ABILIFY

WARNING

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. ABILIFY (aripiprazole) is not approved for the treatment of patients with dementia-related psychosis.

DESCRIPTION

Aripiprazole is a psychotropic drug that is available as ABILIFY® (aripiprazole) tablets, ABILIFY® DISCMELT (aripiprazole) orally disintegrating tablets, ABILIFY® (aripiprazole) oral solution, and ABILIFY® (aripiprazole) injection, a solution for intramuscular injection. Aripiprazole is 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyril. The empirical formula is C23H27Cl2N3O2 and its molecular weight is 448.39. 

ABILIFY tablets are available in 2-mg, 5-mg, 10-mg, 15-mg, 20-mg, and 30-mg strengths. Inactive ingredients include cornstarch, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake.

ABILIFY DISCMELT orally disintegrating tablets are available in 10-mg and 15-mg strengths. Inactive ingredients include acesulfame potassium, aspartame, calcium silicate, croscarmellose sodium, crospovidone, crème de vanilla (natural and artificial flavors), magnesium stearate, microcrystalline cellulose, silicon dioxide, tartaric acid, and xylitol. Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake.

ABILIFY is also available as a 1-mg/mL oral solution. The inactive ingredients for this solution include disodium edetate, fructose, glycerin, dl-lactic acid, methylparaben, propylene glycol, propylparaben, sodium hydroxide, sucrose, and purified water. The oral solution is flavored with natural orange cream and other natural flavors.

ABILIFY Injection is available in single-dose vials as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL), clear, colorless, sterile, aqueous solution for intramuscular use only. Inactive ingredients for this solution include 150 mg/mL of sulfobutyletherβ-cyclodextrin (SBECD), tartaric acid, sodium hydroxide, and water for injection.

CLINICAL PHARMACOLOGY

Pharmacodynamics

Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors (Ki values of 0.34, 0.8, 1.7, and 3.4 nM, respectively), moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors (Ki values of 44, 15, 39, 57, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM). Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2Areceptor.

The mechanism of action of aripiprazole, as with other drugs having efficacy in schizophrenia, bipolar disorder, and agitation associated with schizophrenia or bipolar disorder, is unknown. However, it has been proposed that the efficacy of aripiprazole is mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2Areceptors. Actions at receptors other than D2, 5-HT1A, and 5-HT2A may explain some of the other clinical effects of aripiprazole, eg, the orthostatic hypotension observed with aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors.

Pharmacokinetics

ABILIFY activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, 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. The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties. Aripiprazole accumulation is predictable from single-dose pharmacokinetics. At steady state, the pharmacokinetics of aripiprazole are dose-proportional. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4.

Pharmacokinetic studies showed that ABILIFY DISCMELT orally disintegrating tablets are bioequivalent to ABILIFY tablets.

ORAL ADMINISTRATION

Absorption

INTRAMUSCULAR ADMINISTRATION

In two pharmacokinetic studies of aripiprazole injection administered intramuscularly to healthy subjects, the median times to the peak plasma concentrations were at 1 and 3 hours. A 5-mg intramuscular injection of aripiprazole had an absolute bioavailability of 100%. The geometric mean maximum concentration achieved after an intramuscular dose was on average 19% higher than the Cmax of the oral tablet. While the systemic exposure over 24 hours was generally similar between aripiprazole injection given intramuscularly and after oral tablet administration, the aripiprazole AUC in the first 2 hours after an intramuscular injection was 90% greater than the AUC after the same dose as a tablet. In stable patients with schizophrenia or schizoaffective disorder, the pharmacokinetics of aripiprazole after intramuscular administration were linear over a dose range of 1 to 45 mg. Although the metabolism of aripiprazole injection was not systematically evaluated, the intramuscular route of administration would not be expected to alter the metabolic pathways.

