b'T:7.875"S:7"ARISTADA INITIO (aripiprazole lauroxil) extended-release injectableGiven these considerations, antipsychotics should be prescribed in a manner that is 32 suspension, for intramuscular usemost likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic BRIEF SUMMARY OF PRESCRIBING INFORMATION treatment should generally be reserved for patients who suffer from a chronic illness (For complete details, please see full Prescribing Information and Medication Guide.) that is known to respond to antipsychotic drugs. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH satisfactory clinical response should be sought. The need for continued treatment DEMENTIA-RELATED PSYCHOSIS should be reassessed periodically.Elderly patients with dementia-related psychosis treated withIf signs and symptoms of tardive dyskinesia appear in a patient treated with antipsychotic drugs are at an increased risk of death antipsychotics, consider discontinuation of the antipsychotic drug. However, someARISTADA INITIO is not approved for the treatment of patients with patients may require antipsychotic treatment despite the presence of the syndrome.dementia-related psychosis Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and INDICATIONS AND USAGE: ARISTADA INITIO, in combination with oral aripiprazole, isweight gain. While all drugs in the class have been shown to produce some indicated for the initiation of ARISTADA (aripiprazole lauroxil) when used for themetabolic changes, each drug has its own specific risk profile.treatment of schizophrenia in adults. Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and CONTRAINDICATIONS: ARISTADA INITIO is contraindicated in patients with a knownassociated with ketoacidosis or hyperosmolar coma or death, has been reported in hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged frompatients treated with atypical antipsychotics. There have been reports of pruritus/urticaria to anaphylaxis. hyperglycemia in patients treated with oral aripiprazole. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is WARNINGS AND PRECAUTIONS complicated by the possibility of an increased background risk of diabetes mellitus in Increased Mortality in Elderly Patients With Dementia-related Psychosis: Elderlypatients with schizophrenia and the increasing incidence of diabetes mellitus in the patients with dementia-related psychosis treated with antipsychotic drugs are at angeneral population. Given these confounders, the relationship between atypical increased risk of death. Analyses of 17 placebo-controlled trials (modal duration ofantipsychotic use and hyperglycemia-related adverse events is not completely 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk ofunderstood. However, epidemiological studies suggest an increased risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death inhyperglycemia-related adverse reactions in patients treated with the atypical placebo-treated patients. Over the course of a typical 10-week controlled trial, theantipsychotics.rate of death in drug-treated patients was about 4.5%, compared to a rate of aboutPatients with an established diagnosis of diabetes mellitus who are started on 2.6% in the placebo group.atypical antipsychotics should be monitored regularly for worsening of glucose Although the causes of death were varied, most of the deaths appeared to be eithercontrol. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) indiabetes) who are starting treatment with atypical antipsychotics should undergo nature. Observational studies suggest that, similar to atypical antipsychotic drugs,fasting blood glucose testing at the beginning of treatment and periodically during treatment with conventional antipsychotic drugs may increase mortality. The extent totreatment. Any patient treated with atypical antipsychotics should be monitored for which the findings of increased mortality in observational studies may be attributedsymptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and to the antipsychotic drug as opposed to some characteristic(s) of the patients is notweakness. Patients who develop symptoms of hyperglycemia during treatment with clear. ARISTADA INITIO is not approved for the treatment of patients with dementia- atypical antipsychotics should undergo fasting blood glucose testing. In some cases, related psychosis. hyperglycemia has resolved when the atypical antipsychotic was discontinued; Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled trialshowever, some patients require continuation of anti-diabetic treatment despite with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, therediscontinuation of the suspect drug.was a higher incidence of cerebrovascular adverse reactions (cerebrovascularDyslipidemia: Undesirable alterations in lipids have been observed in patients accidents and transient ischemic attacks) including fatalities compared to placebo- treated with atypical antipsychotics. treated patients. ARISTADA INITIO is not approved for the treatment of patients withWeight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical dementia-related psychosis. monitoring of weight is recommended. S:10" T:10.75"Potential for Dosing and Medication Errors: Medication errors, includingPathological Gambling and Other Compulsive Behaviors: Post-marketing case substitution and dispensing errors, between ARISTADA INITIO and ARISTADA couldreports suggest that patients can experience intense urges, particularly for gambling, occur. ARISTADA INITIO is intended for single administration only. Do not substituteand the inability to