PRESCRIBING SUPPORT TEAM AUDIT: Etoricoxib hypertension safety evaluation DATE OF AUTHORISATION: AUTHORISING GP: PRESCRIBING SUPPORT TECHNICIAN: SUMMARY This audit has been designed to ensure that patients prescribed etoricoxib have had their blood pressure measured and that etoricoxib is considered as a potential causal, or exacerbating, factor where hypertension is detected. The patient s risk of adverse cardiovascular and gastrointestinal events will also be assessed and where appropriate an alternative NSAID may be suggested. All non-steroidal anti-inflammatory drugs should be prescribed at the minimum effective dose for the shortest possible duration. OBJECTIVES To review all patients prescribed etoricoxib to determine if the drug is being used in line with its summary of product characteristics and the Commission on Human Medicines (CHM) cardiovascular safety advice. To change the patient to a safer medication based on their individual risk/benefits if necessary. RATIONALE Etoricoxib is licensed for the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis. 3 Hypertension is a common side effect of treatment (occurs >1/100 to <1/10 patients). The summary of product characteristics for etoricoxib (Arcoxia ) contraindicates the drug in patients with hypertension whose blood pressure is persistently >140/90 mmhg. Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2 inhibitors, particularly at high doses. Therefore, hypertension should be controlled before treatment with etoricoxib and special attention should be paid to blood pressure monitoring during treatment with etoricoxib. Blood pressure should be monitored within two weeks after initiation of treatment and periodically thereafter. If blood pressure rises significantly, alternative treatment should be considered. 1
In October 2006 the CHM advised that the lowest effective dose of NSAID or COX-2 inhibitor should be prescribed for the shortest period to control symptoms and the need for long-term treatment should be reviewed periodically 1. COX-2 inhibitors, like etoricoxib, have been associated with an increased risk of thrombotic events (including myocardial infarction and stroke) 1, which may increase with dose and duration of exposure 2. Since this advice was issued prescriptions for COX-2 inhibitors have fallen. The use of COX-2 inhibitors is contraindicated in patients with ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and moderate or severe heart failure (NYHA class II-IV) 1,2. COX-2 inhibitors should be used with caution in patients with a history of cardiac failure, left ventricular dysfunction, hypertension, in patients with oedema for any reason and in patients with risk factors for heart disease (including hyperlipidaemia, diabetes or smoking) 1,2. The patient s risk of developing cardiovascular disease over the next 10years can be assessed using the ASSIGN score (www.assign-score.com). COX-2 inhibitors are as effective as non-selective NSAIDs such as naproxen and diclofenac. 1 COX- 2 inhibitors should not be used in preference to a non-selective non-steroidal anti-inflammatory (NSAID) except when patients are at a particularly high risk of developing gastroduodenal ulceration or bleeding and after assessing their cardiovascular risk 1. In addition, prescribers should take into consideration that the GI benefits of COX-2 inhibitors over traditional NSAID s appears to be lost when they are co-prescribed with low dose aspirin 1-3. Naproxen (1g daily) and low doses of ibuprofen (1.2g per day or less) have not been associated with an increased risk of myocardial infarction 1, and may be preferable to a COX-2 inhibitor, diclofenac or higher doses of ibuprofen in some patients. The cardiac and gastrointestinal risks associated with NSAID s and COX-2 inhibitors may be reduced if they are only used for inflammatory flares of osteoarthritis (OA) and/or the use of alternative painkillers such as paracetamol are used more regularly in OA 1. NHS D&G Formulary 2012 advice for NSAIDs is as follows: All NSAIDs and Cox-2 inhibitors carry a cardiovascular risk. Patients with OA may only require intermittent treatment and may benefit from regular paracetamol. ibuprofen naproxen diclofenac sodium Patients at high risk of serious gastro-intestinal adverse events: NSAID + omeprazole caps Patients at high risk of serious gastro-intestinal adverse events intolerant of NSAIDs celecoxib etoricoxib Patients at high risk but also requiring low dose aspirin for cardiovascular protection: NSAID (see 10.1.1) + omeprazole caps 2
Dose Comparison Data from clinical trials has established that Etoricoxib 30mg daily is equivalent to ibuprofen 800mg tds in the treatment of osteoarthritis 7 Etoricoxib 60mg daily is equivalent to diclofenac 50mg tds in the treatment of osteoarthritis 8 Etoricoxib 90mg daily is equivalent to naproxen 500mg twice daily in the treatment of rheumatoid arthritis 9 For price comparison 5, 6 : Etoricoxib costs 13.99-22.96/month Celecoxib costs 21.55-43.10 per month Ibuprofen is 1.91/month Naproxen 4.88/month Diclofenac 1.44/month Omeprazole 20mg od for GI protection costs 1.49 per month and lansoprazole 15mg od 1.44. METHOD An EMIS search will identify all patients currently being treated with etoricoxib. (EMIS web searches may be used to identify all patients recently prescribed etoricoxib and their latest blood pressure where EMIS web is available). The reviewer will record the following details; Patient s name DOB