is already taking a regular opioid, calculate the 4-hourly dose by taking the total dose given over the previous 24 hours (including doses required for breakthrough pain but excluding those for incident pain) and dividing it by six, and then give the equivalent subcutaneous dose of morphine:
    • The subcutaneous dose of morphine is approximately half of the 4-hourly oral morphine dose.
    • For more detailed information on converting oral morphine to a subcutaneous dose, see the conversion table in Switching from morphine to another strong opioid.
• Following this, seek immediate specialist palliative care advice regarding further management and try to determine the cause of the pain.
• Always take into account the person's circumstances and wishes:
  • If the person wishes to stay at home and is near the end of life, then control of symptoms should be attempted in this setting; if this is not possible, transfer to a hospice or hospital may be needed.

How should I treat persistent pain in a non-emergency situation?

• Prescribe analgesia for continuous pain on a regular basis, in addition to as-required analgesia.
• Consider a stepwise approach, using the World Health Organization analgesic ladder. Start at the appropriate point of the analgesic ladder, moving up the ladder when the maximum dose at each step is reached until the person is comfortable. The steps are:
  • Step 1: non-opioid analgesic such as paracetamol and/or nonsteroidal anti-inflammatory drug (mild pain).
  • Step 2: weak opioid such as codeine, dihydrocodeine, or tramadol (controlled drug), with or without a non-opioid analgesic (mild-to-moderate pain).
  • Step 3: strong opioid such as morphine, with or without a non-opioid analgesic (severe pain).
• Step 2 is not always necessary and can be omitted if this is considered clinically appropriate.
• At any stage, consider the addition of a non-opioid adjuvant drug (any drug that has a primary indication other than for pain management but is analgesic in some painful conditions: for example a tricyclic antidepressant for neuropathic pain).
• Review regularly (consider a telephone call if appropriate), step treatment up or down as necessary, and stop unnecessary medication that has not worked.

Which non-opioid drug should I prescribe?

• Paracetamol and/or a nonsteroidal anti-inflammatory drug (NSAID) are recommended first line.
  • Paracetamol 1 g 4 times daily or reduced to 500 mg 4 times daily if the person has a poor nutritional status or low body weight (less than 50 kg), hepatic impairment, chronic alcohol abuse, or may be on chemotherapy. 
• If an NSAID is appropriate and not contraindicated:
  • The oral route is preferred, but if this is not possible, consider alternative routes (such as rectal).
  • Consider prescribing a proton pump inhibitor with an NSAID. For more information on minimizing the risks associated with NSAID treatment, see the CKS topic on NSAIDs - prescribing issues.
• Non-opioid adjuvant drugs may also be useful for some people with specific pain types:
  • Scenario: Managing neuropathic pain.
  • Scenario: Managing intracranial pressure pain.
  • Scenario: Managing colic.
  • Scenario: Managing muscle spasm pain.
  • Scenario: Spinal cord compression.

Which weak opioid drug should I prescribe?

• Codeine, dihydrocodeine, or tramadol are recommended:
  • If flexibility of dosing and titration of analgesic effect are required, prescribe the weak opioid separately to paracetamol.
  • If compliance is likely to be a problem and analgesic requirements are stable, consider prescribing a product combining 500 mg of paracetamol with 30 mg of codeine.
• To prevent constipation, prescribe a stimulant laxative (such as senna or bisacodyl) and a softening laxative (such as docusate).
  • A laxative with both properties (for example co-danthramer or co-danthrusate) is also an option.
  • Avoid dantron-containing laxatives in people who are incontinent as these drugs can cause a chemical burn (reddening) of the perianal area.
  • Dantron can also colour the urine red, which can cause alarm to the person and carers. 
  • For further information on managing constipation see the CKS topic on Palliative Care - constipation. 

Which strong opioid drug should I prescribe?

Use the oral route of administration where possible.

