Medicine guide

Clozapine

100 mg · Tablet, Orally Disintegrating

Prescription only
Atypical Antipsychotic

Active substance: Clozapine
Used in: Pain, sleep, mood, epilepsy and the brain
Made by: Safecor Health, LLC
Source: Official label

Quoted from the official source. Not yet reviewed by Mediclarum — the leaflet in your pack is authoritative.

At a glance

Quoted from the official label · 2026-03-13

What it is

Atypical Antipsychotic

Used for

Treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment.

The label’s usual adult dose

Recommended starting oral dosage is 12.5 mg once daily or twice daily.

( 2.2 ) Maximum daily dosage is 450 mg twice daily.

Full directions ↓

Serious warning

Orthostatic hypotension, bradycardia, and syncope;

All warnings ↓

Good to know

Prescription only
FDA enforcement reports list no ongoing recall, and none from the last two years, for this product code · checked 2026-10-02

47other products contain Clozapine — compare makers, forms and strengths

Every line above is selected, not written, from the official label. Nothing is reworded. DailyMed

What it is for

Clozapine orally disintegrating tablets (Clozapine ODT) is an atypical antipsychotic indicated for:

Treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment.
Because of the risks of severe neutropenia and of seizure associated with its use, Clozapine ODT should be used only in patients who have failed to respond adequately to standard antipsychotic treatment ( 1.1 ) Reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior ( 1.2 )
1.1 Treatment-resistant Schizophrenia Clozapine Orally Disintegrating Tablets (Clozapine ODT) are indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment.
Because of the risks of severe neutropenia and of seizure associated with their use, Clozapine ODT should be used only in patients who have failed to respond adequately to standard antipsychotic treatment [see Warnings and Precautions (5.1 , 5.4) ].
The effectiveness of Clozapine ODT in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active-controlled study comparing Clozapine ODT and chlorpromazine in patients who had failed other antipsychotics [see Clinical Studies (14.1) ].
1.2 Reduction in the Risk of Recurrent Suicidal Behavior in Schizophrenia or Schizoaffective Disorder Clozapine ODT is indicated for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior, based on history and recent clinical state.
Suicidal behavior refers to actions by a patient that put him/herself at risk for death.
The effectiveness of Clozapine ODT in reducing the risk of recurrent suicidal behavior was demonstrated over a two-year treatment period in the InterSePT™ trial [see Clinical Studies (14.2) ] .

From the official label · 2026-03-13 · DailyMed

How it works

From this product’s own US prescribing label.

The mechanism of action of clozapine is unknown.
However, it has been proposed that the therapeutic efficacy of Clozapine ODT in schizophrenia is mediated through antagonism of the dopamine type 2 (D 2 ) and the serotonin type 2A (5-HT 2A ) receptors.

Peak level after2.3 h

Half-life8 h

Mostly cleared after≈ 40 hfive half-lives — our arithmetic

The shape is a standard model drawn from the two times above, not a measurement. How fast a medicine acts and wears off also depends on the dose, the form and the person.

How the body breaks it down

Metabolism and Excretion Clozapine is almost completely metabolized prior to excretion, and only trace amounts of unchanged drug are detected in the urine and feces.

How it leaves the body

Approximately 50% of the administered dose is excreted in the urine and 30% in the feces.

With food

The study also evaluated the effect of food and chewing on the pharmacokinetics of the 200 mg tablet.

Quoted from the prescribing label, sections “Mechanism of Action” and “Pharmacokinetics”. DailyMed · 2026-03-13

Serious warning

The strongest warning the FDA requires. It is printed in a box at the top of the label.

SEVERE NEUTROPENIA;
ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE;
SEIZURE;
MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY;
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Severe Neutropenia Clozapine Orally Disintegrating Tablets (Clozapine ODT) have caused severe neutropenia which is associated with an increased risk of serious and fatal infections.
Prior to initiating Clozapine ODT treatment, obtain baseline ANC(s).
Clozapine ODT initiation is not recommended in patients with a baseline ANC less than 1500/µL (less than 1000/µL for those with Benign Ethnic Neutropenia (also known as Duffy-null associated neutrophil count)).
See recommendations for dosage modifications based on ANC levels during Clozapine ODT treatment [see Dosage and Administration (2.4 , 2.5) ] .
Consider a hematology consultation before initiating Clozapine ODT or during Clozapine ODT treatment [see Warnings and Precautions (5.1) ] .
Orthostatic Hypotension, Bradycardia, Syncope Orthostatic hypotension, bradycardia, syncope, and cardiac arrest have occurred with clozapine treatment.
The risk is highest during the initial titration period, particularly with rapid dose escalation.
These reactions can occur with the first dose, with doses as low as 12.5 mg per day, or when restarting patients who have had even a brief interruption in treatment with Clozapine ODT.
Initiate treatment at 12.5 mg once or twice daily; titrate slowly; and use divided dosages to minimize risk.
Use Clozapine ODT cautiously in patients with cardiovascular or cerebrovascular disease or conditions predisposing to hypotension (e.g., dehydration, use of antihypertensive medications) [see Dosage and Administration (2.3 and 2.6) , Warnings and Precautions (5.2) ] .
Seizures Seizures have occurred with clozapine treatment.
The risk is dose-related.
Initiate treatment at 12.5 mg, titrate gradually, and use divided dosing.
Use caution when administering Clozapine ODT to patients with a history of seizures or other predisposing risk factors for seizure (CNS pathology, medications that lower the seizure threshold, alcohol abuse).
Caution patients about engaging in any activity where sudden loss of consciousness could cause serious risk to themselves or others [see Dosage and Administration (2.3) , Warnings and Precautions (5.4) ] .
Myocarditis, Pericarditis, Cardiomyopathy and Mitral Valve Incompetence Fatal myocarditis and cardiomyopathy have occurred with clozapine treatment.
Discontinue Clozapine ODT and obtain a cardiac evaluation upon suspicion of these reactions.
Generally, patients with clozapine-related myocarditis or cardiomyopathy should not be rechallenged with Clozapine ODT.
Consider the possibility of myocarditis, pericarditis, or cardiomyopathy if chest pain, tachycardia, palpitations, dyspnea, fever, flu-like symptoms, hypotension, or ECG changes occur [see Warnings and Precautions (5.5) ] .
Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Clozapine ODT is not approved for use in patients with dementia-related psychosis [see Warnings and Precautions (5.6) ] .
WARNING: SEVERE NEUTROPENIA;
ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE;
SEIZURE;
MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY;
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning.
Severe Neutropenia:
Clozapine has caused severe neutropenia, which is associated with an increased risk of serious and fatal infections.
Prior to initiating Clozapine Orally Disintegrating Tablets (Clozapine ODT) treatment, obtain baseline ANC(s).
Clozapine ODT initiation is not recommended in patients with a baseline ANC less than 1500/μL (less than 1000/μL for those with Benign Ethnic Neutropenia (also known as Duffy-null associated neutrophil count)).
See recommendations for dosage modifications based on ANC levels during Clozapine ODT treatment.
( 2.1 , 2.3 , 2.4 , 5.1 ) Orthostatic Hypotension, Bradycardia, and Syncope:
Risk is dose-related.
Starting dose is 12.5 mg.
Titrate gradually and use divided dosages.
( 2.2 , 5.2 ) Seizure: Risk is dose-related.
Titrate gradually and use divided doses.
Use with caution in patients with history of seizure or risk factors for seizure.
( 5.4 ) Myocarditis, Pericarditis, Cardiomyopathy and Mitral Valve Incompetence:
Can be fatal.
Discontinue and obtain cardiac evaluation if findings suggest these cardiac reactions.
( 5.5 ) Increased Mortality in Elderly Patients with Dementia-Related Psychosis:
Clozapine ODT is not approved for this condition.
( 5.6 )

Quoted from the official label, section “Boxed Warning”.

