Comparison of xanthine oxidase inhibitors
Allopurinol | Febuxostat | |
|---|---|---|
| Mechanism of action | XOI Hypoxanthine analog | XOI (more potent than allopurinol) Not a hypoxanthine analog |
| Pharmacokinetics | 80%–90% bioavailability Half-life of 60 minutes Oxipurinol metabolite long-lived (t 1/2 14–28 hours) Max antihyperuricemic effect seen after 7–10 days | ∼50% bioavailability Extensive hepatic metabolism Equal hepatic and renal excretion Max antihyperuricemic effect seen after 5–7 days |
| Adverse events | Common Acute gouty arthritis: use prophylaxis Maculopapular erythematous rash: 3% (risk 3x higher if on ampicillin/amoxicillin) Gastrointestinal symptoms (nausea, diarrhea): 5%–10% Abnormal liver-associated enzymes: 6% Headache Uncommon (<1%) but serious Allopurinol hypersensitivity syndrome DRESS, SJS, TEN, vasculitis Oxipurinol xanthine nephrolithiasis Bone marrow suppression can occur early or late in treatment Hepatitis, peripheral neuropathy, interstitial nephritis, death Cataracts: dose and duration associated The overall incidence of side effects is around 20%, but only 5% of patients discontinue therapy as a result of drug toxicity | Common Acute gouty arthritis: use prophylaxis Nausea, rash, arthralgia: ∼1% Uncommon but serious DRESS, SJS, TEN Abnormal AST or ALT (∼5%) Potential cardiovascular risk |
| Contraindications or cautions to use | Interacting medications, especially azathioprine and 6-MP Avoid if history of rash with allopurinol Dose adjust for renal insufficiency | CrCl 15–29: do not exceed 40 mg daily Not studied and thus consider avoiding in patients with dialysis dependence or severe hepatic disease (Child–Pugh class C) |
| Drug interactions | AZA a : decrease azathioprine dose 50%–75%; safest to avoid concurrent use 6-MP a : dose adjust as with azathioprine Theophylline: metabolized by xanthine oxidase; increased concentration and marrow suppression Ampicillin/amoxicillin: increased risk of rash Thiazide diuretics: decreased allopurinol excretion Cyclophosphamide, warfarin, cyclosporine: levels all increased by allopurinol | AZA a : avoid combination 6-MP a : avoid combination Theophylline: increased plasma concentration |
| Cost | $27/month (30 tablets of 300 mg) | $400/month (40-mg and 80-mg tablets cost the same) With drug discount cards: $325/month |
6-MP, 6-Mercaptopurine; AZA, azathioprine; CrCl, creatinine clearance; DRESS, drug rash with eosinophilia and systemic symptoms; SJS, Stevens–Johnson syndrome; TEN, toxic epidermal necrolysis.
a AZA and 6-MP are both metabolized by xanthine oxidase, and hence use of xanthine oxidase inhibitors increases drug levels of both medications leading to an increased risk of bone marrow toxicity.
