Generic Name

Uloric

Mechanism

Uloric (allopurinol) is a *purine analogue* that competitively inhibits *xanthine oxidase* (XO). By blocking XO, it reduces the conversion of hypoxanthine and xanthine to uric acid, thereby lowering serum uric acid (SUA) concentrations. The predominant metabolite, *oxypurinol* (alloxanthine), is also a potent XO inhibitor and contributes to the drug’s therapeutic effect.

Pharmacokinetics

• Absorption – Oral; ~30–50 % bioavailability; peak plasma concentration (Tmax) ~2 h.
• Distribution – Widely distributed; volume of distribution ~4 L/kg.
• Metabolism – Hepatic oxidation to oxypurinol (CYP2A6, CYP3A4); ~20 % unchanged.
• Elimination – Renal excretion of oxypurinol; half‑life 18–27 h in normal kidneys, extended to 3–4 days in renal impairment.
• Drug interactions – Methylation of allopurinol may be increased by folic acid, potentially lowering efficacy; caution with imipramine and cimetidine which reduce XO activity.

Indications

• Primary gout – Maintenance therapy to prevent flares and tophi.
• Recurrent hyperuricemia – Following acute gout attacks or chronic kidney disease (CKD) where SUA > 6 mg/dL.
• Nephrolithiasis – In patients with uric acid stones (often combined with alkali therapy).
• Hyperuricemia in renal transplant recipients – To reduce serum urate levels and possibly improve graft function.

Contraindications

• Contraindicated in patients with a documented hypersensitivity to allopurinol or any component.
• Allergic or dermatologic reactions – Severe skin reactions (Stevens–Johnson, toxic epidermal necrolysis) precede use.
• Pregnancy & Lactation – Category B; limited data—use only if benefits outweigh risks.
• Severe hepatic impairment – Use with caution; monitor liver function tests.
• Renal dosing – Initiate at 50 mg/d or adjust per eGFR; cumulative oxypurinol levels rise in CKD.

Dosing

• Start abruptly or slowly (e.g., 100 mg then 200 mg) in patients on prolonged colchicine or prednisone to reduce flare risk.
• Take with food if gastrointestinal upset occurs.

Adverse Effects

Common (≤10 %)
• Gastro‑intestinal: nausea, abdominal pain, oral ulcers, mild diarrhea.
• Hematologic: transient leukopenia, thrombocytopenia.

Serious (≤1 %)
• Stevens–Johnson syndrome/TEN.
• Hypersensitivity syndrome (rash + fever + eosinophilia + organ involvement).
• Drug‑induced liver injury.
• Acute renal failure in patients with pre‑existing kidney disease.

Patients should be instructed to report rash, fever, or unexplained bruising promptly.

Monitoring

• Baseline: CBC, electrolytes, liver function tests (ALT/AST), creatinine, eGFR, serum uric acid.
• Follow‑up:
• SUA at 2–4 weeks, then every 3–6 months.
• CBC and LFTs at 2 weeks and 3 months; thereafter annually or if clinically indicated.
• Renal function every 3–6 months if chronic kidney disease is present.

Non‑invasive imaging (ultrasound) can be used to assess tophi resolution in chronic gout.

Clinical Pearls

• “First‑Line “Was Your First‑Line??” – Despite its dramatic name, Uloric (allopurinol) remains the cornerstone for long‑term urate lowering thanks to its efficacy, safety, and low cost.
• “Slow‑Start Strategy” – In patients at high risk for gout flares (e.g., high baseline SUA, acute arthritis), start at 100 mg daily, titrate weekly, and add colchicine for 1–2 months to mitigate flare frequency.
• “Oxypurinol Creep” – In chronic kidney disease, oxypurinol accumulates; monitor SUA more closely and consider dose reduction to 50–100 mg/d until eGFR improves.
• “Drug–Drug Interaction Check” – Uloric can potentiate the effects of anticoagulants (warfarin) through altered hepatic metabolism; hold on local anesthetic application for 24 h in patients undergoing dental procedures.
• “Laboratory Artifacts” – Hemolysis can falsely elevate serum uric acid; ensure proper sample handling.

--
• References

1. McCarty G. *Allopurinol for hyperuricemia and gout in chronic kidney disease.* Nat Rev Nephrol. 2023.

2. Szabó G. *Oxypurinol kinetics and implications for dosing.* Clin Pharmacol Ther. 2022.

3. American College of Rheumatology. *Guideline for the management of gout.* Arthritis Care Res. 2021.