Do not take it if

Clozapine ODT is contraindicated in patients with a history of hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of Clozapine ODT [see Adverse Reactions (6.2) ] .
Known hypersensitivity to clozapine or any other component of Clozapine ODT ( 4 )

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

Recommended starting oral dosage is 12.5 mg once daily or twice daily.
( 2.2 ) If well-tolerated, increase the total daily dosage in increments of 25 mg to 50 mg per day at target dosage of 150 mg to 225 mg twice per day by the end of two weeks.
( 2.2 ) Subsequently may increase the doage in increments up to 100 mg, once or twice weekly.
( 2.2 ) Maximum daily dosage is 450 mg twice daily.
( 2.2 ) Administer with or without food.
Clozapine ODT may be allowed to disintegrate or chewed, and may be taken with or without water.
See additional administration instructions in the full prescribing information.
( 2.2 ) See dosage modification based on ANC results.
( 2.3 , 2.4 ) See recommendations for discontinuing Clozapine ODT treatment ( 2.5 ), restarting Clozapine ODT after interrupting dosing (2.6), dosage modifications for drug interactions ( 2.7 ), dosage recommendations in patients with renal or hepatic impairment and CYP2D6 poor metabolizers ( 2.8 ) in the full prescribing information.
Tablets rapidly disintegrate after placement in the mouth and may be chewed if desired.
No water is needed.
( 2.2 )
2.1 Absolute Neutrophil Count Testing Prior to Clozapine ODT Initiation Prior to initiating Clozapine ODT treatment, obtain a baseline absolute neutrophil count (ANC).
Clozapine ODT initiation is not recommended in patients with an ANC less than 1500/µL [see Warnings and Precautions (5.1) ] .
For patients with documented Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count)), obtain at least two baseline ANC levels.
Clozapine ODT initiation is not recommended in patients with BEN with an ANC less than 1000/µL [see Warnings and Precautions (5.1) ] .
For dosage modifications based on ANC results, see Dosage and Administration (2.3 , 2.4) .
2.2 Recommended Dosage and Administration Recommended Dosage To reduce the risk of orthostatic hypotension, bradycardia, and syncope, the recommended starting dosage is much lower than the target dosage [see Warnings and Precautions (5.2) ] .
The recommended starting oral dosage of Clozapine ODT is 12.5 mg once or twice daily.
If well-tolerated, increase the total daily dose in increments of 25 mg to 50 mg per day to achieve a target dosage of 150 mg to 225 mg twice per day by the end of two weeks.
Subsequently, may increase the dosage in increments of up to 100 mg once weekly or twice weekly.
The maximum recommended Clozapine ODT oral dosage is 450 mg twice daily.
Administration Instructions Clozapine ODT can be taken with or without food, may be allowed to disintegrate or chewed, and may be taken with or without water [see Clinical Pharmacology (12.3) ] .
After removing Clozapine ODT from the bottle, immediately place in the mouth.
2.3 Dosage Modifications Based on ANC Results Table 1 provides recommended Clozapine ODT dosage modifications based on ANC results [see Warnings and Precautions (5.1) ] .
For dosage modifications based on ANC results for patients with Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count), see Table 2 [see Dosage and Administration (2.4) ] .
Table 1:
Clozapine ODT Dosage Modifications Based on ANC Results and Frequency of ANC Testing Recommended Dosage Modification Recommended Frequency of ANC Testing During Clozapine ODT Treatment ANC Within Normal Range (≥ 1500/µL) No dosage modification; continue treatment Day 1 to Month 6:
Weekly Month 7 to Month 12:
Every 2 weeks Month 13 and thereafter:
Every month If Clozapine ODT treatment is reinitiated after a dosage interruption (e.g., patient had neutropenia which required dosage interruption and now has a normal ANC level) for:
< 30 days, continue the previous ANC testing frequency ≥ 30 days, obtain ANC tests according to the frequency for patients who initiate treatment Mild Neutropenia (ANC between 1000 to 1499/µL) Confirm all initial reports of ANC less than 1500/µL with a repeat ANC measurement within 24 hours No dosage modification; continue treatment Three times weekly Once ANC ≥ 1500/µL, recommend returning to the patient’s last Normal Range ANC testing frequency Moderate Neutropenia (ANC between 500 to 999/µL) Interrupt treatment and recommend hematology consultation Resume treatment once ANC ≥ 1000/µL Daily Once ANC ≥ 1000/µL, three times weekly Once ANC ≥ 1500/µL, test weekly for 4 weeks.
If ANC ≥ 1500/µL after monitoring weekly for 4 weeks, return to the patient’s last Normal Range ANC testing frequency Severe Neutropenia (ANC less than 500/µL) Discontinue treatment and recommend hematology consultation Daily Once ANC ≥ 1000/µL, three times weekly Once ANC ≥ 1500/µL, if the benefits outweigh the risks of restarting treatment, resume treatment and obtain ANC tests according to the frequency for patients who initiate treatment
2.4 Dosage Modifications Based on ANC Results for Patients with Benign Ethnic Neutropenia Table 2 provides recommended Clozapine ODT dosage modifications based on ANC results for patients with Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count) [see Warnings and Precautions (5.1) ] .
For dosage modifications based on ANC results for patients without BEN, see Table 1 [see Dosage and Administration (2.3) ] .
Table 2:
Clozapine ODT Dosage Modifications Based on ANC Results and Frequency of ANC Testing in Patients with Benign Ethnic Neutropenia Benign Ethnic Neutropenia (BEN) is also known as Duffy-null associated neutrophil count.
Recommended Dosage Modification Recommended Frequency of ANC Testing During Clozapine ODT Treatment in Patients with BEN ANC Within the Normal Range for Patients with BEN (≥ 1000/µL ) No dosage modification; continue treatment Day 1 to Month 6:
Weekly Month 7 to Month 12:
Every 2 weeks Month 13 and thereafter:
Monthly If Clozapine ODT treatment is reinitiated after a dosage interruption (e.g., patient had neutropenia which required dosage interruption and now their ANC (≥ 1000/µL and ≥ the patient’s ANC baseline prior to treatment) for:
< 30 days, continue previous ANC testing frequency ≥ 30 days, obtain ANC tests according to the frequency for patients with BEN who initiate treatment Neutropenia in Patients with BEN (ANC level between 500 to 999/µL) Confirm all initial reports of ANC less than 1500/µL with a repeat ANC measurement within 24 hours Recommend hematology consultation No dosage modification; continue treatment Three times weekly Once ANC ≥ 1000/µL and ≥ the patient’s ANC baseline, obtain ANC tests weekly for 4 weeks If ANC ≥ 1000/µL and ≥ the patient’s baseline after monitoring for 4 weeks, return to the patient’s last Normal ANC Range testing frequency for patients with BEN.
Severe Neutropenia in Patients with BEN (ANC level less than 500/µL) Discontinue treatment and recommend hematology consultation Daily Once ANC ≥ 500/µL, obtain ANC three times weekly Once ANC ≥ 1000/µL and ≥ the patient’s baseline, if the benefits outweigh the risks of restarting treatment, resume treatment and obtain ANC tests according to the frequency for patients with BEN who initiate treatment
2.5 Discontinuation of Clozapine ODT Treatment If discontinuing Clozapine ODT in patients with:
Moderate or severe neutropenia, see Table 1 [see Dosage and Administration (2.4) ] .
Normal or mild neutropenia, reduce the dosage gradually over a period of 1 to 2 weeks, and continue monitoring ANC levels until their ANC is ≥ 1500/µL.
If discontinuing Clozapine ODT in patients with Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count) with:
Neutropenia, see Table 2 [see Dosage and Administration (2.5) ] .
ANC within their normal range of ANC reduce the dosage gradually over a period of 1 to 2 weeks.
When discontinuing Clozapine ODT, monitor patients for the symptoms related to psychotic recurrence and cholinergic rebound (e.g., profuse sweating, headache, nausea, vomiting, diarrhea).
2.6 Restarting Clozapine ODT Treatment After Interrupting Clozapine ODT When restarting Clozapine ODT in patients who have interrupted Clozapine ODT treatment, use a lower dosage to minimize the risk of hypotension, bradycardia, and syncope [see Warnings and Precautions (5.2) ] .
If one day’s dosage is missed, resume Clozapine ODT treatment at 40% to 50% of the previous dosage.
If two days of dosing is missed, resume Clozapine ODT treatment at approximately 25% of the previous dosage.
For longer interruptions, restart Clozapine ODT treatment with a dosage of 12.5 mg once or twice daily.
If this dosage is well-tolerated, may increase the dosage to the previous dosage more quickly than recommended than for initial Clozapine ODT treatment.
2.7 Dosage Modifications for Drug Interactions See Table 3 for recommended dosage modifications to reduce the risk of Clozapine ODT-associated adverse reactions or reduce the risk of lower effectiveness [see Drug Interactions (7) ] .
Table 3:
Clozapine ODT Dosage Modifications for Drug Interactions Strong CYP1A2 Inhibitors Administer one third of the Clozapine ODT dosage.
Moderate or Weak CYP1A2 Inhibitors Consider reducing the Clozapine ODT dosage if necessary.
CYP2D6 or CYP3A4 Inhibitors Strong CYP3A4 Inducers Concomitant use is not recommended.
However, if concomitant use is necessary, it may be necessary to increase the Clozapine ODT dosage.
Monitor for decreased effectiveness.
Moderate or weak CYP1A2 or CYP3A4 Inducers Consider increasing the Clozapine ODT dosage if necessary.
2.8 Dosage Recommendations in Patients with Renal or Hepatic Impairment, or CYP2D6 Poor Metabolizers It may be necessary to reduce the Clozapine ODT dosage in patients with significant renal impairment or hepatic impairment, or in CYP2D6 poor metabolizers [see Use in Specific Populations (8.6 , 8.7) ] .

Quoted from the official label, section “Dosage & Administration”.

