bysanti

Important safety information

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). ( 5.2 ) QTc Interval Prolongation: may be associated with torsade de pointes and sudden death. Avoid concomitant use of BYSANTI with other drugs that prolong the QTc interval, and in patients with a significant risk of developing torsade de pointes; consider decreasing the BYSANTI dosage when prescribing BYSANTI with other drugs that inhibit milsaperidone metabolism or in CYP2D6 poor metabolizers. Monitor serum potassium and magnesium at baseline and during treatment in patients at risk for significant electrolyte disturbances ( 5.3 , 7.1 , 7.2 ) Neuroleptic Malignant Syndrome (NMS): If NMS is suspected, immediately discontinue BYSANTI and provide intensive symptomatic treatment and close monitoring. ( 5.4 ) Tardive dyskinesia: Discontinue if clinically appropriate. ( 5.5 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.6 ) Orthostatic hypotension and Syncope: Monitor heart rate and blood pressure in patients who are vulnerable to hypotension, and in those with known cardiovascular or cerebrovascular disease. ( 5.7 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold. ( 5.9 ) Leukopenia, Neutropenia, and Agranulocytosis: Patients with a pre-existing low white blood cell count (WBC) or absolute neutrophil count or a history of drug induced leukopenia or neutropenia should have frequent monitoring of their complete blood count during the first few months of BYSANTI therapy and should discontinue BYSANTI at the first sign of a decline in WBC in the absence of other causative factors. Discontinue BYSANTI in patients with absolute ANC <1000/mm3 and follow their WBC until recovery. ( 5.10 ) Priapism: Severe priapism may require surgical intervention. ( 5.14 ) Potential for Cognitive and Motor Impairment: Use caution about driving a motor vehicle or operating hazardous machinery until patients are reasonably certain that therapy with BYSANTI does not adversely affect them. ( 5.15 ) Intraoperative Floppy Iris Syndrome (IFIS): IFIS during cataract surgery may require modifications to the surgical cataract technique. ( 5.16 ) 5.1 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. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks) largely in patients taking atypical antipsychotic drugs for dementia-related psychosis, revealed a risk of death in antipsychotic drug-treated patients was 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the incidence of death in antipsychotic drug-treated patients was about 4.5%, compared to an incidence of about 2.6% in placebo-treated patients. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. BYSANTI is not approved for the treatment of patients with dementia-related psychosis [see Indications and Usage (1) ] . 5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials in elderly patients with dementia-related psychosis treated with risperidone, aripiprazole, or olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke compared to those treated with placebo. BYSANTI is not approved for the treatment of patients with dementia-related psychosis [see Indications and Usage (1) ] . 5.3 QTc Interval Prolongation In a QTc study, the use of iloperidone (iloperidone and milsaperidone rapidly interconvert in vivo) was associated with QTc interval prolongation, especially with concomitant use of a CYP2D6 inhibitor or a CYP3A4 inhibitor. No cases of torsade de pointes or other severe cardiac arrhythmias were observed in the iloperidone studies. Risk Factors for Clinically Significant Risks of QTc Interval Prolongation Certain circumstances may increase the risk of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including ischemic cardiomyopathy; hypokalemia; genetic predisposition, concomitant use of other drugs that prolong the QTc interval or increases the exposure of the drug; and elevated baseline QTc interval. Steps to Prevent or Mitigate Clinically Significant Adverse Reactions or Risks Associated with QTc Interval Prolongation The concomitant use of BYSANTI should be avoided with other drugs that prolong the QTc interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic drugs that prolong the QTc interval (e.g., chlorpromazine, thioridazine), antibiotics that prolong the QTc interval (e.g., gatifloxacin, moxifloxacin), or any other class of drugs known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone). BYSANTI should also be avoided in other patients with significant risk of developing torsades de pointes including those with congenital long QT syndrome, recent myocardial infarction, ischemic cardiomyopathy, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. When BYSANTI is used concomitantly with other drugs (e.g., strong CYP2D6 inhibitors, strong CYP3A4 inhibitors, and taking both a CYP2D6 inhibitor and a CYP3A4 inhibitor) [see Drug Interactions (7.1) ] or in patients with decreased activity of CYP2D6 [see Clinical Pharmacology (12.5) ] decrease the BYSANTI dosage [see Dosage and Administration (2.x) ] . Patients being considered for BYSANTI treatment who are at risk for significant electrolyte disturbances should have baseline serum potassium and magnesium measurements with periodic monitoring because hypokalemia (and/or hypomagnesemia) may increase the risk of QTc interval prolongation and arrhythmia. BYSANTI should be discontinued in patients who are found to have persistent QTc measurements >500 msec. If patients taking BYSANTI experience symptoms that could indicate the occurrence of arrhythmias, e.g., dizziness, palpitations, or syncope, the health care provider should initiate further evaluation, including cardiac monitoring. 5.4 Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with administration of antipsychotic drugs, including iloperidone (iloperidone and milsaperidone rapidly interconvert in vivo). Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue BYSANTI and provide intensive symptomatic treatment and monitoring. 5.5 Tardive Dyskinesia Tardive dyskinesia (TD), may develop in patients treated with antipsychotic drugs, including BYSANTI. TD can develop after relatively brief treatment period at low dosages and may also occur after discontinuation of treatment. If antipsychotic drug treatment is discontinued, TD may partially or completely remission. Antipsychotic treatment, however, may suppress or partially suppress the signs and symptoms of TD, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of TD is unknown. The TD risk in patients treated with antipsychotic drugs appears to be…