What medications can cause gout flare-ups in a patient with a history of gout?

Medications That Can Cause Gout Flare-Ups

Diuretics (Highest Risk)

Thiazide and loop diuretics are the most common medication-related triggers for gout flares and should be switched to alternative antihypertensives when feasible. 1

Thiazide Diuretics

• Hydrochlorothiazide significantly suppresses urate excretion with prolonged use, leading to hyperuricemia 2
• Associated with 1.70-fold increased risk of incident gout compared to past use 3
• The 2020 ACR guidelines conditionally recommend switching hydrochlorothiazide to an alternate antihypertensive when feasible for all patients with gout, regardless of disease activity 1

Loop Diuretics

• Furosemide causes sustained suppression of urate excretion with long-term use 2
• Associated with 2.64-fold increased risk of incident gout—the highest risk among individual diuretic classes 3
• Combined use of loop and thiazide diuretics carries the highest risk (4.65-fold increase) 3

Thiazide-Like Diuretics

• Associated with 2.30-fold increased risk of incident gout 3
• Should be avoided or switched when managing gout patients 1

Potassium-Sparing Diuretics

• Not associated with increased gout risk (OR 1.06, not statistically significant) 3
• May be a safer diuretic alternative if diuretic therapy cannot be discontinued 3

Calcineurin Inhibitors

Cyclosporine and tacrolimus elevate serum urate levels and should be eliminated when non-essential for optimal management of comorbidities 1

• These immunosuppressants are commonly used post-transplant and in autoimmune conditions 1
• The ACR recommends discontinuation only when not essential for managing major organ transplant or other critical conditions 1

Niacin (Nicotinic Acid)

• Causes uric acid underexcretion 1
• Should be eliminated when non-essential for hyperlipidemia management 1
• The ACR specifically recommends against switching cholesterol-lowering agents to fenofibrate solely for urate-lowering effects, despite fenofibrate's modest urate-lowering properties 1

Low-Dose Aspirin

Low-dose aspirin (≤325 mg daily) modestly elevates serum urate but should NOT be discontinued in patients taking it for cardiovascular prophylaxis. 1

• The 2020 ACR guidelines conditionally recommend against stopping low-dose aspirin for patients taking it for appropriate cardiovascular indications, regardless of gout disease activity 1
• The cardiovascular benefits far outweigh the modest hyperuricemic effects 1
• The ACR Task Force Panel viewed the relative risks specifically attributable to low-dose aspirin's effects on serum urate as negligible in gout management 1

Urate-Lowering Therapy Initiation (Paradoxical Flares)

Allopurinol and febuxostat can paradoxically trigger gout flares when first initiated due to mobilization of urate from tissue deposits. 1, 4

• This occurs due to changing serum uric acid levels resulting in mobilization of urate crystals from tissue deposits 4
• Anti-inflammatory prophylaxis with colchicine, NSAIDs, or low-dose corticosteroids is mandatory when starting urate-lowering therapy 1, 4
• Prophylaxis should continue for at least 6 months, or 3 months after achieving target serum urate if no tophi present 1
• The ACR strongly recommends starting ULT at low doses and titrating gradually to mitigate flare risk 1

Safer Antihypertensive Alternatives

Losartan (Preferred Alternative)

• Losartan increases urinary excretion of uric acid and has modest urate-lowering effects 1, 5
• The 2020 ACR guidelines conditionally recommend choosing losartan preferentially as an antihypertensive when feasible for patients with gout, regardless of disease activity 1
• Current use of losartan slightly attenuates gout risk in patients taking diuretics 3

Calcium Channel Blockers

• Current use slightly attenuates gout risk in patients taking diuretics 3
• Represent a safer alternative to diuretics for blood pressure management in gout patients 3

Clinical Algorithm for Medication Review

1. Identify all diuretics: Prioritize switching thiazide and loop diuretics to losartan or calcium channel blockers when blood pressure control allows 1, 3

2. Assess aspirin use: Continue low-dose aspirin if prescribed for cardiovascular prophylaxis—do not discontinue 1

3. Review immunosuppressants: Evaluate whether calcineurin inhibitors are essential for transplant or critical autoimmune management 1

4. Evaluate lipid therapy: Do not switch statins to fenofibrate solely for urate-lowering—maintain optimal lipid management 1

5. Screen for niacin: Consider alternative lipid-lowering agents if niacin is contributing to hyperuricemia 1

6. When initiating ULT: Always provide prophylactic anti-inflammatory therapy (colchicine 0.6 mg daily, low-dose NSAID, or prednisone <10 mg/day) for at least 6 months 1, 4

Important Caveats

• The association between diuretics and gout may be partially confounded by underlying cardiovascular disease, which independently increases gout risk 6
• However, the preponderance of evidence supports a direct causal relationship between diuretic use and gout flares 2, 3
• Medication changes should only be considered when potential serum urate/gout benefits exceed the risks of the medication change 1
• Never discontinue medications essential for managing life-threatening conditions (e.g., heart failure requiring loop diuretics, transplant requiring calcineurin inhibitors) 1