Special Populations

In general, no dosage adjustment for ABILIFY is required on the basis of a patient’s age, gender, race, smoking status, hepatic function, or renal function (see DOSAGE AND ADMINISTRATION:Dosage in Special Populations). The pharmacokinetics of aripiprazole in special populations are described below.

Drug-Drug Interactions

Clinical Studies

INDICATIONS AND USAGE

Schizophrenia

ABILIFY is indicated for the treatment of schizophrenia. The efficacy of ABILIFY in the treatment of schizophrenia was established in short-term (4- and 6-week) controlled trials of schizophrenic inpatients (see CLINICAL PHARMACOLOGY: Clinical Studies).

The efficacy of ABILIFY in maintaining stability in patients with schizophrenia who had been symptomatically stable on other antipsychotic medications for periods of 3 months or longer, were discontinued from those other medications, and were then administered ABILIFY 15 mg/day and observed for relapse during a period of up to 26 weeks was demonstrated in a placebo-controlled trial (see CLINICAL PHARMACOLOGY: Clinical Studies). The physician who elects to use ABILIFY for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Bipolar Disorder

ABILIFY is indicated for the treatment of acute manic and mixed episodes associated with Bipolar Disorder.

The efficacy of ABILIFY was established in two placebo-controlled trials (3 week) of inpatients with DSM-IV criteria for Bipolar I Disorder who were experiencing an acute manic or mixed episode with or without psychotic features (see CLINICAL PHARMACOLOGY: Clinical Studies).

The efficacy of ABILIFY in maintaining efficacy in patients with Bipolar I Disorder with a recent manic or mixed episode who had been stabilized and then maintained for at least 6 weeks, was demonstrated in a double-blind, placebo-controlled trial. Prior to entering the double-blind, randomization phase of this trial, patients were clinically stabilized and maintained their stability for 6 consecutive weeks on ABILIFY. Following this 6-week maintenance phase, patients were randomized to either placebo or ABILIFY and monitored for relapse (see CLINICAL PHARMACOLOGY: Clinical Studies). Physicians who elect to use ABILIFY for extended periods, that is, longer than 6 weeks, should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Agitation Associated with Schizophrenia or Bipolar Mania

ABILIFY Injection is indicated for the treatment of agitation associated with schizophrenia or bipolar disorder, manic or mixed. “Psychomotor agitation” is defined in DSM-IV as “excessive motor activity associated with a feeling of inner tension.” Patients experiencing agitation often manifest behaviors that interfere with their diagnosis and care (eg, threatening behaviors, escalating or urgently distressing behavior, or self-exhausting behavior), leading clinicians to the use of intramuscular antipsychotic medications to achieve immediate control of the agitation.

The efficacy of ABILIFY Injection for the treatment of agitation associated with schizophrenia or Bipolar I Disorder was established in three short-term (24-hour), placebo-controlled trials in agitated inpatients with schizophrenia or Bipolar I Disorder (manic or mixed episodes) (see CLINICAL PHARMACOLOGY: Clinical Studies).

CONTRAINDICATIONS

ABILIFY is contraindicated in patients with a known hypersensitivity to the product.

WARNINGS

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. ABILIFY (aripiprazole) is not approved for the treatment of patients with dementia-related psychosis (seeBoxed WARNING).

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including aripiprazole. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection, etc) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.

The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

Tardive Dyskinesia

A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and, thereby, may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, ABILIFY should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on ABILIFY, drug discontinuation should be considered. However, some patients may require treatment with ABILIFY despite the presence of the syndrome.

Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia-Related Psychosis

In placebo-controlled clinical studies (two flexible dose and one fixed dose study) of dementia-related psychosis, there was an increased incidence of cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, in aripiprazole-treated patients (mean age: 84 years; range: 78-88 years). In the fixed-dose study, there was a statistically significant dose response relationship for cerebrovascular adverse events in patients treated with aripiprazole. Aripiprazole is not approved for the treatment of patients with dementia-related psychosis. (See also Boxed WARNING, WARNINGS: Increased Mortality in Elderly Patients with Dementia-Related Psychosis, and PRECAUTIONS:Use in Patients with Concomitant Illness: Safety Experience in Elderly Patients with Psychosis Associated with Alzheimer’s Disease.)

