Clozapine Information
Clozapine (Clozapine) Prescribing Information
Before prescribing Clozapine (Clozapine) , the physician should be thoroughly familiar with the details of this prescribing information.
Clozapine (Clozapine) Description
Clozapine (Clozapine) , an atypical antipsychotic drug, is a tricyclic dibenzodiazepine derivative, 8-chloro-11-(4-methyl-1-piperazinyl)-5-dibenzo [,] [1,4] diazepine. Clozapine (Clozapine) ’s structural formula, molecular formula, and molecular weight are as follows:
Clozapine (Clozapine) , USP is a yellow, crystalline powder, very slightly soluble in water.
Clozapine (Clozapine) tablets, for oral administration, are available containing 25 mg, 50 mg, 100 mg and 200 mg of Clozapine (Clozapine) . In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate. In addition, the 25 mg tablets contain FD&C Red No. 40 Aluminum Lake and the 50 mg, 100 mg and 200 mg tablets contain FD&C Blue No. 2 Aluminum Lake.
Clozapine (Clozapine) Clinical Pharmacology
Clozapine (Clozapine) is classified as an ‘atypical’ antipsychotic drug because its profile of binding to dopamine receptors and its effects on various dopamine mediated behaviors differ from those exhibited by more typical antipsychotic drug products. In particular, although Clozapine (Clozapine) does interfere with the binding of dopamine at D, D, D and D receptors, and has a high affinity for the D receptor, it does not induce catalepsy nor inhibit apomorphine-induced stereotypy. This evidence, consistent with the view that Clozapine (Clozapine) is preferentially more active at limbic than at striatal dopamine receptors, may explain the relative freedom of Clozapine (Clozapine) from extrapyramidal side effects.
Clozapine (Clozapine) also acts as an antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors.
In man, Clozapine (Clozapine) tablets (25 mg and 100 mg) are equally bioavailable relative to a Clozapine (Clozapine) solution. Following a dosage of 100 mg b.i.d., the average steady-state peak plasma concentration was 319 ng/mL (range: 102 to 771 ng/mL), occurring at the average of 2.5 hours (range: 1 to 6 hours) after dosing. The average minimum concentration at steady-state was 122 ng/mL (range: 41 to 343 ng/mL), after 100 mg b.i.d. dosing. Food does not appear to affect the systemic bioavailability of Clozapine (Clozapine) . Thus, Clozapine (Clozapine) may be administered with or without food.
Clozapine (Clozapine) is approximately 97% bound to serum proteins. The interaction between Clozapine (Clozapine) and other highly protein bound drugs has not been fully evaluated but may be important. (See .)
Clozapine (Clozapine) is almost completely metabolized prior to excretion and only trace amounts of unchanged drug are detected in the urine and feces. Approximately 50% of the administered dose is excreted in the urine and 30% in the feces. The demethylated, hydroxylated and N-oxide derivatives are components in both urine and feces. Pharmacological testing has shown the desmethyl metabolite to have only limited activity, while the hydroxylated and N-oxide derivatives were inactive.
The mean elimination half-life of Clozapine (Clozapine) after a single 75 mg dose was 8 hours (range: 4 to 12 hours), compared to a mean elimination half-life, after achieving steady-state with 100 mg b.i.d. dosing, of 12 hours (range: 4 to 66 hours). A comparison of single-dose and multiple-dose administration of Clozapine (Clozapine) showed that the elimination half-life increased significantly after multiple dosing relative to that after single-dose administration, suggesting the possibility of concentration dependent pharmacokinetics. However, at steady-state, linearly dose proportional changes with respect to AUC (area under the curve), peak and minimum Clozapine (Clozapine) plasma concentrations were observed after administration of 37.5 mg, 75 mg, and 150 mg b.i.d.
In contrast to more typical antipsychotic drugs, Clozapine (Clozapine) therapy produces little or no prolactin elevation.
As is true of more typical antipsychotic drugs, clinical EEG studies have shown that Clozapine (Clozapine) increases delta and theta activity and slows dominant alpha frequencies. Enhanced synchronization occurs, and sharp wave activity and spike and wave complexes may also develop. Patients, on rare occasions, may report an intensification of dream activity during Clozapine (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.
