• Either immediate-release or modified-release formulations are recommended for the initiation of morphine:
• Immediate-release oral morphine has a rapid onset of action (about 20 minutes) that makes it suitable for initiating treatment of severe pain (and for treating breakthrough pain), 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. Consequently, they cannot be rapidly titrated for people in severe pain. However, in many people, they provide continuous analgesia that is ideal for titration, especially for those at home.
• Take care 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 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.
• Starting regimens of oral morphine are listed below as a guide and are based on suggested doses in UK and European guidelines and the Palliative Care Formulary. However, some experts advocate a more cautious approach with lower starting doses. Clinical judgement is therefore required.
• For people not currently taking an opioid:
• In elderly or frail people, start with morphine 2–5 mg every 4 hours plus as required (up to 2-hourly) for breakthrough pain. Cautious dose titration can help to reduce initial drowsiness, confusion, and unsteadiness.
• In young and middle-aged people, start with morphine 5–10 mg every 4 hours plus as required (up to 2-hourly) for breakthrough pain.
• For people previously on a weak opioid (such as codeine) at a full therapeutic dose, start with:
• Immediate-release morphine 10 mg every 4 hours plus as required (up to 2-hourly) for breakthrough pain, or
• Modified-release morphine 20–30 mg every 12 hours plus breakthrough doses of immediate-release morphine as required (up to 2-hourly). For information on calculating the breakthrough dose, see Management of breakthrough pain.
• Consider starting at a lower dose and titrating carefully if the person is elderly or frail.
• 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, 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.

In depth

• 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.
• However, 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.
• 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:
• Increases of 30–50% have been recommended in the literature. However, expert feedback suggests that it may be safer to limit increases to 30% in primary care to avoid toxicity (especially at higher doses). A report from the National Patient Safety Agency advises ensuring that where a dose increase is intended, the calculated dose is safe for the person (for example, for oral morphine in adults, not normally more than 50% higher than the previous dose).
• Immediate-release morphine:
• If the total 24-hour dose is 90 mg (6 x 10 mg regular doses + 3 x 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 (Morphgesic^® SR tablets, MST Continus^® tablets or suspension, Zomorph^® capsules), divide the total 24-hour dose of morphine by two. For example, if the total 24-hour dose is 120 mg (2 x 40 mg regular modified-release doses + 4 x 10 mg as-required doses), the new 12-hourly modified-release dose would be 60 mg.
• For a 24-hourly modified-release preparation (MXL^® capsules), the dose is equivalent to the total 24-hour dose of morphine.
• If switching from regular immediate-release to modified-release morphine, give the first dose of modified-release morphine 4 hours after the last dose of immediate-release morphine (and discontinue the immediate-release preparation).
• Because the pharmacokinetic profiles of modified-release products differ, and differences in appearance may be confusing for people, it is best to keep the person on the same brand of modified-release morphine.
• Continue to provide immediate-release morphine tablets or solution for as-required treatment of breakthrough pain.

In depth