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Fazaclo (Clozapine) - Summary




Clozapine treatment has caused agranulocytosis, defined as an absolute neutrophil count (ANC) less than 500/mm3. Agranulocytosis can lead to serious infection and death. Prior to initiating treatment with FAZACLO, obtain a baseline white blood cell count (WBC) and ANC. The ANC must be greater than or equal to 2000/mm3 and the WBC must be greater than or equal to 3500/mm3 for a patient to begin treatment with FAZACLO. During treatment, patients must have regular monitoring of ANC and WBC. Discontinue FAZACLO and do not rechallenge if the ANC is less than 1000/mm3 or the WBC is less than 2000/mm3. Advise patients to immediately report symptoms consistent with agranulocytosis or infection (e.g., fever, weakness, lethargy, or sore throat) [see Dosage and Administration and Warnings and Precautions].

Because of the risk of agranulocytosis, FAZACLO is available only through a restricted program called the FAZACLO Patient Registry. Under the FAZACLO Patient Registry, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions].

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. Initiate treatment at 12.5 mg once or twice daily; titrate slowly; and use divided dosages. Use FAZACLO cautiously in patients with cardiovascular/cerebrovascular disease or conditions predisposing to hypotension (e.g., dehydration, use of antihypertensive medications) [see Dosage and Administration (2.3, 2.6) and Warnings and Precautions ].


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 FAZACLO 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, Warnings and Precautions].

Myocarditis and Cardiomyopathy

Fatal myocarditis and cardiomyopathy have occurred with clozapine treatment. Discontinue FAZACLO and obtain a cardiac evaluation upon suspicion of these reactions. Generally, patients with FAZACLO-related myocarditis or cardiomyopathy should not be rechallenged with FAZACLO. Consider the possibility of myocarditis or cardiomyopathy if chest pain, tachycardia, palpitations, dyspnea, fever, flu-like symptoms, hypotension, or ECG changes occur [see Warnings and Precautions].

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. FAZACLO is not approved for use in patients with dementia-related psychosis [see Warnings and   Precautions].



FAZACLO™ (clozapine, USP), an atypical antipsychotic drug, is a tricyclic dibenzodiazepine derivative, 8-chloro-11-(4-methyl-1-piperazinyl)-5 H -dibenzo[ b,e ][1,4]diazepine.

FAZACLO™ (clozapine, USP) 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, FAZACLO™ (clozapine, USP) 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 WARNINGS.)

The effectiveness of clozapine in a treatment-resistant schizophrenic population was demonstrated in a 6-week study comparing clozapine and chlorpromazine. Patients meeting DSM-III criteria for schizophrenia and having a mean Brief Psychiatric Rating Scale (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 to chlorpromazine was documented in statistical analyses employing both categorical and continuous measures of treatment effect.

Because of the significant risk of agranulocytosis and seizures, 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.

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Published Studies Related to Fazaclo (Clozapine)

Non-glutamatergic clozapine augmentation strategies: a review and meta-analysis. [2014]
Persistent negative symptoms and cognitive impairment are major clinical problems in the treatment of schizophrenia. There is no convincing evidence regarding the efficacy of augmentation of clozapine with a second antipsychotic, ethyl eicosapentaenoic acid (E-EPA), an antidepressant, a mood stabilizer or extract of Ginkgo biloba in clozapine-resistant schizophrenia.

Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia. [2013]
INTRODUCTION: A substantial number of patients with treatment-resistant schizophrenia respond only partially to clozapine... DISCUSSION: In this well controlled clinical trial of patients with treatment-resistant schizophrenia currently receiving clozapine, pimozide augmentation was not an effective strategy to maximize the benefit for better control of positive and negative symptoms or improving neurocognitive function.

Choice of randomization to clozapine versus other second generation antipsychotics in the CATIE schizophrenia trial. [2012]
There is evidence to suggest that clozapine is underutilized in treatment-refractory schizophrenia. Data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), a multi-phase, randomized comparative effectiveness trial for schizophrenia, were used to identify factors associated with choosing randomization to clozapine...

