Gout Medication: Complete Guide to Treatment Options

What Medications Are Used to Treat Gout?

Gout treatment involves two medication categories: anti-inflammatory drugs (NSAIDs, colchicine, corticosteroids) for acute attacks, and urate-lowering therapies (allopurinol, febuxostat, probenecid, pegloticase) for long-term prevention by reducing uric acid levels.

Gout management requires understanding that this condition has two distinct phases that need different treatment approaches. During an acute flare, the primary goal is rapid pain relief and inflammation control. Between attacks, the focus shifts to lowering serum uric acid to prevent future flares and reverse existing urate crystal deposits in joints and soft tissues.

Acute Gout Medications

When a gout attack strikes, treatment should begin as quickly as possible—ideally within the first 24 hours of symptom onset. The three main options for acute treatment include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs): Indomethacin, naproxen, and other NSAIDs reduce inflammation and pain. They work best when started at full dose at the first sign of an attack.
• Colchicine: This medication specifically targets the inflammatory pathways involved in gout. Low-dose regimens are now preferred over older high-dose protocols.
• Corticosteroids: Prednisone or methylprednisolone provide effective relief, particularly for patients who cannot take NSAIDs or colchicine. Injectable forms can treat individual joints directly.

Urate-Lowering Therapies

Long-term management focuses on reducing serum uric acid to below 6 mg/dL (360 µmol/L), or below 5 mg/dL for patients with tophi. Options include:

• Xanthine oxidase inhibitors: Allopurinol and febuxostat block uric acid production and are first-line options for most patients.
• Uricosuric agents: Probenecid and lesinurad increase uric acid excretion through the kidneys. They work best for under-excretors with normal kidney function.
• Uricase therapy: Pegloticase breaks down uric acid directly and is reserved for severe, treatment-refractory gout.

How Do NSAIDs Work for Acute Gout Attacks?

NSAIDs work by blocking cyclooxygenase (COX) enzymes, which reduces prostaglandin production and decreases the inflammation, pain, and swelling of acute gout. They provide relief within 24-48 hours when started at full therapeutic doses.

Nonsteroidal anti-inflammatory drugs remain a cornerstone of acute gout treatment due to their rapid onset of action and widespread availability. When urate crystals trigger inflammation in a joint, the body releases prostaglandins that amplify pain signals and recruit more inflammatory cells. NSAIDs interrupt this cascade by inhibiting the enzymes responsible for prostaglandin synthesis.

Commonly Used NSAIDs for Gout

How to Take NSAIDs for Best Results

For maximum effectiveness in gout, NSAIDs should be started at full anti-inflammatory doses rather than typical analgesic doses used for headaches or minor pain. Treatment should begin at the first sign of an attack and continue for 1-2 days after symptoms completely resolve to prevent rebound inflammation.

Taking NSAIDs with food can reduce stomach irritation, though it may slightly delay absorption. For many patients, combining an NSAID with a proton pump inhibitor (like omeprazole) helps protect the stomach lining during short-term high-dose treatment.

Who Should Avoid NSAIDs

NSAIDs are not appropriate for everyone with gout. Patients with the following conditions should consider alternative treatments:

• Chronic kidney disease (especially stage 3 or higher)
• Active peptic ulcer disease or history of gastrointestinal bleeding
• Heart failure or significant cardiovascular disease
• Current use of anticoagulants or antiplatelet medications
• Uncontrolled hypertension
• History of NSAID allergy or aspirin-exacerbated respiratory disease

How Does Colchicine Work for Gout?

Colchicine works by disrupting microtubule formation in inflammatory cells, which prevents neutrophils from migrating to the affected joint and releasing inflammatory chemicals. The current low-dose regimen (1.2 mg followed by 0.6 mg one hour later) is as effective as higher doses with far fewer side effects.

Colchicine has been used for gout for over 2,000 years, making it one of the oldest medications still in regular clinical use. Unlike NSAIDs, which broadly suppress inflammation, colchicine specifically targets the inflammatory processes unique to crystal-induced arthritis. It interferes with microtubule assembly inside white blood cells, preventing them from reaching the joint and releasing the inflammatory mediators that cause pain and swelling.

Acute Gout Treatment with Colchicine

Modern colchicine dosing has changed significantly from historical practices. The older approach of hourly dosing until diarrhea developed caused severe side effects and is no longer recommended. Current guidelines favor a low-dose regimen that has been shown in clinical trials to be equally effective with a much better safety profile:

• Initial dose: 1.2 mg (two 0.6 mg tablets) at the first sign of a flare
• Second dose: 0.6 mg one hour later
• Maximum in first 24 hours: 1.8 mg total
• Subsequent days: 0.6 mg once or twice daily until flare resolves

The key to colchicine effectiveness is early administration. When taken within 12 hours of symptom onset, colchicine works remarkably well. When started more than 36 hours after a flare begins, response rates drop significantly, making NSAIDs or corticosteroids better choices for late-presenting attacks.

