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AA-CLOZAPINE is a brand name for Clozapine, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AA-CLOZAPINE (clozapine) tablet is indicated in the management of symptoms of treatment- resistant schizophrenia. In controlled clinical trials, clozapine was found to improve both positive and negative symptoms. Due to the significant risk of neutropenia and seizure associated with its use, clozapine should be…
Verbatim from this product's HC label. Tap a section to expand.
AA-CLOZAPINE is available only through a distribution system AA-CLOZAPINE Patient Care Network (“AASPIRE”) that ensures weekly, every-two-week or every-four-week hematological testing prior to the dispensing of the next period's supply of AA-CLOZAPINE (see 7 WARNINGS AND PRECAUTIONS, Hematologic).
This requires: • registration of the patient, their current location, treating physician, testing laboratory and dispensing pharmacist in the AA-CLOZAPINE Patient Care Network • maintenance of a national AA Pharma monitoring system of the hematological results of all patients on AA-CLOZAPINE and provides timely feedback (within 24 hours of receipt of the blood test results) to the treating physician and dispensing pharmacist/or pharmacy • the ability to identify patients who have been assigned "Non-rechallengeable Status" (see 7 WARNINGS AND PRECAUTIONS).
This requires that AA Pharma Inc. both provide to, and obtain from, all other approved suppliers† of clozapine, the Non-rechallengeable Status / Hematological Status of all patients (see 4 DOSAGE AND ADMINISTRATION). AA Pharma Inc. must be able to provide this information within 24 hours of receiving a written request.
† “approved supplier” is a manufacturer who holds a valid Notice of Compliance (NOC) for clozapine AA-CLOZAPINE (Clozapine Tablets) Page 5 of 55 Physicians should not prescribe AA-CLOZAPINE until the non-rechallengeable status and the hematological status of the patient has been verified.
For the distribution system to be effective, treating physicians must ensure that the hematological testing is performed at the required frequency (see 7 WARNINGS AND PRECAUTIONS, Hematologic) and that arrangements are made for the hematological results to be sent to AA-CLOZAPINE Patient Care Network.
Physicians may obtain details on the AA- CLOZAPINE Patient Care Network by calling a toll-free phone number (1-877-276-2569). Other monitoring and distribution systems Between 1991 and 2003, clozapine was distributed by a single manufacturer, and patients were monitored by this manufacturer's specific registry and distribution system.
The introduction of clozapine from other manufacturers has now resulted in the establishment of manufacturer- specific registry and distribution systems. In order to ensure the safe use and continued monitoring of all patients taking clozapine, the physician must have obtained consent from the patient for the potential sharing of hematological and other safety data between clozapine registries.
1 Adverse Reaction Overview The most serious adverse reactions experienced with clozapine are neutropenia, seizure, cardiovascular effects and fever (see 7 WARNINGS AND PRECAUTIONS, Hematologic). The most common side effects are drowsiness/sedation, dizziness, hypersalivation, tachycardia, and constipation.
Adverse Events Leading to Discontinuation Of 1080 patients who received clozapine in premarketing clinical trials, 16% discontinued treatment due to an adverse event, including both those that could be reasonably attributed to clozapine treatment and those that might more appropriately be considered intercurrent illness.
The more common events considered to be causes of discontinuation included:
CNS (psychotic disorder), primarily drowsiness/sedation, somnolence, seizures, dizziness (excluding vertigo)/syncope; cardiovascular, primarily tachycardia, hypotension and ECG changes; gastrointestinal, primarily nausea/vomiting; hematologic, primarily neutropenia and fever.
7% of all discontinuations attributed to adverse clinical event. Most Frequent Adverse Events Adverse events observed in association with the use of clozapine in clinical trials at an incidence of greater than 5% were: central nervous system complaints, including drowsiness/sedation, dizziness/vertigo, headache and tremor; autonomic nervous system complaints, including salivation, sweating, dry mouth and visual disturbances; cardiovascular findings, including AA-CLOZAPINE (Clozapine Tablets) Page 26 of 55 tachycardia, hypotension and syncope; and gastrointestinal complaints, including constipation and nausea; and fever.
