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Home , Benzbromarone, Febuxostat

Treatment and Management Guidelines Acute Gout Management - pharmacological Acute Management – non-

pharmacological Management should be a combination of both lifestyle changes and 2 5 medications , . In addition to pharmacological treatment, Start anti-inflammatory/analgesic therapy straight away and continue for 1 – modification of lifestyle and risk factors is 2 weeks required

st 2, 4 1 Line: NSAID (Naproxen) or COX-2 inhibitor (etoricoxib) Affected joints should be rested and kept Naproxen: 750mg (stat) initially then 250mg every 8 hours until attack has cool. Ice packs are effective adjunctive 10 passed . Can increase to 1000mg/day (in divided doses) if required non pharmacological treatments 1, 2. 9 Etoricoxib: 120mg once a day for up to 8 days 2, 4 - Maximum dose of NSAID or COX 2 inhibitor must be prescribed Patients should be given advice 2 (verbal - 2, 3 Patients should be co-prescribed PPI agent whilst on treatment and written) - 8 Continue 48 hrs after attack has resolved - causes and consequences of gout nd 2 2 Line: – 500 micrograms 2-4 times a day . - how to manage acute attacks 4, 8 - More effective if taken within 12 -24 hours of attack - aims and objectives of treatment - Maximum 6mg per treatment course. Course not to be repeated - lifestyle advice (diet, 6, 7 within 3 days consumption and obesity) rd 2 3 Line: Corticosteroids Review medications2

Oral – Prednisolone 20 -40mg once a day for 5 days - Drug induced gout STAT intramuscular injection – Methylprednisolone acetate 40 -120mg or - Serum level (sUA) increasing triamcinolone acetonide 40-80mg treatments – diuretics (excluding STAT intraarticular injection (monoarticular gout) (off license use) potassium sparing diuretics), ACEis o Methylprednisolone acetate 10 – 80mg and ARBs (excluding )11 o Hydrocortisone acetate 12.5 – 25mg Treat cardiovascular risk factors 2 and For patients with poor response to monotherapy, combination treatment can co-morbid conditions such as renal be considered i.e. NSAIDS plus corticosteroids or colchicine disease, diabetes and hypertension.

PATIENT INFORMATION LEAFLETS AVAILABLE FROM Review at 4 – 6 weeks – perform a serum uric acid level (sUA) and renal function test 2 www.ukgoutsociety.org (The UK gout society is a registered charity and was established in 2002 to provide basic information to people Does patient have any of the following? living with gout) - Definite diagnosis of gout ≥2 attacks within 12 months - Tophi - Erosive arthropathy Abbreviations - Uric acid nephropathy or nephrolithiasis - Gout with renal insufficiency (creatinine clearance <60 mL/minute)  COX-2 – cyclooxygenase -2 - Diuretic therapy use NO  NSAIDS – non-steriodal - Primary gout starting at a young age anti-inflammatory drug  PPI – proton pump inhibitor  STAT – statim – YES immediately Confirm diagnosis of gout and offer urate lowering  2 ACEi – angiotensin therapy .Provide information regarding lifestyle converting modifications. inhibitor Long term treatment and  ARB – angiotensin II management with urate Note - asymptomatic hyperuricaemia does not blocker lowering therapies is strongly require treatment 2.  CrCl – creatinine clearance  advised in the patient group 2. SJS – steven Johnson Refer persistent symptoms without definitive syndrome  GI – gastrointestinal diagnosis to secondary care  LFT – liver function test Gout Treatment and Management Guidelines

Long Term Gout Management - Pharmacological

Commence – starting 1 -2 weeks after last attack

st 1 Line: Allopurinol 100mg daily (see additional prescribing information) - Titrated by 100mg every 4 weeks until sUA target is achieved (maximum dose 900mg daily in divided doses) - Target sUA: <300µmol/L2 - Co-prescribe prophylaxis colchicine – 500mcg twice a day for up to 6 months. If patient is intolerant of colchicine, prescribe Naproxen 250mg twice a day (with PPI) or etoricoxib 30mg once a day (with PPI).

If allopurinol is contraindicated or there is inefficacy despite dose titration to a maximum 900mg daily then commence

nd 2 Line: Febuxostat – 80mg once a day (see additional prescribing information) - Increase after 4 weeks if necessary to 120mg daily to achieve therapeutic - Target of sUA <300µmol/L. - Co-prescribe prophylaxis colchicine – 500mcg twice a day for up to 6 months. If patient is intolerant of colchicine, prescribe naproxen 250mg twice a day (with PPI) or etoricoxib 30mg once a day (with PPI).