Other warnings

See ( 5.1 ) Gastrointestinal Hypomotility with Severe Complications:
Severe gastrointestinal adverse reactions have occurred with the use of clozapine.
If constipation is identified, close monitoring and prompt treatment is advised.
( 5.7 ) Eosinophilia:
Assess for organ involvement (e.g., myocarditis, pancreatitis, hepatitis, colitis, nephritis).
Discontinue if these occur.
( 5.8 ) QT Interval Prolongation: Can be fatal.
Consider additional risk factors for prolonged QT interval (disorders and drugs).
( 5.9 ) Metabolic Changes:
Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk.
These metabolic changes include ( 5.10 ):
Monitor for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.
Monitor glucose regularly in patients with diabetes or at risk for diabetes.
Dyslipidemia:
Undesirable alterations in lipids have occurred in patients treated with atypical antipsychotics.
Weight Gain: Significant weight gain has occurred.
Monitor weight gain.
Neuroleptic Malignant Syndrome (NMS): Immediately discontinue and monitor closely.
Assess for co-morbid conditions.
( 5.11 ) Hepatotoxicity: Can be fatal.
Monitor for hepatotoxicity.
Discontinue treatment if hepatitis or transaminase elevations combined with other symptoms occur.
( 5.12 ) Fever: Evaluate for infection and for neutropenia, NMS.
( 5.13 ) Pulmonary Embolism (PE):
Consider PE if respiratory distress, chest pain, or deep vein thrombosis occurs.
( 5.14 ) Anticholinergic Toxicity:
When possible,
avoid use with other anticholinergic drugs and use with caution in patients with a current diagnosis or prior history of constipation, urinary retention, clinically significant prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions.
( 5.15 , 7.1 ) Interference with Cognitive and Motor Performance:
Advise caution when operating machinery, including automobiles.
( 5.16 )
5.1 Severe Neutropenia Clozapine has caused severe neutropenia (absolute neutrophil count (ANC) less than 500/µL) [see Adverse Reactions (6.1 , 6.2) ] and is associated with an increased risk of serious and potentially fatal infections.
Severe neutropenia occurred in a small percentage of clozapine-treated patients.
The risk of severe neutropenia appears greatest during the first 18 weeks of Clozapine ODT treatment.
The mechanism by which Clozapine ODT causes neutropenia is unknown.
Neutropenia is not dose-dependent.
Consider a hematology consultation before initiating Clozapine ODT treatment or during treatment.
ANC Monitoring and Dosage Modifications Prior to initiating Clozapine ODT treatment, obtain a baseline ANC.
Throughout Clozapine ODT treatment, regularly monitor ANC.
Table 1 provides recommendations for dosage modifications (dosage interruption and treatment discontinuation), based on ANC levels, during Clozapine ODT treatment and frequency of ANC monitoring [see Dosage and Administration (2.4) ] .
ANC Monitoring and Dosage Modification in Patients with Benign Ethnic Neutropenia Patients with Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count) generally have lower baseline neutrophil counts but they are not at higher risk for developing infections, and they are not at increased risk for developing Clozapine ODT-induced neutropenia.
For patients with documented BEN, obtain at least two baseline ANC levels prior to Clozapine ODT initiation.
There are different ANC dosage modification recommendations in Clozapine ODT-treated patients with BEN due to their lower baseline ANC levels.
Table 2 provides recommendations on dosage modifications (dosage interruption and treatment discontinuation), based on ANC monitoring, during Clozapine ODT treatment in patients with BEN and recommended frequency of ANC testing [see Dosage and Administration (2.4) ] .
Management of Clozapine ODT-Treated Patients Who Develop a Fever For patients who develop a fever during Clozapine ODT treatment:
Interrupt Clozapine ODT in those who develop a temperature of 101.3 °F (38.5 °C) or greater and obtain an ANC level.
If the ANC is less than 1000/µL in patients without BEN, initiate appropriate workup and treatment for infection.
Refer to Table 1 or Table 2 for dosage modifications based on ANC monitoring [see Dosage and Administration (2.3) ] .
In patients with fever and a normal neutrophil count, see Warnings and Precautions (5.11) for neuroleptic malignant syndrome and Warnings and Precautions (5.13) for fever.
Restarting Clozapine ODT in Patients Who Recovered from Severe Neutropenia Generally, do not rechallenge patients with Clozapine ODT in those who experienced severe neutropenia.
However, for some patients who had resolution of their Clozapine ODT-related severe neutropenia after stopping Clozapine ODT, the risk of schizophrenia exacerbation from not restarting Clozapine ODT treatment may be greater than the risk of neutropenia reoccurrence from restarting Clozapine ODT (e.g., patients who have no treatment options other than Clozapine ODT).
Concomitant Use of Clozapine ODT with Other Drugs Known to Cause Neutropenia If Clozapine ODT is used concomitantly with another drug known to cause neutropenia, consider more frequently ANC monitoring than the recommendations provided in Tables 1 and 2.
5.2 Orthostatic Hypotension, Bradycardia, and Syncope Hypotension, bradycardia, syncope, and cardiac arrest have occurred with clozapine treatment.
These reactions can occur with the first dose, at doses as low as 12.5 mg.
These reactions can be fatal.
The syndrome is consistent with neurally mediated reflex bradycardia (NMRB).
Clozapine ODT treatment must begin at a maximum dose of 12.5 mg once daily or twice daily.
The total daily dose can be increased in increments of 25 mg to 50 mg per day, if well-tolerated, to a target dose of 300 mg to 450 mg per day (administered in divided doses) by the end of 2 weeks.
Subsequently, the dose can be increased weekly or twice weekly, in increments of up to 100 mg.
The maximum Clozapine ODT dosage is 900 mg per day.
Use cautious titration and a divided dosage schedule to minimize the risk of serious cardiovascular reactions [see Dosage and Administration (2.2) ] .
Consider reducing the dose if hypotension occurs.
When restarting Clozapine ODT in patients who have had even a brief interruption in treatment with Clozapine ODT, the dosage must be reduced.
This is necessary to minimize the risk of hypotension, bradycardia, and syncope [see Dosage and Administration (2.6) ] .
Use Clozapine ODT cautiously in patients with cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (e.g., concomitant use of antihypertensives, dehydration and hypovolemia).
5.3 Falls Clozapine ODT may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.
For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic treatment.
5.4 Seizures Seizure has been estimated to occur in association with clozapine use at a cumulative incidence at one year of approximately 5%, based on the occurrence of one or more seizures in 61 of 1743 patients exposed to clozapine during its clinical testing prior to domestic marketing (i.e., a crude rate of 3.5%).
The risk of seizure is dose-related.
Initiate Clozapine ODT treatment with a low dose (12.5 mg), titrate slowly, and use divided dosing.
Use caution when administering Clozapine ODT to patients with a history of seizures or other predisposing risk factors for seizure (e.g., head trauma or other CNS pathology, use of medications that lower the seizure threshold, or alcohol abuse).
Because of the substantial risk of seizure associated with Clozapine ODT use, caution patients about engaging in any activity where sudden loss of consciousness could cause serious risk to themselves or others (e.g., driving an automobile, operating complex machinery, swimming, climbing).
5.5 Myocarditis, Pericarditis, Cardiomyopathy and Mitral Valve Incompetence Myocarditis, pericarditis, and cardiomyopathy have occurred with the use of clozapine.
These reactions can be fatal.
Discontinue Clozapine ODT and obtain a cardiac evaluation upon suspicion of myocarditis, pericarditis, or cardiomyopathy.
Generally, patients with a history of clozapine-associated myocarditis, pericarditis or cardiomyopathy should not be rechallenged with Clozapine ODT.
However, if the benefit of Clozapine ODT treatment is judged to outweigh the potential risks of recurrence, the clinician may consider rechallenge with Clozapine ODT in consultation with a cardiologist.
Consider the possibility of myocarditis or cardiomyopathy in patients receiving Clozapine ODT who present with chest pain, dyspnea, persistent tachycardia at rest, palpitations, fever, flu-like symptoms, hypotension, other signs or symptoms of heart failure, or electrocardiographic findings (low voltages, ST-T abnormalities, arrhythmias, right axis deviation, and poor R wave progression).
Myocarditis and pericarditis most frequently present within the first two months of clozapine treatment.
Symptoms of cardiomyopathy generally occur later than clozapine-associated myocarditis and usually after 8 weeks of treatment.
However, myocarditis, pericarditis, and cardiomyopathy can occur at any period during treatment with Clozapine ODT.
In patients who are diagnosed with cardiomyopathy while taking clozapine, mitral valve incompetence has been reported.
5.6 Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.
Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.
Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality in this population.
The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Clozapine ODT is not approved for the treatment of patients with dementia-related psychosis [see] .
5.7 Gastrointestinal Hypomotility with Severe Complications Severe gastrointestinal adverse reactions have occurred with the use of clozapine, primarily due to its potent anticholinergic effects and resulting gastrointestinal hypomotility.
In post marketing experience, reported effects range from constipation to paralytic ileus.
Increased frequency of constipation and delayed diagnosis and treatment increased the risk of severe complications of gastrointestinal hypomotility, which can result in fecal impaction, megacolon, and intestinal obstruction, ischemia, infarction, perforation, ulceration, or necrosis [see Adverse Reactions (6.2) ] .
These reactions have resulted in hospitalization, surgery, and death.
The risk for severe adverse reactions is further increased with anticholinergic medications (and other medications that decrease gastrointestinal peristalsis); therefore, concomitant use should be avoided when possible [see Warnings and Precautions (5.15) , Drug Interactions (7.1) ] .
Prior to initiating Clozapine ODT, screen for constipation and treat as necessary.
Subjective symptoms of constipation may not accurately reflect the degree of gastrointestinal hypomotility in Clozapine ODT-treated patients.
Therefore, reassess bowel function frequently with careful attention to any changes in the frequency or character of bowel movements, as well as signs and symptoms of complications of hypomotility (e.g., nausea, vomiting, abdominal distension, abdominal pain).
If constipation or gastrointestinal hypomotility are identified, monitor closely and treat promptly with appropriate laxatives, as necessary, to prevent severe complications.
Consider prophylactic laxatives in high risk patients.
5.8 Eosinophilia Eosinophilia, defined as a blood eosinophil count of greater than 700/μL, has occurred with clozapine treatment.
In clinical trials, approximately 1% of patients developed eosinophilia.
Clozapine-related eosinophilia usually occurs during the first month of treatment.
In some patients, it has been associated with myocarditis, pancreatitis, hepatitis, colitis, and nephritis.
Such organ involvement could be consistent with a drug reaction with eosinophilia and systemic symptoms syndrome (DRESS), also known as drug induced hypersensitivity syndrome (DIHS).
If eosinophilia develops during Clozapine ODT treatment, evaluate promptly for signs and symptoms of systemic reactions, such as rash or other allergic symptoms, myocarditis, or other organ-specific disease associated with eosinophilia.
If clozapine-related systemic disease is suspected, discontinue Clozapine ODT immediately.
If a cause of eosinophilia unrelated to Clozapine ODT is identified (e.g., asthma, allergies, collagen vascular disease, parasitic infections, and specific neoplasms), treat the underlying cause and continue Clozapine ODT.
Clozapine-related eosinophilia has also occurred in the absence of organ involvement and can resolve without intervention.
There are reports of successful rechallenge after discontinuation of Clozapine ODT, without recurrence of eosinophilia.
In the absence of organ involvement, continue Clozapine ODT under careful monitoring.
If the total eosinophil count continues to increase over several weeks in the absence of systemic disease, the decision to interrupt Clozapine ODT therapy and rechallenge after the eosinophil count decreases should be based on the overall clinical assessment, in consultation with an internist or hematologist.
5.9 QT Interval Prolongation QT prolongation, Torsades de Pointes and other life-threatening ventricular arrhythmias, cardiac arrest, and sudden death have occurred with clozapine treatment.
When prescribing Clozapine ODT, consider the presence of additional risk factors for QT prolongation and serious cardiovascular reactions.
Conditions that increase these risks include the following:
history of QT prolongation, long QT syndrome, family history of long QT syndrome or sudden cardiac death, significant cardiac arrhythmia, recent myocardial infarction, uncompensated heart failure, treatment with other medications that cause QT prolongation, treatment with medications that inhibit the metabolism of clozapine, and electrolyte abnormalities.
