HPE Grunenthal handbook - Page 14

elevations in serum creatinine, mostly transient, were observed with higher doses during pivotal clinical trials. 13 Reducing serum urate levels should follow label indications and applicable recommendations, rely on the clinical experience of the prescribing physician, and bear in mind the safety profiles, both for gout and comorbid conditions. Therefore, prescription should be individually tailored in order to achieve target effectively with the best efficacy to safety ratio. Patients should be informed and educated on the convenience of maintaining sUA life-long below the saturation threshold, with medication if needed, to avoid recurrence of gout. 14 the European Union, although availability, labels, and indications differ among different nations. Allopurinol and febuxostat are xanthine oxidase inhibitors (XOIs) differing in structure (allopurinol is a purine analogue, whereas febuxostat is not), in pharmacodynamics (potency of inhibition of XO), and in pharmacokinetics (allopurinol is excreted by the kidney while febuxostat shows combined liver and kidney excretion). The maximum labelled dose of allopurinol varies widely among countries, and up to 900mg/day in some countries, whereas the dose of febuxostat is generally 120mg/day for most countries in Europe. Several uricosurics are also available but their availability is less generalised than that of XOIs. These include probenecid, benzbromarone and lesinurad. While febuxostat and lesinurad have received central approval from the European Commission, the latter to be used only in combination with XOIs, the older drugs may be used either in monotherapy or combination, and except for allopurinol are not widely available and lack appropriately designed and powered clinical trials, especially where long-term safety is concerned. 12 The efficacy of probenecid might be blunted in patients with moderate renal impairment and the use of benzbromarone, which may be useful in patients with moderate kidney disease, has been restricted due to the potential risk of severe liver toxicity. Both drugs are mostly prescribed in combination, by specialists. Lesinurad is useful in achieving target sUA at the approved dose of 200mg/day in patients concomitantly treated with a XOI; Although it is accepted that most gout patients can be effectively evaluated and treated in primary care, specialised advice might be considered in some instances 14 | 2018 | hospitalpharmacyeurope.com Figure 1 Symmetric polyarticular involvement of the interphalangeal joints mimicking rheumatoid arthritis Prevention of flares Initiation of urate-lowering medications at full dose has been associated to an increase in the rate of flares, which is proportionate to the urate-lowering effect: the fastest and highest reduction, the highest the risk of flares. 15 Different interventions might reduce this risk while initiating urate-lowering therapy. Slow, low-dose increases in urate-lowering medications might be helpful even if no medication for prophylaxis is specifically prescribed. 16 Colchicine has been proved to be useful and it is approved in some countries in the EU, while low- dose non-steroidal anti-inflammatories (NSAIDs) and corticosteroids are suggested as alternatives by experts, but lack any other evidence-based support. Prophylaxis is recommended for a period of at least five to six months by the European Medicines Agency in the label of the most recently approved urate-lowering medications such as lesinurad, and febuxostat, respectively. Patients should be informed and educated that there is a risk of suffering flares during the initial period of urate-lowering treatment, that medications should not be withdrawn in order to achieve desirable long-term effects: definitive control of flares and debulk of urate deposits. Treating flares As commented before, there is a risk of suffering flares even after adequate implementation of urate- lowering and prophylactic measures. Adequate measures should be prescribed for early recognition and self-management of the episodes of acute inflammation. Prescription of on-demand NSAIDs, colchicine or corticosteroids is advised, depending of the clinical profile, especially of comorbid conditions, 17 and to avoid the risk of inadequate treatment. 18 In patients in whom other medications are contraindicated, or not convenient due to a high risk of developing severe adverse events, inhibitors of interleukin-1, such as canakinumab (approved in the EU for acute flares), or anakinra (off-label) might be considered by specialists. Difficult gout: looking for advice Practising clinicians sometimes need support from other colleagues in areas in which they do not have the knowledge, experience, or resources to cope with a particular health problem. Although it is accepted that most gouty patients can be effectively evaluated and treated in primary care, specialised advice might be considered in some instances. Difficult diagnosis Gout may infrequently present as arthritis with polyarticular distribution, in the joints of the hand, or may mimic rheumatoid or psoriatic arthritis in