East & South East England Specialist Pharmacy Services East of England, London, South Central & South East Coast NSAIDS – Efficacy and Safety Expert speaker Slide set Key content from the NPC NSAIDS QIPP slides is gratefully acknowledged.

East & South East England Specialist Pharmacy Services NICE CG 59 Osteoarthritis Feb 2008 All oral NSAIDs/COX-2 inhibitors have analgesic effects of a similar magnitude They vary in their potential GI, liver and cardio- renal toxicity When choosing the agent and dose, healthcare professionals should take into account individual patient risk factors, including age Consideration should be given to appropriate assessment and/or ongoing monitoring of these risk factors

East & South East England Specialist Pharmacy Services Efficacy of NSAIDs About 60% of patients will respond to any NSAIDAbout 60% of patients will respond to any NSAID Those who do not respond to one may well respond to anotherThose who do not respond to one may well respond to another Pain relief starts from the first dose, with full analgesic effects obtained within a weekPain relief starts from the first dose, with full analgesic effects obtained within a week Anti-inflammatory effects may not be achieved for up to 3 weeksAnti-inflammatory effects may not be achieved for up to 3 weeks [BNF 63 March 2012]

East & South East England Specialist Pharmacy Services What about paracetamol? No strong evidence to suggest NSAIDs have a consistent benefit over paracetamol Some patients obtain greater symptom relief from NSAIDs Clinicians should consider offering paracetamol for pain relief in addition to core treatment; Regular dosing may be required Paracetamol and/or topical NSAIDs should be considered ahead of oral NSAIDs, COX-2 inhibitors or opioids NPC QIPP slides/NICE OA NB REVISED DRAFT NICE GUIDANCE ON OSTEOARTHRITIS OUT FOR CONSULTATION AUG 2013 – ADVICE ON PARACETAMOL MAY CHANGE A LOT!DECISION FEB 2014

East & South East England Specialist Pharmacy Services NSAID adverse effects in an older population of an average PCG Based on an average PCG of 100,000 patients where 3,800 over '65s take NSAIDs Bandolier 2000;79:6-8 EventCases per year Upper GI bleed18 Acute renal failure10 Congestive heart failure22

East & South East England Specialist Pharmacy Services GI adverse effects Risk factors includeRisk factors include -Age over 65 -History of GI bleed or ulcer -Concurrent use of drugs that increase the risk of GI adverse events -Heavy smoking or alcohol use -Prolonged NSAID use -Particular NSAID and high dose -Serious co-morbidity

East & South East England Specialist Pharmacy Services Age Chance of GI bleed due to NSAID Risk in any one year Chance of death due to NSAID GI bleed Risk in any one year in in in in in in 3353 >75 1 in in 647 [Bandolier NSAIDs and adverse effects]

East & South East England Specialist Pharmacy Services Risk of upper GI bleeding Lanas A et al Gut 2006;55:1731–38

East & South East England Specialist Pharmacy Services Reducing GI risk Ibuprofen Celecoxib? co-prescribed with a proton pump inhibitor Oral NSAIDs or coxibs should be co-prescribed with a proton pump inhibitor, choosing the one with the lowest acquisition cost [NICE CG59 OA 2008]

East & South East England Specialist Pharmacy Services Renal risks On going reports of renal failure in patients taking NSAIDs Patients at risk of renal impairment or failure (particularly elderly people) should avoid NSAIDs if possible. If NSAID is essential, renal function should be monitored during treatment Contributing risk factors include co- administration of ACE inhibitors, A2RAs and diuretics MHRA Drug Safety Update May 2009

East & South East England Specialist Pharmacy Services CV RISKS Painkiller heart alert ‘A painkiller taken by millions can increase the risk of heart attack and stroke by 40 per cent, a study has found’

East & South East England Specialist Pharmacy Services MHRA October 2006 Non selective NSAIDs - small increased risk of thrombotic events (eg heart attack or stroke) Coxibs - about three additional thrombotic events per 1000 patients per year in the general population Diclofenac - thrombotic risk profile similar to that of at least one coxib (etoricoxib) Naproxen and ibuprofen (1200mg or less) no increased risk

East & South East England Specialist Pharmacy Services MHRA January 2010 NSAIDs and CV risk in the general population Two important studies since 2006 found a very small increase in the risk of cardiovascular events: May apply to all users of NSAIDs, not only those with baseline cardiovascular risk factors After relatively short-term NSAID use (that may increase with increasing duration of use)

East & South East England Specialist Pharmacy Services MHRA June 2013 DICLOFENAC Contraindicated in established - ischaemic heart disease - congestive heart failure - cerebrovascular disease - peripheral arterial disease Switch such patients at next routine appointment Only initiate diclofenac after careful consideration if significant risk factors for CV events

East & South East England Specialist Pharmacy Services MHRA Advice on OTC diclofenac Ask questions to exclude supply to people with established CV disease or significant risk factors for CV events (eg hypertension, hyperlipidaemia, diabetes, smoking)

East & South East England Specialist Pharmacy Services ETORICOXIB Contraindicated if uncontrolled hypertension > 140/90mmHg Regular BP monitoring required during treatment 3% NSAID Rx items, 13% Rx costs

East & South East England Specialist Pharmacy Services

NSAID QIPP comparators 1.How much NSAID per patient? 2.What proportion of total NSAID prescribing is for ibuprofen and naproxen?

East & South East England Specialist Pharmacy Services Local prescribing data [insert local data here]

East & South East England Specialist Pharmacy Services Summary Consider individual patient risk factors and safety profiles of individual NSAIDs Lowest effective dose for shortest period of time Low-dose ibuprofen (≤1200mg per day) first choice NSAID: low GI and CV risk Low-dose ibuprofen or naproxen 1000mg/day for patients with CV risk Consider a PPI with any NSAID to reduce the risk of adverse GI effects, particularly if high GI risk (includes anybody aged 65 years or older) and long-term NSAID users MeReC Extra 30 Nov 2007