A patient on clozapine develops an absolute neutrophil count (ANC) of 450/mm³. According to current monitoring guidelines, the appropriate action is:

• A Continue clozapine with increased monitoring frequency to twice weekly
• B Withhold clozapine and do not rechallenge if ANC remains below 500/mm³
• C Interrupt clozapine; monitor ANC daily; only rechallenge after ANC recovers above 1000/mm³ if risk-benefit favourable ✓
• D Reduce clozapine dose by 50% and recheck ANC in 1 week

Explanation

An ANC < 500/mm³ defines severe neutropenia (agranulocytosis threshold), a life-threatening clozapine side effect occurring in 0.5–1.5% of patients. Per REMS (FDA) and most international guidelines: clozapine must be immediately withheld, the patient should be monitored for infection, ANC should be checked daily until recovery, and rechallenge may be considered only when ANC recovers above 1000/mm³ in consultation with haematology and only with enhanced monitoring. An ANC between 500–999/mm³ defines moderate neutropenia requiring interruption and daily monitoring. Dose reduction (option D) is insufficient; the drug must be stopped.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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