1. Clinical Knowledge Summaries CKS Analgesia – mild to moderate pain Prescribing analgesics for mild to moderate pain in adults and children. Educational slides based on the CKS topic Analgesia – mild to moderate pain (September 2015).

2. Key learning points and objectives To be able to: o Outline key points to consider before prescribing analgesics. o Outline the stepwise strategy for pain management in adults and children. o Describe the factors that should be considered when choosing an NSAID or a weak opioid for adults and children. Educational slides based on the CKS topic Analgesia – mild to moderate pain (September 2015).

3. Analgesia for mild to moderate pain in adults

4. Points to consider before prescribing analgesics Treat the underlying cause of the pain (where possible). For people who have continuous pain: o Perform a full clinical assessment and o Give regular analgesia. Before switching to a different analgesic ensure a full therapeutic dose is used. Avoid prescribing effervescent preparations especially in people with hypertension (high salt content). Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

5. Choosing an analgesic — adults A stepwise strategy is recommended: o Step 1 — prescribe paracetamol. o Suitable first-line choice for most people with mild-to-moderate pain. o Increase to the maximum dose of 1 gram four times a day, before switching to (or combining with) another analgesic. o Step 2 — substitute the paracetamol with low- dose ibuprofen (400 mg three times a day). o Increase to a maximum of 2.4 grams daily. o If the person is unable to take an NSAID, titrate up to a full therapeutic dose of a weak opioid (such as codeine 60 mg every 4–6 hours; maximum 240 mg daily). Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

6. Choosing an analgesic - adults Step 3 — add paracetamol (1 gram four times a day) to low-dose ibuprofen (400 mg three times a day): o If necessary, increase the dose of ibuprofen to a maximum of 2.4 grams daily). o If the person is unable to tolerate an NSAID, add paracetamol to a weak opioid. Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

7. Choosing an analgesic - adults Step 4 — continue with paracetamol 1 gram four times a day. Replace ibuprofen with an alternative NSAID, such as naproxen 250 mg to 500 mg twice a day. Step 5 — start a full therapeutic dose of a weak opioid such as: o Codeine 60 mg up to four times a day (maximum 240 mg daily) in addition to full-dose paracetamol (1 gram four times a day) and/or an NSAID. Note: tolerance and dependence can occur, and elderly people are more prone to adverse effects. Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

8. Choosing an NSAID Low-dose ibuprofen (400 mg three times a day) or naproxen up to 500 mg twice a day are preferred. NSAIDs are associated with: o Cardiovascular and renal complications e.g. cardiac failure, hypertension, and renal failure; diclofenac, coxibs and some others increase the risk of myocardial infarction and stroke. o Dyspepsia and other upper GI complications e.g. ulcer, perforation, or bleeding. Based on the CKS topic Analgesia – mild to moderate pain (September 2015), MHRA - NSAIDs and coxibs: balancing of cardiovascular and gastrointestinal risks (2007), and a Drug Safety Update; Non-steroidal anti-inflammatory drugs: cardiovascular risk (2009).

9. Choosing an NSAID Ibuprofen (<1200 mg per day) and naproxen (1000 mg per day) are not associated with an increased cardiovascular risk. Ibuprofen is associated with the lowest risk of GI adverse effects. When prescribing use the lowest effective dose for the shortest possible time. Based on the CKS topic Analgesia – mild to moderate pain (September 2015), MHRA - NSAIDs and coxibs: balancing of cardiovascular and gastrointestinal risks (2007), and a Drug safety update; Non-steroidal anti-inflammatory drugs: cardiovascular risk (2009).

10. Cardiovascular adverse effects Some NSAIDs are associated with a small absolute increased risk of thrombotic adverse effects. o Coxibs increase the risk of atherothrombosis by about 3 events per 1000 people per year (compared with placebo). o Diclofenac has a similar risk profile to coxibs. Based on the CKS topic Analgesia – mild to moderate pain (September 2015), MHRA - NSAIDs and coxibs: balancing of cardiovascular and gastrointestinal risks (2007), and a Drug Safety Update; Non-steroidal anti-inflammatory drugs: cardiovascular risk (2009).

11. Cardiovascular adverse effects Naproxen 1000 mg daily has a lower thrombotic risk than coxibs. o Overall data do not suggest an increased risk of myocardial infarction. For Ibuprofen at high doses (e.g. 2400 mg daily) there may be a small thrombotic risk, but For ibuprofen at lower doses (< 1200 mg daily) data do not suggest an increased risk of myocardial infarction. Based on the CKS topic Analgesia – mild to moderate pain (September 2015), MHRA - NSAIDs and coxibs: balancing of cardiovascular and gastrointestinal risks (2007), and a Drug safety update; Non-steroidal anti-inflammatory drugs: cardiovascular risk (2009).

