What are the potential side effects of allopurinol (Zyloprim)?

Potential Side Effects of Allopurinol (Zyloprim)

The most common side effects of allopurinol include skin rash, which can be severe and potentially fatal, gastrointestinal disturbances, and acute gout attacks during initial therapy. Severe hypersensitivity reactions, though rare, can be life-threatening and require immediate discontinuation of the medication.

Common Side Effects

• Skin reactions (less than 1% with current usage) 1

  • Pruritic maculopapular rash
  • Can progress to severe reactions including Stevens-Johnson syndrome or toxic epidermal necrolysis
  • Risk increases with renal insufficiency

• Gastrointestinal effects 1

  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal pain
  • Elevated liver enzymes (alkaline phosphatase, SGOT/SGPT)

• Acute gout attacks (less than 1% with current usage) 1

  • Typically occurs during initiation of therapy
  • Reduced incidence with gradual dose titration

Severe Adverse Reactions

Hypersensitivity Syndrome

• Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)/Drug Hypersensitivity Syndrome (DHS) 1, 2

  • Potentially life-threatening with 25% mortality rate
  • Features include:
    • Fever
    • Widespread skin rash
    • Eosinophilia
    • Multi-organ involvement (liver, kidneys, heart, lungs)
    • Typically develops within 1 week of starting therapy

• Risk factors for hypersensitivity 2, 3, 4

  • HLA-B*58:01 genetic variant (6-7% in East Asian populations, 1% in European descent)
  • Renal insufficiency
  • Concomitant thiazide diuretic use
  • Higher starting doses

Organ-Specific Side Effects

Hepatic Effects

• Hepatotoxicity 1
• Elevated liver enzymes
• Granulomatous hepatitis
• Hepatic necrosis (rare)

Renal Effects

• Worsening renal function 1, 5
• Renal failure (rare)
• Risk increased with pre-existing renal impairment

Hematologic Effects

• Eosinophilia 1
• Leukocytosis or leukopenia
• Thrombocytopenia
• Rare: aplastic anemia, agranulocytosis, pancytopenia

Drug Interactions

• Significant interactions requiring dose adjustments 2, 6, 1
  • Azathioprine and 6-mercaptopurine: Require 65-75% dose reduction when used with allopurinol
  • Ampicillin/amoxicillin: Increased risk of skin rash
  • Thiazide diuretics: Increased risk of hypersensitivity in patients with renal dysfunction
  • Other potential interactions: dicumarol, cyclophosphamide, chlorpropamide, cyclosporine

Monitoring and Prevention

• Monitoring recommendations

  • Regular liver function tests for patients with pre-existing liver disease 1
  • Renal function monitoring
  • Complete blood counts, especially during first few months of therapy 6

• Prevention strategies 3, 4

  • Genetic testing for HLA-B*58:01 in high-risk populations (Korean patients with CKD stage 3 or worse, Han-Chinese or Thai descent) 2
  • Lower starting doses in patients with renal impairment
  • Dose adjustment based on creatinine clearance
  • Patient education about early signs of hypersensitivity

Important Warnings

• ALLOPURINOL SHOULD BE DISCONTINUED IMMEDIATELY AT THE FIRST APPEARANCE OF SKIN RASH 1
• Patients should be advised to report any skin changes, fever, or signs of liver dysfunction promptly
• Drowsiness may occur; caution with activities requiring alertness 1

Remember that while severe reactions are uncommon, they can be life-threatening and require immediate medical attention. Early recognition and discontinuation of allopurinol at the first sign of hypersensitivity is critical for preventing progression to severe adverse reactions.