Prior to initiating treatment with Clozapine ODT, perform a careful physical examination, medical history, and concomitant medication history.
Consider obtaining a baseline ECG and serum chemistry panel.
Correct electrolyte abnormalities.
Discontinue Clozapine ODT if the QTc interval exceeds 500 msec.
If patients experience symptoms consistent with Torsades de Pointes or other arrhythmias (e.g., syncope, presyncope, dizziness, or palpitations), obtain a cardiac evaluation and discontinue Clozapine ODT.
specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmic medications (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).
Clozapine is primarily metabolized by CYP isoenzymes 1A2, 2D6, and 3A4.
Concomitant treatment with inhibitors of these enzymes can increase the concentration of clozapine [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] .
Hypokalemia and hypomagnesemia increase the risk of QT prolongation.
Hypokalemia can result from diuretic therapy, diarrhea, and other causes.
Use caution when treating patients at risk for significant electrolyte disturbance, particularly hypokalemia.
Obtain baseline measurements of serum potassium and magnesium levels, and periodically monitor electrolytes.
Correct electrolyte abnormalities before initiating treatment with Clozapine ODT.
5.10 Metabolic Changes Atypical antipsychotic drugs, including clozapine, have been associated with metabolic changes that can increase cardiovascular and cerebrovascular risk.
These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain.
While atypical antipsychotic drugs may produce some metabolic changes, each drug in the class has its own specific risk profile.
Hyperglycemia and Diabetes Mellitus Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including clozapine.
Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population.
Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse reactions is not completely understood.
However, epidemiological studies suggest an increased risk of treatment-emergent, hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics.
Precise risk estimates for hyperglycemia-related adverse reactions in patients treated with atypical antipsychotics are not available.
Patients with an established diagnosis of diabetes mellitus who are started on Clozapine ODT should be monitored regularly for worsening of glucose control.
Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.
Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.
Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing.
In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
In a pooled data analysis of 8 studies in adult subjects with schizophrenia, the mean changes in fasting glucose concentration in the clozapine and chlorpromazine groups were +11 mg/dL and +4 mg/dL, respectively.
A higher proportion of the clozapine group demonstrated categorical increases from baseline in fasting glucose concentrations, compared to the chlorpromazine group (Table 4).
The clozapine doses were 100 to 900 mg per day (mean modal dose: 512 mg per day).
The maximum chlorpromazine dose was 1800 mg per day (mean modal dose: 1029 mg per day).
The median duration of exposure was 42 days for clozapine and chlorpromazine.
Table 4:
Categorical Changes in Fasting Glucose Level in Studies in Adult Subjects with Schizophrenia Laboratory Parameter Category Change (at least once) from Baseline Treatment Arm N n (%) Fasting Glucose Normal (< 100 mg/dL) to High (≥ 126 mg/dL) Clozapine 198 53 (27) Chlorpromazine 135 14 (10) Borderline (100 to 125 mg/dL) to High (≥ 126 mg/dL) Clozapine 57 24 (42) Chlorpromazine 43 12 (28) Dyslipidemia Undesirable alterations in lipids have occurred in patients treated with atypical antipsychotics, including clozapine.
Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using Clozapine ODT, is recommended.
In a pooled data analysis of 10 studies in adult subjects with schizophrenia, clozapine treatment was associated with increases in serum total cholesterol.
No data were collected on LDL and HDL cholesterol.
The mean increase in total cholesterol was 13 mg/dL in the clozapine group and 15 mg/dL in the chlorpromazine group.
In a pooled data analysis of 2 studies in adult subjects with schizophrenia, clozapine treatment was associated with increases in fasting serum triglyceride.
The mean increase in fasting triglyceride was 71 mg/dL (54%) in the clozapine group and 39 mg/dL (35%) in the chlorpromazine group (Table 5).
In addition, clozapine treatment was associated with categorical increases in serum total cholesterol and triglyceride, as illustrated in Table 6.
The proportion of patients with categorical increases in total cholesterol or fasting triglyceride increased with the duration of exposure.
The median duration of clozapine and chlorpromazine exposure was 45 days and 38 days, respectively.
The clozapine dose range was 100 mg to 900 mg daily; the maximum chlorpromazine dose was 1800 mg daily.
Table 5:
Mean Changes in Total Cholesterol and Triglyceride Concentration in Studies in Adult Subjects with Schizophrenia Treatment Arm Baseline Total Cholesterol Concentration (mg/dL) Change from Baseline mg/dL (%) Clozapine (N = 334) 184 +13 (7) Chlorpromazine (N = 185) 182 +15 (8) Baseline Triglyceride Concentration (mg/dL) Change from Baseline mg/dL (%) Clozapine (N = 6) 130 +71 (54) Chlorpromazine (N = 7) 110 +39 (35) Table 6:
Categorical Changes in Lipid Concentrations in Studies in Adult Subjects with Schizophrenia Laboratory Parameter Category Change (at least once) from Baseline Treatment Arm N n (%) Total Cholesterol (random or fasting) Increase by ≥ 40 mg/dL Clozapine 334 111 (33) Chlorpromazine 185 46 (25) Normal (< 200 mg/dL) to High (≥ 240 mg/dL) Clozapine 222 18 (8) Chlorpromazine 132 3 (2) Borderline (200 to 239 mg/dL) to High (≥ 240 mg/dL) Clozapine 79 30 (38) Chlorpromazine 34 14 (41) Triglycerides (fasting) Increase by ≥ 50 mg/dL Clozapine 6 3 (50) Chlorpromazine 7 3 (43) Normal (< 150 mg/dL) to High (≥ 200 mg/dL) Clozapine 4 0 (0) Chlorpromazine 6 2 (33) Borderline (≥ 150 mg/dL and < 200 mg/dL) to High (≥ 200 mg/dL) Clozapine 1 1 (100) Chlorpromazine 1 0 (0) Weight Gain Weight gain has occurred with the use of antipsychotics, including clozapine.
Monitor weight during treatment with Clozapine ODT.
Table 7 summarizes the data on weight gain by the duration of exposure pooled from 11 studies with clozapine and active comparators.
The median duration of exposure was 609, 728, and 42 days, in the clozapine, olanzapine, and chlorpromazine group, respectively.
Table 7:
Mean Change in Body Weight (kg) by Duration of Exposure from Studies in Adult Subjects with Schizophrenia Metabolic Parameter Exposure Duration Clozapine (N = 669) Olanzapine (N = 442) Chlorpromazine (N = 155) n Mean n Mean n Mean Weight change from baseline 2 weeks (Day 11 to 17) 6 +0.9 3 +0.7 2 -0.5 4 weeks (Day 21 to 35) 23 +0.7 8 +0.8 17 +0.6 8 weeks (Day 49 to 63) 12 +1.9 13 +1.8 16 +0.9 12 weeks (Day 70 to 98) 17 +2.8 5 +3.1 0 0 24 weeks (Day 154 to 182) 42 -0.6 12 +5.7 0 0 48 weeks (Day 322 to 350) 3 +3.7 3 +13.7 0 0 Table 8 summarizes pooled data from 11 studies in adult subjects with schizophrenia demonstrating weight gain ≥ 7% of body weight relative to baseline.
The median duration of exposure was 609, 728, and 42 days, in the clozapine, olanzapine, and chlorpromazine group, respectively.
Table 8:
Proportion of Adult Subjects in Schizophrenia Studies with Weight Gain ≥ 7% Relative to Baseline Body Weight Weight Change Clozapine Olanzapine Chlorpromazine N 669 442 155 ≥ 7% (inclusive) 236 (35%) 203 (46%) 13 (8%)
5.11 Neuroleptic Malignant Syndrome Antipsychotic drugs including Clozapine ODT can cause a potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS).
Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).
Associated findings can include elevated creatine phosphokinase (CPK), myoglobinuria, rhabdomyolysis, and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated.
It is important to consider the presence of other serious medical conditions (e.g., severe neutropenia, infection, heat stroke, primary CNS pathology, central anticholinergic toxicity, extrapyramidal symptoms, and drug fever).
The management of NMS should include (1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, (2) intensive symptomatic treatment and medical monitoring, and (3) treatment of co-morbid medical conditions.
There is no general agreement about specific pharmacological treatments for NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered.
NMS can recur.
Monitor closely if restarting treatment with antipsychotics.
NMS has occurred with clozapine monotherapy and with concomitant CNS-active medications, including lithium.
5.12 Hepatotoxicity Severe, life threatening, and in some cases fatal hepatotoxicity including hepatic failure, hepatic necrosis, and hepatitis have been reported in patients treated with clozapine [see Adverse Reactions (6.2) ] .
Monitor for the appearance of signs and symptoms of hepatotoxicity such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, coagulopathy, and hepatic encephalopathy.
Perform serum tests for liver injury and consider permanently discontinuing treatment if hepatitis or transaminase elevations combined with other systemic symptoms are due to Clozapine ODT.
5.13 Fever During clozapine therapy, patients have experienced transient, clozapine-related fever.
The peak incidence is within the first 3 weeks of treatment.
While this fever is generally benign and self-limited, it may necessitate discontinuing treatment.
The fever can be associated with an increase or decrease in WBC count.
Carefully evaluate patients with fever to rule out severe neutropenia or infection [see Warnings and Precautions (5.1) ] .
Consider the possibility of NMS [see Warnings and Precautions (5.11) ] .
5.14 Pulmonary Embolism Pulmonary embolism and deep vein thrombosis have occurred in patients treated with clozapine.
Consider the possibility of pulmonary embolism in patients who present with deep vein thrombosis, acute dyspnea, chest pain, or with other respiratory signs and symptoms.
Whether pulmonary embolus and deep vein thrombosis can be attributed to clozapine or some characteristic(s) of patients is not clear.
5.15 Anticholinergic Toxicity Clozapine ODT has potent anticholinergic effects.
Treatment with Clozapine ODT can result in CNS and peripheral anticholinergic toxicity, especially at higher dosages, or in overdose situations [see Overdosage (10) ] .
Use with caution in patients with a current diagnosis or prior history of constipation, urinary retention, clinically significant prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions.
When possible,
avoid concomitant use with other anticholinergic medications because the risk for anticholinergic toxicity or severe gastrointestinal adverse reactions is increased [see Warnings and Precautions (5.7) , Drug Interactions (7.1) ] .
5.16 Interference with Cognitive and Motor Performance Clozapine ODT can cause sedation and impairment of cognitive and motor performance.
Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that Clozapine ODT does not affect them adversely.
These reactions may be dose-related.
Consider reducing the dose if they occur.
5.17 Tardive Dyskinesia Tardive dyskinesia (TD) has occurred in patients treated with antipsychotic drugs, including clozapine.
The syndrome consists of potentially irreversible, involuntary, dyskinetic movements.
The risk of TD and the likelihood that it will become irreversible are believed to increase with greater durations of treatment and higher total cumulative doses.
However, the syndrome can develop after relatively brief treatment periods at low doses.
Prescribe Clozapine ODT in a manner that is most likely to minimize the risk of developing TD.
Use the lowest effective dose and the shortest duration necessary to control symptoms.
Periodically assess the need for continued treatment.
Consider discontinuing treatment if TD occurs.
However, some patients may require treatment with Clozapine ODT despite the presence of the syndrome.
TD may remit partially or completely if treatment is discontinued.
Antipsychotic treatment, itself, may suppress (or partially suppress) the signs and symptoms, and it has the potential to mask the underlying process.
The effect of symptom suppression on the long-term course of TD is unknown.
5.18 Patients with Phenylketonuria Phenylketonuric patients should be informed that Clozapine ODT contain phenylalanine (a component of aspartame).
Each 25 mg, orally disintegrating tablet contains 1.90 mg phenylalanine.
Each 100 mg, orally disintegrating tablet contains 7.59 mg phenylalanine.
Each 150 mg, orally disintegrating tablet contains 11.38 mg phenylalanine.
Each 200 mg, orally disintegrating tablet contains 15.18 mg phenylalanine.
5.19 Cerebrovascular Adverse Reactions In controlled trials, elderly patients with dementia-related psychosis treated with some atypical antipsychotics had an increased risk (compared to placebo) of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities.
The mechanism for this increased risk is not known.
An increased risk cannot be excluded for Clozapine ODT or other antipsychotics or other patient populations.
Clozapine ODT should be used with caution in patients with risk factors for cerebrovascular adverse reactions.
5.20 Recurrence of Psychosis and Cholinergic Rebound after Abrupt Discontinuation of Clozapine ODT If abrupt discontinuation of Clozapine ODT is necessary (because of severe neutropenia or another medical condition, for example) [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) ] , monitor carefully for the recurrence of psychotic symptoms and adverse reactions related to cholinergic rebound, such as profuse sweating, headache, nausea, vomiting, and diarrhea.

