versacloz

Recommended starting oral dosage is 12.5 mg once daily or twice daily (2.2). If well-tolerated, increase the total daily dosage in increments of 25 mg to 50 mg per day to achieve a target dosage of 150 mg to 225 mg twice per day by the end of two weeks (2.2). Subsequently may increase the dosage in increments up to 100 mg once or twice weekly (2.2). Maximum daily dosage is 450 mg twice daily (2.2). Administer with or without food. See important administration instructions in the full prescribing information (2.3). See the dosage modifications based on ANC results and recommended frequency of ANC testing in the full prescribing information (2.4, 2.5). See recommendations for discontinuing VERSACLOZ treatment (2.6), restarting VERSACLOZ after interrupting dosing (2.7), dosage modifications for drug interactions (2.8), dosage recommendations in patients with renal or hepatic impairment and CYP2D6 poor metabolizers (2.9) in the full prescribing information. 2.1 Absolute Neutrophil Count Testing Prior to VERSACLOZ Initiation Prior to initiating VERSACLOZ treatment, obtain a baseline absolute neutrophil count (ANC). VERSACLOZ initiation is not recommended in patients with an ANC less than 1500/µL [see Warnings and Precautions (5.1)] . For patients with documented Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count)), obtain at least two baseline ANC…

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 and Severe Complications [see Warnings and Precautions (5.7)]. Eosinophilia [see Warnings and Precautions (5.8) ]. QT Interval Prolongation [see Warnings and Precautions (5.9) ]. Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain) [see Warnings and Precautions (5.10) ]. Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.11) ]. Hepatotoxicity [see Warnings and Precautions (5.12) ]. Fever [see Warnings and Precautions (5.13) ]. Pulmonary Embolism [see Warnings and Precautions (5.14) ]. Anticholinergic Toxicity [see Warnings and Precautions (5.15) ]. Interference with Cognitive and Motor Performance [see Warnings and Precautions (5.16) ]. Tardive Dyskinesia [see Warnings and Precautions (5.17) ]. Cerebrovascular Adverse Reactions [see Warnings and…

VERSACLOZ 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 VERSACLOZ [see Adverse Reactions (6.2) ] . Known hypersensitivity to clozapine or any other component of VERSACLOZ ( 4 ).

Experience The most commonly reported signs and symptoms associated with clozapine 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 VERSACLOZ. Establish and maintain an airway; ensure adequate oxygenation and ventilation. Monitor cardiac status and vital signs. Use general symptomatic and supportive measures. Consider the possibility of multiple-drug involvement. Contact a Certified Poison Control Center for the most up to date information on the management of overdosage (1-800-222-1222).

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Concomitant use of Strong CYP1A2 Inhibitors : Reduce VERSACLOZ 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 VERSACLOZ 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 ( 5.8 , 5.16 , 7.1 ). 7.1 Potential for Other Drugs to Affect VERSACLOZ Clozapine is a substrate for many cytochrome P450 isozymes, in particular CYP1A2, CYP3A4, and CYP2D6. Use caution when administering VERSACLOZ concomitantly with drugs that are inducers or inhibitors of these enzymes. CYP1A2 Inhibitors Concomitant use of VERSACLOZ and CYP1A2 inhibitors can increase plasma levels of clozapine, potentially resulting in adverse reactions. Reduce the VERSACLOZ dose to one third of the original dose when VERSACLOZ is coadministered with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin). The VERSACLOZ dose should be increased to the original dose when coadministration of strong CYP1A2 inhibitors is discontinued [see Dosage and Administration (2.8) , Clinical Pharmacology (12.3) ]. Moderate or weak CYP1A2 inhibitors include oral contraceptives and caffeine. Monitor patients closely when VERSACLOZ is coadministered with these inhibitors. Consider reducing the VERSACLOZ dosage if necessary [see Dosage and Administration (2.8) ] . CYP2D6 and CYP3A4 Inhibitors Concomitant treatment with VERSACLOZ and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology (12.3) ] . Use caution and monitor patients closely when using such inhibitors. Consider reducing the VERSACLOZ dose [see Dosage and Administration (2.8) ] . CYP1A2 and CYP3A4 Inducers Concomitant treatment with drugs that induce CYP1A2 or CYP3A4 can decrease the plasma concentration of clozapine, resulting in decreased effectiveness of VERSACLOZ. Tobacco smoke is a moderate inducer of CYP1A2. Strong CYP3A4 inducers include carbamazepine, phenytoin, St. John’s wort, and rifampin. It may be necessary to increase the VERSACLOZ dose if used concomitantly with inducers of these enzymes. However, concomitant use of VERSACLOZ and strong CYP3A4 inducers is not recommended [see Dosage and Administration (2.8) ]. Consider reducing the VERSACLOZ dosage when discontinuing coadministered enzyme inducers, because discontinuation of inducers can result in increased clozapine plasma levels and an increased risk of adverse reactions [see Dosage and Administration (2.8) ]. Anticholinergic Drugs Concomitant treatment with clozapine and other drugs with anticholinergic activity (e.g., benztropine, cyclobenzaprine, diphenhydramine) can increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions related to hypomotility. Avoid concomitant use of VERSACLOZ with anticholinergic drugs when possible [see Warnings and Precautions ( 5.7 , 5.15 )]. Drugs that Cause QT Interval Prolongation Use caution when administering concomitant medications that prolong the QT interval or inhibit the metabolism of VERSACLOZ. Drugs that cause QT prolongation include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, and pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmics (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) [see Warnings and Precautions (5.9) ] . 7.2 Potential for VERSACLOZ to Affect Other Drugs Concomitant use of VERSACLOZ with other drugs metabolized by CYP2D6 can increase levels of these CYP2D6 substrates. Use caution when coadministering VERSACLOZ 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).