control these urges while taking aripiprazole. Other compulsive ARISTADA INITIO for ARISTADA because of differing pharmacokinetic profiles.urges, reported less frequently include: sexual urges, shopping, eating or binge eating, and other impulsive or compulsive behaviors. Because patients may not Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimesrecognize these behaviors as abnormal, it is important for prescribers to ask patients referred to as Neuroleptic Malignant Syndrome (NMS) may occur in association withor their caregivers specifically about the development of new or intense gambling antipsychotic drugs, including ARISTADA INITIO. Clinical manifestations of NMS areurges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomicother urges while being treated with aripiprazole. It should be noted that impulse-instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiaccontrol symptoms can be associated with the underlying disorder. In some cases, dysrhythmia). Additional signs may include elevated creatine phosphokinase,although not all, urges were reported to have stopped when the dose was reduced or myoglobinuria (rhabdomyolysis), and acute renal failure. the medication was discontinued. Compulsive behaviors may result in harm for the The diagnostic evaluation of patients with this syndrome is complicated. In arriving atpatient and others if not recognized. If compulsive urges develop, consider a diagnosis, it is important to identify cases in which the clinical presentationdiscontinuing aripiprazole. includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) andOrthostatic Hypotension: Aripiprazole may cause orthostatic hypotension, perhaps untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Otherdue to its a 1 -adrenergic receptor antagonism. Associated adverse reactions related important considerations in the differential diagnosis include central anticholinergicto orthostatic hypotension can include dizziness, lightheadedness and tachycardia. toxicity, heat stroke, drug fever, and primary central nervous system pathology. Generally, these risks are greatest at the beginning of treatment and during dose The management of NMS should include: (1) immediate discontinuation ofescalation. Patients at increased risk of these adverse reactions or at increased risk antipsychotic drugs and other drugs not essential to concurrent therapy; (2) intensiveof developing complications from hypotension include those with dehydration, symptomatic treatment and medical monitoring; and (3) treatment of anyhypovolemia, treatment with antihypertensive medication, history of cardiovascular concomitant serious medical problems for which specific treatments are available.disease (e.g., heart failure, myocardial infarction, ischemia, or conduction There is no general agreement about specific pharmacological treatment regimensabnormalities), history of cerebrovascular disease, as well as patients who are for uncomplicated NMS. antipsychotic-nave. In such patients, monitor orthostatic vital signs.If a patient appears to require antipsychotic drug treatment after recovery from NMS,Falls: Antipsychotics including ARISTADA INITIO may cause somnolence, postural reintroduction of drug therapy should be closely monitored, since recurrences of NMShypotension, or motor and sensory instability, which may lead to falls and, have been reported. consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskineticwhen initiating antipsychotic treatment and recurrently for those patients on movements may develop in patients treated with antipsychotic drugs. Although thelong-term antipsychotic therapy.prevalence of the syndrome appears to be highest among the elderly, especiallyLeukopenia, Neutropenia, and Agranulocytosis: In clinical trials and/or elderly women, it is impossible to predict which patients will develop the syndrome.postmarketing experience, events of leukopenia and neutropenia have been reported Whether antipsychotic drug products differ in their potential to cause tardivetemporally related to antipsychotic agents. Agranulocytosis has also been reported.dyskinesia is unknown. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood The risk of developing tardive dyskinesia and the likelihood that it will becomecell count (WBC)/absolute neutrophil count (ANC) and history of drug-induced irreversible appear to increase as the duration of treatment and the total cumulativeleukopenia/neutropenia. In patients with a history of a clinically significant low WBC/dose of antipsychotic drugs administered to the patient increase, but the syndromeANC or drug-induced leukopenia/neutropenia, perform a complete blood count (CBC) can develop after relatively brief treatment periods at low doses, although this frequently during the first few months of therapy. In such patients, consider is uncommon. discontinuation of antipsychotics at the first sign of a clinical significant decline in Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment isWBC in the absence of other causative factors.withdrawn. Antipsychotic treatment itself may suppress (or partially suppress) theMonitor patients with clinically significant neutropenia for fever or other symptoms or signs and symptoms of the syndrome and may thus mask the underlying process.signs of infection and treat promptly if such symptoms or signs occur. Discontinue The effect of symptomatic suppression on the long-term course of the syndrome antipsychotics in patients with severe neutropenia (absolute neutrophil countis unknown. 1000/mm3) and follow their WBC until recovery.'