b'ARISTADA INITIO (aripiprazole lauroxil) extended-release injectableGiven these considerations, antipsychotics should be prescribed in a manner that isSeizures: As with other antipsychotic drugs, use ARISTADA INITIO cautiously inCardiac Disorders: bradycardia, atrial flutter, cardiorespiratory arrest,suspension, for intramuscular usemost likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychoticpatien ts with a history of seizures or with conditions that lower the seizure threshold.atri oventricular block, atrial fibrillation, myocardial ischemia, myocardial infarction,75BRIEF SUMMARY OF PRESCRIBING INFORMATION treatment should generally be reserved for patients who suffer from a chronic illnessConditions that lower the seizure threshold may be more prevalent in a population ofcardiopulmonary failure (For complete details, please see full Prescribing Information and Medication Guide.) that is known to respond to antipsychotic drugs. In patients who do require chronic65 years or older. Eye Disorders: photophobia, diplopia treatment, the smallest dose and the shortest duration of treatment producing aPotential for Cognitive and Motor Impairment: ARISTADA INITIO, like otherGastrointestinal Disorders: gastroesophageal reflux disease WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH satisfactory clinical response should be sought. The need for continued treatmentantipsychotics, has the potential to impair judgment, thinking or motor skills. PatientsGeneral Disorders and Administration-Site Conditions: peripheral edema, chest pain, DEMENTIA-RELATED PSYCHOSIS should be reassessed periodically. should be cautioned about operating hazardous machinery, including automobiles,face edemaE lderly patients with dementia-related psychosis treated with If signs and symptoms of tardive dyskinesia appear in a patient treated withuntil they are reasonably certain that therapy with ARISTADA INITIO does not affectHepatobiliary Disorders: hepatitis, jaundice antipsychotic drugs are at an increased risk of death antipsychotics, consider discontinuation of the antipsychotic drug. However, somethem adversely. Immune System Disorders: hypersensitivityARISTADA INITIO is not approved for the treatment of patients with patients may require antipsychotic treatment despite the presence of the syndrome. Body Temperature Regulation: Disruption of the bodys ability to reduce core bodyInjury, Poisoning, and Procedural Complications: fall, heat strokedementia-related psychosis Metabolic Changes: Atypical antipsychotic drugs have been associated withtemperature has been attributed to antipsychotic agents. Appropriate care is advisedInvestigations: weight decreased, hepatic enzyme increased, blood glucose metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, andwhen prescribing ARISTADA INITIO for patients who will be experiencing conditionsincreased, blood lactate dehydrogenase increased, gamma glutamyl transferase INDICATIONS AND USAGE: ARISTADA INITIO, in combination with oral aripiprazole, isweight gain. While all drugs in the class have been shown to produce somewhich may contribute to an elevation in core body temperature, (e.g., exercisingincreased, blood prolactin increased, blood urea increased, blood creatinine indicated for the initiation of ARISTADA (aripiprazole lauroxil) when used for themetabolic changes, each drug has its own specific risk profile. strenuously, exposure to extreme heat, receiving concomitant medication withincreased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated treatment of schizophrenia in adults. Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme andanticholinergic activity, or being subject to dehydration). hemoglobin increased associated with ketoacidosis or hyperosmolar coma or death, has been reported inMetabolism and Nutrition Disorders: anorexia, hypokalemia, hyponatremia, CONTRAINDICATIONS: ARISTADA INITIO is contraindicated in patients with a knownpatients treated with atypical antipsychotics. There have been reports ofDysphagia: Esophageal dysmotility and aspiration have been associated withhypoglycemia hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged fromantipsychotic drug use. ARISTADA INITIO and other antipsychotic drugs should beMusculoskeletal and Connective Tissue Disorders: muscle tightness, rhabdomyolysis, pruritus/urticaria to anaphylaxis. hyperglycemia in patients treated with oral aripiprazole. Assessment of theused cautiously in patients at risk for aspiration pneumonia. mobility decreased relationship between atypical antipsychotic use and glucose abnormalities isNervous System Disorders: memory impairment, cogwheel rigidity, hypokinesia, WARNINGS AND PRECAUTIONS complicated by the possibility of an increased background risk of diabetes mellitus inADVERSE REACTIONS bradykinesia, akinesia, myoclonus, coordination abnormal, speech disorder, Increased Mortality in Elderly Patients With Dementia-related Psychosis: Elderlypatients with schizophrenia and the increasing incidence of diabetes mellitus in theClinical Studies Experience: Because