• Initially offer oral sustained-release morphine or oral immediate-release morphine (depending on the person's preference) with rescue doses of oral immediate-release morphine for breakthrough pain.
  • For detailed advice on how to initiate morphine and titrate the dose, see Initiation of oral morphine and Titration of oral morphine.
  • Seek specialist advice if the person has moderate to severe renal or hepatic impairment.
• If the person's compliance with oral morphine is good, but pain is inadequately controlled:
  • Review the cause of the pain.
  • Consider seeking specialist advice and using a non-opioid adjuvant drug to treat a specific type of pain. For more information, see:
    • Scenario: Managing neuropathic pain.
    • Scenario: Managing intracranial pressure pain.
    • Scenario: Managing colic.
    • Scenario: Managing bone pain.
    • Scenario: Managing muscle spasm pain.
    • Scenario: Spinal cord compression.
• If compliance with oral morphine is good, but the person cannot tolerate an adequate dose, consider using an alternative oral opioid — seek specialist advice.
• If the oral route is not appropriate (such as the person has nausea and vomiting, cannot swallow, or has poor compliance with oral analgesia):
  • Unstable analgesic requirements — consider switching to a subcutaneous morphine infusion and seek specialist advice where needed. For more information, see Switching from morphine to another strong opioid.
  • Stable analgesic requirements — consider switching to a transdermal patch if the person has previously tolerated opioids. Seek specialist advice.
  • Note: buprenorphine patches and fentanyl patches are contraindicated in people who are opioid naive.
  • They are also contraindicated for acute pain and in severe uncontrolled pain requiring rapid dose titration, due to their long elimination half-life.
  • They also should be used with caution in people with cachexia as absorption may be unpredictable, so conversion charts may not accurately translate for these people.  
    • If fentanyl patches are prescribed, advise the person that accidental exposure to fentanyl can cause life-threatening harm. This can occur if the patch is swallowed or accidentally transferred to another person.
    • To reduce this risk, advise the person:
      • To choose the patch application site carefully.
      • To check the adhesion of the patch once applied, especially the edges.
      • To fold the used patch as soon as it is removed so that the adhesive side of the patch sticks firmly to itself, and dispose of the folded patch safely.
      • If a patch is accidentally transferred to another person, remove it immediately and seek medical advice.
      • If a patch is swallowed, seek medical help immediately.
• When prescribing a strong opioid:
  • Prescribe an anti-emetic such as metoclopramide for gastric stasis, otherwise low-dose haloperidol (nausea usually settles within the first week of treatment):
    • If the person has experienced nausea with opioids, give regularly for the first week to prevent opioid-induced nausea and vomiting and then reassess, or
    • If the person experiences nausea with morphine but has not experienced nausea with opioids, prescribe for use on an as-required basis for 1 week.
    • For more information on managing nausea see the CKS topic Palliative care - nausea and vomiting. 
  • To prevent constipation, prescribe a stimulant laxative such as senna or bisacodyl and a softening laxative such as docusate.
    • Constipation is common, usually persistent, and worse with increased doses of opioids. People who take strong opioids should always be prescribed a laxative.
    • A laxative with both properties (for example co-danthramer or co-danthrusate) is also an option.
    • Avoid dantron-containing laxatives in people who are incontinent as these drugs can cause a chemical burn (reddening) of the perianal area.
    • Dantron can also colour the urine red and alarm the person.
    • For more information on managing constipation see the CKS topic Palliative Care - constipation. 
• Seek specialist palliative care advice if:
  • There is doubt about how to manage a person's pain.
  • Adverse effects limit treatment and cannot be adequately managed.
  • An unfamiliar opioid or route of administration is being considered.
  • The pain is still at 50% or more of its starting level after 2 weeks.

How should I manage breakthrough pain?

