Introduction
Zyloprim (allopurinol) is a xanthine oxidase inhibitor used primarily for the management of hyperuricemia in patients with gout, and for the prevention and treatment of tumor lysis syndrome. First approved by the FDA in 1966, it remains a cornerstone therapy for chronic uric acid control.
Mechanism of Action
Zyloprim and its active metabolite oxypurinol inhibit xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid. By blocking this final step in uric acid production, Zyloprim reduces serum and urinary uric acid concentrations without disrupting the biosynthesis of purines.
Indications
- Management of hyperuricemia associated with gout (chronic therapy)
- Prevention and treatment of hyperuricemia secondary to chemotherapy in patients with leukemia, lymphoma, or other malignancies
- Prevention of recurrent uric acid nephrolithiasis
- Management of tumor lysis syndrome
Dosage and Administration
Adults:
- Gout: Initial dose 100-300 mg/day; maintenance dose 200-600 mg/day (maximum 800 mg/day)
- Prevention of tumor lysis syndrome: 600-800 mg/day starting 1-2 days before chemotherapy
Renal impairment:
- CrCl 10-20 mL/min: Max 200 mg/day
- CrCl 3-10 mL/min: Max 100 mg/day
- CrCl <3 mL/min: Max 100 mg with extended intervals
Administration:
- Oral administration with meals to minimize GI upset
- Adequate fluid intake (2-3 L/day) to prevent renal stone formation
- Dose adjustment required in renal impairment
Pharmacokinetics
- Absorption: Approximately 90% orally absorbed, peak concentrations in 1.5 hours
- Distribution: Widely distributed throughout body tissues, Vd ≈ 1.6 L/kg
- Metabolism: Hepatic metabolism to active metabolite oxypurinol
- Elimination: Renal excretion (oxypurinol half-life 18-30 hours, prolonged in renal impairment)
- Protein binding: Minimal (<1%)
Contraindications
- Hypersensitivity to allopurinol or any component of the formulation
- Patients who have experienced severe reactions to allopurinol (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
Warnings and Precautions
- Severe skin reactions: Discontinue immediately at first sign of rash
- Hepatotoxicity: Monitor liver function tests periodically
- Bone marrow suppression: May cause leukopenia, thrombocytopenia
- Renal impairment: Requires dose reduction; monitor renal function
- Acute gout flares: May occur during initial therapy; concurrent NSAID or colchicine prophylaxis recommended
- Xanthine deposition: May occur in patients with very high uric acid levels
Drug Interactions
- Azathioprine/6-mercaptopurine: Allopurinol inhibits metabolism; reduce dose by 65-75%
- Warfarin: May enhance anticoagulant effect; monitor INR closely
- Theophylline: May increase theophylline concentrations
- Ampicillin/amoxicillin: Increased risk of skin rash
- Diuretics: May increase risk of hypersensitivity reactions
- ACE inhibitors: Possible increased risk of hypersensitivity reactions
Adverse Effects
Common (>10%):
- Rash (may be dose-related)
- Nausea, vomiting, diarrhea
- Elevated liver enzymes
Serious (<1% but potentially life-threatening):
- Stevens-Johnson syndrome/toxic epidermal necrolysis
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Hepatotoxicity (including fatal hepatic necrosis)
- Bone marrow suppression (agranulocytosis, aplastic anemia)
- Acute renal failure
- Vasculitis
Monitoring Parameters
- Serum uric acid levels (target <6 mg/dL for gout)
- Renal function (BUN, creatinine) at baseline and periodically
- Liver function tests at baseline and periodically
- Complete blood count with differential
- Signs/symptoms of hypersensitivity reactions
- Fluid intake/output for stone prevention
- Signs of acute gout flare during initiation
Patient Education
- Take medication exactly as prescribed, usually with meals
- Maintain adequate fluid intake (8-10 glasses of water daily)
- Report any skin rash, fever, sore throat, unusual bleeding, or yellowing of skin/eyes immediately
- Do not discontinue medication without consulting healthcare provider
- Be aware that gout attacks may increase during initial treatment
- Avoid alcohol consumption as it may decrease effectiveness and increase uric acid levels
- Inform all healthcare providers about Zyloprim use, especially before new prescriptions
- Regular follow-up appointments are essential for monitoring
References
1. Becker MA, Schumacher HR, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450-2461.
2. Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum. 2012;64(8):2529-2536.
3. FDA Prescribing Information: Zyloprim (allopurinol). Revised 2016.
4. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29-42.
5. Terkeltaub RA. Clinical practice. Gout. N Engl J Med. 2003;349(17):1647-1655.
6. Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984;76(1):47-56.