The effectiveness of Clozapine (Clozapine) in reducing the risk of recurrent suicidal behavior was assessed in the International Suicide Prevention Trial (InterSePT™), which was a prospective, randomized, international, parallel-group comparison of Clozapine (Clozapine) vs. Zyprexa (olanzapine) in patients with schizophrenia or schizoaffective disorder (DSM-IV) who were judged to be at risk for reexperiencing suicidal behavior. Only about one-fourth of these patients (27%) were considered resistant to standard antipsychotic drug treatment, and the remainder were not. Patients met one of the following criteria:
Dosing regimens for each treatment group were determined by individual investigators and were individualized by patient. Dosing was flexible, with a dose range of 200 to 900 mg/day for Clozapine (Clozapine) and 5 to 20 mg/day for Zyprexa. For the 956 patients who received Clozapine (Clozapine) or Zyprexa in this study, there was extensive use of concomitant psychotropics: 84% with antipsychotics; 65% with anxiolytics; 53% with antidepressants, and 28% with mood stabilizers. There was significantly greater use of concomitant psychotropic medications among the patients in the Zyprexa group.
The primary efficacy measure was time to (1) a significant suicide attempt, including a completed suicide, (2) hospitalization due to imminent suicide risk (including increased level of surveillance for suicidality for patients already hospitalized), or (3) worsening of suicidality severity as demonstrated by “much worsening” or “very much worsening” from baseline in the Clinical Global Impression of Severity of Suicidality as assessed by the Blinded Psychiatrist (CGI-SS-BP) scale. A determination of whether or not a reported event met criterion 1 or 2 above was made by the Suicide Monitoring Board (SMB, a group of experts blinded to patient data).
A total of 980 patients were randomized to the study and 956 received study medication. Sixty-two percent of the patients were diagnosed with schizophrenia, and the remainder (38%) were diagnosed with schizoaffective disorder. Only about one-fourth of the total patient population (27%) was identified as “treatment resistant” at baseline. There were more males than females in the study (61% of all patients were male). The mean age of patients entering the study was 37 years (range 18 to 69). Most patients were Caucasian (71%), 15% were Black, 1% were Oriental, and 13% were classified as being of “other” races.
Data from this study indicate that Clozapine (Clozapine) had a statistically significant longer delay in the time to recurrent suicidal behavior in comparison with Zyprexa. This result should be interpreted only as evidence of the effectiveness of Clozapine (Clozapine) in delaying time to recurrent suicidal behavior, and not a demonstration of the superior efficacy of Clozapine (Clozapine) over Zyprexa.
The probability of experiencing (1) a significant suicide attempt, including a completed suicide, or (2) hospitalization due to imminent suicide risk (including increased level of surveillance for suicidality for patients already hospitalized) was lower for Clozapine (Clozapine) patients than for Zyprexa patients at Week 104: Clozapine (Clozapine) 24% vs. Zyprexa 32%; 95% C.I. of the difference: 2%, 14% (Figure 1).
Clozapine (Clozapine) Indications And Usage
Clozapine (Clozapine) is indicated for the management of severely ill schizophrenic patients who fail to respond adequately to standard drug treatment for schizophrenia. Because of the significant risk of agranulocytosis and seizure associated with its use, Clozapine (Clozapine) should be used only in patients who have failed to respond adequately to treatment with appropriate courses of standard drug treatments for schizophrenia, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. (See .)
The effectiveness of Clozapine (Clozapine) in a treatment resistant schizophrenic population was demonstrated in a 6-week study comparing Clozapine (Clozapine) and chlorpromazine. Patients meeting DSM-III criteria for schizophrenia and having a mean BPRS total score of 61 were demonstrated to be treatment resistant by history and by open, prospective treatment with haloperidol before entering into the double-blind phase of the study. The superiority of Clozapine (Clozapine) to chlorpromazine was documented in statistical analyses employing both categorical and continuous measures of treatment effect.
Because of the significant risk of agranulocytosis and seizure, events which both present a continuing risk over time, the extended treatment of patients failing to show an acceptable level of clinical response should ordinarily be avoided. In addition, the need for continuing treatment in patients exhibiting beneficial clinical responses should be periodically reevaluated.
Clozapine (Clozapine) 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 reexperiencing suicidal behavior, based on history and recent clinical state. Suicidal behavior refers to actions by a patient that puts him/herself at risk for death.
The effectiveness of Clozapine (Clozapine) in reducing the risk of recurrent suicidal behavior was demonstrated over a 2-year treatment period in the InterSePT Trial (see Clinical Trial Data under ). Therefore, Clozapine (Clozapine) treatment to reduce the risk of suicidal behavior should be continued for at least 2 years (see ).