3rd line: – specialist only - Patients who are resistant to or intolerant of allopurinol or/and febuxostat - Benzbromarone - 50 -100mg /day in patient with mild to moderate renal impairment

Treatment is unlicensed in the UK and obtained through parallel importing

Refer to secondary care Immediately - if septic arthritis is suspected Routine referral: - if unresponsive to uric acid - Gout persists despite uric acid <300µmol/l - Patient suffers complications relating to gout. e.g. nephropathy

Table 2: Dose adjustments in renal impairment Allopurinol CrCl 10-20ml/min: Maximum 100 - Table 1: Starting regime of allopurinol 200mg/day 2 according to glomerular filtration rate (GFR) CrCl<10ml/min: Maximum 100mg/day Estimated GFR Allopurinol starting Febuxostat Mild to moderate impairment - no dose 2 ml/min/1.73m dose adjustments required <5 50mg/week CrCl<30ml/min – no data available about 5 -15 50mg twice weekly efficacy and safety 16 – 30 50mg every 2 days Colchicine CrCl 10-50ml/min: Reduce dose or increase 31 – 45 50mg/day interval 46 – 60 50mg and 100mg on alternate days CrCl<10ml/min: Contraindicated 61 – 90 100mg/day Naproxen Avoid if possible/use with caution in renal 91 – 130 150mg/day impairment. Use the lowest effective dose >130 200mg/day and monitor renal function Etoricoxib Mild to moderate impairment - no dose adjustments required CrCl<30ml/min – contraindicated Gout Treatment and Management Guidelines Prescribing Information – please refer to individual summary of product characteristics (SPCs) for full details

Allopurinol Febuxostat - Renal impairment: see table above (table 1 +2) - Renal impairment: see table above (table 2) - Side effects - Cautions o Skin Rash – can be but not limited to pruritic, o Use in patients with ischaemic heart disease and congestive maculopapular, scaly. Rash is usually one of the first heart failure is not recommended signs of severe but rare hypersensitivity syndromes o Use is cautioned in patients with thyroid disorders. including SJS 12. Patients should be advised to stop - Side effects allopurinol immediately if rash occurs and seek o Skin Rash – Rash is usually one of the first signs of severe but medical advice. For mild reactions, allopurinol may, if rare hypersensitivity syndromes including SJS 13. Patients desired, be re-introduced at a small dose (e.g. 50 should be advised to stop febuxostat immediately if signs or mg/day) and gradually increased. If the rash recurs, symptoms of hypersensitivity reactions occur and seek medical allopurinol should be permanently withdrawn as more advice. Febuxostat should be permanently withdrawn13, 14. severe hypersensitivity may occur 12. o GI intolerances – nausea and diarrhoea – usually can be o GI intolerances – nausea and vomiting – usually can avoided by taking tablets after meals 13. be avoided by taking tablets after meals 12. o Deranged LFTS – increased hepatic transaminase - Contraindications o Oedema o Patients with hypersensitivity to allopurinol. o Headaches o Patient with HLA-B*5801 allele - Contraindications - Drug interactions o Patients with hypersensitivity to febuxostat. o and 6- – allopurinol - Drug interactions inhibits metabolism leading to accumulation of o Azathioprine and 6-mercaptopurine – febuxostat inhibits metabolites. Avoid combination. metabolism leading to accumulation of metabolites. Avoid o Increase incidence of skin rash when given combination. concomitantly with amoxicillin. Avoid combination if o or with high dose (120mg) possible febuxostat – increases drug levels – concomitant use is Do not start allopurinol during an acute attack – allopurinol can cautioned prolong attack. However, continue treatment if an attack develops Do not start febuxostat during an acute attack – febuxostat can prolong whilst patient is on treatment. This attack should be treated as per attack. However, continue treatment if an attack develops whilst patient in on acute management guidelines. treatment. This attack should be treated as per acute management guidelines.

Colchicine - Renal impairment: see table above (table 2) - Cautions o Use in patients with ischaemic heart disease and congestive heart failure is not recommended o Use is cautioned in patients with thyroid disorders. - Side effects o GI symptoms – nausea, vomiting, diarrhoea and abdominal pain. o Bone marrow suppression - Contraindications o Patients with hypersensitivity to colchicine o Patients with blood dyscrasias o Patients with severe hepatic impairment - Drug interactions o CYP3A4 inhibitors e.g. Clarithromycin, Verapamil, Diltiazem – increases colchicine levels - see SPC for guidance o Ciclosporin – increases colchicine levels - see SPC for guidance o Statins – risk of myopathy and rhabdomyolysis

