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Clozapine 25 mg Tablet, Orally Disintegrating, 100-count

by Aurobindo Pharma Limited · 100 TABLET, ORALLY DISINTEGRATING in 1 BOTTLE (59651-261-01)

NDC 59651-0261-01

🏷️ FDA NDC (as labeled) 59651-261-01 billing pads the product segment with a zero

This package

Contains100-count Cost per ea$1.69 NADAC Per package$168.73 / 100 tablets Pack sizes2 compare ↓

Also priced by: Part D plans $14.60/unit — full pricing hub ↓

Also comes in: 6 tablets 59651-0261-48

Rx only Generic On market Non-controlled

🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm

📋 All sources & update times →

This page is curated, coded, and maintained by Dr. Brian Staiger, PharmD

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 59651-261-01

Product NDC 59651-261

11-digit billing NDC 59651026101

NCPDP billing unit EA — each (per item)

RxCUI 476177, 476179, 721773, 996921, 1006801

UNII J60AR2IKIC

Application # ANDA212923

SPL Set ID caf2d4a6-2a23-4992-a807-560c4204afc4

Established class (EPC) Atypical Antipsychotic

DEA schedule Non-controlled

Marketing category ANDA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2024-12-12

Route ORAL

Dosage form TABLET, ORALLY DISINTEGRATING

Substance CLOZAPINE

GPI-14 59152020007220

GCN Seq No 053994

GCN 21784

HICL code 004834

Ingredient (HICL) Clozapine

HIC1 code H

Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)

HIC2 code H7

Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 1)

HIC3 code H7T

Therapeutic class — specific (HIC3) Antipsychotic,Atypical,Dopamine,Serotonin Antagnst

AHFS code 28:16.08.04

AHFS class Atypical Antipsychotics

FDB label name CLOZAPINE ODT 25 MG TABLET

FDB brand name Clozapine Odt

Legend status F — Federal legend — prescription drug or device

TE code (Orange Book) AB · RLD · RS

Why two NDCs? The FDA registers this code as 59651-261-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 59651-0261-01. Same drug, same package — only the format differs.

Where does this data come from?

Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Atypical Antipsychotic class.

Pharmacologic class Atypical Antipsychotic

Drug family (ATC) Diazepines, oxazepines, thiazepines and oxepines

Where does this data come from?

Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerAurobindo Pharma Limited

Application holderAUROBINDO PHARMA LTD

FDA applicationANDA212923 (ANDA)

Labeler code59651

First marketedDec 2024

Product typeHuman Prescription Drug

Portfolio1,449 products on file

🔎 All NDCs from Aurobindo Pharma Limited

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).

Where does this data come from?

Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name CLOZAPINE ODT 25 MG TABLET Ingredient Clozapine

📖 What it is MedlinePlus · NLM

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 ↗

📗 Our plain-language guide HelloPharmacist

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?

📖 Read our full Clozapine guide →

Patient education

📘 MedlinePlus patient leaflet ↗

Supplement & herbal interactions

Some supplements/herbs that may interact with Clozapine — tap one for details:

Activated CharcoalMajor Coffee CharcoalModerate European MandrakeModerate GlucomannanModerate Guar GumModerate Gum ArabicModerate Slippery ElmModerate TragacanthModerate

🌿 Every supplement checked against Clozapine (212 interactions) — ranked by severity →

Nutrient depletion considerations

Clozapine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

SELENIUM Insufficient Evidence

🧪 Full Clozapine nutrient depletion report →

An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.

Where does this data come from?

Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color Yellow

ShapeRound

ImprintCLO;200

Size16 mm

ScoringNot scored

FlavorPeppermint

One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.

Where does this data come from?

Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

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.
UNII 6B46OH7T95
Crospovidone is a synthetic polymer derived from a plant-based material. It works as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs properly.
UNII 40UAA97IT9
Crospovidone is a synthetic polymer derived from povidone. It absorbs liquid quickly and swells, helping tablets and capsules break apart and dissolve faster in your stomach.
UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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.
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.
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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.
UNII 32K497ZK2U
Polyvinyl acetate is a synthetic plastic polymer derived from vinyl acetate. It acts as a binder and film-forming agent in medicines, helping to hold ingredients together and create protective coatings on tablets or capsules.
UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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.
UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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.

13 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?

Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

Are inactive ingredients the same for every manufacturer?

No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.

Why might an inactive ingredient be missing?

Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.

Can inactive ingredients matter?

Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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	$1.687	$168.73 / 100 tablets
Medicaid paysCMS SDUD · 12 mo	No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026	$14.60	$1,459.63 / 100 tablets

NADAC price history (per ea) — tap or hover for the price & month

▲ Up 8% over the last 8 months.

Where does this data come from?

NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Clozapine 25 mg 00093-5417-01	Teva	100 tablets	$1.687	AB	Availability likely	—
Clozapine 25 mg 00378-3813-01	Mylan	100 tablets	$1.687	AB	Availability likely	—
Clozapine 25 mgthis 59651-0261-01	Aurobindo	100 tablets	$1.687	AB	Availability likely	—

About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.

Where does this data come from?

Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️

2024

On the market since

Dec 2024

📍

2026

Currently FDA-listed

2 years listed

🔓

Generic on the market

this product is a generic

✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?

Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Clozapine — the program that covers self-administered drugs. 5 manufacturers.

⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Clozapine. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.

Period

Total Part D spend

$22.15M

Claims incl. refills

275.1K

Beneficiaries

61.3K

Spend / beneficiary

$361.20

Spend / claim

$80.54

Trend by period

💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for CLOZAPINE — the ingredient across all brands.

Top reported reactions

Neutropenia18,897

Hospitalisation12,426

Death12,036

Schizophrenia4,692

White Blood Cell Count Increased4,508

White Blood Cell Count Decreased4,481

Neutrophil Count Increased4,167

Age at onset

Neonate60

Infant19

Child135

Adolescent434

Adult18,209

Elderly5,752

Reporter sex

Male · 61%

Female · 39%

Unknown · 0%

Serious outcomes

Hospitalization54,631

Death22,311

Life-threatening6,593

Disabling1,246

Reports over time (by year) — tap or hover for the count & year

Most recent year is provisional (FAERS lags ~3 months).

Where does this data come from?

Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDC	Description	Per unit	Per pack	Marketing start	Status
59651-0261-01 You're viewing this	100 TABLET, ORALLY DISINTEGRATING in 1 BOTTLE (59651-261-01)	$1.69 / ea	$168.73	2024-12-12	Active
59651-0261-48	8 BLISTER PACK in 1 CARTON (59651-261-48) / 6 TABLET, ORALLY DISINTEGRATING in 1 BLISTER PACK	—	—	2024-12-12	Active

Pack size FAQ

What quantity is in NDC 59651-0261-01?

NDC 59651-0261-01 is a 100-count package — 100 tablet, orally disintegrating in 1 bottle.

What NDC number is used to bill for this package of Clozapine 25 mg Tablet, Orally Disintegrating?

Bill NDC 59651-0261-01 — the 11-digit billing format is 59651026101. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.

🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide

🚨 Boxed Warning ~2 min read ▾

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) has caused severe neutropenia which is associated with an increased risk of serious and potentially 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 d…

🎯 Indications and Usage ~1 min read ▾

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 ~3 min read ▾

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 dosage 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 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 ( 2.3 ).

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 (2.4 , 2.5) .

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 (5.3) ]. 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) ].

Just prior to use, peel the foil from the blister and gently remove the orally disintegrating tablet (ODT). Do not push the ODT through the foil, because this could damage the ODT. After removing Clozapine ODT from the blister pack or 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 (2.5) ]. Table 1: Clozapine ODT Dosage Modifications Based on ANC Results and Frequency of ANC Testing 1 Confirm all initial reports of ANC less than 1500/μL with a repeat ANC measurement within 24 hours 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 t…

💊 Dosage Forms and Strengths 157 words ▾

3 DOSAGE FORMS AND STRENGTHS Clozapine Orally Disintegrating Tablets are available as: 12.5 mg: yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “12.5” on the other side. 25 mg: yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “25” on the other side. 100 mg: yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “100” on the other side.

