Efficacy and Tolerability of Probenecid as Urate-lowering Therapy in Gout; Clinical Experience in High-prevalence Population

Pui, Karen; Gow, Peter; Dalbeth, Nicola

doi:10.3899/jrheum.121301

Cited by 63 publications

(36 citation statements)

References 21 publications

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“…Graham et al have developed a pharmacokinetic model that suggests that baseline urate prior to treatment is the single most important factor in final allopurinol dose (24). A similar association has been observed between baseline urate and achieving target with probenecid (30). If the predicted dose is higher than the clinician feels comfortable using in an individual then an alternate first line urate lowering therapy may need to be considered.…”

Section: Can We Predict Partial Resistance To Allopurinol?supporting

confidence: 77%

Impaired response or insufficient dosage?—Examining the potential causes of “inadequate response” to allopurinol in the treatment of gout

Stamp

Merriman

Barclay

et al. 2014

Seminars in Arthritis and Rheumatism

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Objectives Gout is one of the most common forms of arthritis. It is well established that urate lowering therapy that aims for a serum urate less than at least 0.36mmol/l (6mg/dL) is required for successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor is the most commonly used urate lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol, these patients can be considered to have “inadequate response” to allopurinol. Herein we examine the potential mechanisms and implications of inadequate response to allopurinol. Methods The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol. Results The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be “partially resistant” to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and or function such that oxypurinol is rendered less effective, and/or drug interactions. Conclusions It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician toward making a therapeutic choice that is more likely to result in achieving the serum urate target.

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Section: Can We Predict Partial Resistance To Allopurinol?supporting

confidence: 77%

Impaired response or insufficient dosage?—Examining the potential causes of “inadequate response” to allopurinol in the treatment of gout

Stamp

Merriman

Barclay

et al. 2014

Seminars in Arthritis and Rheumatism

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“…Whereas benzbromarone has been shown to be a potent inhibitor of URAT1 renal tubular transporter, with remarkable efficacy in reducing sUr [29,31] even in patients who have moderate renal function impairment [32], who are on diuretics, and who are on renal transplant medications [33], sulfinpyrazone and probenecid are less potent uricosurics and exert only a mild-to-moderate reduction of sUr, an effect that is supposed to be blunted in patients with moderate renal function impairment, contrary to the data reported in a recent retrospective study [34].…”

Section: Uricosuric Agentscontrasting

confidence: 51%

Treatment of Hyperuricemia in Gout

Pérez-Ruiz¹,

Herrero-Beites²

2014

Managing Gout in Primary Care

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“…84 The EULAR recommendation to consider addition of a uricosuric when treat ment with allopurinol alone has failed to lower the SU to target levels is based on observational studies of an effective combination of allopuri nol with benzbromarone 85 or probenecid. 86 Since the completion of the 2016 EULAR recommen dations, the EMA has granted marketing autho rization for the novel uricosuric lesinurad for combination therapy with an XOI for the treat ment of hyperuricemia associated with gout in patients who have not achieved SU target levels with an XOI alone. In phase III placebo controlled RCTs, the addition of lesinurad (200 mg/d) to pa tients receiving allopurinol (300 mg/d) was safe and effective in increasing the number of patients achieving target SU reduction by 55%, 87 but high er doses and monotherapy are not recommended as they can cause renal impairment.…”

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confidence: 99%

Current management of gout: practical messages from EULAR 2016 guidelines

Nuki¹,

Doherty²,

Richette³

2017

Polish Archives of Internal Medicine

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REVIEW ARTICLE Current management of gout: practical messages from 2016 EULAR guidelines 267 where these differ significantly from the earli er guidelines and other recent national and in ternational recommendations for the manage ment of gout.Why do we need updated recommendations? There were at least half a dozen good reasons why the EULAR recommendations needed to be up dated in 2016. 1 Knowledge of the pathophysiology of uric acid (UA) transport, urate crystal inflammation, and the comorbidities associated with gout had ad vanced considerably. 2 New pharmaceutical options had become available and the evidence base for the efficacy and safety of available drugs had expanded in the last decade. 3 The incidence, prevalence, and severity of gout had continued to increase 7 despite the availability Introduction Gout is a chronic crystal deposition disorder in which crystals of monosodium urate can cause chronic arthritis, tophi, urolithiasis and renal disease, as well as recurrent acute arthritis and bursitis. Gouty arthritis and tophi can lead to chronic disability and impairment of health related quality of life, 1 but gout is also frequently associated with comorbidities such as obesity, di abetes mellitus, hypertension, and cardiovascular disease, 2,3 as well as with increased mortality. 3,4 The ABSTRACTThe European League Against Rheumatism published updated recommendations for the management of gout in 2016, comprising 3 overarching principles and 11 key recommendations for clinical practice. Patient education about the pathophysiology of gout and its comorbidities, as well as the existence of effective treatments are important, and understanding the principles of managing acute attacks and eliminating urate crystals by lifelong lowering of the serum urate (SU) below a target level are essential. Advice about lifestyle, diet, weight, and other risk factors, as well as the need to screen for and manage comorbidities are emphasized. For the treatment of flares, colchicine, nonsteroidal anti -inflammatory drugs (NSAIDs), and oral or intraarticular steroids, or a combination thereof, are recommended. In patients with frequent flares and contraindications to colchicine, NSAIDs, and corticosteroids, an interleukin -1 blocker should be considered. Urate -lowering therapy (ULT) should be discussed from the first presentation of the disease, and SU levels should be maintained at less than 6 mg/dl (360 µmol/l), or less than 5 mg/dl (300 µmol/l) in patients with severe gout. Allopurinol is recommended as first -line ULT with dose adjustment according to renal function. If the SU target cannot be achieved with allopurinol,

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Efficacy and Tolerability of Probenecid as Urate-lowering Therapy in Gout; Clinical Experience in High-prevalence Population

Abstract: Probenecid has moderate efficacy as ULT in clinical management of patients with complex gout who have a lack of efficacy or intolerance to allopurinol. Patients with chronic kidney disease may respond to probenecid with similar rates of adverse events.

Cited by 63 publications

References 21 publications

Impaired response or insufficient dosage?—Examining the potential causes of “inadequate response” to allopurinol in the treatment of gout

Impaired response or insufficient dosage?—Examining the potential causes of “inadequate response” to allopurinol in the treatment of gout

Treatment of Hyperuricemia in Gout

Current management of gout: practical messages from EULAR 2016 guidelines

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