Adult Opioid Prescribing Guidelines for Acute or Persistent Pain

Author: Community Health Services Pharmacist Sponsor/Executive: Medical Director Responsible committee: Medicines Governance Group Approved Medicines Governance Group Consultation & Approval: 1st June 2020 (Committee/Groups which signed off the policy, including date) Quality, Safety & Governance Committee 24 June 2020 This document replaces: V3 Date approved: 24 June 2020 Date issued: 15 September 2020 May 2023 Review date:

Version: V4 Policy Number: MM42 To provide a guide containing key points for safe prescribing and monitoring for Purpose of the Guidelines: adults who are prescribed opioid medication for acute or persistent pain. If developed in partnership with another agency, ratification details N/A of the relevant agency

Signed on behalf of the Trust:………………………………………………….. Chief Executive

Elizabeth House, Fulbourn Hospital, Fulbourn, Cambs CB21 5EF

Version Control Page

Version Date Author Comments 2.0 May 2013 Lucy Oakley Developed and ratified by Cambridgeshire Community Services NHS Trust 3.0 March 2016 Lucy Oakley Updated following new guidance from the ‘Faculty of pain medicine Dose equivalence of conversion from oral morphine to transdermal patch medication updated in line with the BNF, SPC and Faculty of Pain Medicine. Naloxone dosing changed in line with Patient Safety alert on naloxone.

4.0 January 2020 Lucy Oakley Updated. Includes advice on tapering opioids, accidental exposure to patches, referral to Cambridgeshire and Peterborough netformulary.

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Scope Medical / nursing staff who prescribe, administer or care for adults on opioid medication for acute or persistent pain. This does not include palliative care.

Purpose of document To provide a guide containing key points for safe prescribing and monitoring for adults who are prescribed opioid medication for acute or persistent pain.

To provide information on opioid medication to support the NPSA rapid response report ‘Reducing Dosing Errors with opioid medicines’.

To provide a resource for medical / nursing staff caring for people on opioids for acute or persistent pain.

Monitoring Incidents will be monitored via the Datix reporting system Review Review March 2018 or earlier is there is new national guidance, changes in treatment or legislation.

References

1. BNF online; https://bnf.nice.org.uk/ 2. NPSA Rapid Response Report Reducing Dosing Errors with Opioid Medicines July 2008 https://webarchive.nationalarchives.gov.uk/20081008133250/http://www.npsa.nhs.uk/nrls/alerts-and- directives/rapidrr/reducing-dosing-errors-with-opioid-medicines/ 3. National Patient Safety Agency. Ensuring safer practice with high dose ampoules of diamorphine and morphine. Issued- 25th May 06. Available at: https://webarchive.nationalarchives.gov.uk/20100306052101/http://www.nrls.npsa.nhs.uk/resources/clinical- specialty/surgery/?entryid45=59803&cord=ASC 4. The electronic Medicines Compendium (eMC) http://www.medicines.org.uk/emc 5. The Faculty of pain medicine, Royal College of Anaesthetists; funded by Public Health England: ‘Opioids aware: a good practice resource to support opioid prescribing; a web-based resource available on the website since 30th December 2015; http://www.fpm.ac.uk/faculty-of-pain-medicine/opioids-aware 6. Arthur Rank Hospice Charity Factsheets; http://www.arhc.org.uk/pro-information-resources.asp; 7. Patient Safety Alert – risk of distress and death from inappropriate doses of naloxone in patients on long-term opioid or opiate treatment; 20th November 2014; NHS England. https://www.england.nhs.uk/2015/10/psa-naloxone-2/ 8. What naloxone doses should be used in adults to urgently reverse the effects of opioids? December 2019 https://www.sps.nhs.uk/articles/what-naloxone-doses-should-be-used-in-adults-to-reverse-urgently-the-effects-of-opioids- or-opiates/ 9. Medicines optimisation in chronic pain; NICE guidance; January 2017, updated Sept 2019; https://www.nice.org.uk/advice/ktt21/chapter/Evidence-context 10. CPFT Pain guidelines 11. Transdermal fentanyl patches: life-threatening and fatal opioid toxicity from accidental exposure, particularly in children; Drug Safety Update; 11 October 2018; https://www.gov.uk/drug-safety-update/transdermal-fentanyl- patches-life-threatening-and-fatal-opioid-toxicity-from-accidental-exposure-particularly-in-children

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Contents

Page 5. Decide What is the type of pain and is it appropriate to prescribe an opioid?

