Why allopurinol contraindicated in acute gout

However, it can cause abnormalities in liver function tests and routine monitoring of bloodwork is recommended. Similar to allopurinol, there are interactions of febuxostat with azathioprine, 6MP, and theophylline. Uricase is an enzyme that converts poorly soluable urate uric acid to the more soluable allantoin excreted in the urine. Uricase is present in most mammals, and these mammals with uricase do not develop gout. However, humans and some primates lack uricase because of evoluationary gene inactivation and lack the ability to make uric acid more soluable and hence, have gout.

Pegloticase is a porcine uricase which was approved by the FDA in September for the treatment of gout in patients who have failed conventional therapy. Pegloticase is administered by intravenous infusion every 2 weeks. Patients should be treated prophylactically for allergic reations to the infusion with steroids and anti-histamines and monitored closely for the development of an infusion reaction.

Caution should be used in prescribing this treatment in patients with a known cardiac history. Avoidance of purine rich foods and alcohol may help lower uric acid levels and prevent significant fluctuations in serum uric acid that may precipitate acute attacks.

Obesity and increased fat distribution are risk factors for gout. Eating a healthy balanced diet of low-fat proteins, low-fat dairy and vegetables will help maintain a healthy weight which is beneficial for the prevention of gout attacks as well. All information contained within the Johns Hopkins Arthritis Center website is intended for educational purposes only. Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained within this site.

Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website. Acute Gout Attack The goal of treatment during an acute gout attack is suppression of inflammation and control of pain.

Treatment should be discontinued when symptoms resolve. Colchicine: Intravenous colchicine is associated with serious toxicities and side effects, so it should be used as an oral formulation only.

The pain is severe, and patients often cannot wear socks or touch bedsheets during flare-ups. Even without treatment, the attacks typically subside within five to seven days. Acute gout sometimes resembles cellulitis and can lead to skin desquamation over the inflamed area. Gout can also cause acute bursitis or tenosynovitis of periarticular structures.

Acute polyarticular gout is less common but has a more dramatic presentation. If the diagnosis is unclear, bacteriologic cultures of the synovial fluid and blood are warranted, and corticosteroid injections should be deferred.

Frequent, recurrent acute attacks often cause chronic tophaceous gout. Tophi are deposits of monosodium urate crystals in soft tissue that may occur in the helix of the ear, over olecranon processes, and over interphalangeal joints.

Tophi can occur over osteoarthritic Heberden's or Bouchard's nodes in the distal and proximal interphalangeal joints, especially in older women.

Occasionally, polyarticular tophaceous gout presents as subcutaneous nodules that can mimic rheumatoid arthritis. In this case, the presence of monosodium urate crystals in the nodule aspirate can confirm gout. Plain radiograph showing severe tophaceous gout with erosions arrow around the proximal phalanx. Classification criteria to aid in the diagnosis of gout have been proposed by the American College of Rheumatology Table 1 , 16 and a consensus panel of experts from the European League Against Rheumatism EULAR has reviewed the evidence and made recommendations for diagnosing gout.

Gout may be diagnosed if one of the following criteria is present:. Asymmetric swelling within a joint on a radiograph. First metatarsophalangeal joint is tender or swollen i.

Maximal inflammation developed within one day. Monoarthritis attack. More than one acute arthritis attack. Redness observed over joints. Subcortical cysts without erosions on a radiograph. Suspected tophi. Synovial fluid culture negative for organisms during an acute attack. Unilateral first metatarsophalangeal joint attack. Unilateral tarsal joint attack. Preliminary criteria for the classification of the acute arthritis of primary gout.

Arthritis Rheum ; Lower extremities: metatarsophalangeal, midtarsal, or knee joints; initial attacks may be less common in upper extremities. Asymmetric swelling shown on a radiograph 16 , Monosodium urate crystals in synovial fluid 16 , Podagra first meta-tarsophalangeal joint involvement 16 — Tophi confirmed 16 — Information from references 16 through Table 3 presents data for the accuracy of key elements in the diagnosis of gout.

The presence of monosodium urate crystals in synovial fluid is confirmatory, although a synovial fluid analysis is not always feasible. In the appropriate clinical scenario, a patient with hyperuricemia and classic podagra can be diagnosed and treated empirically. However, if a gout diagnosis is in question, synovial fluid analysis should be attempted.

Serum uric acid measurements are not sufficient for confirming or ruling out gout because they may be normal during an acute attack.