• Give adequate instructions (written if possible) on how to control breakthrough pain. Inform other healthcare team members, including out-of-hours staff, as appropriate.
• The person should take breakthrough analgesia before the pain gets severe, as it may take 30–60 minutes for the analgesia to reach full effect.
• When deciding whether more than one breakthrough dose is needed, consider the time required for medication to take effect and its potential for adverse effects before administering another dose.
• In a person taking regular analgesia, breakthrough pain indicates a need for reassessment of the analgesic dosage and the underlying cause of pain. For more information on how to increase the dose of oral morphine, see Initiation of oral morphine and Titration of oral morphine.
• If the person is taking regular paracetamol and/or a nonsteroidal anti-inflammatory drug (NSAID), consider:
  • Treating with an additional dose of the regular analgesic as long as it does not exceed the maximum licensed dose, or
  • Adding in a weak opioid on an as-required or regular basis.
• If the person is taking regular paracetamol and/or an NSAID plus a weak opioid, consider:
  • Treating with an additional dose of the regular analgesic as long as it does not exceed the maximum licensed dose, or
  • Switching to a strong opioid.
• For people taking oral morphine:
  • If the person is using immediate-release or modified-release morphine regularly — treat with immediate-release oral morphine (tablets or liquid), at a dose of one sixth to one tenth of the total daily oral morphine dose, to be taken when required and repeated no more than 2-hourly or a maximum of 6 doses in 24 hours.
    • The breakthrough dose may need to be individually titrated to between 5% and 20% of the regular daily dose.
    • If the person is in severe pain and needs another dose sooner than 2 hourly or 3 or more doses have been given within 4 hours with limited benefit, seek specialist advice. If more than 6 doses are required within 24 hours seek advice or review. 
    • The onset of action of immediate-release morphine is about 20–30 minutes.
    • Revise the dose of the breakthrough dose if the regular dose has been altered. 
  • Seek specialist advice if pain is not controlled despite optimizing drug treatment.
• If the person is receiving a subcutaneous infusion of morphine:
  • Treat with a subcutaneous bolus dose at one sixth to one tenth of the 24-hour infusion dose, when required, and repeated no more than 2-hourly. If the person is in severe pain and needs another dose sooner, seek specialist advice.
  • Oramorph^® is an alternative for people who can manage liquids but are on an infusion because they cannot swallow tablets. It allows the person and their family greater control over managing episodes of breakthrough pain without having to wait for a healthcare professional to attend to give a breakthrough subcutaneous dose.
    • Specialist advice should be sought in this situation to check the oral route is appropriate and to clarify the dose of Oramorph^® because the doses suggested by experts vary.
• If using other strong opioid analgesics, seek specialist advice.
• If the person's background pain is satisfactorily controlled but they experience incident pain (pain on movement or particular events, such as micturition, wound dressing, bed care, travel):
  • Do not keep increasing the 24-hour dose of opioid.
  • Give a breakthrough dose of an immediate-release opioid approximately 30 minutes before the precipitating factor occurs. In some situations, transmucosal fentanyl can be useful for this purpose, but this should be used only on the advice of a specialist.
  • Do not include the breakthrough doses administered for incident pain when reassessing maintenance opioid analgesia requirements.

What advice should I give regarding strong opioids?

• Ask the person if they have any specific concerns regarding treatment with a strong opioid, for example addiction, tolerance, or adverse effects.
• Reassure the person that:
  • Strong opioids are not addictive when they are used to treat pain.
  • Tolerance may occur but this should not affect how their pain is managed.
  • Strong opioids are being prescribed because of the level of pain they are experiencing and not because they are near to the end of life.
• Provide verbal and written information on:
  • Why a strong opioid is being prescribed and how it should be taken.
  • The indications for strong opioids, how effective they are, how quickly they take to work, and how long pain relief should last.
    • For more information, see the prescribing information on Strong opioids.
  • What adverse effects may occur (including signs of toxicity) and how these are usually managed.
  • Safe storage of strong opioids.
    • Strong opioids should be kept in a safe place out of the reach of children and stored in the original container.
    • Any unused strong opioids should be returned to a pharmacy.
  • Who to contact out of hours (especially during the titration phase), when they will be followed up, and how frequently their treatment will be reviewed.

How should I manage neuropathic pain?

• Consider whether there is a treatable underlying cause (for example nerve compression from bone metastases or soft-tissue disease) and seek specialist advice regarding further treatment of the cause (for example surgical stabilization for bone metastases or radiotherapy for soft-tissue disease).
• If pain is purely neuropathic and reversible conditions (for example vitamin B12 deficiency) have been excluded:
  • Consider offering a tricyclic antidepressant (such as amitriptyline) or pregabalin (or gabapentin if there is a local decision to prefer gabapentin over pregabalin).
  • Titrate the dosage according to response and tolerability.
  • For further information on contraindications, cautions, managing adverse effects, and second-line options if amitriptyline or pregabalin are not effective, see the CKS topic on Neuropathic pain - drug treatment.
• If pain is of mixed origin, use standard analgesics in addition to a tricyclic antidepressant or pregabalin (or gabapentin) if pain is not adequately controlled with standard analgesia alone. For more information on standard analgesics, see Scenario: Managing pain - non-emergency.
• Seek specialist advice or consider referral if pain persists.

How should I manage pain from raised intracranial pressure?