Effects of sertindole on cognition in clozapine-treated schizophrenia patients. [2012]
CONCLUSION: The clozapine-treated patients displayed marked cognitive deficits at

Augmentation of clozapine with a second antipsychotic - a meta-analysis. [2012]
CONCLUSION: Augmentation with a second antipsychotic is modestly beneficial in

more studies >>

Clinical Trials Related to Fazaclo (Clozapine)

Equivalence of Generic Clozapine to Orally Dissolving Clozapine in Schizophrenia or Schizoaffective Disorder [Completed]

FazaClo Outcomes in the Control of Schizophrenia (FOCUS) Study Survey [Completed]
AZUR Pharma has received several reports from practicing psychiatrists prescribing FazaClo showing that FazaClo patients start losing body weight instead of keep gaining it, after being switched from other clozapine products or other atypical antipsychotics treatments. Another important clinical observation reported by doctors is a considerable reduction in hypersalivation when FazaClo administration is compared to other antipsychotic treatments. Based on the findings described above, and on the real need for effective and safer treatments for schizophrenia, AZUR Pharma has decided to design and conduct an observational study in a large number of patients taking FazaClo to prove the received clinical reports from physicians. Better understanding and evaluation of these beneficial findings are necessary to provide physicians information for improved treatment decision.

Study of the Effect of Dosing on Clozapine Levels [Not yet recruiting]
The objectives of this 15-day study are: 1. To compare steady-state trough plasma concentrations of clozapine and its metabolite norclozapine when given once daily and twice daily (at the same total daily dose) 2. To determine if frequency of clozapine administration has an effect on: 1. Symptoms of schizophrenia 2. Adverse effects of clozapine 3. Fasting blood glucose, lipids, creatinine, and urea 4. Weight and waist circumference

Clozapine Versus Amisulpride in Treatment-resistant Schizophrenia Patients [Recruiting]
Background: schizophrenia is a debilitating mental disorder affecting about 1% of the general population. About 30% of patients will not react to current drug treatment and defined as treatment-resistant schizophrenia patients (TRSP). The best studied therapeutic option for this population is clozapine therapy. Clozapine was shown to be effective than any other antipsychotic drug in TRSP. Moreover, augmentation of clozapine was not demonstrated to be more effective than clozapine monotherapy. Albeit Clozapine superiority in TRSP, its use may be involved with many adverse effects, some of them are life-threatening, and need for routine blood tests. Amisulpride is an atypical antipsychotic drug with a different mechanism of action than clozapine, with less adverse effects. No study compared directly amisulpride and clozapine in TRSP. Study objective: to compare, for the first time, the broad clinical effectiveness of clozapine and amisulpride and their combination in TRSP. Study Design: a clinical, prospective, naturalistic, randomized, comparative study simulating a real-world approach of clinical decision making. Methods: a total of 140 TRSP will be recruited from a large regional mental health center. Participants will be randomized into two treatment groups (70 in each group): clozapine monotherapy and amisulpride monotherapy. Assessment will be done following 10 and 20 weeks of treatment. In case of treatment failure (insufficient clinical response or severe adverse effect) participants will be offered either to switch to clozapine treatment (for failed amisulpride treatment) or to augment clozapine with amisulpride (for failed clozapine monotherapy patients). Thereafter, participants will be followed-up for a year. Assessment will be made using clinician rated scales and self-completed questionnaires, rating the broad phenomenology of schizophrenia (psychosis, mood, anxiety, obsessive-compulsive, cognitive and quality of life) and drug-related adverse effects (objective and subjective). Analysis: comparison of the effectiveness of the three treatment groups: amisulpride, clozapine and their combination, in the various dimensions of TRSP.

Treatment of Schizophrenia and Comorbid Cannabis Use Disorder: Comparing Clozapine to Treatment-as-Usual [Completed]
Many individuals with schizophrenia also suffer from marijuana addiction. Clozapine, an atypical antipsychotic medication, may prove useful at preventing drug relapse in schizophrenic individuals who are seeking treatment for marijuana addiction. The purpose of this study is to compare the effectiveness of clozapine, vs. treatment-as-usual with other oral antipsychotics at reducing marijuana use in schizophrenic individuals.

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Page last updated: 2015-08-10

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