Clozapine 150 mg Tablet, Orally Disintegrating, 100-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Atypical Antipsychotic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Clozapine is used to treat schizophrenia (a mental illness that affects how a person thinks, feels or behaves) in certain people. Clozapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.
Read the full MedlinePlus article ↗- Clozapine is reserved for situations where other antipsychotics haven't provided enough relief. If you're taking it for schizophrenia, it means your care team determined that stand...
- Why am I on clozapine instead of a regular antipsychotic?
- This is genuinely one of the most important parts of being on clozapine. The medication can cause a dangerous drop in the white blood cells that fight infection — a condition calle...
- Why do I have to get blood tests so often?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Clozapine — tap one for details:
Clozapine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII Z0H242BBR1
Aspartame is an artificial sweetener made from amino acids. It's added to medicines to improve taste, making bitter or unpleasant-tasting drugs easier to take.
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UNII 68401960MK
Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
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UNII H77VEI93A8
A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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UNII 7T9FYH5QMK
A plant-derived powder that serves as a binder and filler in tablets and capsules. It helps hold ingredients together, adds bulk, and aids in smooth tablet disintegration when swallowed.
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UNII V95R5KMY2B
Peppermint is a flavoring agent derived from the peppermint plant. It's added to medicines to improve taste and mask bitter or unpleasant flavors, making them easier to take.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 7CV7WJK4UI
Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.
9 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $14.971 | $1,497.08 / 100 tablets |
| Medicaid paysCMS SDUD · 12 mo | $16.67 | $1,666.91 / 100 tablets |
| Medicare drug plans payPart D · Q2 2026 | $14.60 | $1,459.63 / 100 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Clozapine 150 mg 00093-5376-01 | Teva | 100 tablets | $14.971 | AB | Availability likely | — |
| Clozapine 150 mgthis 00378-3816-01 | Mylan | 100 tablets | $14.971 | AB | Availability likely | — |
| Clozapine 150 mg 59651-0263-01 | Aurobindo | 100 tablets | $14.971 | AB | Availability likely | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00378-3816-01 You're viewing this | 100 TABLET, ORALLY DISINTEGRATING in 1 BOTTLE, PLASTIC (0378-3816-01) | 2023-08-16 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: 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 mo…
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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 )
1.1Treatment-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) ].
1.2Reduction 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) ] .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • 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 )
2.1Absolute 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) .
2.2Recommended 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.
2.3Dosage 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 2…
💊 Dosage Forms and Strengths ▾
3 DOSAGE 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 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Severe neutropenia: See Boxed Warning ( 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 ): o Hyperglycemia and Diabetes Mellitus: Monitor for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. o Dyslipidemia: Undesirable alterations in lipids have occurred in patients treated with atypical antipsychotics. o 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 )
5.1Severe 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. Clozapine ODT initiation is not recommended in patients with a baseline ANC less than 1500/µL. 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. Clozapine ODT initiation is not recommended in patients with BEN with an ANC less than 1000/µL. There are different ANC dosage modification recommendations in Clozapine ODT-treated patients with BEN due to their lower baseline ANC levels.
Table 2 provides recomme…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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.
6.1Clinical 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…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • 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 )
7.1Potential 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, methadon…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactaton: Infants exposed to Clozapine ODT through breast milk should be monitored for excess sedation and neutropenia. ( 8.2 )
8.1Pregnancy 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.
8.2Lactation 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 c…
🤰 Pregnancy ▾
8.1Pregnancy 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.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of clozapine in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric 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 [see Boxed Warning and 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) ] .
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Overdosage 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.
10.2Management 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).
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and other dopaminergic and serotonergic receptors.
12.2Pharmacodynamics Clozapine demonstrated binding affinity to the following receptors: histamine H 1 (K i 1.1 nM), adrenergic α 1A (K i 1.6 nM), serotonin 5-HT 6 (K i 4 nM ) , serotonin 5-HT 2A (K i 5.4 nM), muscarinic M 1 (K i 6.2 nM), serotonin 5-HT 7 (K i 6.3 nM), serotonin 5-HT 2C (K i 9.4 nM), dopamine D 4 (K i 24 nM), adrenergic α 2A (K i 90 nM), serotonin 5-HT 3 (K i 95 nM), serotonin 5-HT 1A (K i 120 nM), dopamine D 2 (K i 160 nM), dopamine D 1 (K i 270 nM), dopamine D 5 (K i 454 nM), and dopamine D 3 (K i 555 nM).
