HPE Grunenthal handbook - Page 5

day in the case of CKD. Higher doses can lead to the risk of adverse reactions. The dosage is gradually increased by 50 (1/2 cp) or 100mg (1 cp) per month, and adapted to the uricaemia observed: the aim is to reach the therapeutic target. Physicians should avoid clinical or therapeutic inertia, so the dose of allopurinol is not increased while the sUA target is not reached. 7 Once found, the allopurinol dosage is maintained. Clinical follow-up tells the patient if he/she has had any new gout attacks, and if he/ she has been able to treat them as soon as possible (‘colchicine in the pocket’). Biological monitoring is essential: uricaemia and renal function (serum creatinine and estimation of glomerular filtration rate according to the MDRD or CKD-EPI formulas). Monitoring is initially carried out monthly until the target uricaemia is reached, then semi-annually. The patient should be informed of possible adverse events in the first few months of treatment: a simple rash and pruritus requires the permanent discontinuation of allopurinol. Re-introduction could cause serious forms of skin reaction. Very rarely, severe rashes such as Lyell’s syndrome, Stevens-Johnson’s syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) are encountered. DRESS is a generalised rash with blood eosinophilia, and haematological, renal and hepatic damage, which is regularly fatal. The factors favouring DRESS are an initial dose of allopurinol that is too high, Asian or African origin (HLA B58*01 gene with a high risk of DRESS to allopurinol), and CKD. Febuxostat is more expensive than allopurinol but generics will soon be available. It is available in Europe as 80 and 120mg tablets – not breakable, which does not allow for titration of dose as easily. Febuxostat can be used in CKD 3. Febuxostat is effective in lowering uricaemia within a few weeks; however, the rapid decrease will lead to regular gout attacks at the beginning of treatment. It is therefore essential to gradually increase the dose by cutting the tablets or by giving only alternate doses in one-month increment (80mg twice a week for one month, then 80mg three times a week, and finally, every other day). Its use should be discussed in cases of unstable coronary insufficiency or heart failure because its cardiovascular safety is still under evaluation. White blood cell count, transaminases and thyroid-stimulating hormone should be monitored in addition to uricaemia and estimated glomerular filtration rate (eGFR) as for allopurinol. Uricosurics The available uricosurics were probenecid and benzbromarone and, more recently, a third drug (lesinurad) is now available in Europe after quality clinical studies. All are antagonists of uric acid transporters through the cells of the renal tubule. Probenecid requires twice-daily dosing. There is a risk of lithiasis due to its uricosuric effect. It interacts with other drugs, which can also limit its use. Benzbromarone is quickly effective but its use also carries a risk of lithiasis (the risk can be reduced by adequate fluid intake and alkalinisation of the urine). Lesinurad (200mg) is used in combination with an XOI, if the uricaemia is not sufficiently lowered, for example, through allopurinol at doses of 200 or 300mg/day. Lesinurad is well tolerated, but transient increases in serum creatinine can be observed. The risk of lithiasis is decreased because urinary uric Table 2 Six key indicators for gout management 1 Treat to target Goal to reduce sUA level below 6.0, or even 5.0mg/dl Start low, go slow Start allopurinol at 100mg daily, increase by 50 or 100mg every month (for convenience) because there is no reason to reduce sUA level abruptly ‘Chi va piano va sano’ The start low and go slow approach reduces flares and helps avoid skin rashes or DRESS Tight control Increase allopurinol steadily up to optimal dosage to achieve sUA target Avoid clinical inertia Do not hesitate/do not be afraid to increase allopurinol dosage and switch to febuxostat and/or add uricosurics where appropriate. Treat to target always and always up to tophi resolution Monitor regularly Check sUA level and eGFR every six months when target is achieved. Use for patient adherence *According to ACR and EULAR, 6.0mg/dl is the sUA target (whereas 5.0mg/dl is the new 2017 British Society for Rheumatology target) for all patients starting treatment. acid excretion is already reduced through the use of allopurinol. Table 2 shows six key indicators for the management of gout. What difficulties are encountered with gout patients? It has been established that, as with all chronic diseases, compliance can be poor and up to 50% of patients no longer take their ULT after one year. This poor compliance is more pronounced in younger patients, and pharmacists, nurses and especially the attending physician or rheumatologist should be involved in attempting to improve compliance. Patients (and their families/carers) should be fully informed and educated about their condition and medication. 8 Gout is fairly simple to understand and explain: it is a genetic disease that is caused by the accumulation of urate crystals due to a failure to eliminate excess uric acid in the urine. The kidney and intestine are the two organs involved in this process. Urate crystals give rise to acute inflammatory attacks. The importance of dietary modifications should be explained. Sweetened carbonated drinks and beers and strong alcohols are discouraged or even prohibited; caloric and protein intake from meat and animal products should be reduced. 6 It should be explained that continuous hypouricaemic treatment (which reduces uric acid) is key: the crystals will gradually disappear and so will the painful attacks. Attacks are possible at the beginning of treatment by crystal release and these can be avoided by taking colchicine daily for six months (prophylaxis). There are a number of ways of helping to improve compliance such as daily cellphone messages, dedicated and trained nurses who regularly contact or receive regular calls from the patient, therapeutic education workshops, and pharmacy-based monitoring. In a controlled trial of dedicated nurses versus general practitioners, nurse-led interventions led to better outcomes in gout patients than with general practitioners. 8,9 References 1 Pascart T, Lioté F. Gout: state of the art after a decade of developments. Rheumatology (Oxford) 2018 Mar 13. doi: 10.1093/rheumatology/key002. 2 Major TJ et al. An update on the genetics of hyperuricaemia and gout. Nat Rev Rheumatol 2018;14(6):341–53. 3 Jamnik J et al. Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohortstudies. BMJ Open 2016;6(10):e013191 4 Neogi T et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2015;74(10):1789–98. 5 Khanna D et al; American College of Rheumatology. 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. 6 Richette P et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76(1):29–42. 7 Maravic M et al. Persistent clinical inertia in gout in 2014: An observational French longitudinal patient database study. Joint Bone Spine 2018;85(3):311–15. 8 Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis 2013;72(6):826–30. 9 Abhishek A et al. Long-term persistence and adherence on urate-lowering treatment can be maintained in primary care- 5-year follow-up of a proof-of- concept study. Rheumatology (Oxford) 2017;56(4):529–33. hospitalpharmacyeurope.com | 2018 | 5