Clozapine Associated Agranulocytosis Monitoring

Patient with treatment resistant schizophrenia is admitted for fifth time this year secondary to worsening of psychotic symptoms. He is compliant with medications and have failed trials of haloperidol, risperidone, olanzapine and ziprasidone. You decided to initiate clozapine during this inpatient admission. After clozapine dose of 150 mg HS was reached, he developed ANC (absolute neutrophil count) of 1100/uL. What will you do next?

First step:- Confirm all initial reports of ANC less than 1500/μL (ANC < 1000/μL for benign ethnic neutropenia patients) with a repeat ANC measurement within 24 hours.

Second Step:- Assess if patient has benign ethnic neutropenia. 

Clozapine REMS program recommends following guidelines for general population and population with benign ethnic neutropenia (BEN):-

 

ANC LEVEL (General Population)

TREATMENT RECOMMENDATIONS

ANC MONITORING

Normal Range for New Patient: General Population (ANC ≥ 1500/μL)

  • Initiate treatment
  • If treatment interrupted:
  • < 30 days: continue monitoring as before
  • > 30 days: monitor as if new patient
  • Discontinuation for reasons other than neutropenia
    • Weekly from initiation to 6 months

 

    • Every 2 weeks from 6 to 12 months

 

  • Monthly after 12 months

Mild Neutropenia (1000 to 1499/μL)

  • Continue treatment
  • Three times weekly until ANC ≥ 1500/μL
  • Once ANC ≥ 1500/μL, return to patient’s last “Normal Range” ANC monitoring interval.

Moderate Neutropenia (500 to 999/μL)

    • Recommend hematology consultation

 

    • Interrupt treatment for suspected clozapine induced neutropenia

 

  • Resume treatment once ANC normalizes to ≥ 1000/μL
    • Daily until ANC ≥ 1000/μL, then

 

    • Three times weekly until ANC ≥ 1500/μL

 

  • OnceANC≥1500μL, check ANC weekly for 4weeks, then return to patient’s last “Normal Range” ANC monitoring interval.
Severe Neutropenia (less than 500/μL)
  • Recommend hematology consultation
  • Interrupt treatment for suspected clozapine induced neutropenia
  • Do not rechallenge unless prescriber determines benefits outweigh risks.
    • Daily until ANC ≥ 1000/μL

 

    • Three times weekly until ANC ≥ 1500/μL

 

  • If patient rechallenged, resume treatment as a new patient under “Normal Range” monitoring once ANC ≥ 1500/μL.

 

ANC LEVEL (BEN Population)

TREATMENT RECOMMENDATIONS

ANC MONITORING

Normal Range for New Patient: BEN Population (ANC ≥ 1000/μL)

  • OBTAIN AT LEAST TWO BASELINE ANC LEVELS BEFORE INITIATING TREATMENT.
  • Initiate treatment
  • If treatment interrupted:
  • < 30 days: continue monitoring as before
  • > 30 days: monitor as if new patient
  • Discontinuation for reasons other than neutropenia
    • Weekly from initiation to 6 months

 

    • Every 2 weeks from 6 to 12 months

 

  • Monthly after 12 months

Mild Neutropenia 

(1000 to 1499/μL)

    • Mild Neutropenia is normal range for BEN population, continue treatment

 

    • Obtain at least two baseline ANC levels before initiating treatment

 

    • If treatment interrupted for:

 

    • < 30 days: continue monitoring as before

 

    • > 30 days: monitor as if new patient

 

  • Discontinuation for reasons other than neutropenia
    • Weekly from initiation to 6 months

 

    • Every 2 weeks from 6 to 12 months

 

  • Monthly after 12 months

Moderate Neutropenia

(500 to 999/μL)

  • Recommend hematology consultation
  • Continue treatment
    • Three times weekly until ANC ≥ 1000/μL or ≥ patient’s known baseline.

 

  • Once ANC ≥ 1000/μL or patient’s known baseline, then check ANC weekly for 4 weeks, then return to patient’s last “Normal BEN Range” ANC monitoring interval

Severe Neutropenia

(less than 500/μL)

    • Recommend hematology consultation

 

    • Interrupt treatment for suspected clozapine induced neutropenia

 

  • Do not rechallenge unless prescriber determines benefits outweigh risks
    • Daily until ANC ≥ 500/μL

 

    • Three times weekly until ANC ≥ patients established baseline

 

  • If patient rechallenged, resume treatment as a new patient under “Normal Range” monitoring once ANC ≥1000/μL or at patient’s baseline

 

Source: Clozapine and the Risk of Neutropenia: An Overview for Healthcare Providers.

Please do post your questions or comments below. 


Dr. Harvinder Singh, M.D. (Admin)


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