HPE Grunenthal handbook - Page 8

table 1 Characteristics of common urate-lowering therapies Drug Starting dose Increments dosage Usual dosage Maximum dosage Renal impairment Contraindications Allopurinol 100mg/day 100mg 300mg/day 900mg/day Starting dosage: 50mg Treatment with azathioprine or mercaptopurine Hypersensitivity Febuxostat 40mg/day 40mg 80mg/day 120mg/day No adjustment Treatment with azathioprine or mercaptopurine Probenecid 250mg 2x/day 500mg 500mg 2x/day 500mg 2x/day Contraindicated History of nephrolithiasis Benzbromarone 100mg/day 50mg 100mg/day 200mg/day Not effective if CrCl <30ml/min History of nephrolithiasis Hepatic disease Lesinurad 200mg/day – 200mg/day 200mg/day Caution is recommended with CrCl 30–45ml/min CrCl <30ml/min CrCl, creatinine clearance ≤360µmol/l (6mg/dl) is generally recommended for all patients with gout and should be maintained lifelong. BSR recommends a target of ≤300µmol/l (5mg/dl) for all patients, whereas other guidelines reserve this target for patients with severe gout (tophi, gouty arthropathy, frequent attacks). 6 There is no consensus on how low sUA can be brought to and whether this can be done safely. T2T, ACR and BSR guidelines suggest increasing the sUA target to 360µmol/l in patients with severe gout who remain free of symptoms and in whom tophi have resolved. 2,6,9 Two xanthine oxidase inhibitors (XOI) are currently available: allopurinol and febuxostat. Allopurinol is the recommended first-line ULT. Most guidelines suggest using febuxostat as an alternative treatment when allopurinol is not tolerated or sUA target cannot be reached with an appropriate allopurinol dose. ACR recommends febuxostat as first line ULT similarly to allopurinol. The starting dose for allopurinol is 100mg/ day and should be adjusted upwards by 100-mg increments every 2–5 weeks until target sUA is reached. The maximum doses for allopurinol is 900mg/day. For patients with chronic kidney disease, the starting dose should be reduced to 50mg/day and increments by 50mg. Maximal allopurinol dosage should also be adjusted to creatinine clearance. Genetic HLA testing should be considered in selected patients (Korean with chronic kidney disease, Han Chinese, Thai) who have a high risk of presenting serious drug toxicity (ACR). Febuxostat dosage does not need to be adjusted to renal function. Febuxostat starting dose is 40mg/day and can be increased to 80mg, and further to 120mg/ day if the sUA target is not reached. When the sUA target cannot be reached with a XOI, the alternative XOI can be tried or a uricosuric can be added and used in combination with the XOI. Available uricosurics are probenecid, sulfinpyrazone, benzbromarone and lesinurad. Guidelines usually recommend using probenecid as the first-line uricosuric. Lesinurad is only recently available so has not been included in guidelines. Uricosuric dosages also need to be adjusted to creatinine clearance and are usually contraindicated 8 | 2018 | hospitalpharmacyeurope.com References 1 Khanna D et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012;64(10):1447–61. 2 Khanna D et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012;64(10):1431–46. 3 Richette P et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76(1):29–42. 4 Kiltz U et al. Treat-to-target (T2T) recommendations for gout. Ann Rheum Dis 2017;76(4):632–8. 5 Qaseem A et al; Clinical Guidelines Committee of the American College of Physicians. Management of acute and recurrent gout: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2017;166(1):58–68. 6 Hui M et al. The British Society for Rheumatology Guideline for the management of gout. Rheumatology (Oxford) 2017;56(7):1246. 7 So A, Dumusc A, Nasi S. The role of IL-1 in gout: from bench to bedside. Rheumatology (Oxford) 2018;57(suppl_1):i12–19. 8 Slobodnick A et al. Update on colchicine, 2017. Rheumatology 2018;57(suppl_1):i4–11. 9 Perez-Ruiz F et al. Treat to target in gout. Rheumatology 2018;57(suppl_1):i20–6. in patients with a history of nephrolithiasis. Pegloticase should be considered for patients with severe debilitating gout who are refractory to appropriately dosed ULT, used either as monotherapy or in combination (ACR, EULAR, BSR). 2,6,9 Table 1 shows characteristics of common ULTs. Lifestyle and diet counselling All patients should receive information and education about diet and lifestyle modification. Patients should receive oral and written information about management of gout and diet advice. Illness perceptions and barriers to care should be discussed with patients. Caregivers should support patients in body weight reduction and incite patients to exercise regularly (EULAR, BSR, ACR). Dietary advice should encourage low-fat dairy products and vegetables consumption. Excessive intake of alcohol, sugar- sweetened soft drinks and high-purine foods, such as meat and seafood, should be discouraged (EULAR, ACR, BSR, T2T). 2,3,6,9 Patients with gout and a history of urolithiasis should be advised to avoid dehydration and drink adequately (>2l). Clinicians may consider urine alkalinisation with potassium citrate in recurrent stone-formers (BSR). If possible, diuretics and other non-essential medications that induce hyperuricaemia should be avoided. Losartan has a weak uricosuric effect and is preferred to other angiotensin blockers in the treatment of hypertension or heart failure. All guidelines recommend annual (or regular) screening of cardiovascular risk factors and regular assessment of comorbidities and renal function. Conclusions An increasing number of therapeutic options have become available to treat patients with gout. A treat- to-target approach with appropriate monitoring of sUA is recommended for most patients. However, clinicians should be aware that patient education is mandatory to improve long-term drug adherence and outcomes.