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. There have been few reports of hyperglycemia in patients treated with ABILIFY. Although fewer patients have been treated with ABILIFY, it is not known if this more limited experience is the sole reason for the paucity of such reports. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies which did not include ABILIFY suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics included in these studies. Because ABILIFY was not marketed at the time these studies were performed, it is not known if ABILIFY is associated with this increased risk. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available.

Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (eg, obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

PRECAUTIONS

General

Use in Patients with Concomitant Illness

Clinical experience with ABILIFY in patients with certain concomitant systemic illnesses (see CLINICAL PHARMACOLOGY: Special Populations:Renal Impairment and Hepatic Impairment) is limited.

ABILIFY has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from premarketing clinical studies.

Information for Patients

Physicians are advised to discuss the following issues with patients for whom they prescribe ABILIFY:

Drug-Drug Interactions

Given the primary CNS effects of aripiprazole, caution should be used when ABILIFY is taken in combination with other centrally acting drugs and alcohol. Due to its α1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Labor and Delivery

The effect of aripiprazole on labor and delivery in humans is unknown.

Nursing Mothers

Aripiprazole was excreted in milk of rats during lactation. It is not known whether aripiprazole or its metabolites are excreted in human milk. It is recommended that women receiving aripiprazole should not breast-feed.

Pediatric Use

Safety and effectiveness in pediatric and adolescent patients have not been established.

Geriatric Use

Of the 8456 patients treated with oral aripiprazole in clinical trials, 1000 (12%) were ≥65 years old and 794 (9%) were ≥75 years old. The majority (87%) of the 1000 patients were diagnosed with dementia of the Alzheimer’s type.

Placebo-controlled studies of oral aripiprazole in schizophrenia or bipolar mania did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. There was no effect of age on the pharmacokinetics of a single 15-mg dose of aripiprazole. Aripiprazole clearance was decreased by 20% in elderly subjects (≥65 years) compared to younger adult subjects (18 to 64 years), but there was no detectable effect of age in the population pharmacokinetic analysis in schizophrenia patients.

Of the 749 patients treated with aripiprazole injection in clinical trials, 99 (13%) were ≥65 years old and 78 (10%) were ≥75 years old. Placebo-controlled studies of aripiprazole injection in patients with agitation associated with schizophrenia or bipolar mania did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Studies of elderly patients with psychosis associated with Alzheimer’s disease have suggested that there may be a different tolerability profile in this population compared to younger patients with schizophrenia (see Boxed WARNING, WARNINGS: Increased Mortality in Elderly Patients with Dementia-Related Psychosis;Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia -Related Psychosis, and PRECAUTIONS:Use in Patients with Concomitant Illness). The safety and efficacy of ABILIFY in the treatment of patients with psychosis associated with Alzheimer’s disease has not been established. If the prescriber elects to treat such patients with ABILIFY, vigilance should be exercised.

ADVERSE REACTIONS

Aripiprazole has been evaluated for safety in 8456 patients who participated in multiple-dose, clinical trials in schizophrenia, bipolar mania, and dementia of the Alzheimer’s type, and who had approximately 5635 patient-years of exposure to oral aripiprazole and 749 patients with exposure to aripiprazole injection. A total of 2442 patients were treated with oral aripiprazole for at least 180 days and 1667 patients treated with oral aripiprazole had at least 1 year of exposure.

The conditions and duration of treatment with aripiprazole included (in overlapping categories) double-blind, comparative and noncomparative open-label studies, inpatient and outpatient studies, fixed- and flexible-dose studies, and short- and longer-term exposure.

