Drugs that induce CYP3A4 (eg carbamazepine), could cause an increase in aripiprazole clearance and lower blood levels Inhibitors of CYP3A4 ( eg ketoconazole ) or CYP2D6 ( eg quinidine , fluoxetine or paroxetine ) can inhibit aripiprazole elimination and cause increased blood levels.

Increased CNS depression with ethanol

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

ARISTADA® safely and effectively. See full prescribing information for ARISTADA®. ARISTADA® (aripiprazole lauroxil) extended-release injectable suspension, for intramuscular use

Initial U.S. Approval: 2015

WARNING: RELINCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-ATED PSYCHOSIS

See full prescribing information for complete boxed warning.

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. 

• ARISTADA is not approved for the treatment of patients with dementia-related psychosis.

 RECENT MAJOR CHANGES

Dosage and Administration  06/2017

Warnings and Precautions, Falls  02/2017

Warnings and Precautions, Pathological Gambling and Other Compulsive Behaviors  07/2016

INDICATIONS AND USAGE

ARISTADA is an atypical antipsychotic indicated for the treatment of schizophrenia 

DOSAGE AND ADMINISTRATION

• To be administered by intramuscular injection in the deltoid (441 mg dose only) or gluteal (441 mg, 662 mg, 882 mg or 1064 mg) muscle by a healthcare professional 

• For patients naïve to aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with ARISTADA 

• In conjunction with the first ARISTADA injection, administer treatment with oral aripiprazole for 21 consecutive days for 441 mg, 662 mg, 882 mg, and 1064 mg 

• ARISTADA can be initiated at a dose of 441 mg, 662 mg or 882 mg administered monthly, 882 mg dose every 6 weeks, or 1064 mg dose every 2 months 

• Dosing regimen adjustments may be required for missed doses 

• Dose adjustments are required for 1) known CYP2D6 poor metabolizers and               2) for patients taking CYP3A4 inhibitors, CYP2D6 inhibitors, or CYP3A4 inducers for more than 2 weeks

 DOSAGE FORMS AND STRENGTHS

For extended-release injectable suspension: 441 mg, 662 mg, 882 mg or 1064 mg single-use pre-filled syringe 

Headache, insomnia, somnolence, dyspepsia

, constipation, pain, nausea, vomiting,

asthenia, dizziness,

abdominal pain,dry mouth,

anxiety, akathisia,

orthostatic hypotension,

hypertonia, tremor,

blurred vision,

Contraindicated in patients with known hypersensitivity to the product.

Lactation. Children

Warnings-

Ariprazole should be used with caution in patients with known cardiovascular diseases(history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerbrovascular diseases,or conditions , which predispose patients to hypotension (dehydration hypovalemia, and treatment with antihypertensive medications),

Alzheimers disease, and dementia.

Patients should be cautioned about operating hazardous machinery, including automobiles when taking aripiprazole

Special precautions-

Patients with known CV diseases or conditions which would predispose patients to hypotension.

Alzheimers disease and dementia

Pregnancy

Date of Approval   2003

Indications-

Schizophrenia

Dosage-

The recommended staring and target dose for aripiprazole is 10 or 15 mg/day administered on a once a day schedule without regard to meals.

Dosage increases should not be made before 2 weeks, the time needed to acheive steady state

At least 1 or 2 weeks and sometimes up to 4 weeks may pass before aripiprazole reaches its full efect.

 PATIENT COUNSELING INFORMATION

Advise patients to read FDA-approved patient labeling (Medication Guide).

Pathological Gambling and Other Compulsive Behaviors                                   Advise patients and their caregivers of the possibility that they may experience compulsive urges to shop, intense urges to gamble, compulsive sexual urges, binge eating and/or other compulsive urges and the inability to control these urges. In some cases, but not all, the urges were reported to have stopped when the dose was reduced or stopped 

 Neuroleptic Malignant Syndrome                                                                        Counsel patients about a potentially fatal adverse reaction referred to as NMS that has been reported in association with administration of antipsychotic drugs. Advise patients to contact a healthcare provider or report to the emergency room if they experience signs or symptoms of NMS

Tardive Dyskinesia                                                                                                    Advise patients that abnormal involuntary movements have been associated with administration of antipsychotic drugs. Counsel patients to notify their healthcare provider if they notice any movements which they cannot control in their face, tongue, or other body part 

Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight  Gain)                                                                                                           Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia and diabetes mellitus, and the need for specific monitoring, including blood glucose, lipids, and weight