150 mg: yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “150” on the other side. 200 mg: yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “200” on the other side. Orally disintegrating tablets: 12.5 mg, 25 mg, 100 mg, 150 mg and 200 mg (3)

⛔ Contraindications 50 words ▾

4 CONTRAINDICATIONS Clozapine ODT is contraindicated in patients with a history of serious 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 ~3 min read ▾

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 ): 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.

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.

( 5.14 ) Pulmonary Embolism (PE) : Consider PE if respiratory distress, chest pain, or deep-vein thrombosis occurs. ( 5.15 ) 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 VERZACLOZ 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 recommendations on dosage modi…

🤒 Adverse Reactions ~2 min read ▾

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, and 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 Aurobindo Pharma USA, Inc. at 1-866-850-2876 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 † Rate based on population of approximately 1700 exposed during premarket clinical evaluatio…

🔄 Drug Interactions ~2 min read ▾

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, methadone, halofant…

👥 Use in Specific Populations ~3 min read ▾

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 CLOZARIL, 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/m 2 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 clozapi…

🤰 Pregnancy ~2 min read ▾

🧒 Pediatric Use 15 words ▾

8.4Pediatric Use Safety and effectiveness of clozapine in pediatric patients have not been established.

🧓 Geriatric Use 150 words ▾

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 128 words ▾

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 ~3 min read ▾

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 were 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 cl…

🧬 Mechanism of Action 63 words ▾

📦 How Supplied / Storage and Handling ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Clozapine Orally Disintegrating Tablets 12.5 mg are yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “12.5” on the other side. Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap NDC 59651-260-01 Clozapine Orally Disintegrating Tablets 25 mg are yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “25” on the other side. Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap NDC 59651-261-01 Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant blisters per card NDC 59651-261-48 Clozapine Orally Disintegrating Tablets 100 mg are yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “100” on the other side.

Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap NDC 59651-262-01 Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant blisters per card NDC 59651-262-48 Clozapine Orally Disintegrating Tablets 150 mg are yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “150” on the other side. Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap NDC 59651-263-01 Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant blisters per card NDC 59651-263-48 Clozapine Orally Disintegrating Tablets 200 mg are yellow to pale yellow color, round shaped tablet, flat faced bevelled edge debossed with “CLO” on one side and “200” on the other side.

Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap NDC 59651-264-01 Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant blisters per card NDC 59651-264-48

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 in a sealed blister until time of use.

This unit-dose package is non child-resistant. Keep Clozapine ODT in the original package until used by the patient. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

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 179 words ▾

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 yellow to pale yellow, and are for oral administration. Each orally disintegrating tablet contains clozapine, USP, equivalent to 12.5 mg, 25 mg, 100 mg, 150 mg, and 200 mg.

The inactive ingredients include aspartame, crospovidone, magnesium stearate, mannitol, polyvinyl acetate, povidone, powdarome peppermint premium, silicified microcrystalline cellulose, sodium lauryl sulfate, sodium stearyl fumarate and yellow iron oxide. Clozapine ODT contains aspartame [see Warnings and Precautions (5.18) ]. Phenylalanine is a component of aspartame.

Each 12.5 mg, orally disintegrating tablet contains 1.25 mg aspartame, thus, 0.70 mg phenylalanine. Each 25 mg, orally disintegrating tablet contains 2.5 mg aspartame, thus, 1.40 mg phenylalanine. Each 100 mg, orally disintegrating tablet contains 10 mg aspartame, thus, 5.61 mg phenylalanine.

Each 150 mg, orally disintegrating tablet contains 15 mg aspartame, thus, 8.42 mg phenylalanine. Each 200 mg, orally disintegrating tablet contains 20 mg aspartame, thus, 11.23 mg phenylalanine. Chemical Structure

💬 Information for Patients ~3 min read ▾

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 health care 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 health care 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 (5.8) , 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 contain 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,…

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Clozapine ( kloe' za peen ) Orally Disintegrating Tablets, for oral use What is the most important information I should know about Clozapine Orally Disintegrating Tablets? Clozapine Orally Disintegrating Tablets can cause serious side effects including: Severe neutropenia (low white blood cell (WBC) counts) that can lead to serious infections and death. Your healthcare provider will do WBC blood tests before starting treatment with clozapine orally disintegrating tablets and weekly for the first 6 months.

