What are the side effects of allopurinol?

Allopurinol Side Effects

Skin rash is the most common adverse reaction to allopurinol and should prompt immediate discontinuation of the medication as it can progress to severe and potentially fatal hypersensitivity reactions. 1

Common Side Effects

• Skin rash (maculopapular, sometimes scaly or exfoliative) - occurs in <1% of patients with current usage patterns 1
• Gastrointestinal disturbances including diarrhea and nausea 1
• Elevated liver enzymes (alkaline phosphatase, SGOT/SGPT) 1
• Acute gout attacks following initiation of therapy (now occurs in <1% of patients with proper dosing) 1, 2

Severe Hypersensitivity Reactions

• Allopurinol Hypersensitivity Syndrome (AHS) - a potentially life-threatening reaction with 25% mortality rate 2
• Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome 1
• Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis 1, 3
• Symptoms typically include:
  • Fever, chills, arthralgias 1
  • Widespread skin eruptions (erythematous, desquamative) 1, 4
  • Eosinophilia and leukocytosis 1, 4
  • Hepatitis and cholestatic jaundice 1, 4
  • Worsening renal function 1, 5
  • Multi-organ involvement (hepatic, renal, cardiac, gastrointestinal, lymphatic, pulmonary, ophthalmic) 1

Risk Factors for Hypersensitivity Reactions

• HLA-B*58:01 genetic variant - particularly prevalent in:
  • Han-Chinese and Thai populations (regardless of kidney function) 2, 6
  • Korean patients with stage 3 or worse chronic kidney disease 2, 6
• Renal impairment 5, 7
• Concomitant use of:
  • Thiazide diuretics 1, 7
  • Ampicillin or amoxicillin 1, 7

Drug Interactions

• Requires 65-75% dose reduction of 6-mercaptopurine or azathioprine when used concomitantly 6, 1
• Potential interactions with:
  • Cyclophosphamide and other cytotoxic agents 6
  • Dicumarol 2
  • Thiazide diuretics 2, 1
  • Chlorpropamide 2
  • Cyclosporine 2

Precautions to Minimize Side Effects

• Genetic testing for HLA-B*58:01 is recommended before initiating therapy in high-risk ethnic groups 2, 6
• Dose reduction of at least 50% in patients with renal insufficiency 2, 6, 5
• Start with low doses (100 mg daily) and titrate gradually to minimize risk of acute gout attacks 6
• Monitor liver function in patients with pre-existing liver disease 1
• Be cautious with concomitant use of thiazides in patients with decreased renal function 1
• Consider drowsiness as a potential side effect that may impact activities requiring alertness 1

When to Discontinue Allopurinol

• At the first appearance of skin rash or other signs of allergic reaction 1
• If anorexia, weight loss, or pruritus develops (may indicate hepatotoxicity) 1
• If signs of severe hypersensitivity reactions appear 1

The FDA label emphasizes that allopurinol should be discontinued immediately at the first sign of a skin rash, as this can progress to more severe and potentially fatal hypersensitivity reactions 1.