Xycloza-100 Tablets

Clozapine orally disintegrating tablets (Clozapine ODT) is an atypical antipsychotic indicated for: 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 ODT should be used only in patients who have failed to respond adequately to standard antipsychotic treatment ( 1.1 ) 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 ( 1.2 ) 1.1 Treatment-resistant Schizophrenia Clozapine Orally Disintegrating Tablet …

• Recommended starting oral dosage is 12.5 mg once daily or twice daily
• If well-tolerated, increase the total daily dosage in increments of 25 mg to 50 mg per day at target dosage of 150 mg to 225 mg twice per day by the end of two weeks
• Subsequently may increase the doage in increments up to 100 mg, once or twice weekly
• Maximum daily dosage is 450 mg twice daily
• Administer with or without food
• Clozapine ODT may be allowed to disintegrate or chewed, and may be taken with or without water
• See additional administration instructions in the full prescribing information
• See dosage modification based on ANC results
• See recommendations for discontinuing Clozapine ODT treatment , restarting Clozapine ODT after interrupting dosing , dosage modifications for drug interactions , dosage recommendations in patients with renal or hepatic impairment and CYP2D6 poor metabolizers in the full prescribing information
• Tablets rapidly disintegrate after placement in the mouth and may be chewed if desired
• No water is needed
• Absolute Neutrophil Count Testing Prior to Clozapine ODT Initiation Prior to initiating Clozapine ODT treatment, obtain a baseline absolute neutrophil count (ANC)
• Clozapine ODT initiation is not recommended in patients with an ANC less than 1500/µL [see Warnings and Precautions ]
• For patients with documented Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count)), obtain at least two baseline ANC levels. …

Clozapine Orally Disintegrating Tablets are available containing 25 mg, 100 mg, 150 mg or 200 mg of clozapine, USP. The 25 mg tablets are peach, round, unscored tablets debossed with C over 25 on one side of the tablet and blank on the other side. The 100 mg tablets are peach, round, unscored tablets debossed with C over 100 on one side of the tablet and blank on the other side. …

• Safety and effectiveness of clozapine
• Pediatric patients have not been established

There have not been sufficient numbers of geriatric patients in clinical studies utilizing clozapine to determine whether those over 65 years of age differ from younger subjects in their response to clozapine. Orthostatic hypotension and tachycardia can occur with Clozapine ODT treatment [seeand Warnings and Precautions (5.2) ] . …

• Advise the patient to read the FDA-approved patient labeling ( Medication Guide )
• Discuss the following issues with patients and caregivers: Severe Neutropenia: Instruct patients (and caregivers) [see Warnings and Precautions ]: About the risk of developing severe neutropenia and infection with Clozapine ODT treatment
• To immediately report to their healthcare provider any symptom or sign of infection during Clozapine ODT treatment About the importance of having frequent ANC testing Orthostatic Hypotension, Bradycardia, and Syncope: Inform patients and caregivers about the risk of orthostatic hypotension and syncope, especially during the period of initial dose titration. …

• Clozapine ODT is contraindicated in patients with a history of hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of Clozapine ODT [see Adverse Reactions ]
• Known hypersensitivity to clozapine or any other component of Clozapine ODT

Concomitant use of Strong CYP1A2 Inhibitors : Reduce Clozapine ODT dose to one-third when coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, enoxacin). ( 2.7 , 7.1 ) Concomitant use of Strong CYP3A4 Inducers is not recommended. ( 2.7 , 7.1 ) Discontinuation of CYP1A2 or CYP3A4 Inducers: Consider reducing Clozapine ODT dose when CYP1A2 (e.g., tobacco smoke) or CYP3A4 inducers (e.g., carbamazepine) are discontinued. ( 2.7 , 7.1 ) Anticholinergic drugs: Concomitant use may increase the risk for anticholinergic toxicity. …

Severe neutropenia: See ( 5.1 ) Gastrointestinal Hypomotility with Severe Complications: Severe gastrointestinal adverse reactions have occurred with the use of clozapine. If constipation is identified, close monitoring and prompt treatment is advised. ( 5.7 ) Eosinophilia: Assess for organ involvement (e.g., myocarditis, pancreatitis, hepatitis, colitis, nephritis). Discontinue if these occur. ( 5.8 ) QT Interval Prolongation: Can be fatal. Consider additional risk factors for prolonged QT interval (disorders and drugs). ( 5.9 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. …

The following adverse reactions are discussed in more detail in other sections of the labeling: Severe Neutropenia [see Warnings and Precautions (5.1) ] Orthostatic Hypotension, Bradycardia, and Syncope [see Warnings and Precautions (5.2) ] Falls [see Warnings and Precautions (5.3) ] Seizures [see Warnings and Precautions (5.4) ] Myocarditis, Pericarditis, Cardiomyopathy, and Mitral Valve Incompetence [see Warnings and Precautions (5.5) ] Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.6) ] Gastrointestinal Hypomotility with Severe Complications [see Warnings and Precautions (5.7) ] Eosinophilia [see Warnings and Precautions (5.8) ] QT …

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Clozapine ODT, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Atypical Antipsychotics at1-866-961-2388 or visiting http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. …

10.1 Overdosage Experience The most commonly reported signs and symptoms associated with Clozapine ODT overdose are: sedation, delirium, coma, tachycardia, hypotension, respiratory depression or failure; and hypersalivation. There are reports of aspiration pneumonia, cardiac arrhythmias, and seizure. Fatal overdoses have been reported with clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g. 10.2 Management of Overdosage There are no specific antidotes for Clozapine ODT overdose. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.