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Clozapine ODT, during pregnancy.
Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Atypical Antipsychotics at1-866-961-2388 or visiting http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
Risk Summary Neonates exposed to antipsychotic drugs, including Clozapine ODT, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery ( see Clinical Considerations ).
Available data from published epidemiologic studies over decades of use with clozapine during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes ( see Data ).
There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including Clozapine ODT, during pregnancy ( see Clinical Considerations ).
In animal reproduction studies, no adverse developmental effects were observed when clozapine was administered orally to pregnant rats or rabbits during the period of organogenesis, or to pregnant rats during pregnancy and lactation, at doses up to approximately 0.4 and 0.9 times the maximum recommended human dose (MRHD) of 900 mg/day, for rats and rabbits respectively, based on mg/m2 body surface area ( see Data ).
The background risk of major birth defects and miscarriage for the indicated populations is unknown.
All pregnancies have a background risk of birth defects, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide.
Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth.
It is not known if this is a direct result of the illness or other comorbid factors.
Fetal/Neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who have been exposed to antipsychotic drugs, including Clozapine ODT, during the third trimester of pregnancy.
These symptoms have varied in severity.
Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.
Data Animal Data In embryofetal developmental studies, clozapine had no effects on maternal parameters, litter sizes, or fetal parameters when administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 0.4 and 0.9 times, respectively, the MRHD of 900 mg/day on a mg/m 2 body surface area basis.
In peri/postnatal developmental studies, pregnant female rats were administered clozapine over the last third of pregnancy and until day 21 postpartum.
Observations were made on fetuses at birth and during the postnatal period; the offspring were allowed to reach sexual maturity and mated.
Clozapine caused a decrease in maternal body weight but had no effects on litter size or body weights of either F1 or F2 generations at doses up to 0.4 times the MRHD of 900 mg/day on a mg/m 2 body surface area basis.
IN SPECIFIC POPULATIONS Lactaton:
Infants exposed to Clozapine ODT through breast milk should be monitored for excess sedation and neutropenia.
( 8.2 )
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Clozapine ODT, during pregnancy.
Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Atypical Antipsychotics at1-866-961-2388 or visiting http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
Risk Summary Neonates exposed to antipsychotic drugs, including Clozapine ODT, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery ( see Clinical Considerations ).
Available data from published epidemiologic studies over decades of use with clozapine during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes ( see Data ).
There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including Clozapine ODT, during pregnancy ( see Clinical Considerations ).
In animal reproduction studies, no adverse developmental effects were observed when clozapine was administered orally to pregnant rats or rabbits during the period of organogenesis, or to pregnant rats during pregnancy and lactation, at doses up to approximately 0.4 and 0.9 times the maximum recommended human dose (MRHD) of 900 mg/day, for rats and rabbits respectively, based on mg/m2 body surface area ( see Data ).
The background risk of major birth defects and miscarriage for the indicated populations is unknown.
All pregnancies have a background risk of birth defects, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide.
Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth.
It is not known if this is a direct result of the illness or other comorbid factors.
Fetal/Neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who have been exposed to antipsychotic drugs, including Clozapine ODT, during the third trimester of pregnancy.
These symptoms have varied in severity.
Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.
Data Animal Data In embryofetal developmental studies, clozapine had no effects on maternal parameters, litter sizes, or fetal parameters when administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 0.4 and 0.9 times, respectively, the MRHD of 900 mg/day on a mg/m 2 body surface area basis.
In peri/postnatal developmental studies, pregnant female rats were administered clozapine over the last third of pregnancy and until day 21 postpartum.
Observations were made on fetuses at birth and during the postnatal period; the offspring were allowed to reach sexual maturity and mated.
Clozapine caused a decrease in maternal body weight but had no effects on litter size or body weights of either F1 or F2 generations at doses up to 0.4 times the MRHD of 900 mg/day on a mg/m 2 body surface area basis.
8.2 Lactation Risk Summary Clozapine is present in human milk.
There is one case report of sedation and a report of agranulocytosis in an infant exposed to clozapine through human milk (see Clinical Considerations ) .
There is no information on the effects of clozapine on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Clozapine ODT and any potential adverse effects on the breastfed child from Clozapine ODT or from the underlying maternal condition.
Clinical Considerations Infants exposed to Clozapine ODT should be monitored for excess sedation and neutropenia.
8.4 Pediatric Use Safety and effectiveness of clozapine in pediatric patients have not been established.
8.5 Geriatric Use There have not been sufficient numbers of geriatric patients in clinical studies utilizing clozapine to determine whether those over 65 years of age differ from younger subjects in their response to clozapine.
Orthostatic hypotension and tachycardia can occur with Clozapine ODT treatment [seeand Warnings and Precautions (5.2) ] .
Elderly patients, particularly those with compromised cardiovascular functioning, may be more susceptible to these effects.
Elderly patients may be particularly susceptible to the anticholinergic effects of Clozapine ODT, such as urinary retention and constipation [see Warnings and Precautions (5.15) ] .
Carefully select Clozapine ODT doses in elderly patients, taking into consideration their greater frequency of decreased hepatic, renal, or cardiac function, as well as other concomitant disease and other drug therapy.
Clinical experience suggests that the prevalence of tardive dyskinesia appears to be highest among the elderly; especially elderly women [see Warnings and Precautions (5.17) ] .
8.6 Patients with Renal or Hepatic Impairment Dose reduction may be necessary in patients with significant impairment of renal or hepatic function.
Clozapine concentrations may be increased in these patients, because clozapine is almost completely metabolized and then excreted [see Dosage and Administration (2.8) , Clinical Pharmacology (12.3) ] .
8.7 CYP2D6 Poor Metabolizers Dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.
Clozapine concentrations may be increased in these patients, because clozapine is almost completely metabolized and then excreted [see Dosage and Administration (2.8) , Clinical Pharmacology (12.3) ] .