After your first 6 months of treatment, your healthcare provider will determine how frequent you will have blood tests. If you have symptoms of severe neutropenia or an infection, your healthcare provider will do more frequent WBC blood test(s) to check if clozapine orally disintegrating tablets are causing your symptoms and may send you to see a blood specialist (hematologist). Tell your health care provider right away if you have any of the following symptoms or signs of neutropenia or infection: º feel like you have the flu º wounds that take a long time heal º fever or chills º skin, throat, vaginal, urinary tract, or lung infection º feel extremely tired or weak º pain or burning while peeing º sores or ulcers inside your mouth, gums, or on your skin º unusual vaginal discharge or itching º sores or pain in or around your rectal area º abdominal pain or bloating Orthostatic hypotension (decreased blood pressure), bradycardia (slow heart rate), or syncope (fainting) that can lead to death .

You may feel lightheaded or faint when you rise too quickly from a sitting or lying position. Tell your healthcare provider right away if you feel dizzy or pass out. Seizures.

See “ What should I avoid while taking clozapine orally disintegrating tablets?” Myocarditis (heart muscle inflammation), pericarditis (inflammation of outer layer of the heart) and cardiomyopathy (heart muscle weakness) that can lead to death. Symptoms of myocarditis, pericarditis, and cardiomyopathy include: º chest pain º flu-like symptoms º fast heartbeat or palpitations º feel tired or faint º shortness of breath º swollen legs, ankles, or feet º fever Increased risk of death in elderly people with dementia-related psychosis.

Medicines like clozapine orally disintegrating tablets can increase the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and dementia. Clozapine orally disintegrating tablets is not for treatment of elderly people with dementia-related psychosis. What is clozapine orally disintegrating tablets?

Clozapine orally disintegrating tablets are a prescription antipsychotic medicine used to treat people: Who are severely ill with schizophrenia not helped by other schizophrenia medicines With schizophrenia or schizoaffective disorder who have been suicidal and may be at risk of suicidal behavior again It is not known if clozapine orally disintegrating tablets are safe and effective in children. Who should not take clozapine orally disintegrating tablets? Do not take clozapine orally disintegrating tablets if you: are allergic to clozapine or any of the ingredients in clozapine orally disintegrating tablets.

See the end of this Medication Guide for a complete list of ingredients in clozapine orally disintegrating tablets. Before taking clozapine orally disintegrating tablets, tell your healthcare provider about all your medical conditions, including if you: have or have had heart problems or a family history of heart problems including heart attack, heart failure, abnormal heart rhythm or long QT syndrome, or stroke have or have had low or high blood pressure have or have had kidney or liver problems have or have had seizures (convulsions) have or have had stomach or intestinal problems including constipation, slow emptying of your stomach, or diarrhea have or have had low levels of potassium or magnesium in your blood have or have had diabetes or high blood sugar in you or your family…

Glossary — plain-language definitions of medical terms used in this label:

case report: A written account of what happened to one patient, useful as a signal but not proof of cause.

contraindicated: Should not be used in that situation, because the risk is considered too high.

serotonergic: Acting on serotonin, a chemical messenger involved in mood, sleep, and digestion.

abdominal distension: A swollen or stretched feeling in the belly, often from gas or fluid.

abdominal pain: Pain, cramping, or discomfort felt anywhere in the belly area.

absolute neutrophil count: A blood test number showing how many infection-fighting neutrophil white blood cells you have.

Absorption: How a medicine moves from where it is taken, such as the stomach or gut, into the bloodstream.

abuse: Using a medicine in a way it was not meant to be used, such as taking more than prescribed to feel a high.

active metabolite: A substance made when the body breaks down a medicine that still has an effect of its own.

active-controlled: Describes a study that compares a new medicine against another medicine already known to work, instead of a dummy pill.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

agitation: A state of feeling restless and upset and being unable to relax, sometimes with pacing or fidgeting.

agranulocytosis: A severe drop in a certain type of infection-fighting white blood cell, greatly raising the risk of serious infections.