• Consider whether a treatable underlying cause is present.
• Discuss with an oncologist regarding the need for radiotherapy.
• Use standard analgesics in a stepwise approach. For more information, see Scenario: Managing pain - non-emergency.
• Also consider a trial of dexamethasone at a dose of 8–16 mg daily (taken in the morning), titrated down to the lowest dose that controls symptoms:
  • If the volume of tablets or injection is difficult to manage in a single dose, it is acceptable to split the dose, in which case it should be given at 8 am and 12 pm (noon).
  • Have a low threshold for considering gastroprotection with a proton pump inhibitor.
  • Response to dexamethasone should be assessed after 3 days, but extensive cerebral oedema may take 2–3 weeks to resolve.
  • If there has been no response, discontinue dexamethasone immediately.
  • If there has been a benefit, review frequently and reduce to the lowest dose that controls symptoms (for example reduce by 2 mg every fifth day).

How should I manage intestinal colic?

• Consider whether there is a treatable underlying cause:
  • It may be possible to treat certain causes of colicky pain (for example bowel colic due to constipation) in primary care — see the CKS topic on Palliative cancer care - constipation.
  • However some causes (for example bowel obstruction) need specialist management and possibly surgical intervention, provided the person is fit enough for surgery and wants to be admitted.
• If symptomatic management is appropriate, consider hyoscine butylbromide (an antispasmodic), 20 mg immediately by subcutaneous injection, then 60–100 mg/24 hours via syringe driver continuous infusion.

How should I manage bone pain?

• Consider whether there is a treatable underlying cause and discuss with an oncologist if this is suspected (for example regarding radiotherapy or bisphosphonates for bone metastases).
• Seek urgent advice from an orthopaedic surgeon if there is evidence or suspicion of an actual or imminent fracture.
• For symptomatic relief:
  • Apply hot or cold packs.
  • Use standard analgesia in a stepwise approach (see Scenario: Managing pain - non-emergency).
  • If incident pain occurs on movement, encourage the person to take a dose of their breakthrough analgesia 20–30 minutes before anticipated movement. See Management of breakthrough pain.
• If pain is difficult to manage, seek advice from a specialist (such as a palliative care specialist or an anaesthetist with an interest in chronic pain).

How should I manage muscle spasm?

• Consider whether there is a treatable underlying cause.
• Try simple measures (such as heat pad, massage, relaxation).
• Consider transcutaneous electric nerve stimulation over the trigger point if the pain is myofascial.
• If trigger points are multiple or the muscle spasm is widespread, consider a muscle relaxant — benzodiazepines (such as diazepam) or baclofen:
  • Several different doses of diazepam have been suggested by experts. These range from 2–10 mg at night to 2–5 mg three times a day; the higher doses may be helpful if there is co-existing anxiety. The dose may need to be reduced depending on clinical response.
  • The suggested dose of baclofen to treat muscle spasm is 5–10 mg three times a day. However baclofen should be titrated slowly, which may limit its usefulness in people requiring palliative care.
  • The choice of drug will also depend on any other actions (for example benzodiazepines may be more appropriate for people with co-existing anxiety) and the potential for limiting adverse effects.
• If these measures are not effective, or there are only a few trigger points, consider referral. Other drugs or injection of trigger points with local anaesthetic may be considered in secondary care.

When should I suspect spinal cord compression?

• Suspect spinal metastases if any of the following features are present:
  • Pain in the middle (thoracic) or upper (cervical) spine.
  • Progressive lower (lumbar) spinal pain.
  • Severe unremitting lower spinal pain.
  • Spinal pain aggravated by straining (for example when passing stool or when coughing or sneezing).
  • Localized spinal tenderness.
  • Nocturnal spinal pain preventing sleep.
• Suspect spinal cord compression if any of the following features are present:
  • Neurological symptoms (including radicular pain, any limb weakness, difficulty in walking, sensory loss, or bladder or bowel dysfunction).
  • Neurological signs of spinal cord or cauda equina compression.

How should I manage spinal cord compression?

• If spinal metastases are thought to be the cause of the pain, seek urgent (within 24 hours) specialist advice from a metastatic spinal cord compression coordinator if available, or alternatively the person's palliative care consultant or oncologist.
• If there are associated neurological features suggestive of spinal cord compression, seek immediate specialist advice.
• Unless contraindicated (including a significant suspicion of lymphoma), offer all people with metastatic spinal cord compression a loading dose of 16 mg of dexamethasone as soon as possible after assessment.

End of life care

• It can often be difficult to be certain that a person is dying, but it is essential to recognize the signs of dying in order to appropriately care for people at the end of life. For more information see the CKS topic on Palliative care - general issues.
• An individualized care plan including the areas of symptom control and anticipatory prescribing should be created. For more information see the CKS topic on Palliative care - general issues.
• Follow the principles of pain management used at other times when caring for people in the last days of life, for example matching the medicine to the severity of pain and, when possible, using the dying person's preferences for how it is given. Consider non-pharmacological management of pain in a person in the last days of life.