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

Concomitant use of Strong CYP1A2 Inhibitors :
Reduce Clozapine ODT dose to one-third when coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, enoxacin).
( 2.7 , 7.1 ) Concomitant use of Strong CYP3A4 Inducers is not recommended.
( 2.7 , 7.1 ) Discontinuation of CYP1A2 or CYP3A4 Inducers:
Consider reducing Clozapine ODT dose when CYP1A2 (e.g., tobacco smoke) or CYP3A4 inducers (e.g., carbamazepine) are discontinued.
( 2.7 , 7.1 ) Anticholinergic drugs:
Concomitant use may increase the risk for anticholinergic toxicity.
( 5.7 , 5.15 , 7.1 )
7.1 Potential for Other Drugs to Affect Clozapine ODT Clozapine is a substrate for many cytochrome P450 isozymes, in particular CYP1A2, CYP3A4, and CYP2D6.
Use caution when administering Clozapine ODT concomitantly with drugs that are inducers or inhibitors of these enzymes.
CYP1A2 Inhibitors Concomitant use of Clozapine ODT and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions.
Reduce the Clozapine ODT dose to one-third of the original dose when Clozapine ODT is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin).
The Clozapine ODT dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.7) , Clinical Pharmacology (12.3) ] .
Moderate or weak CYP1A2 inhibitors include oral contraceptives and caffeine.
Monitor patients closely when Clozapine ODT is coadministered with these inhibitors.
Consider reducing the Clozapine ODT dosage if necessary [see Dosage and Administration (2.7) ] .
CYP2D6 and CYP3A4 Inhibitors Concomitant treatment with Clozapine ODT and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3) ] .
Use caution and monitor patients closely when using such inhibitors.
Consider reducing the Clozapine ODT dose [see Dosage and Administration (2.7) ] .
CYP1A2 and CYP3A4 Inducers Concomitant treatment with drugs that induce CYP1A2 or CYP3A4 can decrease the plasma concentration of clozapine, resulting in decreased effectiveness of Clozapine ODT.
Tobacco smoke is a moderate inducer of CYP1A2.
Strong CYP3A4 inducers include carbamazepine, phenytoin, St.
John’s wort, and rifampin.
It may be necessary to increase the Clozapine ODT dose if used concomitantly with inducers of these enzymes.
However, concomitant use of Clozapine ODT and strong CYP3A4 inducers is not recommended [see Dosage and Administration (2.7) ] .
Consider reducing the Clozapine ODT dosage when discontinuing coadministered enzyme inducers, because discontinuation of inducers can result in increased clozapine plasma levels and an increased risk of adverse reactions [see Dosage and Administration (2.7) ] .
Anticholinergic Drugs Concomitant treatment with Clozapine ODT and other drugs with anticholinergic activity (e.g., benztropine, cyclobenzaprine, diphenhydramine) can increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions related to hypomotility.
Avoid concomitant use of Clozapine ODT with anticholinergic drugs when possible [see Warnings and Precautions (5.7 , 5.15) ] .
Drugs that Cause QT Interval Prolongation Use caution when administering concomitant medications that prolong the QT interval or inhibit the metabolism of clozapine.
Drugs that cause QT prolongation include:
specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, and pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus) [see Warnings and Precautions (5.9) ] .
7.2 Potential for Clozapine ODT to Affect Other Drugs Concomitant use of Clozapine ODT with other drugs metabolized by CYP2D6 can increase levels of these CYP2D6 substrates.
Use caution when coadministering Clozapine ODT with other drugs that are metabolized by CYP2D6.
It may be necessary to use lower doses of such drugs than usually prescribed.
Such drugs include specific antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

10.1 Overdosage Experience The most commonly reported signs and symptoms associated with Clozapine ODT overdose are:
sedation, delirium, coma, tachycardia, hypotension, respiratory depression or failure; and hypersalivation.
There are reports of aspiration pneumonia, cardiac arrhythmias, and seizure.
Fatal overdoses have been reported with clozapine, generally at doses above 2500 mg.
There have also been reports of patients recovering from overdoses well in excess of 4 g.
10.2 Management of Overdosage There are no specific antidotes for Clozapine ODT overdose.
Establish and maintain an airway; ensure adequate oxygenation and ventilation.
Monitor cardiac status and vital signs.
Use general symptomatic and supportive measures.
Consider the possibility of multiple-drug involvement.
Contact a Certified Poison Control Center for the most up to date information on the management of overdosage (1-800-222-1222).

Quoted from the official label, section “Overdosage”.

Use in children

Safety and effectiveness of clozapine in pediatric patients have not been established.

Quoted from the official label, section “Pediatric Use”.

Use in older people

There have not been sufficient numbers of geriatric patients in clinical studies utilizing clozapine to determine whether those over 65 years of age differ from younger subjects in their response to clozapine.
Orthostatic hypotension and tachycardia can occur with Clozapine ODT treatment [seeand Warnings and Precautions (5.2) ] .
Elderly patients, particularly those with compromised cardiovascular functioning, may be more susceptible to these effects.
Elderly patients may be particularly susceptible to the anticholinergic effects of Clozapine ODT, such as urinary retention and constipation [see Warnings and Precautions (5.15) ] .
Carefully select Clozapine ODT doses in elderly patients, taking into consideration their greater frequency of decreased hepatic, renal, or cardiac function, as well as other concomitant disease and other drug therapy.
Clinical experience suggests that the prevalence of tardive dyskinesia appears to be highest among the elderly; especially elderly women [see Warnings and Precautions (5.17) ] .

Quoted from the official label, section “Geriatric Use”.