Drug and dose Indication for COX-2 Latest blood pressure (and date) Whether patient has a history of hypertension Medication for hypertension Any cardiovascular conditions contraindicating the use of a COX-2 inhibitor Any cardiovascular conditions, or risk of cardiovascular condition, where a COX-2 inhibitor should only be used with caution Any current or previous GI conditions (including ulceration, perforation/gi bleed, Barrett s oesophagus, varices, strictures etc.) Previous NSAID s or COX-2 inhibitors prescribed (+ reason for their discontinuation where known) Use of other analgesics (and whether regular paracetamol could be considered) Use of low dose aspirin Whether a PPI is prescribed Balancing up the hypertension, GI and other cardiac risks, the reviewer will make a suggestion as to whether the patient may be treated more safely on an alternative anti-inflammatory +/- PPI. Where a lower-acquisition cost NSAID (+/- PPI) would be an equally safe alternative this should be suggested over the use of another COX-2 inhibitor. The NSAID should be chosen from the formulary recommendations. Where possible the GP should consider whether the patient still requires an NSAID as this may be difficult for the reviewer to ascertain. The patient s usual GP can then choose whether or not the reviewer s suggestion should be implemented. Changes to the patient s medication can be made by the GP themselves or by the prescribing support pharmacist if a change has been authorised. Sample letters are available from the prescribing support team. 3
A report, detailing the number of patients reviewed and the outcomes of the review should be written. This should be compatible with GP appraisal documentation. EXCLUSION CRITERIA Any additional criteria for exclusion to be specified by the authorising GP. REFERENCES 1. BMJ Group/RPS Publishing. British National Formulary 63, March 2012. 2. Pharmacia Limited. Celebrex 100mg and 200mg tablets Summary of Product Characteristics. Pharmacia July 2008. Accessed at www.medicines.org.uk on 31/12/08. 3. Merck Sharp Dohme Limited. Arcoxia 30mg, 60mg, 90mg, 120mg film-coated tablets Summary of Product Characteristics. Merck Sharp Dohme Limited, 15/11/11. Accessed at www.medicines.org.uk on 10 th May 2012 4. MIMS October 2011 5. Scottish Drug Tariff, May 2012 accessed at http://www.isdscotland.org/health- Topics/Prescribing-and-Medicines/Scottish-Drug-Tariff/SDT_Part7_May12v2.xls 6. NHS Dumfries and Galloway Joint Formulary 2012 available at www.dgprescribingmatters.co.uk 7. Wiesenhutter CW, Boice JA, Ko A et al. Evaluation of the comparative efficacy of etoricoxib and ibuprofen for the treatment of patients with osteoarthritis: a randomised, double-blind, placebo controlled trial. Mayo Clin Proc. 2005;80(4):470-479 8. Zacher J, Feldman D, Gerli R et al; for Etoricoxib OA study group. A comparison of the therapeutic efficacy and tolerability of etoricoxb and diclofenac in patients with osteoarthritis. Curr Med Res Opin. 2003;19(18):725-736 9. Collantes E, Curtis SP, Lee KW, et al. for Etoricoxib Rheumatoid Arthritis Study Group. A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis. BMC FAm Pract. 2002;3:1-10. 4
CHANGES TO REPEAT PRESCRIBING 1. The audit must be checked and agreed with a GP in the practice prior to work being undertaken by the reviewer. 2. The reviewer conducts a search of the Practice Clinical System to identify patients prescribed etoricoxib. 3. The patient list is checked to ensure that all patients are still undergoing treatment (recently deceased or recent discontinuation of etoricoxib medication are removed) 4. Patients are assessed, (see risk factors) with respect to potential referral to GP or who require documentation of clinical information held on paper notes only. 5. No patient may be changed beyond the scope of the SPC and no changes will be made unless authorised by the prescriber. 6. All changes to prescribing must be recorded within the prescribing field and, wherever possible, an indication recorded for the medication added. 7. Each patient should be informed of any changes made in accordance with the Practice s preferred mode of communication. The Prescribing Support Team recommends personalised written communication sent from the Practice. Additional information e.g. patient leaflets may be included wherever possible. 8. If the patient is in residential care or has their medication otherwise supervised, information regarding any changes should also be communicated to the relevant service providers and their community pharmacist. 9. The reviewer will communicate information about the review to relevant personnel within the practice e.g. receptionists, nurses and will, if appropriate, create on-screen reminders on the Clinical System. 10. A project file is retained by the Practice containing a list of patients involved, patient letter templates and any individual information sent, a copy of the protocol and prescribing review form and contact details for the Prescribing Support Team. 11. The reviewer may record statistics of the review for report purposes and analysis of the review. No information regarding individual patients leaves the practice. 5
Etoricoxib AUDIT SURGERY APPENDIX 2 - DATA COLLECTION SHEET Patient name & CHI Age COX-2 and dose Indication Latest bp (& date) Indicators of cardiac risk including history of hypertension? Indicators of GI risk PPI? Aspirin? Previous NSAIDs/COX/o ther analgesics Comment/Suggestions Change? 6