• Use the oral route of administration where possible.
• Morphine is recommended.
• For advice on how to initiate morphine and titrate the dose, see Initiation of oral morphine and Titration of oral morphine.
• If the person's compliance with oral morphine is good, but pain is inadequately controlled:
• Review the cause of the pain.
• Consider using a non-opioid adjuvant drug to treat a specific type of pain. See Management of specific types of pain.
• 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 (for example, the person has nausea and vomiting, or cannot swallow, or has poor compliance with oral analgesia), consider:
• Switching to a subcutaneous diamorphine or morphine infusion. For more information, see Switching from morphine to another strong opioid.
• Switching to transdermal fentanyl if the person has stable analgesic requirements and has previously tolerated opioids — seek specialist advice.
• When prescribing a strong opioid:
• Prescribe an anti-emetic (such as metoclopramide for gastric stasis, otherwise low-dose haloperidol):
• If the person has experienced nausea with a previous opioid, 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 a previous opioid, prescribe for use on an as-required basis for 1 week.
• To prevent constipation, prescribe a stimulant (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 and alarm the person.
• 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.

• The recommendations in this section are consistent with expert opinion in palliative care pain management guidelines [MeReC, 2003; NHS Quality Improvement Scotland, 2004; NHS Argyll & Clyde, 2005; Pan-Glasgow Palliative Care Algorithm Group, 2007a; Pan-Glasgow Palliative Care Algorithm Group, 2007b; SIGN, 2008] and a chapter from the ABC of palliative care [Colvin et al, 2006].

Route of administration

• Expert opinion suggests that for analgesic drugs, the oral route is the simplest and preferable [Quigley, 2005].
• If the person cannot take oral morphine, a subcutaneous infusion of opioid is an option because it is probably as effective as intravenous infusion (based on weak evidence) but is easier to administer [SIGN, 2008].
• Expert opinion in palliative care guidelines suggests that if pain is stable and the person cannot take oral medication, transdermal opioid administration can be considered [Hanks et al, 2001; SIGN, 2008].

Choice of drug

• Morphine is generally accepted by palliative care organizations and expert opinion to be the strong oral opioid of choice for managing moderate and severe cancer-related pain [Zech et al, 1995; Hanks et al, 2001; Davis et al, 2005; Quigley, 2005; Wiffen and McQuay, 2007]. It is usually well tolerated, has well-established efficacy and safety in clinical practice, and is familiar to most practitioners [SIGN, 2008]. Morphine is available as a wide variety of oral formulations, allowing flexibility in dosing regimens. It is also the most cost-effective strong opioid analgesic available. No other opioid has been shown to have greater analgesic effect, although use of opioids via the transdermal route have been found to result in less constipation [Tassinari et al, 2008].
• CKS has not recommended alternative oral strong opioid drugs to oral morphine because there is a lack of evidence from high-quality comparative trials to suggest greater benefit in terms of efficacy or adverse effects [SIGN, 2008].
• CKS recommends diamorphine as the opioid of choice for subcutaneous infusion, as it is much more soluble than morphine and therefore easier to administer in higher doses [Twycross and Wilcock, 2007; SIGN, 2008]. Subcutaneous morphine sulphate has been used as an alternative to diamorphine owing to unpredictable manufacturing problems:
• For people with stabilized severe pain who express a preference for a patch formulation or people who cannot take oral morphine, fentanyl patches may be appropriate if the pain is stable [SIGN, 2008]. The Medicines and Healthcare products Regulatory Agency has issued advice that fentanyl patches should be used only in people who have previously tolerated opioids because there is a risk of significant respiratory depression in people who are opioid naive [MHRA, 2008]. Because of these safety issues, CKS recommends seeking specialist advice before starting fentanyl patches.

Anti-emetics and laxatives

• This recommendation is based on expert opinion in the Palliative Care Formulary [Twycross and Wilcock, 2007] and reviewers.