Morphine

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• First-line oral and injectable analgesic for moderate to severe opioid responsive pain (refer to Pain management, Choosing and changing opioids)
• Breathlessness

• Frail or elderly patients need smaller doses less frequently and slower titration.
• Liver impairment: reduced clearance. Dose and dose frequency may need reduced; titrate slowly.
• Renal impairment: Renally excreted, active metabolites. 
• Use with caution in mild to moderate renal impairment.
• Dose and dose frequency may need reduced; titrate slowly and monitor carefully.
• Avoid in chronic kidney disease stages 4 to 5 (eGFR less than 30ml/min).
• Consider other opioids: alfentanil.

Drug interactions

No clinically significant pharmacokinetic drug interactions. Morphine should not be co‑administered with monoamine oxidase inhibitors (MAOIs) or within 2 weeks of such therapy.

Side effects

Nausea and vomiting, drowsiness, constipation, dry mouth, delirium, unsteadiness. Monitor for opioid toxicity: vivid dreams, hallucinations, myoclonus.

Prescribe a stimulant +/- softener laxative (refer to Constipation guideline) and an anti-emetic as needed (for example metoclopramide, domperidone) (refer to Nausea and vomiting guideline).

Immediate release oral morphine

• In opioid naïve:
• prescribe 2mg to 5mg immediate release up to 4 hourly titrating to effect.
• In patients on regular opioids:
• prescribe 1/6th to 1/10th of the 24 hour dose as required for breakthrough pain. If 3 or more doses have been given within 4 hours with little or no benefit seek urgent advice or review.  If more than 6 doses are required in 24 hours seek advice or review.

 or

Modified release (long acting) oral morphine

• Prescribe 12 hourly (or 24 hourly depending on preparation), with 1/6th to 1/10th of the 24 hour dose as immediate release oral morphine for breakthrough pain.
• If the patient has pain when the dose of modified release (long acting) morphine is given, wait an hour before giving a breakthrough dose of immediate release morphine.
• Zomorph® Capsules are licensed to be opened and administered in semi-solid food (e.g. puree, jam, yoghurt) or can be administered via enteral tubes with a diameter of more than 16FG, rinsing the tube with 30ml to 50ml of water.

Morphine injection

• Continuous subcutaneous infusion in a syringe pump over 24 hours.
• In addition, prescribe 1/6th to 1/10th of the 24 hour infusion dose subcutaneously,
  1 to 2 hourly as required for breakthrough pain. If 3 or more doses have been given within 4 hours with little or no benefit seek urgent advice or review.  If more than 6 doses are required in 24 hours seek advice or review.
• With higher subcutaneous infusion doses, consideration needs to be given to the volume of breakthrough medication. Typically an upper limit of 2ml is acceptable by the subcutaneous route in a single site. Consider use of an alternative opioid, for example diamorphine, if volume issues arise.
• Diluent: water for injections.
• Dose conversions are given below.
  If 3 or more doses have been given within 4 hours with little or no benefit seek urgent advice or review.  If more than 6 doses are required in 24 hours seek advice or review.
• Stability and compatibility – refer to Syringe pumps guideline – Compatibility and stability tables for subcutaneous infusion.

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• As with all opioid conversions, these are approximate (≈) doses and should be used as a guide.
• Dose conversions should be conservative and doses rounded to the nearest easily measurable dose.
• Monitor the patient carefully so that the dose can be adjusted if necessary.
• If the patient has opioid toxicity, reduce the dose by 1/3rd when changing opioid (refer to Choosing and changing opioids guideline).

• The pharmacokinetic profiles of the different modified release preparations differ; keep patients on the same brand if possible.
• Modified release preparations should be swallowed whole. Do not crush or chew as this will lead to a rapid release of morphine.
• Doses of liquid preparations should always be expressed as milligrams (mg) rather than millilitres (ml).
• Deaths have occurred from accidental overdose with Morphine Sulphate concentrated oral solution 20mg/ml.  This preparation is rarely used and is 10 times the potency of the 10mg/5ml oral solution, therefore caution is required when prescribing and dispensing this preparation.

Twycross R, Wilcock A, Howard P. Palliative Care Formulary PCF6. 6th ed. England: Pharmaceutical Press; 2017.

Summary of Product Characteristics – MST Continus^® tablets. https://www.medicines.org.uk/emc/medicine/1223