Page 6. Route Which route is most appropriate?

Page 6. Choice of opioid Which opioid is the most appropriate for the patient? Is the patient’s current opioid prescription appropriate?

Page 7. Dose Which formulation? What frequency? PRN doses? Use the dose conversion tables to choose dose when switching between analgesics

Page 9. Side Effects / monitoring What side effects are expected? How can we prevent and treat side effects?

Page 10. Alarm Bells Opioid toxicity – what to look out for

Page 10. Function of kidneys and liver Have the patient’s renal and hepatic function been considered when choosing the opioid and dose?

Page 11. End of life Who to refer to

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Strong opioids in persistent non-malignant pain should really be avoided, except in a very small number of carefully selected patients.

Before prescribing strong opioids, please consider the following points very carefully:

❖ Strong opioids are an extremely effective medication for use in ACUTE pain conditions and end of life care, but there is little evidence that they are helpful for long term pain.

❖ A small proportion of people may obtain effective and sustained pain relief with opioids in the longer term if the dose is kept low and especially if their use is intermittent, but it is difficult to identify these people at the start of treatment. Many long-term effects are dose related and it is recommended that maintenance doses are kept to the lowest effective dose.

❖ Persistent pain is very complex and difficult to treat, with most types of treatment helping less than a third of patients. The decision to prescribe strong opioids in persistent non-malignant pain should only be made after an appropriate risk-benefit analysis (including family and social factors) and with clearly defined treatment parameters as they are not very effective in this type of pain.

❖ Plan an opioid trial for persistent pain to establish whether the patient achieves reduction in pain. Short term response does not predict long term therapy, which may be limited by adverse effects or declining efficacy.

❖ Early escalation of the dose, lack of analgesic efficacy at low doses or the development of drug-seeking behaviour or adverse social behaviour should warrant consideration of drug discontinuation.

❖ The risk of harm increases substantially at doses above an oral morphine equivalent of 120mg/day, but there is no increased benefit.

❖ Opioids should be discontinued if the person is still in pain despite using opioids, even if no other treatment is available. It is usually expected that a reduction in pain of at least 30%, or significant improvement in quality of life / ability to carry out activities of daily living should be demonstrable to justify longer term prescribing.

❖ Avoid the use of breakthrough doses in persistent pain patients, as regular use of short-term opioids may increase the risk of dependency. These may be prescribed for emergency treatment of flare-ups, or to aid rehabilitation/therapy sessions, but their use is discouraged otherwise.

❖ The risk of inadvertent abuse or overdose of the medicine by relatives

This guidance is primarily for use by medical and nursing staff who prescribe, administer or care for adults on opioid medicines in inpatient settings, but can also be used as a resource for staff caring for people on opioid medicines in all settings.

This guidance is not intended for use in palliative care – please refer to the end of life care pathway.

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Decide

1. History taking A full history and examination should be performed to include a detailed assessment of pain, physical health including operations and illness, mental health, together with a full medicine history. (See CPFT pain guidelines)

2. Medicine History As part of the medicine history for all patients find out and document: • Whether the patient has been taking any medicine(s) for pain • Name of the medicine(s) • Formulation (e.g. liquid or solid-dose, immediate release or modified release) • Dose and frequency • When the last dose was taken • How long the patient has been prescribed the medicine(s), and what is the response to it • Dates of any recent increases or decreases in dose, and reasons for changes • Allergy history/sensitivities • Current or past history of addiction to drugs or alcohol (in patient or close family), depression or anxiety. These patients are more likely to develop problems with opioid use. Addiction is a risk particularly in long term use. https://www.rcoa.ac.uk/faculty-of-pain-medicine/opioids-aware/clinical-use-of-opioids/dependence-and-addiction • History of problems with sex drive or infertility (see side effects section)

Sources of information for a medicine history can include: - The patient or carer - Patients own medicines - Repeat prescriptions - GP referral letters - The GP surgery - Compliance aids - Medicine reminder cards - Hospital transfer letters - Discharge summaries - R esidential / nursing home records

3.Fo rAssessing more detailed information pain on medicine history taking, see ‘Standard operating procedure for Reconciliation of Medicines’ on Trust website

Patient Assessment: - Description of pain - What makes it worse? - Where is the pain? - What makes it better? - Does it radiate elsewhere? - What is the effect on sleep? - What does the pain feel like? (aching, burning, stabbing) - What is the effect on mood? - Does it vary in intensity? - What is the effect on physical function? - What is the effect on vocational/social function?

