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clozapine
Clozaril · Versacloz · FazaClo (ODT)
Second-generation antipsychotic⚠ Unverified beta content
At a glance
- Class
- Atypical antipsychotic (dibenzodiazepine); reserved for treatment-resistant schizophrenia
- Black box
- ⚠ Severe neutropenia (ANC <500/µL) can lead to serious infection and death; monitor ANC per labeling
- ⚠ Orthostatic hypotension, bradycardia, syncope, and cardiac arrest – start low, titrate slowly.
- ⚠ Seizures – dose-related risk.
- ⚠ Myocarditis, cardiomyopathy and mitral valve incompetence.
- ⚠ Increased mortality in elderly patients with dementia-related psychosis
- Key monitoring
- ANC (absolute neutrophil count) — Normal ≥1500/µL: continue. Mild 1000–1499: continue, ANC 3×/wk until ≥1500. Moderate…
- Myocarditis screen (troponin, CRP, symptoms)
- Bowel function / constipation
- Usual adult dose
- Initiation: 12.5 mg once or twice daily
- Call provider / escalate if
- Fever ≥100.4 °F (38 °C), sore throat, chills, infection signs (low ANC) • Chest pain, shortness of breath, tachycardia, flu-like illness (myocarditis) • Severe constipation, abdominal pain/distension, vomiting (ileus)
Built-in explanation — generated offline from this app’s structured data (no AI, no network). Still unverified beta content.
What it is
- clozapine (Clozaril, Versacloz, FazaClo (ODT)) — atypical antipsychotic (dibenzodiazepine); reserved for treatment-resistant schizophrenia.
- Used for: Treatment-resistant schizophrenia; Reducing risk of recurrent suicidal behavior in schizophrenia / schizoaffective disorder.
Usual adult dosing
- Initiation: 12.5 mg once or twice daily (Increase by 25–50 mg/day (as tolerated) to 300–450 mg/day by end of week 2; then ≤100 mg once or twice weekly.)
- Usual target: 300–450 mg/day (divided) (Max 900 mg/day.)
- Restarting after missed doses: If ≥2 days missed, re-titrate from 12.5 mg (orthostasis/bradycardia/syncope risk)
Boxed warning
- Severe neutropenia (ANC <500/µL) can lead to serious infection and death; monitor ANC per labeling. (The clozapine REMS program was removed by FDA effective June 13, 2025; ANC monitoring per prescribing information is still recommended.)
- Orthostatic hypotension, bradycardia, syncope, and cardiac arrest – start low, titrate slowly.
- Seizures – dose-related risk.
- Myocarditis, cardiomyopathy and mitral valve incompetence.
- Increased mortality in elderly patients with dementia-related psychosis: not approved for treatment of dementia-related psychosis.
Monitor
- ANC (absolute neutrophil count) — Normal ≥1500/µL: continue. Mild 1000–1499: continue, ANC 3×/wk until ≥1500. Moderate 500–999: interrupt, hematology consult, ANC daily; resume when ≥1000. Severe <500: interrupt/discontinue, daily ANC, hematology; generally do not rechallenge. (BEN: different thresholds – see label) [Weekly through month 6; every 2 weeks months 7–12; monthly thereafter. Confirm any ANC <1500 with repeat within 24 h.]
- Myocarditis screen (troponin, CRP, symptoms) [Baseline and early treatment (first ~4 weeks) per label/facility protocol; any chest pain, fever, dyspnea, tachycardia]
- Bowel function / constipation [Every contact]
- Orthostatic BP / HR [During titration; each dose change]
Nursing priorities
- Baseline ANC (≥1500/µL; ≥1000/µL if documented benign ethnic neutropenia/BEN), ECG, troponin/CRP per protocol, weight, fasting glucose/lipids.
- Bowel pattern at every contact (last BM, abdominal pain/distension).
- Verify a current ANC is available before dispensing/administering per facility protocol; follow ANC action table (see Monitoring).
- Fever ≥38.5 °C (101.3 °F): interrupt clozapine, obtain ANC and notify provider urgently.
- Daily bowel monitoring; stool softener/laxative per orders; report constipation >2–3 days or abdominal pain urgently.
Major interactions
- CYP1A2 inhibitors (fluvoxamine, ciprofloxacin): Large ↑ clozapine levels – dose reduction (e.g., to one-third) / toxicity risk.
- Smoking / CYP1A2 inducers (smoking cessation reverses): Smoking ↓ levels; quitting raises levels – may need ~30–50% dose reduction.
- Other myelosuppressive drugs (carbamazepine, chemotherapy, etc.): Additive neutropenia risk; carbamazepine generally avoided.
- Benzodiazepines / other CNS depressants (esp. IM lorazepam): Respiratory/cardiac depression, collapse reported; use caution.