The prescriber should be aware that a majority of patients in both treatment groups in InterSePT received other treatments as well to reduce suicide risk, such as antidepressants and other medications, hospitalization, and/or psychotherapy. The contributions of these additional measures are unknown.
Clozapine (Clozapine) Contraindications
Clozapine (Clozapine) is contraindicated in patients with a previous hypersensitivity to Clozapine (Clozapine) or any other component of this drug, in patients with myeloproliferative disorders, uncontrolled epilepsy, paralytic ileus, or a history of Clozapine (Clozapine) induced agranulocytosis or severe granulocytopenia. As with more typical antipsychotic drugs, Clozapine (Clozapine) is contraindicated in severe central nervous system depression or comatose states from any cause.
Clozapine (Clozapine) should not be used simultaneously with other agents having a well-known potential to cause agranulocytosis or otherwise suppress bone marrow function. The mechanism of Clozapine (Clozapine) induced agranulocytosis is unknown; nonetheless, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression.
Clozapine (Clozapine) Warnings
Seizure has been estimated to occur in association with Clozapine (Clozapine) use at a cumulative incidence at one year of approximately 5%, based on the occurrence of one or more seizures in 61 of 1,743 patients exposed to Clozapine (Clozapine) during its clinical testing prior to domestic marketing (i.e., a crude rate of 3.5%). Dose appears to be an important predictor of seizure, with a greater likelihood of seizure at the higher Clozapine (Clozapine) doses used.
Caution should be used in administering Clozapine (Clozapine) to patients having a history of seizures or other predisposing factors. Because of the substantial risk of seizure associated with Clozapine (Clozapine) use, patients should be advised not to engage in any activity where sudden loss of consciousness could cause serious risk to themselves or others, e.g., the operation of complex machinery, driving an automobile, swimming, climbing, etc.
Post-marketing surveillance data from four countries that employ hematological monitoring of Clozapine (Clozapine) -treated patients revealed: 30 reports of myocarditis with 17 fatalities in 205,493 U.S. patients (August 2001); seven reports of myocarditis with one fatality in 15,600 Canadian patients (April 2001); 30 reports of myocarditis with eight fatalities in 24,108 U.K. patients (August 2001); 15 reports of myocarditis with five fatalities in 8,000 Australian patients (March 1999). These reports represent an incidence of 5, 16.3, 43.2, and 96.6 cases/100,000 patient years, respectively. The number of fatalities represent an incidence of 2.8, 2.3, 11.5, and 32.2 cases/100,000 patient years, respectively.
The overall incidence rate of myocarditis in patients with schizophrenia treated with antipsychotic agents is unknown. However, for the established market economies (WHO), the incidence of myocarditis is 0.3 cases/100,000 patient years and the fatality rate is 0.2 cases/100,000 patient years. Therefore, the rate of myocarditis in Clozapine (Clozapine) -treated patients appears to be 17 to 322 times greater than the general population and is associated with an increased risk of fatal myocarditis that is 14 to 161 times greater than the general population.
The total reports of myocarditis for these four countries was 82 of which 51 (62%) occurred within the first month of Clozapine (Clozapine) treatment, 25 (31%) occurred after the first month of therapy and six (7%) were unknown. The median duration of treatment was 3 weeks. Of 5 patients rechallenged with Clozapine (Clozapine) , three had a recurrence of myocarditis. Of the 82 reports, 31 (38%) were fatal and 25 patients who died had evidence of myocarditis at autopsy. These data also suggest that the incidence of fatal myocarditis may be highest during the first month of therapy.
Therefore, the possibility of myocarditis should be considered in patients receiving Clozapine (Clozapine) who present with unexplained fatigue, dyspnea, tachypnea, fever, chest pain, palpitations, other signs or symptoms of heart failure, or electrocardiographic findings such as ST-T wave abnormalities or arrhythmias. It is not known whether eosinophilia is a reliable predictor of myocarditis. Tachycardia, which has been associated with Clozapine (Clozapine) treatment, has also been noted as a presenting sign in patients with myocarditis. Therefore, tachycardia during the first month of therapy warrants close monitoring for other signs of myocarditis.
Prompt discontinuation of Clozapine (Clozapine) treatment is warranted upon suspicion of myocarditis. Patients with Clozapine (Clozapine) -related myocarditis should not be rechallenged with Clozapine (Clozapine) .