4. WHO analgesic ladder

The World Health Organisation (WHO) analgesic ladder was originally devised for treatment of cancer pain, but is also used for acute pain. Persistent pain has an unpredictable course and may continue for many years, and does not always follow this pathway, but it is a good starting point. If using this ladder, the complexity of the person’s individual needs, preferences for treatment, health priorities and lifestyle must be taken into account to avoid inappropriate prescribing and escalation.

Refer to page 5, point 1 for special considerations with dose.

• Use medicines you know well e.g. paracetamol → codeine → morphine • Use oral medicines first line • At each level on ladder: if pain is not responding to maximum dose of prescribed analgesic, given regularly, move up. If pain partially responding check dose/timing of medicine and possible role for adjuvant analgesic • Discuss plans with the patient at every stage and document • Taper or stop the opioid (deprescribe) if: o The medicine is titrated to 120mg oral morphine equivalent per 24 hours and the person is still in pain o The underlying painful condition resolves o The patient receives a definitive pain relieving intervention o The patient develops intolerable side effects o There is strong evidence that the patient is diverting the medicines to others o Discuss with patient and support their emotional and mental health needs if necessary o The dose of opioid can be tapered by 10% weekly or every two weeks

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Step 3

Step 2 Strong opioid e.g. morphine + non-opioid Step 1 Weak opioid ± adjuvants e.g. codeine + non-opioid Non-opioid e.g. ± adjuvants regular paracetamol ± adjuvants e.g. NSAIDs

Route and Choice of Opioid

Medicines should be used for their licensed indication only

The choice of opioid analgesic should be in line with the Cambridgeshire and Peterborough net- formulary http://www.cambridgeshireandpeterboroughformulary.nhs.uk/

The oral route is the preferred route of administration

▪ ORAL – Weak opioids - Codeine Phosphate (First line choice) - Dihydrocodeine - Tramadol - Meptazinol

▪ ORAL – Strong opioids - Morphine (First line choice) - Oxycodone

Morphine and oxycodone are available in immediate release and modified release formulations. The intended formulation must be clear on the prescription. For example: Both of the above are available in a variety of brands, extra care must be taken to ensure which formulation is correct.

o Morphine sulphate liquid for immediate release, to be used on an as required PRN basis (e.g. Oramorph® ) or modified release to be given every 12 hours regularly (e.g. MST Continus®) o Oxycodone liquid for immediate release to be given on an as required PRN basis (e.g. Oxynorm®). Oxycodone modified release to be given every 12 hours regularly (e.g. Oxycontin®)

• TRANSDERMAL PATCHES (Not for acute pain) - Buprenorphine (first line) - Fentanyl

There is no pharmacological advantage for these products over oral preparations. They are hazardous,and should not be used in opioid naïve patients. However, they may be useful for patients who cannot swallow or who have side effects to oral opioids. Patients must have stable opioid requirements, therefore not suitable for patients with acute pain. The amount absorbed can vary depending on factors including body fat and concomitant sepsis. See Medicine Patch checklist for more detailed information – Trust website

• PARENTERAL - Morphine - Oxycodone

Injectable opioids should not be used in the management of patients with persistent non-cancer pain except in extraordinary circumstances and then only after consultation with a specialised multidisciplinary pain management service.