Complaints of drowsiness/sedation tend to subside with continued therapy or dose reduction. Salivation may be profuse, especially during sleep, but may be diminished with dose reduction. 2 Clinical Trial Adverse Reactions The following table enumerates adverse events that occurred at a frequency of 1% or greater among clozapine patients who participated in clinical trials.
4 Geriatrics 04/2023 7 WARNINGS AND PRECAUTIONS, General, Anticholinergic Activity 04/2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ................................................................................................
2 TABLE OF CONTENTS .................................................................................................................. 2 1 INDICATIONS ...........................................................................................................................
1 Pediatrics ............................................................................................................................... 2 Geriatrics ...............................................................................................................................
5 2 CONTRAINDICATIONS .............................................................................................................. 5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX .........................................................................
6 4 DOSAGE AND ADMINISTRATION.............................................................................................. 1 Dosing Considerations ...........................................................................................................
2 Recommended Dose and Dosage Adjustment ..................................................................... 4 Administration .....................................................................................................................
5 Missed Dose ........................................................................................................................ 10 5 OVERDOSAGE ........................................................................................................................
• AA-CLOZAPINE is contraindicated in patients who are hypersensitive to clozapine or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• Patients with myeloproliferative disorders, a history of toxic or idiosyncratic agranulocytosis or severe granulocytopenia (with the exception of granulocytopenia/ agranulocytosis from previous chemotherapy). [Clozapine should not be used simultaneously with other agents known to suppress bone marrow function].
AA-CLOZAPINE (Clozapine Tablets) Page 6 of 55 • Patients with active liver disease associated with nausea, anorexia, or jaundice; progressive liver disease; hepatic failure. • Patients unable to undergo blood tests. , myocarditis), paralytic ileus, uncontrolled epilepsy.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Clozapine in Canada.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Patients may not be switched from one brand of clozapine to another without the completion of a new registry-specific patient registration form signed by the prescribing physician. If a patient is switched from one brand of clozapine to another, the frequency of hematological monitoring may continue unaltered unless a change is clinically indicated.
1 Pediatrics Pediatrics (< 18 years of age): No pediatric studies have been performed. The safety and efficacy of AA-CLOZAPINE in children and adolescents have not been established. No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.
4 Geriatrics. 2 Recommended Dose and Dosage Adjustment, Dosing Considerations in Special Populations. 2 CONTRAINDICATIONS • AA-CLOZAPINE is contraindicated in patients who are hypersensitive to clozapine or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see
These rates are not adjusted for duration of exposure. Table 4 - Treatment-Emergent Adverse Experience Incidence Among Patients Taking Clozapine in Clinical Trials Body System % Patients Adverse Eventa (N = 842) Nervous System disorders Drowsiness/Sedation 39 Dizziness/Vertigo 19 Headache 7 Tremor 6 Disturbed sleep/Nightmares 4 Hypokinesia/Akinesia 4 Seizures (convulsions) 3b Rigidity 3 Akathisia 3 Confusion 3 Insomnia 2 Hyperkinesia 1 Weakness 1 Lethargy 1 Ataxia 1 Slurred speech 1 Depression 1 Epileptiform movements/Myoclonic jerks 1 Anxiety 1 Psychiatric disorders Agitation 4 Restlessness 4 Cardiac disorders Tachycardia 25b Chest pain/Angina 1 ECG changes/Cardiac abnormality 1 Vascular disorders AA-CLOZAPINE (Clozapine Tablets) Page 27 of 55 Body System % Patients Adverse Eventa (N = 842) Syncope 6 Hypotension 9 Hypertension 4 Gastrointestinal disorders Constipation 14 Nausea 5 Abdominal discomfort/Heartburn 4 Nausea/Vomiting 3 Vomiting 3 Dry mouth 6 Diarrhea 2 Anorexia 1 Hepatobiliary disorders Liver test abnormality 1 Renal and urinary disorders Urinary abnormalities 2 Urinary incontinence 1 Urinary urgency/frequency 1 Urinary retention 1 Reproductive system disorders Abnormal ejaculation 1 Autonomic Nervous System Salivation 31 Sweating 6 Visual disturbances 5 Skin and subcutaneous tissue disorders Rash 2 Musculoskeletal Muscle weakness 1 Pain (back, neck, legs) 1 Muscle spasm 1 Muscle pain, ache 1 Respiratory disorders Throat discomfort 1 Dyspnea, shortness of breath 1 Nasal congestion 1 Blood and lymphatic disorders Leukopenia/Decreased WBC/Neutropenia 3 Agranulocytosis 1b Eosinophilia 1 Metabolism and nutrition disorders AA-CLOZAPINE (Clozapine Tablets) Page 28 of 55 Body System % Patients Adverse Eventa (N = 842) Weight gain 4 Miscellaneous Fever 5 Fatigue 2 Tongue numb/sore 1 a Events reported by at least 1% of clozapine patients are included.