clinical trials are conducted under widelychoreoathetosis patients with dementia-related psychosis treated with antipsychotic drugs are at angeneral population. Given these confounders, the relationship between atypicalvarying conditions, adverse reaction rates observed in the clinical trials of a drugPsychiatric Disorders: aggression, loss of libido, delirium, libido increased, increased risk of death. Analyses of 17 placebo-controlled trials (modal duration ofantipsychotic use and hyperglycemia-related adverse events is not completelycannot be directly compared to rates in the clinical trials of another drug and may notanorgasmia, tic, homicidal ideation, catatonia, sleep walking 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk ofunderstood. However, epidemiological studies suggest an increased risk ofreflect the rates observed in practice.Renal and Urinary Disorders: urinary retention, nocturia 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 atypicalThe safety of ARISTADA INITIO, in combination with oral aripiprazole, for the initiationReproductive System and Breast Disorders: erectile dysfunction, gynaecomastia, placebo-treated patients. Over the course of a typical 10-week controlled trial, theantipsychotics. of ARISTADA when used for the treatment of schizophrenia in adults has beenmenstruation irregular, amenorrhea, breast pain, priapism 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 onestablished and is based on clinical trials of ARISTADA (aripiprazole lauroxil) includingRespiratory, Thoracic, and Mediastinal Disorders: nasal congestion, dyspnea 2.6% in the placebo group.atypical antipsychotics should be monitored regularly for worsening of glucose1019 adult patients with schizophrenia.Skin and Subcutaneous Tissue Disorders: rash, hyperhidrosis, pruritus, 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 ofPatient Exposure: ARISTADA INITIO has been evaluated for safety in 170 adultphotosensitivity reaction, alopecia, urticaria cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) indiabetes) who are starting treatment with atypical antipsychotics should undergopatients in clinical trials in schizophrenia.Vascular Disorders: hypotension, hypertensionnature. Observational studies suggest that, similar to atypical antipsychotic drugs,fasting blood glucose testing at the beginning of treatment and periodically duringIn pharmacokinetic studies, the safety profile of ARISTADA INITIO was generallyPostmarketing Experience: The following adverse reactions have been identified treatment with conventional antipsychotic drugs may increase mortality. The extent totreatment. Any patient treated with atypical antipsychotics should be monitored forconsistent with that observed for ARISTADA.during post-approval use of oral aripiprazole. Because these reactions are reported which the findings of increased mortality in observational studies may be attributedsymptoms of hyperglycemia including polydipsia, polyuria, polyphagia, andARISTADA (Aripiprazole Lauroxil) Trials in Adults with Schizophrenia voluntarily from a population of uncertain size, it is not always possible to reliably to the antipsychotic drug as opposed to some characteristic(s) of the patients is notweakness. Patients who develop symptoms of hyperglycemia during treatment withestimate their frequency or to establish a causal relationship to drug exposure: clear. ARISTADA INITIO is not approved for the treatment of patients with dementia- atypical antipsychotics should undergo fasting blood glucose testing. In some cases,Commonly Observed Adverse Reactions with Aripiprazole Lauroxil:The mostoccurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, related psychosis. hyperglycemia has resolved when the atypical antipsychotic was discontinued;common adverse reaction (incidence 5% and at least twice the rate of placebo inpruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups, blood however, some patients require continuation of anti-diabetic treatment despitepatients treated with aripiprazole lauroxil) was akathisia. glucose fluctuation, oculogyric crisis, and drug reaction with eosinophilia and Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled trialsdiscontinuation of the suspect drug. Adverse Reactions Occurring at an Incidence of 2% or More in Aripiprazole Lauroxil- systemic symptoms (DRESS). with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, thereDyslipidemia: Undesirable alterations in lipids have been observed in patientsTreated Patients: Adverse reactions associated with the use of aripiprazole lauroxilDRUG INTERACTIONSwas a higher incidence of cerebrovascular adverse reactions (cerebrovasculartreated with atypical antipsychotics.