Adult opioid prescribing guide for acute or persistent pain Review date: May 2023 Page 6 of 11 Dose

• Start with the lowest effective dose and titrate up – see analgesic ladder • Dose increases are not normally more than 30 to 50% of current dose • Before each dose increment check there has been a response to morphine (partial/full pain relief with a PRN dose). When opioids do not provide a patient with sufficient analgesia, there is a risk of dose escalation which may not always help and can cause toxicity if the dose is escalated too quickly. • If patients do not achieve relief of pain when titrated to doses up to 120mg morphine equivalent per 24 hours (equivalent to morphine sulphate tablets 60mg twice daily or fentanyl patch 50 micrograms/hour), discussion or referral to a specialist in pain management is strongly recommended, due to possibility of opioid insensitive pain or development of dependence. • Always prescribe the dose in milligrams (mg), not millilitres (mls)

1. Special considerations • If elderly and/or low body weight and/or opioid naïve, start with a lower dose, e.g. morphine sulphate solution 2.5mg • Exercise caution in chronic airways disease, cardiac disease and neurological disease, seek advice / start at a lower dose, e.g morphine sulphate solution 1mg to 2mg • If evidence of renal or hepatic dysfunction start with a lower dose (see overleaf)

2. Considerations for prescribing weak opioids • Paracetamol should be prescribed regularly before stepping up and starting a weak opioid • Consider use of adjuvants (NSAIDs or other) unless contraindicated, prior to starting weak opioids • Weak opioids must be given regularly (at maximum dose) before stepping up to a strong opioid. • The analgesic effects of codeine phosphate rely on it’s conversion to morphine. Patients with genetic variations in the enzymes needed to make this conversion may find codeine less effective (around 10% of patients), but they would still get all the side effects. Consideration of an alternative weak opioid before moving to a strong opioid may be an option here. • Do not use a combination of different weak opioids.

3. Switching a patient to oral morphine from a regular weaker analgesic • Continue non-opioid analgesics e.g. regular paracetamol. Stop weak opioids. • The conversion table below is a guide - use for a few days solely to determine the 24 hour dose of the long- acting medication. Take note of special considerations in 1 above and the individual patient before deciding the starting dose of morphine. • If patients have been taking maximum daily doses of the weak opioid, it is generally safe in practice to start the long-acting preparation, e.g. Morphine sulphate tablets modified release 10mg twice daily (5mg twice daily in the elderly.)

Weak opioid (Oral dose) Approx equiv. oral Example strong opioid dose morphine dose Codeine phosphate 60mg 5mg Codeine phosphate 60mg QDS to morphine sulphate solution 5mg every 4 hours + 5mg PRN Tramadol 5mg Tramadol 50mg to 100mg QDS to morphine sulphate 50mg solution 5mg to 10mg every 4 hours + 5mg to 10mg PRN Meptazinol 200mg 8mg Meptazinol 200mg QDS to morphine sulphate solution 5mg every 4 hours + 5mg PRN

4. Prescribing a PRN dose of oral morphine for breakthrough pain • Give one sixth of the total daily dose of oral morphine for each PRN dose four hourly • Use an immediate release formulation e.g. morphine sulphate solution • NOTE: Limit use of breakthrough doses of opioids in persistent pain due to association of higher risk of dependence or addiction.

5. Converting from immediate release to modified release morphine • Add up the total dose in 24 hours of morphine (including PRN doses). • To convert to morphine sulphate modified release (MR) tablets, divide the total daily morphine requirement by two, and prescribe this dose regularly every 12 hours. • Remember to adjust the PRN immediate release morphine dose to remain at one sixth of the total daily dose. • Give the first dose of morphine sulphate MR tablets at the same time as the last regular morphine sulphate solution dose. Be aware of changing needs and decreasing dosing of opioids when appropriate.

6. Switching from one opioid to another • Should only be recommended by a healthcare practitioner with adequate competence or experience. If unsure, ask for advice.

Adult opioid prescribing guide for acute or persistent pain Review date: May 2023 Page 7 of 11 • Switch opioids only if patient obtains pain relief from one opioid and is suffering severe side effects, no longer able to take via the same route, or due to renal / hepatic dysfunction. • In most cases, the calculated dose equivalent must be reduced to ensure safety. The starting point for dose reduction from the calculated equi-analgesic dose is around 25% to 50%. • A dose reduction of at least 50% is recommended when switching at high doses, in elderly or frail patients, or because of intolerable side effects. • Withdrawal symptoms (sweating, yawning, abdominal cramps, restlessness, anxiety) occur if an opioid is stopped or if the dose is reduced abruptly.

