---
title: "Clozapine"
url: https://mghmclean.org/residents/handbk/part2c/cloz.htm
description: "· explain risks/side effects to patient; obtain signed consent"
published: 2026-08-10
updated: 2026-08-10
---

# Clozapine

Published 2026-08-10

PART 3 / CH 56

Roy Perlis and George Papakostas

## A. Prior to initiating treatment

· check WBC with differential

· explain risks/side effects to patient; obtain signed consent

· contact Clozaril National Registry for rechallenge number:

## 1-800-448-5938

B. Dosing

· start 12.5hs day 1, 25hs on day 2, then increase by 25 qd until 150, then by 50qd up to 300.

· if more than 2d skipped, restart at low dose

· clearance: 50% renal, 20% hepatic. N-desmethyl metabolite is active.

· elimination t1/2 is 8-12 hours

C. Major side effect is agranulocytosis

· agranulocytosis = ANC<500

(ANC=%neutrophils x WBC)

· seen in 0.8% of patients on clozapine within 1 year,

most within 3 months; 95% within 6 months

· genetics: associated with HLA-B38, DR4, DQW3

· consequences: risk of sepsis, fatal in 0.03% of clozapine patients.

· benign neutropenia seen in up to 22% of patients

· eosinophilia (>500) seen in up to 32% of patients, hold clozapine until eos<3000.

·check WBC with differential weekly;

(if continuously treated for 6 months without WBC<3.5,

can check every other week)

| Result | Action |
|---|---|
| WBC<3.5k –or-WBC ¯3k in 3wk | begin biweekly WBC with diff. |
| WBC<3k –or-ANC<1.5k | Stop drug immediatelyCheck WBC with diff. qdMonitor for infectionMay resume when WBC again >3k. |
| WBC<2k –or-ANC<1k | D/C drug foreverCheck WBC with diff. qdConsult hematologist |

C. Clozapine side effects

| Effect | Incidence | Management |
|---|---|---|
| CNS |  |  |
| NeutropeniaAgranulocytosisEosinophilia | 22%0.8%32% | see table |
| Seizure | <300: 1%<600: 3%>600: 5% | titrate slowly,prophylax at dose>550 (avoid carbamazepine) |
| SedationVertigoTremor, HA | 40%18%5% | tolerancedose qhs or q7pm |
| OCD symptoms | up to 10% | ? decrease dose,add SSRI |
| Anticholinergic Delirium | Esp. older pts | decrease dose,eliminate other meds |
| CV |  |  |
| Tachycardia | 25% | tolerance |
| OrthostasisHypotension/syncope | 10%5% | tolerancehydration, hs dosing |

## GI

| Hypersalivation | 31% | towel on pillow,anticholinergics,prokinetic agents |
|---|---|---|
| Constipation | 15% | fluids, bowel regimen, avoid anticholinergics |
| Nausea | 10% | antiemetics |
| ­LFT | 30% | usually transient, benign. W/u jaundice |
| Other |  |  |
| Enuresis | up to 30% | avoid oversedationditropan 5-15qd, or ddAVP 1 puff each nostril qhs, or tolterodine 2qd |
| Fever (<100F) | 5% | transient; if T>100, fever workup |
| Weight gain | >75% | Diet/exercise, follow for type 2 DM |

source: Young CR et al (1998) Schizophrenia Bull. 24:381-390.