(incidence of 2% or greater, rounded to the nearest percent and aripiprazole lauroxil accidents and transient ischemic attacks) including fatalities compared to placebo- Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinicalincidence greater than placebo) that occurred were: injection site pain, increasedTable 1: Clinically Important Drug Interactions With ARISTADA INITIO treated patients. ARISTADA INITIO is not approved for the treatment of patients withmonitoring of weight is recommended. weight, increased blood creatinine phosphokinase, akathisia, headache, insomnia,Strong CYP3A4 Inhibitors and CYP2D6 Inhibitors dementia-related psychosis. Pathological Gambling and Other Compulsive Behaviors: Post-marketing caseand restlessness. Potential for Dosing and Medication Errors: Medication errors, includingreports suggest that patients can experience intense urges, particularly for gambling,Injection Site ReactionsClinical Impact Concomitant use of oral aripiprazole with strong CYP3A4 or substitution and dispensing errors, between ARISTADA INITIO and ARISTADA couldand the inability to control these urges while taking aripiprazole. Other compulsiveARISTADA INITIOCYP2D6 inhibitors increased the exposure of aripiprazole occur. ARISTADA INITIO is intended for single administration only. Do not substituteurges, reported less frequently include: sexual urges, shopping, eating or bingeIn pharmacokinetic studies evaluating ARISTADA INITIO, the incidences of injectioncompared to the use of oral aripiprazole aloneARISTADA INITIO for ARISTADA because of differing pharmacokinetic profiles.eating, and other impulsive or compulsive behaviors. Because patients may notsite reactions with ARISTADA INITIO were similar to the incidence observed withIntervention Avoid concomitant use of ARISTADA INITIO with strong Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimesrecognize these behaviors as abnormal, it is important for prescribers to ask patientsaripiprazole lauroxil.CYP3A4 or strong CYP2D6 inhibitors because the dosage of referred to as Neuroleptic Malignant Syndrome (NMS) may occur in association withor their caregivers specifically about the development of new or intense gamblingARISTADA (Aripiprazole Lauroxil)ARISTADA INITIO cannot be modifiedantipsychotic drugs, including ARISTADA INITIO. Clinical manifestations of NMS areurges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, orInjection site reactions were reported by 4% of patients treated with 441 mg hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomicother urges while being treated with aripiprazole. It should be noted that impulse- aripiprazole lauroxil and 5% of patients treated with 882 mg aripiprazole lauroxilExamples itraconazole, clarithromycin, quinidine, fluoxetine, paroxetine instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiaccontrol symptoms can be associated with the underlying disorder. In some cases,compared to 2% of patients treated with placebo. Most of these were injection siteStrong CYP3A4 Inducers dysrhythmia). Additional signs may include elevated creatine phosphokinase,although not all, urges were reported to have stopped when the dose was reduced orpain (3%, 4% and 2% in the 441 mg aripiprazole lauroxil, 882 mg aripiprazole lauroxil myoglobinuria (rhabdomyolysis), and acute renal failure. the medication was discontinued. Compulsive behaviors may result in harm for theand placebo groups, respectively). Other injection site reactions (induration, swellingClinical Impact Concomitant use of oral aripiprazole and carbamazepine The diagnostic evaluation of patients with this syndrome is complicated. In arriving atpatient and others if not recognized. If compulsive urges develop, considerand redness) occurred at less than 1%.decreased the exposure of aripiprazole compared to the use a diagnosis, it is important to identify cases in which the clinical presentationdiscontinuing aripiprazole.Extrapyramidal Symptoms: In a schizophrenia efficacy study in aripiprazole lauroxil- of oral aripiprazole aloneincludes both serious medical illness (e.g., pneumonia, systemic infection, etc.) andOrthostatic Hypotension: Aripiprazole may cause orthostatic hypotension, perhapstreated patients, the incidence of other EPS-related events, excluding akathisia andIntervention Avoid concomitant use of ARISTADA INITIO with strong untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Otherdue to its a 1 -adrenergic receptor antagonism. Associated adverse reactions relatedrestlessness, was 5% and 7% for patients on 441 mg and 882 mg, respectively,CYP3A4 inducers because the dosage of ARISTADA INITIO important considerations in the differential diagnosis include central anticholinergicto orthostatic hypotension can include dizziness, lightheadedness and tachycardia.versus 4% for placebo-treated patients.cannot be modified. 