12. GI adverse effects Of the traditional NSAIDs low dose ibuprofen offers the lowest risk. Naproxen is thought to have an intermediate risk. For people who are at an increased risk of GI adverse effects: o Consider prescribing paracetamol. o If an NSAID is necessary, prescribe low-dose ibuprofen or naproxen with a proton pump inhibitor (PPI). Based on the CKS topic Analgesia – mild to moderate pain (September 2015), and MHRA - NSAIDs and coxibs: balancing of cardiovascular and gastrointestinal risks (2007).

13. GI adverse effects A coxib plus a PPI may also be considered, but: o Although coxibs are associated with a lower GI risk than standard NSAIDs, their benefits are equivocal. o Coxibs are significantly more expensive than ibuprofen or naproxen. o There is a lack of evidence that adding a PPI to a coxib is more beneficial than adding a PPI to a standard NSAID. Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

14. Weak opioids Tolerance and dependence can occur in people taking long-term opioids. o For elderly people – always start with a lower dose and titrate up slowly. They are more susceptible to opioid adverse effects. Codeine, dihydrocodeine, or tramadol are possible options. Codeine and dihydrocodeine are recommended by: o The British Pain Society and o The Medicines and Healthcare products Regulatory Agency (MHRA). Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

15. Weak opioids Tramadol is effective for treating pain, however There has been a recent significant increase in tramadol related deaths (when not obtained on prescription)*: o 83 deaths in 2008. o 175 deaths in 2012. Tramadol has now been reclassified as a schedule 3 controlled drug. Based on the CKS topic Analgesia – mild to moderate pain (September 2015). * Office for National Statistics; Deaths related to drug poisoning in England and Wales 2012.

16. When to use fixed dose combinations Prescribe single-constituent analgesics where possible, to allow independent titration of each drug. Consider fixed-dose combination analgesics: o For people with chronic stable pain. o To reduce the number of tablets taken. Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

17. Fixed dose combinations Avoid fixed-dose combination analgesics containing low doses of opioids such as: o Codeine 8 mg plus paracetamol 500 mg, or o Dihydrocodeine 10 mg plus paracetamol 500 mg. Little evidence that they are more effective than paracetamol alone, and They can cause opioid adverse effects (e.g. constipation). Based on the CKS topic Analgesia – mild to moderate pain (September 2015) and Merec Bulletin Volume 16, number 4 (2006).

18. Summary - adults Use a stepwise approach to pain management – paracetamol is the preferred step 1 analgesic. Before switching analgesics – ensure a full therapeutic dose is being prescribed. If using an NSAID: o Low dose ibuprofen (400 mg three times a day) or naproxen is generally preferred. o Consider the need for gastroprotection. o Prescribe the lowest possible dose for the shortest possible time. If using a weak opioid: o Consider codeine or dihydrocodeine. o Tramadol is being reclassified as a schedule 3 controlled drug later in 2014. o Be aware of tolerance and dependence. o Start with lower doses and titrate slowly in older people. Avoid effervescent preparations (high salt content). Avoid fixed dose combinations, consider if the person has chronic stable pain or there is a need to reduce the number of tablets.

19. Analgesia for mild to moderate pain in children

20. Choosing an analgesic – children For children under 16 years: o Prescribe either paracetamol or ibuprofen alone. Both are suitable first-line choices for treating mild-to-moderate pain in children. If the child does not respond to the first analgesic: o Check their concordance, and that an appropriate dose is being taken. o If paracetamol has been used, switch to ibuprofen alone. o If ibuprofen has been used, switch to paracetamol alone. Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

21. Choosing an analgesic – children If switching has been unsuccessful, or distress persists or recurs before the next dose is due consider alternating paracetamol and ibuprofen: o Add a dose of the second drug (e.g. after 2 or 3 hours), if the parents are confident to do this. o Take care not to exceed the maximum daily dose. o A treatment diary may be useful to avoid administration errors. If the child is still in pain consider referral to a paediatrician. Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

22. Treatments not recommended for children in primary care Administering paracetamol and ibuprofen at the same time of the day. o Taking both drugs together is complicated and there is an increased risk of exceeding the maximum daily dose. Aspirin. o Unless specifically indicated by a specialist. o Risk of Reye’s syndrome. Naproxen. o Only licensed for use in children with juvenile rheumatoid arthritis. Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

23. Treatments not recommended for children in primary care Diclofenac. o Most preparations of diclofenac are only licensed for juvenile rheumatoid arthritis. o A liquid formulation is not available in primary care (which would allow for dose adjustment against the child's age). Weak opioids. o Children have a lower threshold for the adverse effects of weak opioids (e.g. respiratory depression). o Codeine use is restricted in children following reports of serious adverse effects and children who died after taking codeine for pain relief (post surgical). Based on the CKS topic Analgesia – mild to moderate pain (September 2015).

24. Summary - children Prescribe either paracetamol or ibuprofen alone. If the first analgesic is unsuccessful, switch to either paracetamol or ibuprofen (whichever has not been used). Consider alternating between paracetamol or ibuprofen. Weak opioids are not recommended – increased reports of serious adverse effects and deaths in children given codeine post surgery. Consider referral if pain continues despite optimal drug management.