Can Clozaril (clozapine) cause eosinophilia?

Clozapine and Eosinophilia

Yes, clozapine does cause eosinophilia in approximately 1% of patients, typically occurring during the first month of treatment and requiring careful monitoring for associated organ involvement. 1

Incidence and Timing

• Eosinophilia (defined as blood eosinophil count >700/μL) occurs in approximately 1% of patients taking clozapine 1
• Typically develops during the first month of treatment, most commonly between weeks 3-5 2
• Women appear to be at significantly higher risk (23%) compared to men (7%) 2

Clinical Significance and Monitoring

Potential Complications

Clozapine-related eosinophilia can be associated with serious systemic reactions including:

• Myocarditis
• Pancreatitis
• Hepatitis
• Colitis
• Nephritis 1

These organ involvements may represent drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome 1.

Monitoring Protocol

If eosinophilia develops during clozapine treatment:

1. Promptly evaluate for signs and symptoms of systemic reactions:

   • Rash or allergic symptoms
   • Myocarditis (chest pain, ECG changes)
   • Other organ-specific diseases 1

2. Management algorithm:

   • If systemic disease is suspected: Discontinue clozapine immediately
   • If unrelated cause identified (asthma, allergies, parasites): Treat underlying cause and continue clozapine
   • If no organ involvement: Continue clozapine with careful monitoring 1
   • If eosinophil count continues to increase over several weeks without systemic disease: Consider temporary interruption and rechallenge after eosinophil count decreases 1

Case Examples and Course

• Cases of successful rechallenge after discontinuation have been reported without recurrence of eosinophilia 1, 3
• In many cases, eosinophilia resolves spontaneously despite continued clozapine treatment, suggesting a possible acute allergic reaction 3
• Resolution typically occurs within 3 weeks without medical or psychiatric complications 2

Rare Manifestations

Several unusual presentations of clozapine-associated eosinophilia have been documented:

• Eosinophilic colitis 4
• Asymptomatic pancreatitis with eosinophilia 5
• Peripheral and pleural fluid eosinophilia 6

Clinical Implications

• Eosinophilia should be considered a common side effect of clozapine treatment 2
• Regular monitoring of complete blood counts is essential, particularly during the first 1-2 months
• The presence of eosinophilia without organ involvement does not necessarily require discontinuation of clozapine 3
• Careful clinical assessment and consultation with specialists (internist or hematologist) is recommended for persistent eosinophilia 1

Pitfalls and Caveats

• Do not automatically discontinue clozapine upon detecting eosinophilia without evidence of organ involvement, as this may unnecessarily deprive patients of an effective treatment 3
• Be vigilant for subtle signs of organ involvement that may indicate DRESS syndrome
• Consider monitoring pancreatic enzymes during the first 6 weeks of treatment, as asymptomatic pancreatitis may occur 5
• Remember that eosinophilia monitoring is separate from the mandatory monitoring for agranulocytosis

Clozapine remains a valuable medication for treatment-resistant schizophrenia despite these potential adverse effects, and with proper monitoring, many patients with transient eosinophilia can safely continue treatment.