In a patient receiving the standard four‑drug anti‑tuberculosis regimen (isoniazid, rifampin, ethambutol, pyrazinamide) who develops an acute gout flare, should the TB drugs be continued and what is the recommended acute gout treatment?

Management of Acute Gout Flare During TB Treatment

Continue all TB medications without interruption and treat the acute gout flare with standard anti-inflammatory therapy—pyrazinamide should NOT be discontinued for an acute gout attack. 1

Key Principle: Distinguish Gout from Contraindications to Pyrazinamide

The critical distinction is between pre-existing severe gout (a relative contraindication to starting pyrazinamide) versus an acute gout flare that develops during treatment (not a reason to stop pyrazinamide). 1

• The American Thoracic Society/CDC/IDSA guidelines list "gout" as an example where pyrazinamide "may be withheld" when initiating therapy, but this refers to severe, uncontrolled gout present before treatment starts. 1
• Once a patient is already on the four-drug regimen and develops an acute gout attack, stopping pyrazinamide would compromise TB treatment efficacy and potentially lead to drug resistance. 1

Management Algorithm

Step 1: Continue All TB Medications

• Do not stop pyrazinamide, rifampin, isoniazid, or ethambutol. 1
• Interrupting the standard four-drug regimen increases the risk of treatment failure and acquired drug resistance. 1
• The standard 6-month regimen (2 months of HRZE followed by 4 months of HR) should be completed as planned. 1

Step 2: Treat the Acute Gout Flare

• NSAIDs (e.g., indomethacin 50 mg three times daily or naproxen 500 mg twice daily) are first-line for acute gout in patients without contraindications. [@General Medicine Knowledge@]
• Colchicine (1.2 mg loading dose, then 0.6 mg one hour later, followed by 0.6 mg once or twice daily) is an alternative, particularly if NSAIDs are contraindicated. [@General Medicine Knowledge@]
• Corticosteroids (e.g., prednisone 30-40 mg daily for 5-7 days) can be used if both NSAIDs and colchicine are contraindicated or ineffective. [@General Medicine Knowledge@]

Step 3: Monitor for Hepatotoxicity

• Pyrazinamide is a known hepatotoxin, and the combination of isoniazid, rifampin, and pyrazinamide carries hepatotoxicity risk. 2
• Check liver function tests (AST/ALT, bilirubin) if the patient develops symptoms of hepatitis (nausea, vomiting, jaundice, abdominal pain). 1, 2
• If AST/ALT rises to 5 times the upper limit of normal or bilirubin rises significantly, stop rifampin, isoniazid, and pyrazinamide temporarily and manage as drug-induced hepatotoxicity. 1

When Pyrazinamide Should Actually Be Withheld

Pyrazinamide should only be omitted or stopped in these specific circumstances:

• Severe pre-existing liver disease with abnormal baseline liver function tests. 1
• Drug-induced hepatotoxicity during treatment (AST/ALT ≥5× upper limit of normal or rising bilirubin). 1, 2
• Documented pyrazinamide resistance on drug susceptibility testing. 1

If pyrazinamide must be stopped, the regimen should be modified to isoniazid, rifampin, and ethambutol daily for 2 months, followed by isoniazid and rifampin for 7 additional months (total 9 months of treatment). 1

Common Pitfalls to Avoid

• Do not confuse hyperuricemia (asymptomatic elevation of uric acid) with acute gout. Pyrazinamide commonly causes hyperuricemia in up to 40% of patients, but this alone is not a reason to stop the drug. [@General Medicine Knowledge@]
• Do not stop pyrazinamide for an acute gout flare. This would necessitate extending TB treatment from 6 months to 9 months and reduce treatment efficacy. 1
• Do not use allopurinol or febuxostat during the acute gout attack. Urate-lowering therapy should not be initiated during an acute flare as it can worsen symptoms; these agents are for chronic gout prophylaxis only. [@General Medicine Knowledge@]
• Avoid rifampin drug interactions. If using corticosteroids for gout, be aware that rifampin induces hepatic enzymes and may reduce corticosteroid efficacy, potentially requiring higher doses. 3, 4

Special Considerations

• If the patient has recurrent gout flares during TB treatment, consider prophylactic colchicine 0.6 mg once or twice daily after the acute attack resolves, while continuing all TB medications. [@General Medicine Knowledge@]
• Ensure adequate hydration (at least 2-3 liters of fluid daily) to help reduce uric acid levels and minimize further gout risk. [@General Medicine Knowledge@]
• Monitor renal function if using NSAIDs or colchicine, as both can have renal toxicity, and pyrazinamide is also renally cleared. [@General Medicine Knowledge@]