Colchicine for Flare Prevention

Low-dose colchicine plays an important role in preventing gout flares, particularly when starting urate-lowering therapy. As uric acid levels drop, existing crystals begin to dissolve, paradoxically triggering inflammation and increased flare risk during the first several months of treatment. Prophylactic colchicine at 0.6 mg once or twice daily reduces this risk by up to 85%.

Guidelines recommend continuing prophylactic colchicine for at least 3 to 6 months after reaching target uric acid levels, or longer in patients with tophi or frequent previous attacks. Many clinicians continue prophylaxis until the patient has been flare-free for 6 months with uric acid consistently below target.

Colchicine Side Effects and Precautions

The most common side effects of colchicine involve the gastrointestinal system, including diarrhea, nausea, vomiting, and abdominal cramping. These effects are dose-related and much less common with modern low-dose regimens. Serious but rare side effects include bone marrow suppression and neuromuscular toxicity, which occur primarily with overdose or prolonged high-dose use.

Dose Adjustments

Patients with kidney or liver disease require reduced colchicine doses because the drug is eliminated through both organs. Those with severe kidney impairment (creatinine clearance below 30 mL/min) should use colchicine cautiously and may need alternative treatments. Combining colchicine with certain medications that inhibit CYP3A4 or P-glycoprotein requires significant dose reductions or avoidance altogether.

When Are Corticosteroids Used for Gout?

Corticosteroids are first-line alternatives when NSAIDs and colchicine are contraindicated or ineffective. Oral prednisone (30-40 mg daily for 5-7 days), intra-articular injections, or intramuscular methylprednisolone provide rapid relief with different risk profiles depending on the route of administration.

Corticosteroids offer powerful anti-inflammatory effects that make them excellent options for acute gout, particularly in patients who cannot tolerate or have contraindications to NSAIDs and colchicine. They work by suppressing multiple inflammatory pathways simultaneously, including cytokine production, neutrophil recruitment, and prostaglandin synthesis.

Oral Corticosteroids

Prednisone is the most commonly prescribed oral corticosteroid for gout. A typical regimen starts at 30-40 mg daily and continues for 5-7 days, with or without a taper depending on physician preference and patient factors. Studies comparing prednisone to NSAIDs have shown equivalent effectiveness for pain relief, though some patients experience faster initial improvement with higher corticosteroid doses.

Key advantages of oral corticosteroids include:

• Safe in patients with kidney disease (unlike NSAIDs)
• No gastrointestinal bleeding risk from direct mucosal effects
• Can be used with anticoagulant therapy
• Effective for polyarticular gout affecting multiple joints

Intra-articular Corticosteroid Injections

When gout affects a single, accessible joint, direct injection of corticosteroids (such as triamcinolone acetonide or methylprednisolone acetate) provides rapid, targeted relief while minimizing systemic exposure. This approach is particularly useful for patients with diabetes or other conditions where systemic corticosteroids could cause complications.

Joint aspiration before injection serves a dual purpose: it confirms the diagnosis by allowing crystal analysis and provides immediate mechanical relief by removing inflammatory fluid. Many patients notice significant improvement within hours of the procedure.

Intramuscular Corticosteroids

A single intramuscular injection of methylprednisolone or triamcinolone provides an alternative when oral therapy is impractical or when multiple joints are involved but intra-articular injection is not feasible. This route provides consistent drug levels and avoids concerns about medication adherence during an acute attack.

Corticosteroid Precautions

Short courses of corticosteroids for acute gout are generally well-tolerated, but certain patients need closer monitoring:

• Diabetes: Expect temporary blood glucose elevations; may need insulin adjustment
• Infection: Corticosteroids can mask infection symptoms; rule out septic arthritis before treatment
• Hypertension: Sodium retention may worsen blood pressure control temporarily
• Psychiatric conditions: Mood changes or insomnia may occur
• Glaucoma: Intraocular pressure may increase

How Does Allopurinol Work to Prevent Gout?

Allopurinol inhibits xanthine oxidase, the enzyme that converts purines to uric acid. By blocking this final step in purine metabolism, allopurinol reduces uric acid production and, over time, allows existing urate crystals to dissolve. Starting at 100 mg daily and titrating to achieve target levels maximizes effectiveness while minimizing adverse reactions.

Allopurinol has been the foundation of gout prevention for over 50 years and remains the first-line urate-lowering therapy recommended by all major rheumatology guidelines. Its long track record, proven efficacy, favorable safety profile, and low cost make it the default choice for most patients requiring long-term uric acid management.