Initiation of oral morphine

• Initially prescribe either immediate-release or modified-release oral morphine:
  • Immediate-release oral morphine has a rapid onset of action (about 20 minutes) but it requires administration every 4 hours to maintain a continuous analgesic effect. Consequently, it is difficult to cover pain throughout 24 hours, unless the person is being closely monitored.
    • Immediate-release morphine is useful for titration if the person's pain is severe and rapid titration is required, usually on an inpatient basis. Oramorph^® solution and Sevredol^® tablets are both immediate-release morphine products.
  • Modified-release morphine preparations have a slower onset of action (1–2 hours) and later peak levels (4 hours) than immediate-release preparations. Although they cannot be rapidly titrated for people in severe pain, in many people they provide continuous analgesia that is ideal for titration, especially for those at home.
• For people not currently taking an opioid or taking a weak opioid:
  • If titrating with immediate-release morphine:
    • In young and middle-aged people, start with morphine 5 mg every 4 hours plus as required (up to 2-hourly) for breakthrough pain.
    • In elderly or frail people, start with morphine 2 mg every 4 hours plus as required (up to 2-hourly) for breakthrough pain. Use cautious dose titration in the elderly or frail, this can help to reduce initial drowsiness, confusion, and unsteadiness.
  • If titrating with modified-release morphine
    • In young and middle-aged people, start with modified-release morphine 10–15 mg every 12 hours plus breakthrough doses of immediate-release morphine as required (up to 2-hourly).
    • Consider starting at a lower dose and titrating carefully if the person is elderly or frail.
  • Once treatment has started review the person after 24 hours and recalculate the total morphine requirement and titrate the dose as required.
    • For more information see Titration of oral morphine.
• For people previously on an alternative strong opioid:
  • CKS recommends seeking specialist advice because of the differences in opinion regarding conversion ratios.
• Seek specialist palliative care advice for people with renal impairment, hepatic impairment, people with increased intracranial pressure, or people at risk of respiratory depression.
  • For people with renal impairment, a lower or less frequent regular dose of morphine may be preferable, or a different opioid may be more appropriate.

 [National Collaborating Centre for Cancer, 2016; ABPI, 2020a; NHS Scotland, 2021]

Titration of oral morphine

• After 24 hours, recalculate the total morphine requirement: the new 24-hour dose is the total of all the doses given in the previous 24 hours.
  • Care should be taken when calculating morphine requirements for people who are pain free at rest but have pain on movement. If all the analgesia for this incident pain is incorporated into the new morphine dose the person is likely to be excessively sedated at rest or possibly opioid toxic. CKS therefore recommends that incident pain doses are excluded when calculating the new 24-hour dose.
• Increasing the dose of morphine
  • If the person takes two or more as-required doses in 24 hours, increase the regular dose of morphine every 2–3 days (using the as-required amount of morphine used as a guide) until there is adequate pain relief or adverse effects prevent further dose increases.
  • In general, dose increases should be limited to no more than 30% of the total 24-hour morphine dose.
• Immediate-release morphine
  • If the total 24-hour dose is 90 mg (6 × 10 mg regular doses + 3 × 10 mg as-required doses), the new 4-hourly dose would be 15 mg.
  • Once the pain is controlled and a stable 24-hour requirement of morphine is established, the daily dose can be switched to a modified-release preparation in a single daily dose, or in two divided doses.
• Modified-release morphine
  • For a 12-hourly modified-release preparation divide the total 24-hour dose of morphine by two. For example if the total 24-hour dose is 120 mg (2 × 40 mg regular modified-release doses + 4 × 10 mg as-required doses), the new 12-hourly modified-release dose would be 60 mg.
  • For a 24-hourly modified-release preparation the dose is equivalent to the total 24-hour dose of morphine.
• Switching from immediate-release to modified-release morphine
  • If switching from regular immediate-release to modified-release morphine, give the first dose of modified-release morphine within 4 hours after the last dose of immediate-release morphine (and discontinue the immediate-release preparation).
• If possible, keep the person on the same brand of modified-release morphine. This is because the pharmacokinetic profiles of modified-release products differ, and differences in appearance may be confusing for people.
• Continue to provide immediate-release morphine tablets or solution for as-required treatment of breakthrough pain.

