b'IMPORTANT SAFETY INFORMATION FOR ARISTADA INITIO AND ARISTADA (continued)Contraindication: Known hypersensitivity reaction to aripiprazole.antipsychotics. Monitor complete blood count in patients with Reactions have ranged from pruritus/urticaria to anaphylaxis.pre-existing low white blood cell count (WBC)/absolute neutrophil Cerebrovascular Adverse Reactions, Including Stroke: Increasedcount or history of drug-induced leukopenia/neutropenia. Discontinue incidence of cerebrovascular adverse reactions (e.g., stroke, transientARISTADA INITIO and/or ARISTADA at the first sign of a clinically ischemic attack), including fatalities, have been reported in placebo- significant decline in WBC and in severely neutropenic patients. controlled trials of elderly patients with dementia-related psychosisSeizures: Use with caution in patients with a history of seizures or treated with risperidone, aripiprazole, and olanzapine. ARISTADAwith conditions that lower the seizure threshold. INITIO and ARISTADA are not approved for the treatment of patientsPotential for Cognitive and Motor Impairment: ARISTADA INITIO and with dementia-related psychosis.ARISTADA may impair judgment, thinking, or motor skills. Patients Potential for Dosing and Medication Errors: Medication errors,should be cautioned about operating hazardous machinery, including including substitution and dispensing errors, between ARISTADAautomobiles, until they are certain therapy with ARISTADA INITIO INITIO and ARISTADA could occur. ARISTADA INITIO is intended forand/or ARISTADA does not affect them adversely. single administration in contrast to ARISTADA which is administeredBody Temperature Regulation: Disruption of the bodys ability to monthly, every 6 weeks, or every 8 weeks. Do not substitute ARISTADAreduce core body temperature has been attributed to antipsychotic INITIO for ARISTADA because of differing pharmacokinetic profiles. agents. Advise patients regarding appropriate care in avoiding Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptomoverheating and dehydration. Appropriate care is advised for patients complex may occur with administration of antipsychotic drugs,who may exercise strenuously, may be exposed to extreme heat, including ARISTADA INITIO and ARISTADA. Clinical manifestations ofreceive concomitant medication with anticholinergic activity, or NMS include hyperpyrexia, muscle rigidity, altered mental status, andare subject to dehydration.evidence of autonomic instability (irregular pulse or blood pressure,Dysphagia: Esophageal dysmotility and aspiration have been tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signsassociated with antipsychotic drug use; use caution in patients at may include elevated creatine phosphokinase, myoglobinuriarisk for aspiration pneumonia. (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugsConcomitant Medication: ARISTADA INITIO is only available at a single and other drugs not essential to concurrent therapy; 2) intensivestrength as a single-dose pre-filled syringe, so dosage adjustments are symptomatic treatment and medical monitoring; and 3) treatmentnot possible. Avoid use in patients who are known CYP2D6 poor of any concomitant serious medical problems for which specificmetabolizers or taking strong CYP3A4 inhibitors, strong CYP2D6 treatments are available.inhibitors, or strong CYP3A4 inducers, antihypertensive drugs or Tardive Dyskinesia (TD): The risk of developing TD (a syndrome ofbenzodiazepines. abnormal, involuntary movements) and the potential for it to becomeDepending on the ARISTADA dose, adjustments may be recommended irreversible are believed to increase as the duration of treatment andif patients are 1) known as CYP2D6 poor metabolizers and/or 2) taking the total cumulative dose of antipsychotic increase. The syndrome canstrong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 develop, although much less commonly, after relatively brief treatmentinducers for greater than 2 weeks. Avoid use of ARISTADA 662 mg, periods at low doses. Prescribing antipsychotics should be consistent882 mg, or 1064 mg for patients taking both strong CYP3A4 inhibitors with the need to minimize TD. Discontinue ARISTADA if clinicallyand strong CYP2D6 inhibitors. (See Table 4 in the ARISTADA full appropriate. TD may remit, partially or completely, if antipsychoticPrescribing Information.)treatment is withdrawn.Commonly Observed Adverse Reactions: In pharmacokinetic studies Metabolic Changes: Atypical antipsychotic drugs have beenthe safety profile of ARISTADA INITIO was generally consistent with associated with metabolic changes that include:that observed for