increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.vilanterol/fluticasone furoate inhaledMonitor Closely (1)aripiprazole and vilanterol/fluticasone furoate inhaled both increase QTc interval. Use Caution/Monitor.vilazodoneMonitor Closely (1)vilazodone, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).voclosporinMonitor Closely (1)aripiprazole and voclosporin both increase QTc interval. Use Caution/Monitor.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)aripiprazole and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.vorinostatSerious - Use Alternative (1)aripiprazole and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xylometazolineMonitor Closely (1)aripiprazole increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)aripiprazole increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ziconotideMonitor Closely (1)aripiprazole and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (2)aripiprazole and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. aripiprazole and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)aripiprazole and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (1)zolmitriptan, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).zotepineMonitor Closely (2)aripiprazole and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. aripiprazole and zotepine both increase sedation. Use Caution/Monitor. >10% Weight gain (8-30%) Headache (27%) Agitation (19%) Insomnia (18%) Anxiety (17%) Nausea and vomiting (11-15%) Akathisia (10-13%) Lightheadedness (11%) Constipation (10-11%) 1-10% Dizziness (10%) Dyspepsia (9%) Somnolence (5-8%) Fatigue (6%) Restlessness (6%) Tremor (6%) Dry mouth/xerostomia (5%) Extrapyramidal disorder (5%) Orthostatic hypotension (1-5%) Musculoskeletal stiffness (4%) Abdominal discomfort (3%) Blurred vision (3%) Cough (3%) Pain (3%) Myalgia (2%) Rash Rhinitis Aripiprazole lauroxil Extrapyramidal symptoms (5-7%) Injection site reactions (4%) Pain at injection site (<2%) Increased weight (<2%) Increased creatinine phosphokinase (<2%) Akathisia (<2%) Headache (<2%) Insomnia (<2%) Restlessness (<2%) <1% Altered mental status Autonomic instability Dysphagia Hyperpyrexia Muscle rigidity Neuroleptic malignant syndrome (NMS) Seizure Tardive dyskinesia Aripiprazole lauroxil Cardiac – Angina pectoris, tachycardia, palpitations Gastrointestinal disorders – Constipation, dry mouth General disorders – Asthenia Musculoskeletal – Muscular weakness Nervous system disorders – Dizziness Psychiatric disorders – Anxiety, suicide Postmarketing Reports Pathological gambling Hiccups Falls Oculogyric crisis, and drug reaction with eosinophilia and systemic symptoms (DRESS) Aripiprazole lauroxil Occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups and blood glucose fluctuation Black Box Warnings Dementia-related Psychosis Not approved for dementia-related psychosis; patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; deaths reported in trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature Suicidal thoughts and behaviors Aripiprazole PO and Abilify injection only Antidepressants increased risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses, as shown in short-term studies; monitor for worsening and emergence of suicidal thoughts and behaviors Contraindications Hypersensitivity to aripiprazole Cautions Risk of extrapyramidal symptoms (EPS) (eg, pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia; monitor Tardive dyskinesia may occur; may consider discontinuation of therapy if clinically indicated Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity and/or autonomic instability May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy Use caution in patients with known cardiovascular disease, cerebrovascular disease, or predisposition to hypotension; may increase incidence of cerebrovascular adverse reactions (eg, stroke, transient ischemic attack, including fatalities) Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope Use caution in patients with Parkinson disease; may aggravate motor disturbances May increase risk of suicidal tendencies in children and adolescents (see Black Box Warnings) FDA warning regarding off-label use for dementia in elderly (see Black Box Warnings) Patients may act on dangerous impulses (eg, gambling) Monitor for orthostatic hypotension May cause seizures or convulsions; use cautiously in patients with history of seizures or with conditions that lower the seizure threshold May cause CNS depression, which may impair physical or mental abilities; use caution when operating heavy machinery Use caution in patients at risk of pneumonia; antipsychotic therapy has been associated with esophageal dysmotility and aspiration Impairment of core body temperature regulation possible; use caution in dehydration, heat exposure, strenuous exercise, and concomitant medication possessing anticholinergic effects Potential dosing and medication errors Aristada and Aristada Initio Medication errors (eg, substitution, dispensing errors) between Aristada and Aristada Initio may occur Aristada Initio is intended only for single administration Do not substitute Aristada Initio for Aristada because of differing pharmacokinetic profiles Leukopenia, neutropenia, and agranulocytosis Leukopenia/neutropenia and agranulocytosis reported; possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and history of drug-induced leukopenia/neutropenia If patient has history of clinically significant low WBC count or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of