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.