 [National Collaborating Centre for Cancer, 2016; Wilcock, 2020; BNF, 2021; NHS Scotland, 2021]

Management of opioid adverse effects

• Exclude any underlying illness or other drugs (such as antipsychotics) that may mimic opioid-induced adverse effects (such as dehydration).
• Drowsiness is common at the start of treatment or after dose increases. Warn people to avoid activities (such as driving) in which drowsiness may be detrimental. Most people develop tolerance to drowsiness within a few days. Persistent sedation can usually be resolved by dose reduction.
  • If the person drives, give advice about driving while taking opioids:
    • You should not drive if you feel drowsy, dizzy, unable to concentrate or make decisions, or if you have blurred or double vision.
    • It is now an offence to drive if you have more than a specified amount of opioid in your body whether your driving is impaired or not.
    • It may be helpful to keep evidence with you while you are driving that you are taking an opioid in accordance with medical advice. Suitable evidence may include: your medication box with the pharmacy label on, the other half of your prescription with the list of medicines prescribed by your doctor, or the package insert if the medicine was bought over-the-counter.
• Nausea and vomiting subside after the first few days in many people but can be an ongoing problem for others. An anti-emetic (for example metoclopramide if the problem is gastric stasis, or low-dose haloperidol) should be prescribed.
  • For more information, see the CKS topic on Palliative care - nausea and vomiting.
• Constipation — tolerance does not develop, but constipation can usually be treated. To prevent constipation, prescribe a stimulant laxative (such as senna or bisacodyl) and a softening laxative (such as docusate):
  • A laxative with both properties (for example co-danthramer or co-danthrusate) is also an option. Some people taking dantron-containing laxatives may experience a chemical burn (reddening) of the perianal area; these agents are therefore unsuitable for incontinent people. Dantron can also colour the urine red and alarm the person.
  • For more information, see the CKS topic on Palliative care - constipation.
• Dry mouth can be troublesome. Consider reducing the dose of, or stopping, any drugs that also cause dry mouth. People should be encouraged to use simple measures first:
  • Cold, unsweetened drinks.
  • Frequent sips or sprays of cold water.
  • Ice cubes, crushed ice, or ice lollies.
  • Lubricant on the lips.
  • Sugar-free products — chewing gum, mints, boiled sweets, or pastilles.
  • For more information, and what to do if simple measures are not adequate, see the CKS topic on Palliative care - oral.

[Regnard, 2022; National Collaborating Centre for Cancer, 2016; Wilcock, 2020; NHS Scotland, 2021]

Switching from morphine to another strong opioid

• Seek specialist advice, or consult local guidelines (where available), when selecting the opioid and dose to switch to. This is because experience in primary care is likely to be limited and alternative oral opioids are best initiated by a person with experience in palliative care.
  • See Table 4 for information on approximate equivalent potencies of oral opioids to oral morphine, which is produced by the UKMI in the Q&A document What are the equivalent doses of oral morphine to other oral opioids when used as analgesics in adult palliative care? [McKie, 2016].
• Particular attention to monitoring and dose titration up or down is needed when:
  • Switching between opioids at high doses.
  • There has been a recent rapid escalation of the first opioid.
• In primary care, when switching the route of administration of one strong opioid to another, the most common switch is from oral morphine sulphate to subcutaneous morphine. See Table 5.
  
  • The oral to subcutaneous potency ratio of morphine is between 1:2 and 1:3 (that is, the subcutaneous dose is one third to one half of the oral dose). In practice, most centres divide the oral dose by two and re-titrate as necessary. See Table 4.

Table 4. Approximate equivalent potencies of oral opioids to oral morphine.

Table 5. Equivalent doses of oral morphine sulphate to the subcutaneous route.

[National Collaborating Centre for Cancer, 2016; Wilcock, 2020; BNF, 2021; NHS Scotland, 2021] 

Avoiding prescribing errors

• In order to avoid prescribing errors:
  • Prescribe by mass (for example 2 mg) rather than by volume (for example 2 mL).
  • Avoid decimal points in doses if possible (for example 2.5 mg) to minimize the risk of dose errors, and try to avoid prescribing awkward doses.
  • If using morphine 10 mg/5 mL oral solution, doses without a decimal point are easier to measure (for example 2 mg [1 mL of solution]).
• Final doses of morphine cannot be predicted from age, body weight, or body surface area. The starting dose of oral morphine should take into account previous exposure to opioids.
• These recommendations are pragmatic and based on what CKS considers to be good practice.