Clozapine causes little or no prolactin elevation. Clinical electroencephalogram (EEG) studies demonstrated that clozapine increases delta and theta activity and slows dominant alpha frequencies. Enhanced synchronization occurs.
Sharp wave activity and spike and wave complexes may also develop. Patients have reported an intensification of dream activity during clozapine therapy. REM sleep was found to be increased to 85% of the total sleep time.
In these patients, the onset of REM sleep occurred almost immediately after falling asleep.
12.3Pharmacokinetics Absorption In humans, Clozapine ODT (25 mg and 100 mg) is equally bioavailable relative to a clozapine oral solution. Clozapine ODT is bioequivalent to Clozaril ® (clozapine) tablets. Following a dosage of 100 mg twice daily, the average steady-state peak plasma concentration was 413 ng/mL (range: 132 to 854 ng/mL), occurring at the average of 2.3 hours (range: 1 to 6 hours) after dosing.
The average minimum concentration at steady-state was 168 ng/mL (range: 45 to 574 ng/mL), after 100 mg b.i.d. dosing. A comparative bioequivalence/bioavailability study was conducted in 32 patients (with schizophrenia or schizoaffective disorder) comparing Clozapine ODT 200 mg to 2 × Clozapine ODT 100 mg (the approved reference product) under fasted conditions. The study also evaluated the effect of food and chewing on the pharmacokinetics of the 200 mg tablet.
Under fasted conditions, the mean AUC ss and C min,ss of clozapine for the 200 mg oral disintegrating tablets were equivalent to those of the 2 x 100 mg tablets. The mean C max,ss of clozapine for Clozapine ODT 200 mg was 85% that for 2 x 100 mg Clozapine ODT. This decrease in C max,ss for Clozapine ODT 200 mg is not clinically significant.
For Clozapine ODT 200 mg, food significantly increased the C min,ss of clozapine by 21%. However, this increase is not clinically significant. The mean AUC ss and C max,ss of clozapine under fed conditions were equivalent to those under fasted conditions.
Food delayed clozapine absorption by 1.5 hours, from a median T max of 2.5 hours under fasted conditions to 4 hours under fed conditions. The mean C max,ss of clozapine under chewed conditions for Clozapine ODT 200 mg was about 86% that for 2 x 100 mg Clozapine ODT under non-chewed conditions, while the AUC ss and C min,ss values were similar between the chewed and non-chewed conditions. In a food-effect study, a single dose of Clozapine ODT 12.5 mg was administered to healthy volunteers under fasting conditions and after a high-fat meal.
When Clozapine ODT was administered after a high-fat meal, the C max of both clozapine and its active metabolite, desmethylclozapine, were decreased by approximately 20%, compared to administration under fasting conditions, while the AUC values were unchanged. This decrease in C max is not clinically significant. Therefore, Clozapine ODT can be taken without regard to meals.
Distribution Clozapine is approximately 97% bound to serum proteins. The interaction between…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and other dopaminergic and serotonergic receptors.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied 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. They are available as follows: NDC 0378-3813-01 bottles of 100 tablets 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 0378-3815-01 bottles of 100 tablets The 150 mg tablets are peach, round, unscored tablets debossed with C150 on one side of the tablet and blank on the other side. They are available as follows: NDC 0378-3816-01 bottles of 100 tablets The 200 mg tablets are peach, round, unscored tablets debossed with C200 on one side of the tablet and blank on the other side. They are available as follows: NDC 0378-3817-01 bottles of 100 tablets
16.2Storage and Handling Store Clozapine Orally Disintegrating Tablets (referred to as Clozapine ODT) 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.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. 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.
📋 Description ▾
11 DESCRIPTION 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
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION 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, thinki…