Mechanism of Action

In normal purine metabolism, the body breaks down purines (from food and cellular turnover) through a series of enzymatic reactions that eventually produce uric acid. Xanthine oxidase catalyzes the final two steps of this pathway, converting hypoxanthine to xanthine and then xanthine to uric acid. Allopurinol and its active metabolite oxipurinol bind to xanthine oxidase and prevent these conversions, leading to lower uric acid production and increased excretion of more soluble precursors.

Starting and Titrating Allopurinol

The key principle in allopurinol dosing is "start low, go slow." Beginning with low doses and gradually increasing reduces the risk of hypersensitivity reactions and paradoxical gout flares. A typical approach includes:

• Starting dose: 100 mg daily (50 mg in patients with chronic kidney disease)
• Titration: Increase by 100 mg every 2-4 weeks
• Target: Achieve serum uric acid below 6 mg/dL (or below 5 mg/dL with tophi)
• Maximum dose: 800 mg daily (though most patients achieve target at lower doses)

Regular monitoring of uric acid levels during titration ensures the appropriate dose is reached. Once stable, annual monitoring is typically sufficient. Importantly, patients with kidney impairment can still use allopurinol—they may simply require more gradual titration and potentially lower maintenance doses.

Allopurinol Hypersensitivity Syndrome

The most serious risk associated with allopurinol is hypersensitivity syndrome, a rare but potentially life-threatening reaction that can include severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), fever, hepatitis, kidney failure, and eosinophilia. Risk factors include:

• HLA-B*5801 genetic marker (common in certain Asian and African populations)
• Starting at high doses
• Chronic kidney disease
• Concurrent thiazide diuretic use

Genetic testing for HLA-B*5801 before starting allopurinol is recommended for patients of Southeast Asian descent (Korean, Han Chinese, Thai) and may be considered for African Americans and those of other high-risk ethnicities. In carriers of this marker, febuxostat or other alternatives are preferred.

Common Side Effects

Most patients tolerate allopurinol well. Common side effects that are generally mild include:

• Skin rash (usually mild and not indicative of serious hypersensitivity)
• Gastrointestinal upset
• Elevated liver enzymes
• Headache

Is Febuxostat Better Than Allopurinol?

Febuxostat is more potent at lowering uric acid than allopurinol but carries an FDA boxed warning for increased cardiovascular mortality risk based on the CARES trial. Current guidelines recommend febuxostat primarily for patients who cannot tolerate allopurinol, though the cardiovascular signal remains debated among experts.

Febuxostat (brand name Uloric) is a newer xanthine oxidase inhibitor that offers an alternative mechanism of action compared to allopurinol. While allopurinol is a purine analog that requires conversion to its active form, febuxostat is a non-purine selective inhibitor that binds directly to both the oxidized and reduced forms of xanthine oxidase, potentially providing more complete enzyme inhibition.

Efficacy Comparison

Clinical trials have consistently shown that febuxostat is more effective at lowering uric acid than allopurinol at commonly used doses:

• Febuxostat 40 mg daily achieves target uric acid in about 45% of patients
• Febuxostat 80 mg daily achieves target in approximately 70% of patients
• Allopurinol at fixed doses of 300 mg achieves target in about 40% of patients
• However, properly titrated allopurinol (up to 800 mg) can match febuxostat efficacy

The apparent superiority of febuxostat in many trials reflects a comparison against fixed-dose allopurinol rather than titrated dosing. When allopurinol is properly dose-adjusted to achieve target uric acid levels, the clinical outcomes are similar.

The CARES Trial and Cardiovascular Safety

The Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES) trial compared the two drugs in over 6,000 patients with gout and established cardiovascular disease. While overall cardiovascular events were similar between groups, febuxostat was associated with higher rates of cardiovascular death and all-cause mortality. This led to an FDA boxed warning in 2019.

Important caveats about this finding include:

• High dropout rate (over 50% in both groups) complicating interpretation
• Many deaths occurred after patients stopped the study drug
• Subsequent studies (FAST trial) found no cardiovascular difference
• The absolute risk increase was small

When to Consider Febuxostat

Based on current evidence and guidelines, febuxostat is appropriate when:

• Patient has documented allopurinol intolerance or allergy
• Patient cannot achieve target uric acid despite maximum tolerated allopurinol
• Patient carries HLA-B*5801 marker (higher risk of allopurinol hypersensitivity)
• Patient does not have significant cardiovascular disease

What Are the Side Effects of Gout Medications?

Each gout medication class has distinct side effects: NSAIDs can cause gastrointestinal bleeding and kidney damage; colchicine commonly causes diarrhea; allopurinol rarely causes severe hypersensitivity reactions; febuxostat may increase cardiovascular risk; and corticosteroids can affect blood sugar and bone health with prolonged use.

Understanding medication side effects helps patients recognize problems early and work with their healthcare providers to find the safest effective treatment. Most gout medications are well-tolerated when used appropriately, but awareness of potential adverse effects guides monitoring and decision-making.