ANC: A blood test number showing how many infection-fighting neutrophil white blood cells you have.

animal reproduction studies: Tests in pregnant animals used to check whether a medicine might harm a developing baby.

antagonist: A substance that blocks a target in the body so a natural signal or another medicine cannot produce its usual effect.

arrhythmia: A heartbeat that is too fast, too slow, or irregular instead of steady.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

baseline: A person's starting condition, measured before treatment begins, used to see how much they change later on.

Bioavailability: The share of a dose that actually reaches the bloodstream and is able to have an effect.

bioequivalence: A measure showing two versions of a medicine deliver the same amount of drug into the body at the same rate.

Boxed Warning: The strongest safety warning the FDA can require, set inside a bold black border because the risk it describes can be very serious.

bradycardia: A slower-than-normal heart rate, usually under 60 beats per minute.

cardiac arrest: A sudden stop of the heart's pumping that cuts off blood flow to the body, which is a medical emergency.

cardiomyopathy: A disease of the heart muscle that makes it harder for the heart to pump blood.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Clinical Studies: The label section summarizing the research trials used to show that a medicine works and is acceptably safe.

colitis: Swelling and irritation of the inner lining of the large intestine, or colon.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

CYP1A2: A liver enzyme that breaks down certain medicines and whose activity can be changed by cigarette smoke.

CYP2D6: A liver enzyme that breaks down many medicines; people inherit different versions, so it works faster in some and slower in others.

CYP3A4: One of the most important liver and gut enzymes, responsible for breaking down a large share of all medicines.

cytochrome P450: A large family of enzymes, mostly in the liver, that break down many medicines so the body can remove them.

depression: A lasting low mood with loss of interest that affects everyday life.

diarrhea: Loose, watery bowel movements that happen more often than normal.

Distribution: How a medicine spreads from the blood into the body's tissues and organs after it is absorbed.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

double-blind: A study in which neither the patients nor their doctors know who is getting the real medicine and who is getting the dummy.

Drug Interactions: The label section listing other medicines, foods, or substances that can change how a medicine works or raise the chance of side effects.

dyskinesia: Involuntary, uncontrolled movements of the face, arms, legs, or body.

dyslipidemia: Unhealthy levels of fats, such as cholesterol and triglycerides, in the blood.

dyspnea: The medical word for shortness of breath, or the feeling that you cannot get enough air.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

embolism: A blockage of a blood vessel by a clot or other material that has traveled from elsewhere in the body.

eosinophilia: A higher-than-normal level of eosinophils, a type of white blood cell often linked to allergies or drug reactions.

erythema: Redness of the skin caused by increased blood flow, often from irritation or inflammation.

erythema multiforme: A skin reaction with red, target-shaped spots, usually on the hands, arms, or face.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

Full Prescribing Information: The complete, detailed label for a prescription medicine that follows the summary highlights.

heart failure: A condition in which the heart cannot pump blood as well as it should, causing tiredness, breathlessness, and swelling.

hepatic impairment: Reduced liver function, meaning the liver does not work as well as normal at processing substances, including medicines.

hepatitis: Inflammation of the liver, which can be caused by infections, alcohol, or certain medicines.

hepatotoxicity: Damage to the liver caused by a medicine or other substance.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

hyperglycemia: High blood sugar, meaning there is more glucose (sugar) in the blood than normal.

hypersensitivity: An overreaction of the body's defense system to a substance, causing symptoms such as rash, swelling, or trouble breathing.

hypertension: Blood pressure that stays higher than normal, commonly called high blood pressure.

hypotension: Blood pressure that is lower than normal, which can cause dizziness or fainting.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

inducer: A substance that speeds up an enzyme, which can lower the levels of drugs that enzyme breaks down.

lactation: The making and release of milk from a mother's breasts after giving birth.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Medication Guide: An FDA-approved handout written for patients that explains important safety information about certain medicines in plain language.