Side effects

The following adverse reactions are discussed in more detail in other sections of the labeling:
Severe Neutropenia [see Warnings and Precautions (5.1) ] Orthostatic Hypotension, Bradycardia, and Syncope [see Warnings and Precautions (5.2) ] Falls [see Warnings and Precautions (5.3) ] Seizures [see Warnings and Precautions (5.4) ] Myocarditis, Pericarditis, Cardiomyopathy, and Mitral Valve Incompetence [see Warnings and Precautions (5.5) ] Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.6) ] Gastrointestinal Hypomotility with Severe Complications [see Warnings and Precautions (5.7) ] Eosinophilia [see Warnings and Precautions (5.8) ] QT Interval Prolongation [see Warnings and Precautions (5.9) ] Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain) [see Warnings and Precautions (5.10) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.11) ] Hepatotoxicity [see Warnings and Precautions (5.12) ] Fever [see Warnings and Precautions (5.13) ] Pulmonary Embolism [see Warnings and Precautions (5.14) ] Anticholinergic Toxicity [see Warnings and Precautions (5.15) ] Interference with Cognitive and Motor Performance [see Warnings and Precautions (5.16) ] Tardive Dyskinesia [see Warnings and Precautions (5.17) ] Patients with Phenylketonuria [see Warnings and Precautions (5.18) ] Cerebrovascular Adverse Reactions [see Warnings and Precautions (5.19) ] Recurrence of Psychosis and Cholinergic Rebound after Abrupt Discontinuation [see Warnings and Precautions (5.20) ] Most common adverse reactions (≥ 5%) were:
CNS reactions (sedation, dizziness/vertigo, headache, and tremor); cardiovascular reactions (tachycardia, hypotension, and syncope); autonomic nervous system reactions (hypersalivation, sweating, dry mouth, and visual disturbances); gastrointestinal reactions (constipation and nausea); and fever.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The most commonly reported adverse reactions (≥ 5%) across clozapine clinical trials were:
CNS reactions, including sedation, dizziness/vertigo, headache, and tremor; cardiovascular reactions, including tachycardia, hypotension, and syncope; autonomic nervous system reactions, including hypersalivation, sweating, dry mouth, and visual disturbances; gastrointestinal reactions, including constipation and nausea; and fever.
Table 9 summarizes the most commonly reported adverse reactions (≥ 5%) in clozapine-treated patients (compared to chlorpromazine-treated patients) in the pivotal, 6-week, controlled trial in treatment-resistant schizophrenia.
Table 9:
Common Adverse Reactions (≥ 5%) in the 6-Week, Randomized, Chlorpromazine-Controlled Trial in Treatment-Resistant Schizophrenia Adverse Reaction Clozapine (N = 126) (%) Chlorpromazine (N = 142) (%) Sedation 21 13 Tachycardia 17 11 Constipation 16 12 Dizziness 14 16 Hypotension 13 38 Fever (hyperthermia) 13 4 Hypersalivation 13 1 Hypertension 12 5 Headache 10 10 Nausea/vomiting 10 12 Dry mouth 5 20 Table 10 summarizes the adverse reactions reported in clozapine-treated patients at a frequency of 2% or greater across all clozapine studies (excluding the 2 year InterSePT™ Study).
These rates are not adjusted for duration of exposure.
Table 10:
Adverse Reactions (≥ 2%) Reported in Clozapine-treated Patients (N = 842) Across all Clozapine Studies (excluding the 2 year InterSePT™ Study) Body System Adverse Reaction Clozapine N = 842 Percentage of Patients Central Nervous System Drowsiness/Sedation 39 Dizziness/Vertigo 19 Headache 7 Tremor 6 Syncope 6 Disturbed Sleep/Nightmares 4 Restlessness 4 Hypokinesia/Akinesia 4 Agitation 4 Seizures (convulsions) 3 † Rigidity 3 Akathisia 3 Confusion 3 Fatigue 2 Insomnia 2 Cardiovascular Tachycardia 25 † Hypotension 9 Hypertension 4 Gastrointestinal Constipation 14 Nausea 5 Abdominal Discomfort/Heartburn 4 Nausea/Vomiting 3 Vomiting 3 Diarrhea 2 Urogenital Urinary abnormalities 2 Autonomic Nervous System Salivation 31 Sweating 6 Dry mouth 6 Visual disturbances 5 Skin Rash 2 Hemic/Lymphatic Leukopenia/Decreased WBC/Neutropenia 3 Miscellaneous Fever 5 Weight Gain 4 † Rate based on population of approximately 1700 exposed during premarket clinical evaluation of clozapine.
Table 11 summarizes the most commonly reported adverse reactions (≥ 10% of the clozapine or olanzapine group) in the InterSePT™ Study.
This was an adequate and well-controlled, two-year study evaluating the efficacy of clozapine relative to olanzapine in reducing the risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder.
The rates are not adjusted for duration of exposure.
Table 11:
Incidence of Adverse Reactions in Patients Treated with Clozapine or Olanzapine in the InterSePT™ Study (≥ 10% in the clozapine or olanzapine group) Adverse Reactions Clozapine N = 479 % Reporting Olanzapine N = 477 % Reporting Salivary hypersecretion 48% 6% Somnolence 46% 25% Weight increased 31% 56% Dizziness (excluding vertigo) 27% 12% Constipation 25% 10% Insomnia 20% 33% Nausea 17% 10% Vomiting 17% 9% Dyspepsia 14% 8% Dystonia Class effect:
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment.
Dystonic symptoms include:
spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue.
While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs.
An elevated risk of acute dystonia is observed in males and younger age groups.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of clozapine.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Central Nervous System Delirium, EEG abnormal, myoclonus, paresthesia, possible cataplexy, status epilepticus, obsessive compulsive symptoms, and post-discontinuation cholinergic rebound adverse reactions.
Cardiovascular System Atrial or ventricular fibrillation, ventricular tachycardia, QT interval prolongation, Torsades de Pointes, myocardial infarction, cardiac arrest, pericarditis, and periorbital edema.
Endocrine System Pseudopheochromocytoma.
Gastrointestinal System Acute pancreatitis, dysphagia, salivary gland swelling, megacolon, fecal incontinence, and intestinal ischemia, infarction, perforation, ulceration or necrosis.
Hepatobiliary System Cholestasis, hepatitis, jaundice, hepatotoxicity, hepatic steatosis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, liver injury (hepatic, cholestatic, and mixed), and liver failure.
Immune System Disorders Angioedema, leukocytoclastic vasculitis.
Urogenital System Acute interstitial nephritis, nocturnal enuresis, priapism, and renal failure.
Skin and Subcutaneous Tissue Disorders Hypersensitivity reactions:
photosensitivity, vasculitis, erythema multiforme, skin pigmentation disorder, and Stevens-Johnson Syndrome.
Musculoskeletal System and Connective Tissue Disorders Myasthenic syndrome, rhabdomyolysis, and systemic lupus erythematosus.
Respiratory System Aspiration, pleural effusion, pneumonia, lower respiratory tract infection.
Hemic and Lymphatic System Mild, moderate, or severe leukopenia, agranulocytosis, granulocytopenia, WBC decreased, deep vein thrombosis, elevated hemoglobin/hematocrit, erythrocyte sedimentation rate (ESR) increased, sepsis, thrombocytosis, and thrombocytopenia.
Vision Disorders Narrow-angle glaucoma.
Miscellaneous Creatine phosphokinase elevation, hyperuricemia, hyponatremia, and weight loss.

