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FazaClo

Generic Name: Clozapine
Drug Category: Atypical Antipsychotic
Litigation Alert Level: High
This drug has been approved for use by males and females over the age of 18 years old for a maximum duration of 2 years.

Approved Uses

Indicated for:

Treatment-Resistant Schizophrenia:

• 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, FAZACLO should be used only in patients who have failed to respond adequately to standard antipsychotic treatment.

The effectiveness of clozapine in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active controlled study comparing clozapine and chlorpromazine in patients who had failed other antipsychotics

Reduction in the Risk of Recurrent Suicidal Behavior in Schizophrenia or Schizoaffective Disorder:

• 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 in reducing the risk of recurrent suicidal behavior was demonstrated over a two-year treatment period in the InterSePT trial.

The maximum dose is 900 mg per day.

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.

Clozapine treatment has caused severe neutropenia, defined as an absolute neutrophil count (ANC) less than 500/µL. Severe neutropenia can lead to serious infection and death. Prior to initiating treatment with FAZACLO a baseline ANC must be at least 1500/µL for the general population; and must be at least 1000/µL for patients with documented Benign Ethnic Neutropenia (BEN). During treatment, patients must have regular ANC monitoring. Advise patients to immediately report symptoms consistent with severe neutropenia or infection (e.g., fever, weakness, lethargy, or sore throat).

Because of the risk of severe neutropenia, FAZACLO is available only through a restricted program under a Risk Evaluation Mitigation Strategy (REMS) called the Clozapine REMS Program.

Antipsychotic drugs including FAZACLO can cause a potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS).

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 doses. Use FAZACLO cautiously in patients with cardiovascular or cerebrovascular disease or conditions predisposing to hypotension (e.g., dehydration, use of antihypertensive medications).

FAZACLO may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

Tardive dyskinesia (TD) has occurred in patients treated with antipsychotic drugs, including FAZACLO.

Pulmonary embolism and deep vein thrombosis have occurred in patients treated with clozapine.

Treatment with FAZACLO can result in gastrointestinal adverse reactions, including constipation, intestinal obstruction, fecal impaction, and paralytic ileus.

Eosinophilia, defined as a blood eosinophil count of greater than 700/µL, has occurred with clozapine treatment.

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.

FAZACLO has potent anticholinergic effects. Treatment with FAZACLO can result in CNS and peripheral anticholinergic toxicity. Use with caution in the presence of narrow-angle glaucoma, concomitant anticholinergic medications, prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions.

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.

QT prolongation, Torsades de Pointes and other life-threatening ventricular arrhythmias, cardiac arrest, and sudden death have occurred with clozapine treatment. When prescribing FAZACLO, consider the presence of additional risk factors for QT prolongation and serious cardiovascular reactions. Conditions that increase these risks include the following: history of QT prolongation, long QT syndrome, family history of long QT syndrome or sudden cardiac death, significant cardiac arrhythmia, recent myocardial infarction, uncompensated heart failure, treatment with other medications that cause QT prolongation, treatment with medications that inhibit the metabolism of FAZACLO, and electrolyte abnormalities.

It may be necessary to reduce the FAZACLO dose in patients with significant renal or hepatic impairment, or in CYP2D6 poor metabolizers.

Severe, life threatening, and in some cases fatal hepatotoxicity including hepatic failure, hepatic necrosis, and hepatitis have been reported in patients treated with clozapine.

Patients with BEN require a different ANC algorithm for FAZACLO management due to their lower baseline ANC levels.

Atypical antipsychotic drugs, including FAZACLO, have been associated with metabolic changes that can increase cardiovascular and cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain.

FAZACLO can cause sedation and impairment of cognitive and motor performance. Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that FAZACLO does not affect them adversely.

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including FAZACLO.

During clozapine therapy, patients have experienced transient, clozapine-related fever. The peak incidence is within the first 3 weeks of treatment.

Phenylketonuric patients should be informed that FAZACLO contains phenylalanine (a component of aspartame).

Dose adjustments may be necessary in patients with concomitant use of: strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin); moderate or weak CYP1A2 inhibitors (e.g., oral contraceptives, or caffeine); CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline); CYP3A4 inducers (e.g., phenytoin, carbamazepine, St. John’s wort, and rifampin); or CYP1A2 inducers (e.g., tobacco smoking).

Use caution when administering concomitant medications that prolong the QT interval or inhibit the metabolism of FAZACLO. Drugs that cause QT prolongation include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmic medications (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). FAZACLO is primarily metabolized by CYP isoenzymes 1A2, 2D6, and 3A4. Concomitant treatment with inhibitors of these enzymes can increase the concentration of FAZACLO.

Clozapine is a substrate for many cytochrome P450 isozymes, in particular CYP1A2, CYP3A4, and CYP2D6. Use caution when administering FAZACLO concomitantly with drugs that are inducers or inhibitors of these enzymes.