clinically significant WBC decline <1000/mcL in absence of other causative factors, and continue monitoring WBC count until recovery Metabolic changes Atypical antipsychotics have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk, including dyslipidemia and body weight gain Increased risk of hyperglycemia and diabetes; in some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death; monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness; monitor glucose regularly in patients with and at risk for diabetes Significant weight gain reported with therapy; monitor waist circumference and BMI Drug interaction overview See Dosage Modifications Strong CYP3A4 and CYP2D6 inhibitors: Coadministration of oral aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of oral aripiprazole alone Strong CYP3A4 inducers: Coadministration of oral aripiprazole with strong CYP3A4 inducers decreased the exposure of aripiprazole compared to the use of oral aripiprazole alone Antihypertensives: Due to its alpha adrenergic antagonism, aripiprazole may potentiate the effects of certain antihypertensive agents; avoid concomitant use with Aristada Initio Benzodiazepines: Orthostatic hypotension and the intensity of sedation was greater with the combination of oral aripiprazole and lorazepam as compared to that observed with aripiprazole alone; avoid concomitant use with Aristada Initio Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA during pregnancy; For more information, contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ Neonates exposed to antipsychotic drugs during third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery; limited published data on aripiprazole use in pregnant women are not sufficient to inform any drug-associated risks for birth defects or miscarriage; no teratogenicity observed in animal reproductive studies with intramuscular administration of drug Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder reported in neonates exposed to antipsychotic drugs during the third trimester of pregnancy; symptoms have varied in severity; monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately; some neonates recover within hours or days without specific treatment; others required prolonged hospitalization Lactation Aripiprazole is present in human breast milk; there are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole; development and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from treatment or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Atypical antipsychotic; partial agonist at dopamine D2 and serotonin type 1 (5-HT1A) receptors; antagonist at serotonin type 2 (5-HT2A) receptor; also has alpha-blocking activity Aristada Initio Prodrug of aripiprazole and its activity is primarily due to aripiprazole, and to a lesser extent dehydro-aripiprazole (major metabolite of aripiprazole), which has been shown to have affinities for D2 receptors similar to aripiprazole and represents 30-40% of the aripiprazole exposure in plasma Absorption Bioavailability: 87% (tablet); 100% (IM) Peak plasma time: 1-3 hr (IR); 5-7 hr (ER); 3-5 hr (tablet); ~27 days (Aristada Initio) Distribution Protein bound: 99% Vd: 404 L (aripiprazole IV); 268 L (Aristada Initio) Metabolism Metabolized by CYP2D6 and CYP3A4 Metabolites: Dehydroaripiprazole (40%) Elimination Half-life: 75 hr (parent drug); 94 hr (metabolite); 30-47 days (IM); 146 hr (poor metabolizers) Half-life, Aristada Initio: 15-18 days Excretion: Feces (55%), urine (25%) Oral Administration Oral solution can be substituted for tablets on a mg-per-mg basis up to the 25 mg dose level; patient receiving 30 mg tablets should receive 25 mg of solution Tablet May take with or without food Swallow tablet whole; do not divide, crush, or chew ODT Dosing for orally disintegrating tablets (ODT) is the same as for the oral tablets May take with or without food Do not open the blister until ready to take the ODT Remove 1 ODT by opening the package and peeling back the foil on the blister to expose the tablet Do not push the tablet through the foil because this could damage the tablet Immediately upon opening the blister, using dry hands, remove the tablet and place the entire ODT on tongue Tablet disintegration occurs rapidly in saliva; recommended to take without liquid, however, if needed, it can be taken with liquid Do not attempt to split the tablet Abilify MyCite May take with or without food Swallow tablet whole; do not divide, crush, or chew MyCite Patch Apply the MyCite patch only when instructed by the app to the left side of the body just above the lower edge of the rib cage Do not place the patch in areas where the skin is scraped, cracked, inflamed, or irritated, or in a location that overlaps the area of the most recently removed patch Instruct patients to keep the patch on when showering, swimming, or exercising Change patch weekly or sooner as needed The app will prompt patient to change the patch and will direct patient to apply and remove the patch correctly Patients undergoing an MRI need to remove their patch and replace with a new one as soon as possible If there is skin irritation, instruct patients to remove the patch IM Preparation (Abilify Maintena) Do no substitute IM long-acting depot suspension formulations Vial Reconstitute lyophilized power with sterile water for injection (SWI); discard any unused portion of diluent 400 mg/vial: 1.9 mL SWI 300 mg/vial: 1.5 mL SWI Final concentration for either vial is 200 mg/mL following reconstitution Slowly