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      News & Perspective Drugs & Diseases CME & Education Video Decision Point
      Drugs & Diseases > Rheumatology

      Gout and Pseudogout Medication

      Updated: Jan 07, 2024
      • Author: Bruce M Rothschild, MD; Chief Editor: Herbert S Diamond, MD  more...
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      Medication

      Medication Summary

      Acute inflammation due to gout can be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine. NSAIDs are the most commonly used drugs in acute gout. Canakinumab gained approval for gout flares in 2023 and may be considered for gout flares in patients in whom NSAIDs and colchicine are contraindicated, not tolerated, or do not provide an adequate response. 

      Over the long term, gout is treated by decreasing tissue stores of uric acid with the xanthine oxidase inhibitors allopurinol or febuxostat or with the uricosuric agent probenecid. Because agents that lower uric acid can precipitate attacks of gout, low-dose colchicine is typically used as prophylaxis (usually for 6 months) when such therapy is initiated.

      If these measures, along with adjustment of contributing medications (eg, diuretics), do not result in appropriate reduction of serum uric acid levels, uric acid−lowering treatment is escalated as recommended in the 2012 American College of Rheumatology (ACR) gout guidelines. [138, 139]

      Other agents lower uric acid levels as a secondary effect. The angiotensin-receptor blocker (ARB) losartan is moderately uricosuric at 50 mg/day. The lipid-lowering agent fenofibrate reduces serum urate 19% and increases clearance by 36% at 200 mg/day. [53]

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      Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

      Class Summary

      As a class, NSAIDs are the drugs most widely used to treat the pain and inflammation of acute gout attacks in patients who can safely take these medications. Although NSAID effects on pain tend to be patient-specific, naproxen and indomethacin are common choices. Nevertheless, the choice of an NSAID is a matter more of habit than of science. Use of concomitant gastric protection with misoprostol or consideration of a cyclooxygenase-2 (COX-2)–specific NSAID might be considered if the patient has gastrointestinal (GI) risk or is older than 51 years.

      To control the attack as quickly and safely as possible (recalling that it takes 5 half-lives to reach steady state), consider using an NSAID with a short half-life (eg, ketoprofen, ibuprofen, or diclofenac). Use the maximum dosage of NSAID, and taper over approximately 10-14 days, depending on patient response.

      Naproxen (Aleve, Mediproxen, Naprelan, Naprosyn, EC-Naprosyn)

      Naproxen is used for relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing activity of the enzyme cyclooxygenase, which in turn decreases prostaglandin synthesis.

      Ketoprofen

      Ketoprofen is used for the relief of mild-to-moderate pain and inflammation. Small doses are initially indicated in small and elderly patients and in those with renal or liver disease. Individual doses greater than 75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe the patient for response.

      Diclofenac (Dyloject, Zorvolex, Zipsor, Cambria)

      Diclofenac inhibits prostaglandin synthesis by decreasing activity of the enzyme cyclooxygenase, which in turn decreases formation of prostaglandin precursors.

      Indomethacin (Indocin, Tivorbex)

      Indomethacin has been the NSAID traditionally used to treat acute inflammation in gout, though other NSAIDs are effective in this setting as well. Like all NSAIDs, indomethacin blocks cyclooxygenase and thereby reduces the generation of prostaglandins.

      Celecoxib (Celebrex)

      Unlike most NSAIDs, which inhibit both COX-1 and COX-2, the selective COX-2 inhibitor celecoxib offers the possibility of relieving inflammation and pain, but with a lower risk of GI side effects. It has been suggested that COX-2 expression in monocytes is induced in response to urate crystals.

      Several studies have found that selective COX-2 inhibitors are comparable to other NSAIDs for treating acute gouty arthritis. However, celecoxib requires particularly high doses to provide pain relief comparable to that provided by indomethacin in acute gout. [108]

      Selective COX-2 inhibitors may increase the risk of cardiac disease; 1 drug in this class, rofecoxib, was removed from the market for this reason. Celecoxib has been under investigation for associated risk of accelerated cardiac disease. Curiously, the risk appears to be associated with ingestion of 200 mg twice daily, but not with ingestion of 400 mg once daily.

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      Uricosuric Agents

      Class Summary

      Uricosuric agents lower uric acid levels by inhibiting renal tubular reabsorption of uric acid, thereby increasing net renal excretion of uric acid. These agents increase the risk of renal stones, with about a 9-10% risk for probenecid. They should not be started during an attack of acute gouty arthritis. The goal of therapy is to lower serum uric acid to approximately 5-6 mg/dL without causing renal stones.

      Colchicine (Colcrys, Mitigare)

      Colchicine inhibits microtubules and may thereby inhibit phagocytosis, neutrophil mobility, and chemotaxis. It also may inhibit generation of prostaglandins. The traditional approach of giving colchicine until vomiting or diarrhea appears is not appropriate; these are signs of toxicity. Instead, 1.2 mg is given orally, followed by 0.6 mg after 1 hour. Dose reduction is required for coingestion of interacting drugs (eg, P-gp or CYP3A4 inhibitors).

      Probenecid

      Probenecid lowers tissue stores of uric acid by increasing net renal excretion of uric acid through inhibition of tubular reabsorption. Some authorities recommend alkalizing the urine when starting probenecid to reduce the risk for renal stone formation. Probenecid is indicated for long-term management of hyperuricemia associated with gout.

