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