fanapt

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 ) QT prolongation: Prolongs QT interval and may be associated with arrhythmia and sudden death. Avoid use of FANAPT in combination with other drugs that are known to prolong QTc; use caution and consider dose modification when prescribing FANAPT with other drugs that inhibit FANAPT metabolism. Monitor serum potassium and magnesium in patients at risk for electrolyte disturbances. ( 1 , 5.3 , 7.1 , 7.2 , 12.3 ) Neuroleptic Malignant Syndrome (NMS): Manage with immediate discontinuation of drug 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 and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. ( 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 have been reported with antipsychotics. Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia. Consider discontinuing FANAPT if clinically significant decline in WBC occurs in the absence of other causative factors. ( 5.10 ) Priapism: Cases have been reported in association with FANAPT treatment. Severe priapism may require surgical intervention. ( 5.14 ) Potential for cognitive and motor impairment: Use caution when operating machinery. ( 5.15 ) Intraoperative Floppy Iris Syndrome (IFIS): IFIS during cataract surgery may require modifications to the surgical 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 dementia-related psychosis placebo-controlled trials (modal duration of 10 weeks) largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate 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. FANAPT is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions (5.2) ] . 5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. FANAPT is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions (5.1) ] . 5.3 QT Prolongation In an open-label QTc study in patients with schizophrenia or schizoaffective disorder (n=160), FANAPT was associated with QTc prolongation of 9 msec at an iloperidone dose of 12 mg twice daily. The effect of FANAPT on the QT interval was augmented by the presence of CYP450 2D6 or 3A4 metabolic inhibition (paroxetine 20 mg once daily and ketoconazole 200 mg twice daily, respectively). Under conditions of metabolic inhibition for both 2D6 and 3A4, FANAPT 12 mg twice daily was associated with a mean QTcF increase from baseline of about 19 msec. No cases of torsade de pointes or other severe cardiac arrhythmias were observed during the pre-marketing clinical program. The use of FANAPT should be avoided in combination with other drugs that are known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone). FANAPT should also be avoided in patients with a known genetic susceptibility to congenital long QT syndrome and in patients with a history of cardiac arrhythmias. 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 (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval; (5) recent acute myocardial infarction; and/or (6) uncompensated heart failure. Caution is warranted when prescribing FANAPT with drugs that inhibit FANAPT metabolism [see Drug Interactions (7.1) ] , and in patients with reduced activity of CYP2D6 [see Clinical Pharmacology (12.3 , 12.5) ] . It is recommended that patients being considered for FANAPT treatment who are at risk for significant electrolyte disturbances have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia (and/or hypomagnesemia) may increase the risk of QT prolongation and arrhythmia. FANAPT should be avoided in patients with histories of significant cardiovascular illness, e.g., QT prolongation, recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia. FANAPT should be discontinued in patients who are found to have persistent QTc measurements >500 msec. If patients taking FANAPT experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, or syncope, the prescriber should initiate further evaluation, including cardiac monitoring. 5.4 Neuroleptic Malignant Syndrome (NMS) Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with administration of antipsychotic drugs, including FANAPT. Clinical manifestations 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 FANAPT and provide intensive symptomatic treatment and monitoring. 5.5 Tardive Dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. The risk appears to be highest among the elderly, especially elderly women, but it is impossible to predict, which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible increase with the duration of treatment and cumulative dose. The syndrome can develop after relatively brief treatment periods at low doses. It may also occur after discontinuation of treatment. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment itself may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, FANAPT should be prescribed in a manner that is most likely to reduce the risk of…