Use caution when co-administering FAZACLO with other drugs that are metabolized by CYP2D6. It may be necessary to use lower doses of such drugs than usually prescribed. Such drugs include specific antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).

There are no adequate or well-controlled studies of clozapine in pregnant women. 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.

FAZACLO is present in human milk. Because of the potential for serious adverse reactions in nursing infants from FAZACLO, 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.

GoToSource

Off-label Uses

• Dosage greater than 900 mg per day. GoToSource

• Use in patients under the age of 18. GoToSource

• Adjunctive treatment for ADHD. GoToSource

• Treatment-resistant agitation in dementia. GoToSource

• Psychotic refractory depression. GoToSource

• Sleep disturbances. GoToSource

• Severe borderline personality disorder. GoToSource

• Severe conduct disorder. GoToSource

• Post-traumatic stress disorder. GoToSource

• Prevention of substance abuse relapses. GoToSource

• Tourette’s syndrome. GoToSource

• Tic disorders. GoToSource

• Psychosis in patients with idiopathic parkinson’s disease. GoToSource

Adverse Events

Anxiety symptoms and social phobia. GoToSource

Binge eating and other eating disorders. GoToSource

Myocarditis (inflammation of the heart muscle), orthostatic hypotension (sudden drop in blood pressure caused by change in posture) and tachycardia (abnormally rapid heart rate). GoToSource

Cardiomyopathy (disease of the heart muscle). GoToSource

Pityriasis rosea-like eruption (type of skin rash). GoToSource

Type 2 diabetes and raised blood lipids. GoToSource

Gastrointestinal hypomotility which may result in severe constipation, ileus, bowel obstruction and death. GoToSource

Systemic eosinophilia (higher than normal level of a certain type of white blood cell. GoToSource

Increased risk of pneumonia. GoToSource

Diabetic ketoacidosis ( life-threatening condition when body produces high levels of blood acids called ketones). GoToSource

Sedation. GoToSource

Clozapine-induced fever. GoToSource

Leukopenia (low white blood cell count), perimyocarditis (inflammation of the pericardium and the heart muscle) and parenchymal lung disease (lung diseases affecting the tissue and space around the air sacs of the lungs). GoToSource

Seizures, weight gain, metabolic syndrome (cluster of conditions such as increased blood pressure, high blood sugar, excess body fat around the waist and abnormal cholesterol or triglyceride levels), nighttime enuresis (bedwetting) and hypersalivation. GoToSource

Pancytopenia (abnormally low levels of red blood cells, white blood cells and platelets). GoToSource

Atrial fibrillation (irregular rapid heart rate). GoToSource

Acute interstitial nephritis (kidney disorder). GoToSource

Impairment of left ventricular function. GoToSource

Akathisia (movement disorder characterized by feeling of inner restlessness and inability to stay still). GoToSource

Agranulocytosis (decreased granulocytes a type of white blood cell) and granulocytopenia (decreased granulocytes a type of white blood cell). GoToSource

Dry eye syndrome. GoToSource

Increased mortality rates in elderly patients with dementia. GoToSource

Full body deep burning pain. GoToSource

Stuttering. GoToSource

Pulmonary emboli (blockage in one of the pulmonary arteries) and deep venous thrombosis (blood clot in one or more of the deep veins in body). GoToSource

Ego-dystonic suicidal obsessions. GoToSource

Clozapine-withdrawal catatonia (abnormality of movement function and behavior). GoToSource

Serositis (inflammation of serous tissues of the body). GoToSource

Fatal fulminant hepatic failure (development of severe liver injury). GoToSource

Ocular pigmentation. GoToSource

Urinary incontinence and lower urinary tract symptoms. GoToSource

Priapism (persistent and painful erection). GoToSource

Neuroleptic malignant syndrome (life-threatening drug reaction). GoToSource

Microscopic colitis (inflammation of large intestine (colon). GoToSource

Angioneurotic edema (swelling of the lower layer of skin and tissue just under the skin or mucous membranes). GoToSource

Systemic lupus erythematosus (autoimmune disease). GoToSource

Oropharyngeal lesions (injury or disease of mouth and pharynx) and nasal congestion. GoToSource

Serious bowel complications leading to hospitalization or death. GoToSource

Obsessive-compulsive symptoms and panic disorder. GoToSource

Litigation

Lawsuits filed for bowel obstructions, intestinal damage, aspiration and death. 

The material contained in GoToPills is for informational purposes only and not intended to replace the judgment, evaluation and treatment of physicians, pharmacists and other healthcare providers. GoToPills does not provide medical advice, diagnoses or treatment. Always seek the advice of your physician or other qualified health provider regarding a medical condition or treatment.

 

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Site Last Updated March 29, 2024