Adverse events during exposure were obtained by collecting volunteered adverse events, as well as results of physical examinations, vital signs, weights, laboratory analyses, and ECG. Adverse experiences were recorded by clinical investigators using terminology of their own choosing. In the tables and tabulations that follow, MedDRA dictionary terminology has been used to classify reported adverse events into a smaller number of standardized event categories, in order to provide a meaningful estimate of the proportion of individuals experiencing adverse events.

The stated frequencies of adverse events represent the proportion of individuals who experienced at least once, a treatment-emergent adverse event of the type uled. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. There was no attempt to use investigator causality assessments; ie, all reported events are included.

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatment, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse event incidence in the population studied.

ORAL ADMINISTRATION

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of Patients with Schizophrenia

The following findings are based on a pool of five placebo-controlled trials (four 4-week and one 6-week) in which oral aripiprazole was administered in doses ranging from 2 to 30 mg/day.

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of Patients with Bipolar Mania

The following findings are based on a pool of 3-week, placebo-controlled, bipolar mania trials in which oral aripiprazole was administered at doses of 15 or 30 mg/day.

INTRAMUSCULAR ADMINISTRATION

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of Patients with Agitation Associated with Schizophrenia or Bipolar Mania

The following findings are based on a pool of three placebo-controlled trials of patients with agitation associated with schizophrenia or bipolar mania in which aripiprazole injection was administered at doses of 5.25 mg to 15 mg.

Dose-Related Adverse Events

Additional Findings Observed in Clinical Trials

DRUG ABUSE AND DEPENDENCE

Controlled Substance

ABILIFY (aripiprazole) is not a controlled substance.

Abuse and Dependence

Aripiprazole has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. In physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of ABILIFY misuse or abuse (eg, development of tolerance, increases in dose, drug-seeking behavior).

OVERDOSAGE

MedDRA terminology has been used to classify the adverse events.

Human Experience

A total of 76 cases of deliberate or accidental overdosage with oral aripiprazole have been reported worldwide. These include overdoses with oral aripiprazole alone and in combination with other substances. No fatality was reported from these cases. Of the 44 cases with known outcome, 33 recovered without sequelae and one recovered with sequelae (mydriasis and feeling abnormal). The largest known acute ingestion with a known outcome involved 1080 mg of oral aripiprazole (36 times the maximum recommended daily dose) in a patient who fully recovered. Included in the 76 cases are 10 cases of deliberate or accidental overdosage in children (age 12 and younger) involving oral aripiprazole ingestions up to 195 mg with no fatalities.

Common adverse events (reported in at least 5% of all overdose cases) reported with oral aripiprazole overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia.

Management of Overdosage

No specific information is available on the treatment of overdose with aripiprazole. An electrocardiogram should be obtained in case of overdosage and, if QTc interval prolongation is present, cardiac monitoring should be instituted. Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers.

Charcoal: In the event of an overdose of ABILIFY, an early charcoal administration may be useful in partially preventing the absorption of aripiprazole. Administration of 50 g of activated charcoal, one hour after a single 15-mg oral dose of aripiprazole, decreased the mean AUC and Cmax of aripiprazole by 50%.

Hemodialysis: Although there is no information on the effect of hemodialysis in treating an overdose with aripiprazole, hemodialysis is unlikely to be useful in overdose management since aripiprazole is highly bound to plasma proteins.

DOSAGE AND ADMINISTRATION

Schizophrenia

Bipolar Disorder

Oral Solution

The oral solution can be given on a mg-per-mg basis in place of the 5-, 10-, 15-, or 20-mg tablet strengths. Solution doses can be substituted for the tablet doses on a mg-per-mg basis up to 25 mg of the tablet. Patients receiving 30-mg tablets should receive 25 mg of the solution (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Directions for Use of ABILIFY DISCMELT Orally Disintegrating Tablets

Patients should be told the following:

Do not open the buler until ready to administer. For single tablet removal, open the package and peel back the foil on the buler to expose the tablet. Do not push the tablet through the foil because this could damage the tablet. Immediately upon opening the buler, using dry hands, remove the tablet and place the entire ABILIFY DISCMELT orally disintegrating tablet on the tongue. Tablet disintegration occurs rapidly in saliva. It is recommended that ABILIFY DISCMELT be taken without liquid. However, if needed, it can be taken with liquid. Do not attempt to split the tablet.