Key teaching
- You must have regular blood tests (ANC) to keep your white blood cell count safe. Don’t miss them.
- Call right away for fever, sore throat, chills, or flu-like symptoms.
- Constipation can become dangerous. Tell us if you haven’t had a bowel movement in 2 days, or have belly pain/swelling. Drink fluids and eat fiber.
Optional: AI explanation
Off by default. To enable, add your own API key in Settings (stored only on this device).
Boxed warning
- Severe neutropenia (ANC <500/µL) can lead to serious infection and death; monitor ANC per labeling. (The clozapine REMS program was removed by FDA effective June 13, 2025; ANC monitoring per prescribing information is still recommended.)
- Orthostatic hypotension, bradycardia, syncope, and cardiac arrest – start low, titrate slowly.
- Seizures – dose-related risk.
- Myocarditis, cardiomyopathy and mitral valve incompetence.
- Increased mortality in elderly patients with dementia-related psychosis: not approved for treatment of dementia-related psychosis.
Other serious warnings
- Severe GI hypomotility (constipation → ileus, obstruction, bowel necrosis; can be fatal)
- Neuroleptic malignant syndrome
- Metabolic changes (hyperglycemia/DKA, dyslipidemia, weight gain)
- Eosinophilia
- QT prolongation
- Pulmonary embolism / thromboembolism
- Aspiration pneumonia (sedation, sialorrhea)
- Fever – evaluate for neutropenia/infection/NMS/myocarditis
- Anticholinergic toxicity
- Tardive dyskinesia
- Respiratory/cardiac collapse with benzodiazepines
Sources: FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (U · FDA Drug Safety Communication: FDA removes REMS for clozapine (effecti
- ANC (absolute neutrophil count)Target: Normal ≥1500/µL: continue. Mild 1000–1499: continue, ANC 3×/wk until ≥1500. Moderate 500–999: interrupt, hematology consult, ANC daily; resume when ≥1000. Severe <500: interrupt/discontinue, daily ANC, hematology; generally do not rechallenge. (BEN: different thresholds – see label)When: Weekly through month 6; every 2 weeks months 7–12; monthly thereafter. Confirm any ANC <1500 with repeat within 24 h.
- Myocarditis screen (troponin, CRP, symptoms)When: Baseline and early treatment (first ~4 weeks) per label/facility protocol; any chest pain, fever, dyspnea, tachycardia
- Bowel function / constipationWhen: Every contact
- Orthostatic BP / HRWhen: During titration; each dose change
- Metabolic monitoring (ADA/APA)Target: Weight/BMI, BP, fasting glucose/A1c, lipidsWhen: Baseline; weight monthly early; glucose/lipids at 12 wks then annually or more often
- ECG / QTcWhen: Baseline; with dose increases and with QT drugs
- Clozapine (± norclozapine) trough levelTarget: Often ≥350 ng/mL cited for response (not a label requirement)When: Per prescriber; after smoking/interacting drug changes, toxicity, nonadherence
- Seizure activity / EEG as indicatedDose-related risk (higher >600 mg/day)
Sources: FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (U · FDA Drug Safety Communication: FDA removes REMS for clozapine (effecti · ADA/APA Consensus Development Conference on Antipsychotic Drugs and Ob
Assessment
- Baseline ANC (≥1500/µL; ≥1000/µL if documented benign ethnic neutropenia/BEN), ECG, troponin/CRP per protocol, weight, fasting glucose/lipids.
- Bowel pattern at every contact (last BM, abdominal pain/distension).
- Temperature and signs of infection, flu-like illness, chest pain, dyspnea, tachycardia (myocarditis).
- Smoking status and changes (smoking induces CYP1A2).
- Sedation, salivation, orthostasis.
Interventions
- Verify a current ANC is available before dispensing/administering per facility protocol; follow ANC action table (see Monitoring).
- Fever ≥38.5 °C (101.3 °F): interrupt clozapine, obtain ANC and notify provider urgently.
- Daily bowel monitoring; stool softener/laxative per orders; report constipation >2–3 days or abdominal pain urgently.
- Titrate slowly; monitor BP/HR (supine/standing) with each dose increase; fall precautions.
- If ≥2 days of missed doses: hold and call provider for re-titration.
- Sialorrhea: elevate head of bed, towel on pillow; provider may order anticholinergic therapy.
- Check for smoking changes (quitting can raise levels ~50%+).