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ).
Discuss the following issues with patients and caregivers:
Severe Neutropenia:
Instruct patients (and caregivers) [see Warnings and Precautions (5.1) ]:
About the risk of developing severe neutropenia and infection with Clozapine ODT treatment.
To immediately report to their healthcare provider any symptom or sign of infection during Clozapine ODT treatment About the importance of having frequent ANC testing Orthostatic Hypotension, Bradycardia, and Syncope:
Inform patients and caregivers about the risk of orthostatic hypotension and syncope, especially during the period of initial dose titration.
Instruct them to strictly follow the clinician’s instructions for dosage and administration [see Dosage and Administration (2.3 , 2.6) ] .
Advise patients to consult their clinician immediately if they feel faint, lose consciousness, or have signs or symptoms suggestive of bradycardia or arrhythmia [see Warnings and Precautions (5.2) ] .
Falls:
Inform patients of the risk of falls, which may lead to fractures or other injuries [see Warnings and Precautions (5.3) ] .
Seizures:
Inform patients and caregivers about the significant risk of seizure during Clozapine ODT treatment.
Caution them about driving and any other potentially hazardous activity while taking Clozapine ODT [see Warnings and Precautions (5.4) ] .
Gastrointestinal Hypomotility with Severe Complications:
Educate patients and caregivers on the risks, prevention, and treatment of Clozapine ODT-induced constipation, including medications to
avoid when possible (e.g., drugs with anticholinergic activity).
Encourage appropriate hydration, physical activity, and fiber intake and emphasize that prompt attention and treatment to the development of constipation or other gastrointestinal symptoms is critical in preventing severe complications.
Advise patients and caregivers to contact their healthcare provider if they experience symptoms of constipation (e.g., difficulty passing stools, incomplete passage of stool, decreased bowel movement frequency) or other symptoms associated with gastrointestinal hypomotility (e.g., nausea, abdominal distension or pain, vomiting) [see Warnings and Precautions (5.7) , Drug Interactions (7.1) ] .
QT Interval Prolongation:
Advise patients to consult their clinician immediately if they feel faint, lose consciousness or have signs or symptoms suggestive of arrhythmia.
Instruct patients to not take Clozapine ODT with other drugs that cause QT interval prolongation.
Instruct patients to inform their clinicians that they are taking Clozapine ODT before any new drug [see Warnings and Precautions (5.9) and Drug Interactions (7.1) ] .
Metabolic Changes (hyperglycemia and diabetes mellitus, dyslipidemia, weight gain):
Educate patients and caregivers about the risk of metabolic changes and the need for specific monitoring.
The risks include hyperglycemia and diabetes mellitus, dyslipidemia, weight gain, and cardiovascular reactions.
Educate patients and caregivers about the symptoms of hyperglycemia (high blood sugar) and diabetes mellitus (e.g., polydipsia, polyuria, polyphagia, and weakness).
Monitor all patients for these symptoms.
Patients who are diagnosed with diabetes or have risk factors for diabetes (obesity, family history of diabetes) should have their fasting blood glucose monitored before beginning treatment and periodically during treatment.
Patients who develop symptoms of hyperglycemia should have assessments of fasting glucose.
Clinical monitoring of weight is recommended [see Warnings and Precautions (5.10) ] .
Patients with Phenylketonuria:
Inform patients and caregivers that Clozapine ODT contains phenylalanine (a component of aspartame) [see Warnings and Precautions (5.18) ] .
Interference with Cognitive and Motor Performance:
Because Clozapine ODT may have the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Clozapine ODT therapy does not affect them adversely [see Warnings and Precautions (5.16) ] .
Hepatotoxicity:
Instruct patients to immediately report to their physician any symptom or sign of potential liver injury (e.g., fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, coagulopathy, and hepatic encephalopathy) [see Warnings and Precautions (5.12) ] .
Missed Doses and Re-Initiating Treatment:
Inform patients and caregivers that if the patient misses taking Clozapine ODT for 1 day or more, they should not restart their medication at the same dosage but should contact their physician for dosing instructions [see Dosage and Administration (2.6) and Warnings and Precautions (5.1 , 5.2) ] .
Pregnancy:
Patients and caregivers should notify the clinician if the patient becomes pregnant or intends to become pregnant during therapy [see Use in Specific Populations (8.1) ] .
Nursing:
Advise patients and caregivers that the patient should not breast feed an infant if they are taking Clozapine ODT [see ] .
Concomitant Medication:
Advise patients to inform their healthcare provider if they are taking, or plan to take, any prescription or over-the-counter drugs; there is a potential for significant drug-drug interactions [see Dosage and Administration (2.7) , Drug Interactions (7.1) ] .
Administration:
Patients should be advised that Clozapine ODT should remain in the original package until immediately before use [see Dosage and Administration (2.2) ] .
The brands listed are trademarks of their respective owners.
Manufactured for: Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.
Manufactured by: Mylan Laboratories Limited Hyderabad — 500 096, India Revised: 6/2025

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

FORMS AND STRENGTHS Clozapine Orally Disintegrating Tablets are available containing 25 mg, 100 mg, 150 mg or 200 mg of clozapine, USP.
The 25 mg tablets are peach, round, unscored tablets debossed with C over 25 on one side of the tablet and blank on the other side.
The 100 mg tablets are peach, round, unscored tablets debossed with C over 100 on one side of the tablet and blank on the other side.
The 150 mg tablets are peach, round, unscored tablets debossed with C150 on one side of the tablet and blank on the other side.
The 200 mg tablets are peach, round, unscored tablets debossed with C200 on one side of the tablet and blank on the other side.
Orally disintegrating tablets: 25 mg, 100 mg, 150 mg and 200 mg ( 3 )

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

16.1 How Supplied Clozapine Orally Disintegrating Tablets are available containing 100 mg of clozapine, USP.
The 100 mg tablets are peach, round, unscored tablets debossed with C over 100 on one side of the tablet and blank on the other side.
They are available as follows:
NDC 48433-022-04 – Unit dose blister packages of 40 (5 cards of 8 tablets each).
Storage and Handling
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture.
Keep out of reach of children.
Keep Clozapine ODT in the original package until used by the patient.
PHARMACIST: Dispense a Medication Guide with each prescription.
The quantity of Clozapine ODT depends on the ANC testing results [see Warnings and Precautions (5.1) ] .
If a patient is eligible for ANC testing:
Every week, then a 1-week supply of Clozapine ODT can be dispensed.
Every 2 weeks, then a 2-week supply of Clozapine ODT can be dispensed.
Every 4 weeks, then a 4-week supply of Clozapine ODT can be dispensed.

Quoted from the official label, section “How Supplied”.

What is in it

Clozapine, an atypical antipsychotic drug, is a tricyclic dibenzodiazepine derivative, 8-chloro-11-(4-methyl-1-piperazinyl)-5 H -dibenzo [ b,e ] [1,4] diazepine.
The structural formula is:
Clozapine Orally Disintegrating Tablets (referred to as Clozapine ODT) are available as peach, orally disintegrating tablets of 25 mg, 100 mg, 150 mg or 200 mg for oral administration without water.
Clozapine orally disintegrating tablets may be chewed.
Each orally disintegrating tablet contains clozapine, USP equivalent to 25 mg, 100 mg, 150 mg or 200 mg.
The active component of clozapine orally disintegrating tablets is clozapine.
The remaining components are aspartame, crospovidone, FD&C Yellow No. 6 Aluminum Lake, magnesium stearate, mannitol, microcrystalline cellulose, peppermint flavor, silicon dioxide and sodium stearyl fumarate.
Clozapine ODT contains aspartame [see Warnings and Precautions (5.18) ] .
Phenylalanine is a component of aspartame.
Each 25 mg, orally disintegrating tablet contains 3.38 mg aspartame, thus, 1.90 mg phenylalanine.
Each 100 mg, orally disintegrating tablet contains 13.52 mg aspartame, thus, 7.59 mg phenylalanine.
Each 150 mg, orally disintegrating tablet contains 20.28 mg aspartame, thus, 11.38 mg phenylalanine.
Each 200 mg, orally disintegrating tablet contains 27.04 mg aspartame, thus, 15.18 mg phenylalanine. structural formula

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

The stored label for this product has no list of inactive ingredients. The list on the pack is the one to check.

Quoted from the FDA label. A label that does not name an ingredient is not a guarantee that the product is free of it, and formulations change. With an allergy, check the pack and ask a pharmacist.

Every version of this medicine (15)

The same active substance, strength and kind of form, from every company that sells it — with what each label lists.

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Same active substance, strength and form in other countries

Matched on active substance, strength and kind of form only. This is not a statement that the products are equivalent or interchangeable: other ingredients, release and approved uses can differ — ask a pharmacist before swapping.

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France9 matching products

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Canada7 matching products

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Netherlands14 matching products

Every strength and form (46)

Details

Made by	Safecor Health, LLC
Active substance	Clozapine
Used in	Pain, sleep, mood, epilepsy and the brain
Strength	100 mg
Form	Tablet, Orally Disintegrating
Route	Oral
Packs	40 BLISTER PACK in 1 CARTON / 1 TABLET, ORALLY DISINTEGRATING in 1 BLISTER PACK
NDC	48433-022

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

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Other strengths and forms

45 products are sold under this name. Grouped by form; a number on a strength means several companies make it.

Tablet29 products
- 25 mg8
  25 mg · 8 companies
- 50 mg5
  50 mg · 5 companies
- 100 mg9
  100 mg · 9 companies
  +1 more
- 200 mg7
  200 mg · 7 companies
Tablet, Orally Disintegrating16 products
- 12.5 mg2
  12.5 mg · 2 companies
  - Aurobindo Pharma Limited
  - Teva Pharmaceuticals USA, Inc.
- 25 mg3
  25 mg · 3 companies
- 100 mg5
  100 mg · 5 companies
  - Aurobindo Pharma Limited
  - Mylan Institutional Inc.
  - Mylan Pharmaceuticals Inc.
  - Safecor Health, LLC · this page
  - Teva Pharmaceuticals USA, Inc.
- 150 mg3
  150 mg · 3 companies
- 200 mg3
  200 mg · 3 companies

Same active substance

These contain the same substance. That does not mean one can replace another — ask a pharmacist.

Clozapine150 mgPrescription onlyTablet, Orally Disintegrating Teva Pharmaceuticals USA, Inc. · Clozapine Clozapine200 mgPrescription onlyTablet, Orally Disintegrating Teva Pharmaceuticals USA, Inc. · Clozapine Clozapine12.5 mgPrescription onlyTablet, Orally Disintegrating Teva Pharmaceuticals USA, Inc. · Clozapine Clozapine25 mgPrescription onlyTablet, Orally Disintegrating Teva Pharmaceuticals USA, Inc. · Clozapine Clozapine100 mgPrescription onlyTablet, Orally Disintegrating Teva Pharmaceuticals USA, Inc. · Clozapine Clozapine25 mgPrescription onlyTablet Mylan Pharmaceuticals Inc. · Clozapine

See every product with Clozapine