CLOZAPINE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CLOZAPINE (UNII: J60AR2IKIC) (CLOZAPINE - UNII:J60AR2IKIC)

Available from:

Mylan Pharmaceuticals Inc.

INN (International Name):

CLOZAPINE

Composition:

CLOZAPINE 25 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Clozapine tablets 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 its use, clozapine tablets should be used only in patients who have failed to respond adequately to standard antipsychotic treatment [see Warnings and Precautions (5.1, 5.5)] . The effectiveness of clozapine tablets in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active-controlled study comparing clozapine tablets and chlorpromazine in patients who had failed other antipsychotics [see Clinical Studies (14.1)] . Clozapine tablets are 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 tablets 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)] . Clozapine tablets are 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 tablets [see Adverse Reactions (6.2)] . There are no adequate or well-controlled studies of clozapine in pregnant women. Reproduction studies have been performed in rats and rabbits at doses up to 0.4 and 0.9 times, respectively, the maximum recommended human dose (MRHD) of 900 mg/day on a mg/m2 body surface area basis. The studies revealed no evidence of impaired fertility or harm to the fetus due to clozapine. Because animal reproduction studies are not always predictive of human response, clozapine tablets should be used during pregnancy only if clearly needed. Consider the risk of exacerbation of psychosis when discontinuing or changing treatment with antipsychotic medications during pregnancy and postpartum. Consider early screening for gestational diabetes for patients treated with antipsychotic medications [see Warnings and Precautions (5.11)] . Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Monitor neonates for symptoms of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding difficulties. The severity of complications can vary from self-limited symptoms to some neonates requiring intensive care unit support and prolonged hospitalization. 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/m2 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/m2 body surface area basis. Clozapine is present in human milk. Because of the potential for serious adverse reactions in nursing infants from clozapine tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Safety and effectiveness in pediatric patients have not been established. There have not been sufficient numbers of geriatric patients in clinical studies utilizing clozapine tablets to determine whether those over 65 years of age differ from younger subjects in their response to clozapine tablets. Orthostatic hypotension and tachycardia can occur with clozapine tablets treatment [see Boxed Warning and Warnings and Precautions (5.3)] . 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 tablets, such as urinary retention and constipation [see Warnings and Precautions (5.16)] . Carefully select clozapine tablets 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 (5.18)] . Dose reduction may be necessary in patients with significant impairment of renal or hepatic function. Clozapine concentrations may be increased in these patients, because clozapine is almost completely metabolized and then excreted [see Dosage and Administration (2.7), Clinical Pharmacology (12.3)] . Dose reduction may be necessary in patients who are CYP2D6 poor metabolizers. Clozapine concentrations may be increased in these patients, because clozapine is almost completely metabolized and then excreted [see Dosage and Administration (2.7), Clinical Pharmacology (12.3)] . For hospice patients (i.e., terminally ill patients with an estimated life expectancy of six months or less), the prescriber may reduce the ANC monitoring frequency to once every 6 months, after a discussion with the patient and his/her caregiver. Individual treatment decisions should weigh the importance of monitoring ANC in the context of the need to control psychiatric symptoms and the patient’s terminal illness.

Product summary:

Clozapine Tablets, USP are available containing 25 mg, 50 mg, 100 mg or 200 mg of clozapine, USP. The 25 mg tablets are peach, round, functionally scored tablets debossed with C to the left of the score and 7 to the right of the score on one side of the tablet and M on the other side. They are available as follows: NDC 0378-0825-01 bottles of 100 tablets The 50 mg tablets are green, round, functionally scored tablets debossed with C72 above the score and blank below the score on one side of the tablet and M on the other side. They are available as follows: NDC 0378-0972-01 bottles of 100 tablets The 100 mg tablets are green, round, functionally scored tablets debossed with C11 above the score and blank below the score on one side of the tablet and M on the other side. They are available as follows: NDC 0378-0860-01 bottles of 100 tablets NDC 0378-0860-05 bottles of 500 tablets The 200 mg tablets are green, round, functionally scored tablets debossed with C73 above the score and blank below the score on one side of the tablet and M on the other side. They are available as follows: NDC 0378-0973-01 bottles of 100 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep out of reach of children. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

CLOZAPINE- CLOZAPINE TABLET
MYLAN PHARMACEUTICALS INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CLOZAPINE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR CLOZAPINE
TABLETS.
CLOZAPINE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1989
WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND
SYNCOPE; SEIZURE; MYOCARDITIS AND CARDIOMYOPATHY; INCREASED MORTALITY
IN
ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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RECENT MAJOR CHANGES
Boxed Warning 5/2023
Dosage and Administration (2.5) 5/2023
Warnings and Precautions, Orthostatic Hypotension,
Bradycardia, and Syncope (5.3) 5/2023
Warnings and Precautions, Gastrointestinal Hypomotility with Severe
Complications (5.8) 12/2022
INDICATIONS AND USAGE
Clozapine tablets are an atypical antipsychotic indicated for:
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
25 mg, 50 mg, 100 mg and 200 mg tablets with a functional score on one
side (3)
CONTRAINDICATIONS
SEVERE NEUTROPENIA: CLOZAPINE TABLETS CAN CAUSE SEVERE NEUTROPENIA,
WHICH CAN
LEAD TO SERIOUS AND FATAL INFECTIONS. PATIENTS INITIATING AND
CONTINUING TREATMENT
WITH CLOZAPINE TABLETS MUST HAVE A BASELINE BLOOD ABSOLUTE NEUTROPHIL
COUNT (ANC)
MEASURED BEFORE TREATMENT INITIATION AND REGULAR ANC MONITORING DURING
TREATMENT (2.1, 5.1).
CLOZAPINE TABLETS ARE AVAILABLE ONLY THROUGH A RESTRICTED PROGRAM
CALLED THE
CLOZAPINE REMS (5.2).
ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE: RISK IS
DOSE-RELATED. STARTING
DOSE IS 12.5 MG. TITRATE GRADUALLY AND USE DIVIDED DOSAGES. (2.2, 2.5,
5.3)
SEIZURE: RISK IS DOSE-RELATED. TITRATE GRADUALLY AND USE DIVIDED
DOSES. USE WITH
CAUTION IN PATIENTS WITH HISTORY OF SEIZURE OR RISK FACTORS FOR
SEIZURE. (2.2, 5.5)
MYOCARDITIS, CARDIOMYOPATHY AND MITRAL VALVE INCOMPETENCE: CAN BE
FATAL.
DISCONTINUE AND OBTAIN CARDIAC EVALUATION IF FINDINGS SUGGEST THESE
CARDIAC