Orthostatic hypotension with or without syncope can occur with Clozapine (Clozapine) treatment and may represent a continuing risk in some patients. Rarely (approximately one case per 3,000 patients), collapse can be profound and be accompanied by respiratory and/or cardiac arrest. Orthostatic hypotension is more likely to occur during initial titration in association with rapid dose escalation and may even occur on first dose. In one report, initial doses as low as 12.5 mg were associated with collapse and respiratory arrest. When restarting patients who have had even a brief interval off Clozapine (Clozapine) , i.e., 2 days or more since the last dose, it is recommended that treatment be reinitiated with one-half of a 25 mg tablet (12.5 mg) once or twice daily (see ).
Some of the cases of collapse/respiratory arrest/cardiac arrest during initial treatment occurred in patients who were being administered benzodiazepines; similar events have been reported in patients taking other psychotropic drugs or even Clozapine (Clozapine) by itself. Although it has not been established that there is an interaction between Clozapine (Clozapine) and benzodiazepines or other psychotropics, caution is advised when Clozapine (Clozapine) is initiated in patients taking a benzodiazepine or any other psychotropic drug.
Tachycardia, which may be sustained, has also been observed in approximately 25% of patients taking Clozapine (Clozapine) , with patients having an average increase in pulse rate of 10 to 15 bpm. The sustained tachycardia is not simply a reflex response to hypotension, and is present in all positions monitored. Either tachycardia or hypotension may pose a serious risk for an individual with compromised cardiovascular function.
A minority of Clozapine (Clozapine) treated patients experience ECG repolarization changes similar to those seen with other antipsychotic drugs, including S-T segment depression and flattening or inversion of T waves, which all normalize after discontinuation of Clozapine (Clozapine) . The clinical significance of these changes is unclear. However, in clinical trials with Clozapine (Clozapine) , several patients experienced significant cardiac events, including ischemic changes, myocardial infarction, arrhythmias and sudden death. In addition, there have been post-marketing reports of congestive heart failure, pericarditis, and pericardial effusions. Causality assessment was difficult in many of these cases because of serious preexisting cardiac disease and plausible alternative causes. Rare instances of sudden death have been reported in psychiatric patients, with or without associated antipsychotic drug treatment, and the relationship of these events to antipsychotic drug use is unknown.
Clozapine (Clozapine) should be used with caution in patients with known cardiovascular and/or pulmonary disease, and the recommendation for gradual titration of dose should be carefully observed.
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including Clozapine (Clozapine) . Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available.
Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
There have been several reported cases of NMS in patients receiving Clozapine (Clozapine) alone or in combination with lithium or other CNS-active agents.
A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of treatment, which patients are likely to develop the syndrome.
There are several reasons for predicting that Clozapine (Clozapine) may be different from other antipsychotic drugs in its potential for inducing tardive dyskinesia, including the preclinical finding that it has a relatively weak dopamine blocking effect and the clinical finding of a low incidence of certain acute extrapyramidal symptoms, e.g., dystonia. A few cases of tardive dyskinesia have been reported in patients on Clozapine (Clozapine) who had been previously treated with other antipsychotic agents, so that a causal relationship cannot be established. There have been no reports of tardive dyskinesia directly attributable to Clozapine (Clozapine) alone. Nevertheless, it cannot be concluded, without more extended experience, that Clozapine (Clozapine) is incapable of inducing this syndrome.
Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic drug treatment is withdrawn. Antipsychotic drug treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptom suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, Clozapine (Clozapine) should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. As with any antipsychotic drug, chronic Clozapine (Clozapine) use should be reserved for patients who appear to be obtaining substantial benefit from the drug. In such patients, the smallest dose and the shortest duration of treatment should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on Clozapine (Clozapine) , drug discontinuation should be considered. However, some patients may require treatment with Clozapine (Clozapine) despite the presence of the syndrome.
Clozapine (Clozapine) Precautions
Clinical studies of Clozapine (Clozapine) did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects.
Orthostatic hypotension can occur with Clozapine (Clozapine) treatment and tachycardia, which may be sustained, has been observed in about 25% of patients taking Clozapine (Clozapine) (see ). Elderly patients, particularly those with compromised cardiovascular functioning, may be more susceptible to these effects.
Also, elderly patients may be particularly susceptible to the anticholinergic effects of Clozapine (Clozapine) , such as urinary retention and constipation. (See .)
Dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Other reported clinical experience does suggest that the prevalence of tardive dyskinesia appears to be highest among the elderly, especially elderly women (see ).
Clozapine (Clozapine) Adverse Reactions
The following table enumerates adverse events that occurred at a frequency of 1% or greater among Clozapine (Clozapine) patients who participated in clinical trials. These rates are not adjusted for duration of exposure.
The following table enumerates adverse events that occurred at a frequency of 10% for either treatment group in patients who took at least one dose of study medication during their participation in InterSePT, which was an adequate and well controlled 2-year study evaluating the efficacy of Clozapine (Clozapine) relative to Zyprexa in reducing the risk of emergent suicidal behavior in patients with schizophrenia or schizoaffective disorder. These rates are not adjusted for duration of exposure.
This section reports additional, less frequent adverse events which occurred among the patients taking Clozapine (Clozapine) in clinical trials. Various adverse events were reported as part of the total experience in these clinical studies; a causal relationship to Clozapine (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 (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 by organ system.
Post-marketing experience has shown an adverse experience profile similar to that presented above. Voluntary reports of adverse events temporally associated with Clozapine (Clozapine) not mentioned above that have been received since market introduction and that may have no causal relationship with the drug include the following:
Clozapine (Clozapine) Drug Abuse And Dependence
Physical and psychological dependence have not been reported or observed in patients taking Clozapine (Clozapine) .
Clozapine (Clozapine) Overdosage
Establish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia.
There are no specific antidotes for Clozapine (Clozapine) . Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.
In managing overdosage, the physician should consider the possibility of multiple drug involvement.
Up-to-date information about the treatment of overdose can often be obtained from a certified Regional Poison Control Center. Telephone numbers of certified Poison Control Centers are listed in the .
Clozapine (Clozapine) Dosage And Administration
The dosage and administration recommendations outlined above regarding the use of Clozapine (Clozapine) in patients with treatment-resistant schizophrenia should also be followed when treating patients with schizophrenia or schizoaffective disorder at risk for recurrent suicidal behavior.
The InterSePT study demonstrated the efficacy of Clozapine (Clozapine) in treatment of patients with schizophrenia or schizoaffective disorder at risk for recurrent suicidal behavior where the mean daily dose was about 300 mg (range 12.5 mg to 900 mg).
Patients previously treated with other antipsychotics were cross-titrated to Clozapine (Clozapine) over a one-month interval; the dose of the previous antipsychotic was gradually decreased simultaneous with a gradual increase in Clozapine (Clozapine) dose over the first month of the study. Patients on depot antipsychotic medication began Clozapine (Clozapine) after one full dosing interval since the last injection.
Clozapine (Clozapine) How Supplied
Clozapine (Clozapine) Tablets USP, 25 mg, 50 mg, 100 mg and 200 mg are available as follows:
The 25 mg tablets are round, peach, scored tablets debossed with to the left of the score and to the right of the score on one side of the tablet and on the other side. They are available as follows:
NDC 0378-0825-01bottles of 100 tablets
The 50 mg tablets are round, green, scored tablets debossed with above the score and blank below the score on one side of the tablet and on the other side. They are available as follows:
NDC 0378-0972-01bottles of 100 tablets
NDC 0378-0972-05bottles of 500 tablets
The 100 mg tablets are round, green, scored tablets debossed with above the score and blank below the score on one side of the tablet and on the other side. They are available as follows:
NDC 0378-0860-01bottles of 100 tablets
NDC 0378-0860-05bottles of 500 tablets
The 200 mg tablets are round, green, scored tablets debossed with above the score and blank below the score on one side of the tablet and on the other side. They are available as follows:
NDC 0378-0973-01bottles of 100 tablets
NDC 0378-0973-05bottles of 500 tablets
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Drug dispensing should not ordinarily exceed a weekly supply. If a patient is eligible for White Blood Cell (WBC) count and Absolute Neutrophil Count (ANC) testing every 2 weeks, then a 2-week supply of Clozapine (Clozapine) can be dispensed. If a patient is eligible for WBC count and ANC testing every 4 weeks, then a 4-week supply of Clozapine (Clozapine) can be dispensed. Dispensing should be contingent upon the WBC count and ANC test results.
Mylan Pharmaceuticals Inc.Morgantown, WV 26505 U.S.A.
REVISED JANUARY 2011CLOZ:R14
Clozapine (Clozapine)
Clozapine (Clozapine)
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