7. Switching between oral morphine and oral oxycodone Opiate Oral Morphine 20mg Oxycodone 10mg

8. Medicine patches: ❖ Dispose of used patches appropriately to avoid accidental exposure if used patches get stuck to children, vulnerable adults and pets. (New Drug Safety Update; October 2018). ❖ Do not apply heat to patches (e.g. heating pads, electric blankets, hot-water bottles, heated water beds, heat or tanning lamps, intensive sun bathing, hot baths or saunas) as this may increase the delivery rate of medication from the patch causing toxicity and shortening the duration of action of the patch. ❖ Absorption from the patch may also be increased in warm weather and if the patient has a fever. Observe for toxicity. ❖ Switching from oral morphine to opioid patches. The choice of opioid analgesic patch should be in line with the Cambridgeshire and Peterborough netformulary http://www.cambridgeshireandpeterboroughformulary.nhs.uk/ ❖ When changing to a patch, continue the previous oral opioid for 12 hours after patch application (i.e. give last dose of morphine sulphate MR tablet at the same time as the first patch is applied).

For more detailed information on interactions and plasma levels, refer to MMSOP053 Managing Medicine Patches on the medicine management pages of the intranet.

9. Switching from oral morphine to buprenorphine patches - Two transdermal buprenorphine preparations are available in the UK:

o Low strength patch - replaced every 7 days, e.g: Butrans®, Reletrans®, Sevodyne® (licensed for moderate non-malignant pain. Takes approximately 17 to 24 hours to deliver detectable levels of buprenorphine.) o High strength patch - replaced every 4 days, e.g: Transtec®, Bupeaze® (licensed for moderate to severe cancer pain and severe non-cancer pain. Takes 10 to 24 hours to reach minimum effective concentration.)

Approx 24 hr oral morphine dose Low strength Breakthrough dose of morphine sulphate soln. buprenorphine patch 12mg 5 micrograms/hour 2mg (or codeine 15mg 6 hourly) 24mg 10 micrograms/hour 4mg (or codeine 30mg 6 hourly) 48mg 20 micrograms/hour 8mg (or codeine 60mg 6 hourly)

Approx 24 hr oral morphine dose High strength Breakthrough dose of morphine sulphate soln. buprenorphine patch 84mg 35 micrograms/hr 14mg 126mg 52.5 micrograms/hr 20mg 168mg 70 micrograms/hr 28mg

10. Switching from oral morphine to fentanyl patches e.g. Durogesic®, Fencino®, Mezolar Matrix® Very strong opioid, only to be used in patients who have previously tolerated opioids. This patch has a 72 hour duration of action and is replaced every 3 days It takes about 12 hours for the patch to begin to work and 36 to 48 hours to reach stable plasma levels; therefore pain control may be erratic initially. Care – The dose must not be escalated within 72 hours

a. For adults who have been stabilised on oral morphine for a short period of several weeks. (Table below shows conversion ratio of 150:1 based on information from the Faculty of Pain Medicine); https://www.rcoa.ac.uk/node/21126

Approx 24 hr oral morphine dose Fentanyl patch strength Breakthrough morphine sulphate soln. dose 45mg 12 micrograms/hour 7.5mg 90mg 25 micrograms/hour 15mg 135mg 37 micrograms/hour (25+12 microgram/hour) 22.5mg 180mg 50 micrograms/hour 30mg 270mg 75 micrograms/hour 45mg 360mg 100 micrograms/hour 60mg

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b. For adults with persistent pain on a stabilised and well tolerated opioid regimen for a long period. (Table below shows conversion ratio of 100:1 based on the BNF information) Approx 24 hr oral morphine dose Fentanyl patch strength Breakthrough morphine sulphate soln. dose 30mg 12 micrograms/hour 5mg 60mg 25 micrograms/hour 10mg 90mg 37 micrograms/hour (25+12 microgram/hour) 15mg 120mg 50 micrograms/hour 20mg 180mg 75 micrograms/hour 30mg 240mg 100 micrograms/hour 40mg

