Gout

Treatment Options for Gout: Allopurinol, Febuxostat, Probenecid, and Pegloticase

• Allopurinol and Febuxostat are Xanthine Oxidase inhibitors (XOI) used for initiating Urate Lowering Therapy in gout.
• Allopurinol initial dose is 50-100 mg daily, titrated every 2-5 weeks until uric acid levels are less than 6. Maximum dose is 800 mg.
• Febuxostat initial dose is 40 mg daily, increased to 80 mg daily if no response. Maximum dose is 40 mg in severe renal impairment.
• Both Allopurinol and Febuxostat require renal dose adjustments. Allopurinol also requires lower initial dose in CKD Stage 4 or greater.
• Allopurinol can cause agranulocytosis, aplastic anemia, myelosuppression, thrombocytopenia, renal failure, diarrhea, nausea, acute gout flares, rash, and allopurinol hypersensitivity syndrome.
• Allopurinol hypersensitivity syndrome (AHS) can be severe and fatal. Prevention includes HLA-B*5801 screening.
• Febuxostat can cause abnormal LFTs, nausea, mobilization flares, arthralgia, and rash. It has a black box warning for increased cardiovascular death risk in patients with CV disease.
• Probenecid is a uricosuric drug that competitively inhibits post-secretory renal proximal tubular reabsorption of uric acid.
• Probenecid initial dose is 500 mg daily or twice daily, titrated up to 500-2000 mg/day. It should be avoided in patients with CrCl < 50.
• Probenecid can cause flushing, dizziness, fever, headache, alopecia, dermatitis, pruritus, rash, anorexia, dyspepsia, nausea, anemia, gouty arthritis, and hypersensitivity.
• Pegloticase is a pegylated recombinant modified mammalian urate oxidase used for refractory gout.
• Pegloticase dosing is 8 mg infusion over 2 hours every 2 weeks, premedicated with corticosteroids and antihistamines. It can cause gout flares, infusion reactions, nausea, vomiting, bruising, nasopharyngitis, constipation, chest pain, and anaphylaxis.