NSAID Side Effects

Colchicine Side Effects

Gastrointestinal effects are the most common adverse reactions to colchicine:

• Diarrhea: Occurs in up to 25% with low-dose regimens (much higher with older high-dose protocols)
• Nausea and vomiting: Usually mild and transient
• Abdominal cramping: Often precedes diarrhea

Serious toxicity is rare with appropriate dosing but can include:

• Bone marrow suppression (aplastic anemia, agranulocytosis)
• Neuromyopathy (muscle weakness, neuropathy)
• Rhabdomyolysis (especially with statin interactions)
• Multi-organ failure with severe overdose

Allopurinol Side Effects

Common reactions (occurring in 1-10% of patients):

• Mild skin rash
• Elevated liver enzymes
• Diarrhea or nausea
• Gout flares (early in treatment)

Allopurinol hypersensitivity syndrome (rare but serious):

• Severe skin reactions (SJS/TEN): Life-threatening skin blistering
• DRESS syndrome: Drug reaction with eosinophilia and systemic symptoms
• Hepatitis and kidney failure
• Mortality rate of 20-25% if hypersensitivity develops

Febuxostat Side Effects

• Liver enzyme elevation
• Nausea and joint pain
• Rash (less common than with allopurinol)
• Cardiovascular events (boxed warning based on CARES trial)

Corticosteroid Side Effects

Short-term use (less than 2 weeks) generally causes few problems, but effects may include:

• Elevated blood glucose
• Fluid retention
• Mood changes or insomnia
• Increased appetite

Long-term or frequent use poses additional risks:

• Osteoporosis
• Adrenal suppression
• Increased infection risk
• Skin thinning
• Cataracts

How Is Gout Treated in Patients with Kidney Disease or Heart Problems?

Patients with kidney disease require careful medication selection: avoid NSAIDs, use reduced colchicine doses, and titrate allopurinol more slowly starting at 50 mg daily. For heart disease patients, naproxen is the safest NSAID if one must be used, and allopurinol is preferred over febuxostat for urate-lowering therapy.

Gout commonly occurs alongside other conditions that complicate treatment decisions. Kidney disease and cardiovascular disease are particularly important because they both affect medication choices and are themselves affected by uncontrolled hyperuricemia. Thoughtful medication selection allows effective gout management even in these complex scenarios.

Gout Treatment in Chronic Kidney Disease

Kidney impairment creates several treatment challenges:

Acute Flare Management

• NSAIDs: Generally contraindicated in moderate to severe CKD (eGFR below 30) due to risk of acute kidney injury and worsening baseline function
• Colchicine: Reduce dose and frequency; avoid in severe CKD or dialysis patients; requires careful attention to drug interactions
• Corticosteroids: First-line choice in CKD; no dose adjustment needed but monitor blood glucose
• IL-1 inhibitors: Anakinra or canakinumab may be considered for refractory cases

Long-Term Urate-Lowering Therapy

• Allopurinol: Can be used in CKD with appropriate dose adjustment; start at 50 mg daily and titrate slowly; contrary to older beliefs, dose can exceed creatinine clearance-based limits when titrated carefully
• Febuxostat: No dose adjustment needed for mild to moderate CKD; limited data in severe CKD
• Probenecid: Not effective when eGFR below 50 mL/min; contraindicated in patients with kidney stones

Gout Treatment in Cardiovascular Disease

Heart disease requires balancing gout control against cardiovascular risks:

Acute Treatment Considerations

• NSAIDs: Associated with increased cardiovascular events; if used, naproxen has the best safety data; use lowest effective dose for shortest duration
• Colchicine: Generally safe and may have cardioprotective effects; actually being studied for cardiovascular disease prevention
• Corticosteroids: Can cause fluid retention; use caution in heart failure

Urate-Lowering Therapy Considerations

• Allopurinol: Preferred first-line therapy; possible cardiovascular benefits suggested by some observational studies
• Febuxostat: FDA boxed warning advises against use in patients with established cardiovascular disease unless allopurinol fails; use with caution

Other Special Populations

Transplant Recipients

Organ transplant patients on cyclosporine or tacrolimus commonly develop hyperuricemia and gout. Key considerations include:

• Colchicine doses must be dramatically reduced or avoided due to interaction with cyclosporine
• Allopurinol requires caution with azathioprine (major interaction)
• Febuxostat may be preferred when azathioprine is part of the regimen
• Corticosteroids are often part of baseline immunosuppression and can be increased for flares

Elderly Patients

Older adults have increased vulnerability to medication side effects:

• Higher risk of NSAID-related bleeding and kidney injury
• More susceptible to colchicine toxicity
• May have multiple comorbidities limiting options
• Corticosteroids can worsen osteoporosis and glucose control

A comprehensive approach considering all conditions and medications is essential for safe and effective gout management in these populations.