Side effects of opioids • Gastrointestinal effects; Constipation – prescribe regular laxatives for all patients on a long-term basis unless contraindicated. A softener and stimulant combination is preferred (e.g. docusate sodium - has both softener and stimulant effects) Nausea – prescribe PRN anti-emetics for the first week, or regular anti-emetics if the patient has suffered nausea on weak opioids. Consider whether the nausea and vomiting is likely to be multi-factorial and follow appropriate local guidelines or formulary. • Central Nervous System effects; Headache, sleep disturbance, dizziness, confusion. Drowsiness – warn patients that they may feel drowsy initially which may affect their ability to drive or operate machinery, but once their dose is stable, this should improve. New guidance on driving when taking medicines was introduced in February 2015; https://www.gov.uk/drug-driving-law. The Faculty of Pain Medicine web based resource has specific guidance for opioids and driving; http://www.fpm.ac.uk/faculty-of-pain-medicine/opioids- aware/best-professional-practice/opioids-and-driving • Itching – this side effect, if it occurs, tends to persist. Prescribe an antihistamine if appropriate • Respiratory depression – is a much feared complication of the use of opioids for acute pain, but is only likely to be a potential problem in persistent pain on initiation, or if there have been major changes in dose, formulation or route of administration. Accidental overdose is likely to be the commonest cause of respiratory depression. Particular caution is necessary for patients taking more than one class of sedative medication and in those with pre-existing disorders of respiratory control, such as obstructive sleep apnoea. • Hormonal effects – associated with long term use of high dose opioids, with changes to sex and stress hormone function as well as immune function. Clinically this can result in a number of adverse effects including a reduction in sex drive, infertility, depression and fatigue. • Effects on immune system (Immunomodulating effect) • Opioid induced hyperalgesia: (an abnormal pain sensitivity following prolonged use of opioids). Refer to a specialist pain team. • Increased incidence of falls (of particular importance in elderly patients) • Increased absorption may occur from transdermal opioid formulations for patients with a fever or other intercurrent illness, or if the patient has a hot bath or sauna. • Concomitant use of other medicines o Warn patients of the enhanced effects and risks with use of other medicines and substances with sedative properties, including alcohol. o Some medicine combinations can increase the risk of serotonin syndrome, e.g. oxycodone and amitriptyline. Prescribe this combination with caution and monitor patient carefully.

Tapering and Stopping opioids – see Page 5

Adverse drug events & yellow cards Serious adverse drug events associated with opioid administration should be reported to the MHRA Yellow Card Reporting Scheme as well as via the Datix Incident System.

Monitoring Key points for monitoring

The aim of therapy is to achieve good pain control without side effects. The frequency of monitoring following a dose of a strong opioid will vary according to the route of administration. • For oral route, check 30 to 60 minutes after a PRN dose to make sure the dose is effective and there are no adverse effects. • For parenteral route (IM or SC), monitor every 15 minutes for the first hour, then every 30 minutes for the second hour. Refer to End of Life care pathway for monitoring in palliative care.

Adult opioid prescribing guide for acute or persistent pain Review date: May 2023 Page 9 of 11 For all patients receiving opioids monitor: • Pulse • Respiratory rate • Level of consciousness • Pain score

Alarm Bells Opioid toxicity

Myoclonic Jerks – involuntary muscle twitching Objectively drowsy or confused (new) Respiratory rate less than 8 respirations per minute seek medical attention

Pin point pupils Hallucinations / new agitation Sedation If evidence of the above: • Urgently seek medical attention • Investigate the cause of toxicity (e.g. remove patch or stop infusion)

• Review dose, choice of opioid, formulation, renal function/liver function and hydration • Administer high flow oxygen if cyanosed or hypoxic (caution in COPD) • NALOXONE is indicated for patients with respiratory depression (respiratory rate less than 8

respirations per minute) or coma

1. For complete reversal of opioid overdose or intoxication in an opioid naïve patient • Initially 400 micrograms IM or SC, then 800 micrograms for up to 2 doses at 1 minute intervals

if no response to preceding dose, then increased to 2 mg for 1 dose if still no response (4 mg dose may be required in seriously poisoned patients), then review diagnosis; further doses may be required if respiratory function deteriorates, up to a maximum of 10mg; intravenous administration has more rapid onset of action.

2. For partial reversal of opioid toxicity in a patient with persistent / chronic pain medicated with long term opioids • 80 micrograms (0.2ml of 400 micrograms/ml) IM or SC. Repeat this dose every 2 minutes until respiratory rate is above 8. • Too rapid reversal of the opioid effect can lead to intense pain and distress precipitating an acute withdrawal syndrome. This can result in hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest • Patients usually respond after 80 to 160 micrograms with deeper breathing and an improved level of consciousness, but a few patients may need up to 2mg of naloxone. • If there is little or no response to naloxone, opioid toxicity is unlikely, consider other causes.