Naproxen Etoricoxib - Renal impairment: see table above (table 2) - Renal impairment: see table above (table 2) - Cautions - Cautions o Use in patients with ischaemic heart disease and o Use in patients with hepatic impairment; dose accordingly congestive heart failure is not recommended Child-Pugh score 5-6 = 60mg, Child-Pugh score 7-9 = 30mg daily - Side effects o Uncontrolled hypertension o GI symptoms – nausea, vomiting, diarrhoea and - Side effects abdominal pain. o GI symptoms – nausea, vomiting, diarrhoea and abdominal o Bone marrow suppression pain. - Contraindications - Contraindications o Patients with severe ischaemic heart disease and o Patients with severe ischaemic heart disease and congestive congestive heart failure heart failure o Patient with hypersensitivity reactions to NSAIDS and o Patient with hypersensitivity reactions to NSAIDS and salicylates. salicylates. o Patients with severe hepatic impairment o Patients with severe hepatic impairment: Child-Pugh score ≥10 o Patients with history of GI bleeding o Patients with history of GI bleeding Gout Treatment and Management Guidelines References

1. Arthritis Research UK - https://www.arthritisresearchuk.org/arthritis- information/conditions/gout/treatments.aspx accessed 05/02/2018 2. Hui M, Carr A, Cameron S, Davenport G, Doherty M, Forrester H, Jenkins W, Jordan K M, Mallen C D, McDonald T M, Nuki G, Pywell A, Zhang W, Roddy E: The British Society for Rheumatology Guideline for the Management of Gout - Rheumatology, Volume 56, Issue 7, 1 July 2017, Pages e1–e20, https://doi.org/10.1093/rheumatology/kex156 3. National Institute for Health and Care Excellence. Clinical Knowledge Summaries: Gout. http://cks.nice.org.uk/gout (accessed 05/02.2018). 4. Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J, Coyfish M, Guillo S, Jansen T L, Janssen H, Lioté F, Mallen C, Nuki G, Perez-Ruiz F, Pimentao J, Punzi L, Pywell T, So A, Tausche A K, Uhlig T, Zavada J, Zhang W, Tubach F, Bardin T: 2016 updated EULAR evidence-based recommendations for the management of gout – Annals of Rheumatic Diseases 2006;65:1312 – 1324 http://dx.doi.org/10.1136/annrheumdis-2016-209707 accessed 05/02/18 5. Moi JHY, Sriranganathan MK, Falzon L, Edwards CJ, van der Heijde DM and Buchbinder R: Lifestyle Interventions for the Treatment of Gout: A Summary of 2 Cochrane Systematic Reviews The Journal of Rheumatology Supplement September 2014, 92 26-32 - https://doi.org/10.3899/jrheum.140459 accessed 05/02/18 6. Colchicine 500 micrograms Tablets: Wockhardt UK Ltd -Last updated on eMC: 30 Jun 2017. https://www.medicines.org.uk/emc/product/6415. Accessed 05/02/18 7. Clinical Knowledge summaries. Management of gout - Last revised in April 2015. https://cks.nice.org.uk/gout#!scenario accessed 05/02/18 8. Etoricoxib 120mg tablets: ZEntiva UK - Last updated on eMC: 12 Jul 2017. https://www.medicines.org.uk/emc/product/669 accessed 05/02/18 9. Naproxen 250mg tablets – Accord Healthcare Limited - Last updated on eMC: 08 Nov 2016. https://www.medicines.org.uk/emc/product/6034. Accessed 05/02/18 10. Choi HK, Soriano LC, Zhang Y, Rodríguez LAG, Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.d8190 (Published 12 January 2012) 11. Accord Healthcare Limited - Allopurinol 100mg tablets - Last updated on eMC: 02 Feb 2018 – accessed 07/02/2018 12. A. Menarini Farmaceutica Internazionale SR - Adenuric 80 mg film-coated tablets (Febuxostat) - L - Last updated on eMC: 24 Jan 2017 – accessed 07/02/2018 13. Medicines and Healthcare products Regulatory Agency: Febuxostat (Adenuric▼): stop treatment if signs or symptoms of serious hypersensitivity - Published 22 June 2012 - https://www.gov.uk/drug-safety- update/febuxostat-adenuric-stop-treatment-if-signs-or-symptoms-of-serious-hypersensitivity

Document reference Gout treatment and management GUI201807v3.0final Author Mabel Odonkor Consulted with Lauren Steel (Rheumatology registrar) Approved by MEAPC Date approved 19th July 2018 Next review date 19th July 2020

Previous version Key Changes Mid Essex Locality guidelines for the treatment Review against current guidance(BSR 2017) and management of gout – version 2.0 Mar 2015 Benzbromarone added Target sUA level aligned with BSR guidance Option to offer ULT following initial gout attack added Sulfipyrazone removed Mid Essex Locality guidelines for the treatment Document Management added and management of gout – version 1.0 Mar 2012 Review against current guidance