Sources: General nursing drug reference conventions (e.g., Davis Drug Guide / L
- Fever ≥100.4 °F (38 °C), sore throat, chills, infection signs (low ANC)
- Chest pain, shortness of breath, tachycardia, flu-like illness (myocarditis)
- Severe constipation, abdominal pain/distension, vomiting (ileus)
- Fainting, very slow heartbeat, severe dizziness
- Seizure or muscle jerks
- High fever with stiffness and confusion (NMS)
- Calf swelling/pain, sudden dyspnea (PE)
- Missed ≥2 days of doses
- Excess thirst/urination (hyperglycemia)
- Choking/aspiration, productive cough
Sources: FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (U · General nursing drug reference conventions (e.g., Davis Drug Guide / L
- Sedation
- Sialorrhea (hypersalivation)
- Constipation (may be severe)
- Tachycardia
- Orthostatic hypotension / dizziness
- Weight gain, hyperglycemia, dyslipidemia
- Nocturnal enuresis
- Fever (benign, transient early)
Sources: FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (U
- CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) MajorLarge ↑ clozapine levels – dose reduction (e.g., to one-third) / toxicity risk.
- Smoking / CYP1A2 inducers (smoking cessation reverses) MajorSmoking ↓ levels; quitting raises levels – may need ~30–50% dose reduction.
- Other myelosuppressive drugs (carbamazepine, chemotherapy, etc.) MajorAdditive neutropenia risk; carbamazepine generally avoided.
- Benzodiazepines / other CNS depressants (esp. IM lorazepam) MajorRespiratory/cardiac depression, collapse reported; use caution.
- Anticholinergics, opioids MajorAdditive constipation/ileus risk.
- AntihypertensivesAdditive hypotension.
- QT-prolonging drugsAdditive QT effect.
- Strong CYP3A4 inducers/inhibitorsAltered clozapine levels.
Sources: FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (U
- You must have regular blood tests (ANC) to keep your white blood cell count safe. Don’t miss them.
- Call right away for fever, sore throat, chills, or flu-like symptoms.
- Constipation can become dangerous. Tell us if you haven’t had a bowel movement in 2 days, or have belly pain/swelling. Drink fluids and eat fiber.
- Stand up slowly. Dizziness is most common when starting.
- If you miss 2 or more days of doses, do NOT restart on your own – call your provider; the dose may need to start low again.
- Tell your care team if you start or stop smoking, or start any new medicine (some antibiotics raise clozapine levels).
- Drooling at night is common; ask about ways to help.
- Report chest pain, shortness of breath, or fast heartbeat right away.
Sources: General nursing drug reference conventions (e.g., Davis Drug Guide / L
Indications
- Treatment-resistant schizophrenia
- Reducing risk of recurrent suicidal behavior in schizophrenia / schizoaffective disorder
Dosing
- Initiation: 12.5 mg once or twice dailyIncrease by 25–50 mg/day (as tolerated) to 300–450 mg/day by end of week 2; then ≤100 mg once or twice weekly.
- Usual target: 300–450 mg/day (divided)Max 900 mg/day.
- Restarting after missed doses: If ≥2 days missed, re-titrate from 12.5 mg (orthostasis/bradycardia/syncope risk)
Sources: FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (U
Prescriber-oriented details; limited in this beta.
titration
- Day 1: 12.5 mg daily–BID; ↑ 25–50 mg/day to 300–450 mg/day by wk 2; then ≤100 mg once/twice weekly. Max 900 mg/day.
renal Adjustment
- Caution in renal impairment.
hepatic Adjustment
- Caution; may need lower dose.
cyp Notes
- CYP1A2 major; smoking induces; fluvoxamine/cipro inhibit.
discontinuation
- Gradual taper over ≥2 weeks if possible; watch for cholinergic rebound and psychosis relapse.
Sources: FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (U
- Verified
- No – unverified beta
- Last reviewed
- 2026-10-29 (drafted; not clinician-reviewed)
- FDA label (DailyMed): CLOZARIL (CLOZAPINE) TABLET [HLS THERAPEUTICS (USA), INC.]
- FDA Drug Safety Communication: FDA removes REMS for clozapine (effective June 13, 2025); ANC monitoring per labeling continues
- ADA/APA Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes (Diabetes Care 2004) - metabolic monitoring schedule
- General nursing drug reference conventions (e.g., Davis Drug Guide / Lexicomp nursing) - summarized from standard practice; NOT line-by-line verified
Reviewer notes – please double-check
- IMPORTANT: FDA removed the clozapine REMS effective June 13, 2025 (announced Feb 24, 2025). ANC monitoring frequency/thresholds remain in the label. Your facility may still use REMS-style processes – verify policy.
- Myocarditis baseline/serial troponin & CRP schedule and clozapine level target (≥350 ng/mL) are widely used practice patterns; confirm with current label and facility protocol.
- ANC thresholds shown are the general-population thresholds; benign ethnic neutropenia (BEN) uses different thresholds (see label tables).