INTRAMUSCULAR INJECTION

Agitation Associated with Schizophrenia or Bipolar Mania

ANIMAL TOXICOLOGY

Aripiprazole produced retinal degeneration in albino rats in a 26-week chronic toxicity study at a dose of 60 mg/kg and in a 2-year carcinogenicity study at doses of 40 and 60 mg/kg. The 40- and 60-mg/kg doses are 13 and 19 times the maximum recommended human dose (MRHD) based on mg/m2 and 7 to 14 times human exposure at MRHD based on AUC. Evaluation of the retinas of albino mice and of monkeys did not reveal evidence of retinal degeneration. Additional studies to further evaluate the mechanism have not been performed. The relevance of this finding to human risk is unknown.

HOW SUPPLIED

ABILIFY® (aripiprazole) Tablets have markings on one side and are available in the strengths and packages uled in Table 7.

Table 7: ABILIFY Tablet Presentations
Tablet
Strength
Tablet
Color/Shape
Tablet
Markings
Pack
Size
NDC
Code
2 mg green
modified rectangle
“A-006”
and “2”
Bottle of 30

Buler of 100

59148-006-13

59148-006-35

5 mg blue
modified rectangle
“A-007”
and “5”
Bottle of 30

Buler of 100

59148-007-13

59148-007-35

10 mg pink
modified rectangle
“A-008”
and “10”
Bottle of 30

Buler of 100

59148-008-13

59148-008-35

15 mg yellow
round
“A-009”
and “15”
Bottle of 30

Buler of 100

59148-009-13

59148-009-35

20 mg white
round
“A-010”
and “20”
Bottle of 30

Buler of 100

59148-010-13

59148-010-35

30 mg pink
round
“A-011”
and “30”
Bottle of 30

Buler of 100

59148-011-13

59148-011-35

ABILIFY® DISCMELT (aripiprazole) Orally Disintegrating Tablets are round tablets with markings on either side. ABILIFY DISCMELT is available in the strengths and packages uled in Table 8.

Table 8: ABILIFY DISCMELT Orally Disintegrating Tablet Presentations
Tablet
Strength
Tablet
Color
Tablet
Markings
Pack
Size
NDC
Code
10 mg pink (with
scattered specks)
“A” and “640”
“10”
Buler of 30 59148-640-23
15 mg yellow (with
scattered specks)
“A” and “641”
“15”
Buler of 30 59148-641-23

ABILIFY® (aripiprazole) Oral Solution (1 mg/mL) is supplied in child-resistant bottles along with a calibrated oral dosing cup. ABILIFY oral solution is available as follows:

            150-mL bottle      NDC 59148-013-15

ABILIFY® (aripiprazole) Injection for intramuscular use is available as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL) solution in clear, Type 1 glass vials as follows:

            9.75 mg/1.3 mL single-dose vial       NDC 59148-016-65

Storage

Tablets manufactured by Otsuka Pharmaceutical Co, Ltd, Tokyo, 101-8535 Japan or Bristol-Myers Squibb Company, Princeton, NJ 08543 USA

Orally disintegrating tablets, Oral solution and Injection manufactured by Bristol-Myers Squibb Company, Princeton, NJ 08543 USA

Distributed and marketed by Otsuka America Pharmaceutical, Inc, Rockville, MD 20850 USA

Marketed by Bristol-Myers Squibb Company, Princeton, NJ 08543 USA

US Patent Nos: 5,006,528; 6,977,257; and 7,115,587

© 2006, Otsuka Pharmaceutical Co, Ltd, Tokyo, 101-8535 Japan

1216978A2
191707A8
1174/11-06

Rev November 2006

THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.

Leave a Reply

Your email address will not be published. Required fields are marked *