 Orthostatic Hypotension-                                                                                     Educate patients about the risk of orthostatic hypotension (symptoms include feeling dizzy or lightheaded upon standing), particularly at the time of initiating treatment, re-initiating treatment, or increasing the dose

Falls-                                                                                                                          Advise patients and their caregivers of the possibility that they may experience somnolence, postural hypotension, or motor and sensory instability, which may lead to the risk of falls, particularly in patients with diseases, conditions, or medications that could exacerbate these effects

 Leukopenia/ Neutropenia-                                                                                       Advise patients with a pre-existing low WBC count or a history of drug-induced leucopenia/neutropenia that they should have their CBC monitored while receiving ARISTADA

 Interference with Cognitive and Motor Performance-                                       Because ARISTADA may have the potential to impair judgment, thinking or motor skills, instruct patients to be cautious about operating hazardous machinery, including automobiles, until they are reasonably certain that ARISTADA therapy does not affect them adversely

 Heat Exposure and Dehydration -                                                                          Advise patients regarding appropriate care in avoiding overheating and dehydration

 Concomitant Medication -                                                                                       Advise patients to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions

Pregnancy -                                                                                                               Advise patients that ARISTADA may cause extrapyramidal and/or withdrawal symptoms in a neonate and to notify their healthcare provider with a known or suspected pregnancy.

Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA during pregnancy

Manufactured and marketed by:

Alkermes, Inc. 852 Winter Street Waltham, MA 02451-1420 ©2016 Alkermes, Inc. All rights reserved. ALKERMES® is a registered trademark of Alkermes, Inc. and ARISTADA® is a registered trademark used by Alkermes, Inc. under license. Printed in U.S.A. Rev: June 2017

Pharmacololgy:

The mechanism of action of aripiprazole is mediated through a combination of partial agonist activity at D2 and 5-HT14 receptors and antagonist activity at 5-HT24 receptors. Its activity is primarily due to the parent drug aripiprazole, and to a lesser extent, dehydro-aripiprazole ,which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma.

Pharmacokinetics:

Ariprazole is well tolerated with peak plasma concentrations occuring within 3 to 5 hours. The steady-state volume of distribution of aripiprazole following intervenous administration is high (404 L or 4.9 L/kg), including extravascular distribution.

At steady therapeutic concentrations, aripiprazole and its major metabolite are greater than 90% bound to the mean elimination half-lives are about 75 hours and 94 hours for ariprazole and dehydro-aripiprazole , respy.

Steady-state concentrations are attained within 14 days of dosing for both active moieties

Can be administered without regard to meals.

 USE IN SPECIFIC POPULATIONS

1.Pregnancy Teratogenic Effects: Pregnancy Category C

There are no adequate and well-controlled studies of BROVANA Inhalation Solution in pregnant women.

Because animal reproduction studies are not always predictive of human response, BROVANA Inhalation Solution should be used during pregnancy, only if the potential benefit justifies the potential risk to the fetus. 

2. Labor and Delivery                                                                                                     There are no human studies that have investigated the effects of BROVANA Inhalation Solution on preterm labor or labor at term. Because beta-agonists may potentially interfere with uterine contractility, BROVANA                                                           Inhalation Solution should be used during labor and delivery only if the potential benefit justifies the potential risk.

3. Nursing Mothers                                                                                                           . It is not known whether arformoterol is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when BROVANA Inhalation Solution is administered to a nursing woman.

4.Pediatric-                                                                                                                     Use BROVANA Inhalation Solution is approved for use in the long-term maintenance treatment of bronchoconstriction associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. This disease does not occur in children.

The safety and efficacy of BROVANA Inhalation Solution in pediatric patients have not been established.

5. Geriatric Use-                                                                                                               Of the 873 patients who received BROVANA Inhalation Solution in two placebocontrolled clinical studies in adults with COPD, 391 (45%) were 65 years of age or older while 96 (11%) were 75 years of age or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

6. Hepatic Impairment                                                                                           BROVANA Inhalation Solution should be used cautiously in patients with hepatic impairment due to increased systemic exposure in these patients 

7. Renal Impairment-                                                                                                     The systemic exposure to arformoterol was similar to renally impaired patients compared with demographically matched healthy control subjects 

 OVERDOSAGE                                                                                                              The expected signs and symptoms associated with overdosage of BROVANA (arformoterol tartrate) Inhalation Solution are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms