. 2022 Jun 27;36(7):659–679. doi: 10.1007/s40263-022-00932-2

Table 7.

Clozapine treatment recommendations for patients with benign ethnic neutropenia, based on absolute neutrophil count (ANC) monitoring [62]

ANC level	Treatment recommendations	ANC monitoring
Normal BEN range (established ANC baseline ≥ 1,000/μL)	Obtain at least two baseline ANC levels before initiating treatment, consider low-dose lithium augmentation to increase white cell count If treatment interrupted ≤ 30 days, continue monitoring as before; if > 30 days, monitor as if new patient	Weekly from initiation to 6 months Every 2 weeks from 6 to 12 months Monthly after 12 months
Discontinuation of treatment for reasons other than neutropenia	Reduce dose over 1–2 weeks if not urgent For abrupt discontinuation, continue existing monitoring until ANC ≥ 1000/μL or > baseline Additional monitoring is required if fever (≥ 38.5 °C) within 2 weeks after discontinuation
BEN neutropenia 500–999/μL^a	Recommend hematology consultation Continue treatment; consider low-dose lithium augmentation to increase white cell count	Three times weekly until ANC ≥ 1,000/μL or ≥ patient’s known baseline Once ANC ≥ 1,000/μL or at patient’s baseline, check ANC weekly for 4 weeks, then return to patient’s last “normal BEN range” ANC monitoring interval^b
BEN severe neutropenia < 500/μL^a	Recommend hematology consultation Interrupt treatment for suspected clozapine-induced neutropenia Do not rechallenge unless prescriber determines benefits outweigh risks; consider low-dose lithium augmentation to increase white cell count	Daily until ANC ≥ 500/μL, then Three times weekly until ANC ≥ patient’s baseline If patient rechallenged, resume treatment as a new patient under “normal range” monitoring once ANC ≥ 1,000/μL or at patient’s baseline

ANC level

Treatment recommendations

ANC monitoring

Normal BEN range (established ANC baseline ≥ 1,000/μL)

Obtain at least two baseline ANC levels before initiating treatment, consider low-dose lithium augmentation to increase white cell count

If treatment interrupted ≤ 30 days, continue monitoring as before; if > 30 days, monitor as if new patient

Weekly from initiation to 6 months

Every 2 weeks from 6 to 12 months

Monthly after 12 months

Discontinuation of treatment for reasons other than neutropenia

Reduce dose over 1–2 weeks if not urgent

For abrupt discontinuation, continue existing monitoring until ANC ≥ 1000/μL or > baseline

Additional monitoring is required if fever (≥ 38.5 °C) within 2 weeks after discontinuation

BEN

neutropenia

500–999/μL^a

Recommend hematology consultation

Continue treatment; consider low-dose lithium augmentation to increase white cell count

Three times weekly until ANC ≥ 1,000/μL or ≥ patient’s known baseline

Once ANC ≥ 1,000/μL or at patient’s baseline, check ANC weekly for 4 weeks, then return to patient’s last “normal BEN range” ANC monitoring interval^b

BEN severe neutropenia < 500/μL^a

Recommend hematology consultation

Interrupt treatment for suspected clozapine-induced neutropenia

Do not rechallenge unless prescriber determines benefits outweigh risks; consider low-dose lithium augmentation to increase white cell count

Daily until ANC ≥ 500/μL, then

Three times weekly until ANC ≥ patient’s baseline

If patient rechallenged, resume treatment as a new patient under “normal range” monitoring once ANC ≥ 1,000/μL or at patient’s baseline

BEN benign ethnic neutropenia

^aConfirm all initial reports of ANC < 1,000/µL with a repeat ANC measurement within 24 h

^bIf clinically appropriate

This table was adapted from the FDA document "HIGHLIGHTS OF PRESCRIBING INFORMATION - CLOZARIL®”, copyright HLS Therapeutics (USA), Inc. Any changes made to the table are not endorsed by HLS Therapeutics (USA), Inc. CLOZARIL® is a registered trademark of Novartis Pharmaceuticals Corporation [62]