Metabolism: How the body chemically changes a medicine, usually in the liver, into other substances.

metabolite: A new substance formed when the body breaks a medicine down.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

neonatal: Relating to a newborn baby during its first four weeks of life.

neuroleptic malignant syndrome: A rare but serious reaction to certain medicines causing high fever, severe muscle stiffness, confusion, and an unstable heartbeat.

neutropenia: A low level of neutrophils, a type of white blood cell that fights infection, which can make it easier to catch infections.

neutrophil: A type of white blood cell that is one of the body's main defenders against infection.

organogenesis: The early stage of pregnancy when the developing baby's organs are first forming.

orthostatic hypotension: A drop in blood pressure when you stand up from sitting or lying down, which can cause brief dizziness.

Overdosage: The label section describing what can happen if too much of a medicine is taken and how it may be treated.

palpitations: The feeling that your heart is racing, pounding, fluttering, or skipping beats.

pancreatitis: Painful swelling of the pancreas, an organ behind the stomach that helps digest food and control blood sugar.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

photosensitivity: An unusually strong skin reaction, such as burning or rash, after being in sunlight or other ultraviolet light.

plasma concentration: The amount of medicine measured in the liquid part of the blood at a given time.

postpartum: The period of time right after a woman gives birth.

Pregnancy Exposure Registry: A study that collects health information from women who took a medicine while pregnant to learn how safe it is.

Prescribing Information: The official, detailed document approved by the FDA that tells health professionals how to use a prescription medicine.

preterm birth: Birth of a baby earlier than usual, before 37 weeks of pregnancy.

psychosis: A state of losing touch with reality, such as seeing or hearing things that are not there or holding false beliefs.

pulmonary embolism: A blood clot that has traveled to the lungs and blocks blood flow there, which can make breathing hard.

QT prolongation: A longer-than-normal electrical recovery time between heartbeats, seen on a heart tracing (ECG), which can raise the chance of a dangerous heart rhythm.

randomized: Assigned to a treatment group purely by chance, like a coin flip, so the groups being compared start out fair and similar.

rebound: The return of symptoms, sometimes worse than before, after a medicine that was controlling them is stopped.

relapse: The return of a cancer after a period of improvement or disappearance.

respiratory depression: Breathing that becomes too slow or too shallow to move enough air, so the body may not get enough oxygen.

sedation: A calm, sleepy, slowed-down state caused by a medicine that relaxes the brain and body.

seizure: A sudden burst of abnormal electrical activity in the brain that can cause shaking, staring, confusion, or loss of awareness.

somnolence: Feeling very sleepy or drowsy, with trouble staying awake during the day.

Stevens-Johnson syndrome: A rare, serious reaction causing painful blistering and peeling of the skin and the moist linings of the mouth, eyes, and other areas.

substrate: A drug or other substance that a particular enzyme or transporter acts on.

suicidal behavior: Actions a person takes to try to end their own life, or steps taken in preparation for it.

syncope: The medical term for fainting, a brief loss of consciousness from a temporary drop in blood flow to the brain.

tachycardia: A faster-than-normal heart rate, usually over 100 beats per minute.

tardive dyskinesia: Involuntary, repetitive movements—often of the face, mouth, or tongue—that can develop after long-term use of certain medicines.

thrombosis: The forming of a blood clot inside a blood vessel, which can block normal blood flow.

titration: Slowly adjusting a medicine's dose up or down in small steps to find the amount that works best with the fewest side effects.

tremor: Shaking or trembling of part of the body, such as the hands, that a person cannot control.

trimester: One of the three roughly three-month stages that a pregnancy is divided into.

urinary retention: Being unable to empty the bladder fully or at all.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

vertigo: A spinning sensation that makes you feel like you or the room around you is moving.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

withdrawal: Uncomfortable physical or mental symptoms that appear when a medicine the body has gotten used to is reduced or stopped.

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

← 59651-0260-01 · Aurobindo 59651-0262-01 · Aurobindo →

For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.

Clozapine 25 mg Tablet, Orally Disintegrating, 100-count

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