ARISTADA. The most common adverse reaction Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases(5% incidence and at least twice the rate of placebo reported extreme and associated with ketoacidosis, coma, or death, hasby patients treated with ARISTADA 441 mg and 882 mg monthly) been reported in patients treated with atypical antipsychotics.was akathisia.There have been reports of hyperglycemia in patients treated withInjection-Site Reactions: In pharmacokinetic studies evaluating oral aripiprazole. Patients with diabetes should be regularlyARISTADA INITIO, the incidences of injection-site reactions with monitored for worsening of glucose control; those with risk factorsARISTADA INITIO were similar to the incidence observed with for diabetes should undergo baseline and periodic fasting bloodARISTADA. Injection-site reactions were reported by 4%, 5%, and 2% glucose testing. Any patient treated with atypical antipsychoticsof patients treated with 441 mg ARISTADA (monthly), 882 mg should be monitored for symptoms of hyperglycemia, includingARISTADA (monthly), and placebo, respectively. Most of these were polydipsia, polyuria, polyphagia, and weakness. Patients whoinjection-site pain and associated with the first injection and decreased develop symptoms of hyperglycemia should also undergo fastingwith each subsequent injection. Other injection-site reactions blood glucose testing. In some cases, hyperglycemia has resolved(induration, swelling, and redness) occurred at less than 1%. when the atypical antipsychotic was discontinued; however, someDystonia: Symptoms of dystonia, prolonged abnormal contractions patients require continuation of antidiabetic treatment despiteof muscle groups, may occur in susceptible individuals during the first discontinuation of the suspect drug. days of treatment and at low doses. Dyslipidemia: Undesirable alterations in lipids have been observedPregnancy/Nursing: May cause extrapyramidal and/or withdrawal in patients treated with atypical antipsychotics.symptoms in neonates with third trimester exposure. Advise patients Weight Gain: Weight gain has been observed with atypicalto notify their healthcare provider of a known or suspected pregnancy. antipsychotic use. Clinical monitoring of weight is recommended. Inform patients that there is a pregnancy exposure registry that Pathological Gambling and Other Compulsive Behaviors: Compulsivemonitors pregnancy outcomes in women exposed to ARISTADA INITIO or uncontrollable urges to gamble have been reported with use ofand/or ARISTADA during pregnancy. Aripiprazole is present in human aripiprazole. Other compulsive urges less frequently reported includebreast milk. The benefits of breastfeeding should be considered along sexual urges, shopping, binge eating and other impulsive orwith the mothers clinical need for ARISTADA INITIO and/or ARISTADA compulsive behaviors which may result in harm for the patient andand any potential adverse effects on the infant from ARISTADA INITIO others if not recognized. Closely monitor patients and consider doseand/or ARISTADA or from the underlying maternal condition. reduction or stopping aripiprazole if a patient develops such urges.Orthostatic Hypotension: Aripiprazole may cause orthostaticPlease see the Brief Summaries of full Prescribing hypotension which can be associated with dizziness, lightheadedness,Information, including Boxed Warning, for ARISTADA and tachycardia. Monitor heart rate and blood pressure, and warnINITIO and ARISTADA on the following pages. patients with known cardiovascular or cerebrovascular disease and risk of dehydration and syncope. References: 1. US Department of Veterans Affairs website. Pharmacy benefits Falls: Antipsychotics including ARISTADA INITIO and ARISTADAmanagement services. https://www.pbm.va.gov/nationalformulary.asp. Updated may cause somnolence, postural hypotension or motor and sensoryAugust 5, 2019. Accessed August 23, 2019. 2. ARISTADA. Package insert. Alkermes, instability which may lead to falls and subsequent injury. UponInc; 2020. 3. ARISTADA INITIO. Package insert. Alkermes, Inc; 2020. initiating treatment and recurrently, complete fall risk assessments as appropriate.Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia and agranulocytosis have been reported with ALKERMES is a registered trademark of Alkermes, Inc. ARISTADA and logo, and ARISTADA INITIO, are registered trademarks of Alkermes Pharma Ireland Limited, used by Alkermes, Inc., under license.2020 Alkermes, Inc.All rights reserved.ARI-004278Printed in the U.S.A.July 202020-ARI-2760_HCP_NPP_VANF_JournalAd_Med-Directory-fi3.indd 2 8/21/20 8:59 AM'