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      Corticosteroids

      Class Summary

      Corticosteroids are potent and effective anti-inflammatory drugs that can be used to treat acute gout in patients who cannot tolerate NSAIDs or colchicine. They can be given orally, intramuscularly (IM), intravenously (IV), or intra-articularly. Adrenocorticotropic hormone (ACTH) also acts in gout, in part by inducing adrenal steroids. No intrinsic advantage to treating with IV corticosteroids exists unless the patient cannot take oral medications.

      The short-burst corticosteroid regimen used to treat an acute flare of gout is generally well tolerated. Nevertheless, patients may experience the adverse effects seen with long-term steroid use.

      In patients with only 1 or 2 involved joints, intra-articular corticosteroids are a safe and effective treatment option, once infection has been excluded. Water-soluble steroids (eg, dexamethasone) are teleologically inappropriate for use as a depot steroid treatment.

      Prednisone (Deltasone, Prednisone Intensol, Rayos)

      Oral prednisone can be given to abort an attack of gout. By reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity, this agent may decrease inflammation. Steroid dose packs that clearly label the dose to be taken each day can be convenient for some patients.

      Triamcinolone (Kenalog, Zilretta)

      Intra-articular use is considered by some as the treatment of choice for pseudogout and for acute gouty attacks in patients who cannot be given NSAIDs, colchicine, or high-dose systemic corticosteroids.

      Corticotropin (HP Acthar)

      Corticotropin stimulates endogenous production of corticosteroids and directly and rapidly acts on peripheral leukocyte activation. It decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability.

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      Xanthine Oxidase Inhibitors

      Class Summary

      Inhibition of xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine, reduces the synthesis of uric acid without disrupting the biosynthesis of vital purines. This results in the reduction of the tissue stores of uric acid. The goal of therapy is to lower the serum uric acid level to approximately 5-6 mg/dL. These agents should not be started during an attack of acute gouty arthritis without adequate control of the gouty inflammation.

      Allopurinol (Zyloprim, Aloprim)

      Allopurinol reduces production of uric acid, thereby allowing the body to dispose of excess uric acid stores. It is the most effective therapy for lowering serum uric acid. Most patients achieve the target uric acid level of 5 mg/dL at a dosage of 300-400 mg/day. A lower dosage is used if renal insufficiency is present.

      Febuxostat (Uloric)

      Febuxostat is a potential alternative to allopurinol. [126, 127] Like allopurinol, febuxostat is a xanthine oxidase inhibitor that prevents uric acid production and lowers elevated serum uric acid levels. Unlike allopurinol, it is a thiazolecarboxylic acid derivative, not a purine base analogue. Febuxostat physically blocks the channel to the molybdenum-pterin active site of xanthine oxidase and is metabolized by liver oxidation and glucuronidation. [42]

      Common adverse events include upper respiratory tract infections, arthralgias, diarrhea, headache, and liver function abnormalities. Atrioventricular block or atrial fibrillation and cholecystitis also have been reported. [141] As with other uricosuric agents, initiation of febuxostat may precipitate gouty attacks. [42, 141]

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      Selective Uric acid Reabsorption Inhibitor (SURI)

      Class Summary

      May consider adding a SURI to the therapeutic regimen in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.

      Lesinurad (Zurampic)

      Lesinurad is the first selective uric acid reabsorption inhibitor to be approved in the United States. It acts by inhibiting the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid. It also inhibits organic anion transporter 4 (OAT4), a uric acid transporter associated with diuretic-induced hyperuricemia. It is indicated in combination with a xanthine oxidase inhibitor for hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.

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      Rheumatologics, Other

      Class Summary

      Uricase facilitates conversion of urate to allantoin. Unlike uric acid, allantoin is soluble and easily excreted by the kidneys. Thus, hyperuricemia is reduced, with little risk of acute kidney injury.

      Pegloticase (Krystexxa)

      Pegloticase is a pegylated uric acid–specific enzyme that is a polyethylene glycol conjugate of recombinant uricase. It achieves its therapeutic effect by catalyzing oxidation of uric acid to allantoin, thereby lowering serum uric acid levels. Pegloticase is indicated for gout in adults who are refractory to conventional therapy. It is administered as an IV infusion every 2 weeks plus weekly oral methotrexate. Pegloticase alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate.  

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      Interleukin Inhibitors

      Class Summary

      Interleukin-1β (IL-1β) is involved in mediating gouty inflammation. Inhibiting IL-1β has may decrease gout-related pain and inflammation. 

      Canakinumab (Ilaris)

      Indicated for gout flares in adults in whom NSAIDs and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate. 

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      Corticotropic Hormones

      Class Summary

      Corticotropic hormones stimulate synthesis and release of corticosteroid hormones. They are principally used in diagnostic tests to differentiate primary adrenal insufficiency from secondary adrenal insufficiency. They have limited therapeutic value in conditions responsive to corticosteroid therapy, for which a corticosteroid should be the drug of choice.

      Cosyntropin (Cortrosyn)

      Cosyntropin is an adrenocorticotropic hormone (corticotropin) that stimulates the production and release of endogenous steroids. It is an effective treatment of acute crystal-induced arthritis in postoperative patients and in other patients who cannot take oral medications.

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