What are the common side effects of allopurinol?

Common Side Effects of Allopurinol

The most frequent adverse reaction to allopurinol is skin rash, which can range from mild to severe and potentially life-threatening. 1 Other common side effects include gastrointestinal symptoms (diarrhea, nausea), liver enzyme elevations, and acute gout attacks during initial therapy.

Common Side Effects by System

Skin and Hypersensitivity Reactions

• Skin rash: The most common adverse effect, occurring in <1% of patients with current usage 1
• Maculopapular rash, sometimes scaly or exfoliative 1
• Pruritus (itching)
• Severe hypersensitivity reactions including:
  • Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Exfoliative, urticarial, and purpuric lesions 1

Gastrointestinal

• Diarrhea
• Nausea
• Vomiting
• Intermittent abdominal pain
• Gastritis
• Dyspepsia 1

Hepatic

• Elevated liver enzymes (alkaline phosphatase, SGOT/SGPT)
• Hepatic necrosis (rare)
• Granulomatous hepatitis (rare)
• Hepatomegaly
• Hyperbilirubinemia
• Cholestatic jaundice 1

Hematologic

• Thrombocytopenia
• Eosinophilia
• Leukocytosis
• Leukopenia 1

Metabolic

• Acute attacks of gout (particularly during initiation of therapy) 1

Neurological

• Headache
• Drowsiness
• Peripheral neuropathy
• Neuritis
• Paresthesia
• Somnolence 1

Musculoskeletal

• Myopathy
• Arthralgias 1

Risk Factors for Severe Reactions

Certain factors increase the risk of developing serious adverse reactions:

1. Renal insufficiency: Increases the risk of skin rash 1
2. Concurrent medications:
   • Ampicillin or amoxicillin: Increases frequency of skin rash 1
   • Thiazide diuretics: May increase hypersensitivity reactions in patients with decreased renal function 1
3. Genetic factors: HLA-B*58:01 variant (particularly in East Asian populations) increases risk of hypersensitivity reactions 2, 3

Monitoring and Prevention

• Discontinue allopurinol immediately at the first appearance of skin rash or signs of allergic reaction 1
• Monitor liver function if symptoms like anorexia, weight loss, or pruritus develop 1
• Consider genetic testing for HLA-B*58:01 in high-risk populations 3
• Start with lower doses in patients with renal impairment 3
• Be cautious when using allopurinol with thiazides in patients with decreased renal function 1

Allopurinol Hypersensitivity Syndrome (AHS)

This potentially life-threatening condition has a 25% mortality rate 3 and is characterized by:

• Fever
• Severe and profuse skin rash
• Elevated leukocyte counts (particularly eosinophils)
• Lymphadenopathy
• Multi-organ pathologies (especially hepatic and renal systems)
• Symptoms typically develop approximately 1 week after starting therapy 1

Understanding these common side effects and risk factors is essential for monitoring patients on allopurinol therapy and intervening promptly if adverse reactions occur.