A hour urine collection to detect uric acid excretion is not routinely performed. Collection and dietary restrictions are difficult, and most patients receive allopurinol for chronic urate-lowering therapy regardless of the cause of hyperuricemia.

The goals of gout treatment are symptom control for acute attacks, risk factor modification, and pharmacotherapy to prevent recurrence and chronic sequelae. The most important symptoms of gout are pain and swelling, which may be accompanied by systemic symptoms such as fever and malaise. Table 4 summarizes pharmacotherapy for acute gout.

Use with caution in older patients and in patients with renal insufficiency, heart failure, peptic ulcer disease, or liver disease and in those receiving anticoagulation therapy. Indomethacin Indocin , 50 mg three times daily for four to 10 days. Naproxen Naprosyn , mg twice daily for four to 10 days. Sulindac Clinoril , mg twice daily for four to 10 days.

Avoid in patients with joint sepsis and use cautiously in patients with diabetes. Intra-articular therapy may be the treatment of choice if only one or two accessible joints are involved. Prednisone, 20 to 40 mg daily for two or three days, then taper over 10 to 14 days. Intra-articular methylprednisolone Depo-Medrol , one to mg dose.

Intramuscular methylprednisolone, one to mg dose. Avoid in patients with severe renal or hepatic impairment because it can lead to bone marrow suppression and neuromyopathy.

Avoid intravenous use; best if used within the first 24 hours of the attack; the most common adverse effects are nausea, vomiting, and diarrhea; reduce the dosage in older patients.

Suggested renal dosing based on creatinine clearance :. Information from reference Nonsteroidal anti-inflammatory drugs 22 , 23 or corticosteroids 24 are first-line therapies for acute gout, depending on patient comorbidities.

Although colchicine is an effective second-line therapy, in higher doses the risks of adverse effects outweigh the benefits.

All medications should be used cautiously in older persons, in whom the threshold of toxicity is lower. About 60 percent of persons who experience a gout attack will have another attack within 12 months. Substitution of diuretic therapy with other antihypertensives reduces hyperuricemia in many patients. Urate-lowering pharmacotherapy Table 5 21 , 27 using a xanthine oxidase inhibitor or uricosuric agent is recommended for patients with more than two gouty attacks per year, in patients with tophi, and in patients with joint damage seen on a radiograph.

When initiating urate-lowering therapy, concurrent prophylaxis with low-dose colchicine 0. May precipitate acute gout, hypersensitivity syndrome, or mild rash; avoid using with azathioprine Imuran ; interacts with warfarin Coumadin.

Do not initiate until four to six weeks after an acute attack; concurrent prophylaxis with colchicine 0. Suggested initial daily renal dosing based on creatinine clearance :. Probenecid, initially mg twice daily, gradually titrated to mg to 2 g per day.

May precipitate acute gout, nephrolithiasis, gastrointestinal upset, or rash; modifies renal handling of other drugs; use cautiously with heparin.

Maintain hydration about 2 L per day ; avoid using with low-dose aspirin; ineffective if creatinine clearance is less than 50 mL per minute. Investigational medication not yet approved by the U.

Food and Drug Administration. Montvale, N. Cost to the patient will be higher, depending on prescription filling fee. Information from references 21 and Allopurinol is the first-line urate-lowering therapy. In patients with normal renal function, the initial dosage may be mg daily, although many physicians advocate starting with a lower dosage e.

In patients with renal insufficiency, the allopurinol dosage should be adjusted based on the estimated creatinine clearance. Approximately 2 to 5 percent of patients taking allopurinol have minor rashes and other adverse effects.

Rarely, a severe hypersensitivity syndrome occurs with fever, toxic epidermal necrolysis, hepatitis, and eosinophilia; this syndrome has been shown to have a 20 percent mortality rate. Uricosuric agents are second-line therapy for patients who are intolerant of allopurinol, or they may be used in combination with allopurinol in patients with refractory hyperuricemia.

Probenecid is the uricosuric agent most often used in the United States. Uricosuric therapy is contraindicated in patients with a history of nephrolithiasis and is ineffective in those with a creatinine clearance of less than 50 mL per minute 0. Losartan Cozaar and fenofibrate Tricor have uricosuric properties and may be useful adjunctive therapies for patients with gout, hypertension, and hyperlipidemia. Treatment of acute flares should begin as soon as possible. Non-steroidal anti-inflammatory drugs NSAIDs or colchicine are considered first-line agents; oral corticosteroids are reserved for those who cannot tolerate, or who have contraindications, to first-line agents.

Colchicine 1. Even lower colchicine doses are required for those with renal impairment or receiving CYP3A4 or P-glycoprotein inhibitors. Allopurinol should not be stopped during acute flares of gout. In addition, there is a real risk of the allopurinol not being recommenced as well as precipitating another flare when it is recommenced. Historically, there has been concern that starting urate-lowering therapy such as allopurinol could worsen or prolong the acute gout flare.

Two small clinical trials have now found that this is not an issue. Based on these trials, it is reasonable to start allopurinol during an acute flare of gout when combined with acute gout treatment as this does not prolong the flare.

Evidence suggests that it is the starting dose of allopurinol, not the maintenance dose, that increases the risk of allopurinol hypersensitivity syndrome AHS. The American College of Rheumatology recommends that everyone commencing allopurinol start on mg per day, except those with stage 4 or worse chronic kidney disease, where the recommended starting dose is 50 mg per day. For example, in a patient with gout, no tophi and normal kidney function, one might start at mg a day for two to three weeks, then increase to mg per day for two to three weeks, then mg per days for two to three weeks.

If not, the dose is then titrated up to mg per day and the serum urate is checked again. In Australia, the maximum recommended dose of allopurinol is mg. Guidelines recommend testing for this allele in high AHS-risk individuals such as people of Asian descent with renal impairment, then avoiding allopurinol if it is present. Prophylaxis of acute flare of gout is recommended in those commencing on urate-lowering therapy.

Gout flares on starting urate-lowering therapy are very common and prophylaxis aims to prevent them from occurring. NSAIDs or colchicine are the first-line recommended agents.

The recommended duration of prophylaxis is now longer than what has previously been used. The American College of Rheumatology recommends:. This recommendation is in recognition that even after the target serum urate level has been reached, flares may continue to occur for some time.

Once target serum urate has been reached, six-monthly monitoring by testing serum urate is recommended to ensure continuing adequate management and adherence. Adherence with long-term allopurinol is poor and every effort should be made to encourage patients to continue to take it, including involving family members. Febuxostat is a newer agent used to treat gout that works by inhibiting xanthine oxidase — the same mechanism as allopurinol.

One approach is to start the patient on a very low dose of allopurinol eg 1. Research has suggested that patients with gout who lack confidence in their treatments have reduced adherence to their medications. A lack of confidence in treatment can result from their gout flaring after initiation of urate-lowering therapy.

A large intake of sugar or sweetened soft drinks, such as cola or lemonade, is a recognised risk for gout. Patients with gout are advised to limit their intake of these beverages. Although epidemiological evidence suggests that a high-purine diet increases the risk of gout, there is scant evidence that introducing a low-purine diet in those with gout results in a clinically meaningful reduction in gout flares or serum urate.

A comprehensive approach is best, including providing patients with a schema to help them understand important aspects of gout management Box 1. The increasing prevalence and impact of gout mean that greater focus is required to ensure best outcomes for patients.

Newer therapeutic agents are on the horizon, but gout can still be well treated with our current agents, especially in light of recent insights into treatment strategies, such as commencing allopurinol during acute attacks and starting at a low dose and titrating up.

Competing interests: Philip C Robinson has received research funding and consulting fees from AstraZeneca, and consulting fees from Menarini and Novartis. Lisa K Stamp has received consulting fees from AstraZeneca. Provenance and peer review: Not commissioned, externally peer reviewed. Australian Family Physician. Search for: Search AFP. Filter Relevance Date. Issues by year. Volume 45, Issue 5, May Background Gout is a common problem that is increasing in prevalence in Australia.

It is associated with many serious comorbidities such as hypertension, chronic kidney disease, obesity, diabetes and cardiovascular disease. Recent changes include the way that older drugs are used, as well as newer therapeutics becoming available or in development. Objective The objective of this article is to provide an update on the management of gout.

Discussion Developments in treatment strategies for gout and newer agents to treat gout are discussed in this article. The salient points include the need to treat gout to a serum urate target, the ability to start allopurinol during acute attacks, the need to treat with prophylactic anti-inflammatory drugs for adequate time periods, and the availability of a new urate-lowering drug on the Pharmaceutical Benefits Scheme PBS.

Common misconceptions Gout does not occur only in the great toe podagra , although this is a common site for the initial episode. Gout growing in prevalence and impact Gout has often been viewed as a nuisance and non-serious condition. There are treatments that: 1,7 raise serum urate eg thiazide, loop diuretics impair the actions of urate-lowering drugs eg frusemide lower serum urate eg losartan.