NOTE: Patients who have responded satisfactorily to naloxone should be carefully monitored since the duration of action of some opiates may exceed that of naloxone. Repeated doses of naloxone should be administered when necessary. Consider referral to acute hospital for further monitoring / treatment.

Func tion of kidneys and liver It is important to consider renal and hepatic function when selecting a suitable opioid regime.

1. Caution in Kidney Disease Defining renal impairment - Information in this section should be used for patients with moderately reduced kidney function (eGFR 30 to 59ml/min/1.73m2, CKD stage 3a or 3b). For patients with severe or end stage kidney disease (eGFR less than 30ml/min/1.73m2, CKD stage 4 or 5) seek advice from palliative care experts / medicines information / medicines management team.

• The kidneys are a major source of excretion for many medicines. The use of opioids in patients with renal impairment can cause problems as the medicine and active metabolites can accumulate causing toxicity (see opioid toxicity for monitoring advice) • Morphine, codeine and dihydrocodeine can accumulate in renal failure, causing respiratory depression.

General principles for prescribing opioids in renal impairment • Start with a lower dose • Give this dose less frequently • Only use modified release preparations with caution • Monitor for side effects and switch preparation if Adult opioid prescribing guideprobl forematic acute or persistent pain Review date: May 2023 Page 10 of 11

Selecting an opioid in kidney disease • If a weak opioid is required, low dose, reduced frequency tramadol can be used. If opioid requirements are known consider low dose buprenorphine patches (Butrans®). • If a strong opioid is required, low dose oral oxycodone can be used. If opioid requirements are known, consider buprenorphine patch (Transtec® ) or Fentanyl patch. • NSAIDs should not be prescribed as adjuvant analgesia. • For severe renal impairment seek advice – see above.

2. Caution in Liver Disease Defining liver impairment There is no available formula to accurately assess alterations in drug clearance in liver disease. Drug clearance is likely to be reduced in patients with cirrhosis, particularly those with low albumin and raised INR. • Clearance of most opioids is reduced in liver impairment because the liver is responsible for their metabolism. This can lead to a prolonged duration of action and possible toxicity. Opioids can also be sedating and constipating, so their use increases the risk of precipitating hepatic encephalopathy. Many patients also have renal impairment.

General principles for prescribing opioids in liver impairment • Start with a lower dose • Give this dose less frequently

• Only use modified release preparations with caution

• Always ensure laxatives are co-prescribed

Selecting an opioid in liver disease • It is unclear which opioid is preferred for patients with liver impairment. Any opioid prescribed should be used with caution and following the above principles. • NSAIDs should not be prescribed if adjuvant analgesia is being considered. Regular paracetamol can be continued, but consider a reduced dose.

End of life

End of Life Care Pathway Please refer to palliative care team for further advice on prescribing.

Writing a controlled drug (CD) prescription for Schedule 2 and 3 CDs (except Temazepam) – See medicines policy / current BNF

A prescription / discharge prescription for schedule 2 and 3 CDs must contain the following details, written so as to be indelible: o Patient’s full name, address, and where appropriate, age o Name and form of medicine (e.g. morphine sulphate oral solution) o Strength of medicine (e.g. 10mg/5ml) o Dose of medicine (e.g. 10mg QDS PRN) o Total quantity to be dispensed in words and figures (e.g. 100ml, one hundred millilitres) o Doctor’s signature (must be handwritten) and date (does not have to be handwritten) o The address of the prescriber / discharging unit (must be within the UK) o Maximum 30 days supply on discharge

Help/ Further Advice: Palliative Care Team: Can provide advice about opioid prescribing, dose equivalents, commencing syringe pumps or other symptom management issues. 24 hour advice is provided by: Thorpe Hall, Peterborough, Tel: 01733 225900 Arthur Rank Hospice, Cambridge, Tel: 01223 675777

Medicines Information: Community Health Services Pharmacist(s) can be contacted for advice.

Ipswich Regional Medicines Information Centre, Tel: 01473 704432

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