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 riskDystonia: Symptoms of dystonia, prolonged abnormal contractions of muscle groups,Examples carbamazepine, rifampin antipsychotic drugs and other drugs not essential to concurrent therapy; (2) intensiveof developing complications from hypotension include those with dehydration,may occur in susceptible individuals during the first few days of treatment. Dystonic symptomatic treatment and medical monitoring; and (3) treatment of anyhypovolemia, treatment with antihypertensive medication, history of cardiovascularsymptoms include: spasm of the neck muscles, sometimes progressing to tightnessAntihypertensive Drugs concomitant serious medical problems for which specific treatments are available.disease (e.g., heart failure, myocardial infarction, ischemia, or conductionof the throat, swallowing difficulty, difficulty breathing, and/or protrusion of theClinical Impact Due to its alpha adrenergic antagonism, aripiprazoleThere is no general agreement about specific pharmacological treatment regimensabnormalities), history of cerebrovascular disease, as well as patients who aretongue. While these symptoms can occur at low doses, they occur more frequentlyhas the potential to enhance the effect of certain for uncomplicated NMS. antipsychotic-nave. In such patients, monitor orthostatic vital signs. and with greater severity with high potency and at higher doses of first generationantihypertensive agents. Falls: Antipsychotics including ARISTADA INITIO may cause somnolence, posturalantipsychotic drugs. An elevated risk of acute dystonia is observed in males and If a patient appears to require antipsychotic drug treatment after recovery from NMS,hypotension, or motor and sensory instability, which may lead to falls and,younger age groups. Intervention Avoid concomitant use of ARISTADA INITIO with reintroduction of drug therapy should be closely monitored, since recurrences of NMSconsequently, fractures or other injuries. For patients with diseases, conditions, orOther Adverse Reactions Observed in Clinical Studies with Aripiprazole Lauroxil: Theantihypertensive drugs because the dosage of ARISTADA have been reported. medications that could exacerbate these effects, complete fall risk assessmentsfollowing listing does not include reactions: 1) already listed in previous tables orINITIO cannot be modified.Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskineticwhen initiating antipsychotic treatment and recurrently for those patients onelsewhere in labeling, 2) for which a drug cause was remote, 3) which were so movements may develop in patients treated with antipsychotic drugs. Although thelong-term antipsychotic therapy. general as to be uninformative, 4) which were not considered to have significantExamples carvedilol, lisinopril, prazosin prevalence of the syndrome appears to be highest among the elderly, especiallyLeukopenia, Neutropenia, and Agranulocytosis: In clinical trials and/orclinical implications, or 5) which occurred at a rate equal to or less than placebo.Benzodiazepines elderly women, it is impossible to predict which patients will develop the syndrome.postmarketing experience, events of leukopenia and neutropenia have been reportedCardiacangina pectoris, tachycardia, palpitations Whether antipsychotic drug products differ in their potential to cause tardivetemporally related to antipsychotic agents. Agranulocytosis has also been reported. Gastrointestinal disordersconstipation, dry mouthClinical Impact The intensity of sedation was greater with the combination of dyskinesia is unknown. Possible risk factors for leukopenia/neutropenia include pre-existing low white bloodGeneral disordersastheniaoral aripiprazole and lorazepam as compared to that observed The risk of developing tardive dyskinesia and the likelihood that it will becomecell count (WBC)/absolute neutrophil count (ANC) and history of drug-inducedMusculoskeletalmuscular weaknesswith aripiprazole alone. The orthostatic hypotension observed 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/ Nervous system disordersdizzinesswas greater with the combination as compared to that dose of antipsychotic drugs administered to the patient increase, but the syndromeANC or drug-induced leukopenia/neutropenia, perform a complete blood count (CBC)Psychiatric disordersanxiety, suicide observed with lorazepam alone. can develop after relatively brief treatment periods at low doses, although this frequently during the first few months of therapy. In such patients, considerAdverse Reactions Reported in Clinical Trials with Oral Aripiprazole: Intervention Avoid concomitant use of ARISTADA INITIO with is uncommon. discontinuation of antipsychotics at the first sign of a clinical significant decline inThe following is a list of additional adverse reactions that have been reported inbenzodiazepines because the dosage of ARISTADA INITIO Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment isWBC in the absence of other causative factors. clinical trials with oral aripiprazole and not reported above for ARISTADA INITIO orcannot be modified. withdrawn. Antipsychotic treatment itself may suppress (or partially suppress) theMonitor patients with clinically significant neutropenia for fever or other symptoms oraripiprazole lauroxil.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. DiscontinueBlood and Lymphatic System Disorders: thrombocytopeniaExamples lorazepam 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.20-ARI-2760_HCP_NPP_VANF_JournalAd_Med-Directory-fi3.indd 3 8/21/20 8:59 AM 20-ARI-2760_HCP_NPP_VANF_JournalAd_Med-Directory-fi3.indd 4 8/21/20 8:59 AM'