b Rate based on population of approximately 1700 exposed during premarket clinical evaluation of clozapine. Adverse Events Observed During the InterSePT Study Adverse events reported during the InterSePT study were consistent with the known safety profiles for clozapine and olanzapine.
The ten most frequently reported adverse events in the clozapine treatment group were: salivary hypersecretion, somnolence, weight increase, anxiety, depression, dizziness (excluding vertigo), psychotic disorder, suicidal ideation, constipation, and insomnia.
1 Clinical Trial Adverse Reactions (Pediatrics) No pediatric studies have been performed. 3 Less Common Clinical Trial Adverse Reactions Other Adverse Events Observed during Clinical Trials This section reports additional, less frequent adverse events which occurred among the patients taking clozapine in clinical trials.
Various adverse events were reported as part of the total experience in these clinical studies; a causal relationship to clozapine treatment cannot be determined in the absence of appropriate controls in some of the studies. The table above enumerates adverse events that occurred at a frequency of at least 1% of patients treated with clozapine.
The list below includes all additional adverse experiences reported as being temporally associated with the use of the drug which occurred at a frequency less than 1%, enumerated in alphabetical order by organ system. Autonomic Nervous System: dry throat, hot flashes, mydriasis, numbness, polydypsia.
Blood and lymphatic system: anemia and leukocytosis. Cardiac: arrhythmias, bradycardia, cyanosis, edema, ischemic changes, myocardial infarction, nosebleed, palpitations, phlebitis/thrombophlebitis, premature ventricular contraction, sudden death.
Eye: bloodshot eyes, eyelid disorder, nystagmus. Gastrointestinal: abdominal distension, abnormal stools, bitter taste, eructation, gastric ulcer, gastroenteritis, hematemesis, nervous stomach, rectal bleeding. AA-CLOZAPINE (Clozapine Tablets) Page 29 of 55 General: appetite increase, […]
10 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ........................................... 11 7 WARNINGS AND PRECAUTIONS ......................................................................................... 12 Monitoring Schedule Guideline .................................................................................................
1 Special Populations.............................................................................................................. 1 Pregnant Women ..........................................................................................................
2 Breast-feeding............................................................................................................... 3 Pediatrics ......................................................................................................................
4 Geriatrics....................................................................................................................... 24 8 ADVERSE REACTIONS .............................................................................................................
1 Adverse Reaction Overview ................................................................................................. 2 Clinical Trial Adverse Reactions ...........................................................................................
1 Clinical Trial Adverse Reactions (Pediatrics) .................................................................. 3 Less Common Clinical Trial Adverse Reactions .................................................................... 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data ...........................................................................................................................................
5 Post-Market Adverse Reactions........................................................................................... 29 9 DRUG INTERACTIONS.............................................................................................................
2 Drug Interactions Overview ................................................................................................. 3 Drug-Behavioral Interactions ...............................................................................................
4 Drug-Drug Interactions ........................................................................................................ 5 Drug-Food Interactions ........................................................................................................
6 Drug-Herb Interactions ........................................................................................................ 7 Drug-Laboratory Test Interactions .......................................................................................
32 10 CLINICAL PHARMACOLOGY .................................................................................................. 1 Mechanism of Action .........................................................................................................
2 Pharmacodynamics ........................................................................................................... 3 Pharmacokinetics ..............................................................................................................
34 11 STORAGE, STABILITY AND DISPOSAL .................................................................................... 34 12 SPECIAL HANDLING INSTRUCTIONS......................................................................................
34 PART II: SCIENTIFIC INFORMATION ........................................................................................... 35 13 PHARMACEUTICAL […]