Aripiprazole

Brand Name: Abilify

Click here for the most updated version of Aripiprazole (Abilify)

Description

ABILIFY (aripiprazole) is a psychotropic drug (antipsychotic medication) used in the treatment of schizophrenia that is available as tablets for oral administration.

(Note: Below, you'll find additional information on Abilify (aripiprazole) for your convenience. This is not part of the pharmacology section. These are simply links to more info on this schizophrenia medication.)

FIND OUT MORE ABOUT ABILIFY
Are you caring for someone with schizophrenia? Get help. Get information about schizophrenia and treatment, including helpful tools and caregiver support. Click here.

Pharmacology

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-HT2A receptor.

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

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.

Aripiprazole is well absorbed, with peak plasma concentrations occurring within 3 to 5 hours; the absolute oral bioavailability of the tablet formulation is 87%. ABILIFY can be administered with or without food. Administration of a 15-mg ABILIFY tablet with a standard high-fat meal did not significantly affect the Cmax or AUC of aripiprazole or its active metabolite, dehydro-aripiprazole, but delayed Tmax by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole.

The steady-state volume of distribution of aripiprazole following intravenous administration is high (404 L or 4.9 L/kg), indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole and its major metabolite are greater than 99% bound to serum proteins, primarily to albumin. In healthy human volunteers administered 0.5 to 30 mg/day aripiprazole for 14 days, there was dose-dependent D2-receptor occupancy indicating brain penetration of aripiprazole in humans.

AT LEAST 1 TO 2 WEEKS, and sometimes up to 4 weeks, may pass before Abilify reaches its full effect.

Indications and Usage

ABILIFY (aripiprazole) 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 long-term efficacy of aripipazole in the treatment of schizophrenia has not been established. 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.

Contraindications

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

Warnings

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. Two possible cases of NMS occurred during aripiprazole treatment in the premarketing 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 (e.g., 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.

Precautions

Orthostatic Hypotension: Aripiprazole may be associated with orthostatic hypotension, perhaps due to its á1-adrenergic receptor antagonism. The incidence of orthostatic hypotension associated events from five short-term, placebo-controlled trials in schizophrenia (n=926) on ABILIFY (aripiprazole) included: orthostatic hypotension (placebo 1%, aripiprazole 1.9%); orthostatic lightheadedness (placebo 1%, aripiprazole 0.9%), and syncope (placebo 1%, aripiprazole 0.6%). The incidence of a significant orthostatic change in blood pressure (defined as a decrease of at least 30 mmHg in systolic blood pressure when changing from a supine to standing position) for aripiprazole was not statistically different from placebo (14% among aripiprazole-treated patients and 12% among placebo-treated patients).

Aripiprazole should be used with caution in patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease, or conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications).

Seizure: Seizures occurred in 0.1% (1/926) of aripiprazole-treated patients in short-term, placebo-controlled trials. As with other antipsychotic drugs, aripiprazole should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold, e.g., Alzheimer's dementia. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

Potential for Cognitive and Motor Impairment: In short-term, placebo-controlled trials, somnolence was reported in 11% of patients on ABILIFY compared to 8% of patients on placebo; somnolence led to discontinuation in 0.1% (1/926) of patients on ABILIFY in short-term, placebo-controlled trials. Despite the relatively modest increased incidence of somnolence compared to placebo, ABILIFY, like other antipsychotics, may have the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that therapy with ABILIFY does not affect them adversely.

Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing aripiprazole for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer’s dementia. Aripiprazole and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia (see PRECAUTIONS: Use in Patients with Concomitant Illness).

Suicide: The possibility of a suicide attempt is inherent in psychotic illnesses, and close supervision of high-risk patients should accompany drug therapy. Prescriptions for ABILIFY should be written for the smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose.

Use in Patients with Concomitant Illness:
Safety Experience in Elderly Patients with Psychosis Associated with Alzheimer’s Disease:
In a flexible dose (2 to 15 mg/day), 10-week, placebo-controlled study of aripiprazole in elderly patients (mean age: 81.5 years; range: 56 to 95 years) with psychosis associated with Alzheimer’s dementia, 4 of 105 patients (3.8%) who received ABILIFY died compared to no deaths among 102 patients who received placebo during or within 30 days after termination of the double-blind portion of the study. Three of the patients (age 92, 91, and 87 years) died following the discontinuation of ABILIFY in the double-blind phase of the study (causes of death were pneumonia, heart failure, and shock). The fourth patient (age 78 years) died following hip surgery while in the double-blind portion of the study. The treatment-emergent adverse events that were reported at an incidence of=5% and having a greater incidence than placebo in this study were accidental injury, somnolence, and bronchitis. Eight percent of the ABILIFY-treated patients reported somnolence compared to one percent of placebo patients. In a small pilot, open-label, ascending-dose cohort study (n=30) in elderly patients with dementia, ABILIFY was associated in a dose-related fashion with somnolence.

The safety and efficacy of ABILIFY in the treatment of patients with psychosis associated with dementia have not been established. If the prescriber elects to treat such patients with ABILIFY, vigilance should be exercised, particularly for the emergence of difficulty swallowing or excessive somnolence, which could predispose to accidental injury or aspiration.

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.

Usage in Children: Do not give to children under 18 years old.

Pregnancy & Nursing: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with ABILIFY.

Patients should be advised not to breast-feed an infant if they are taking ABILIFY.

Interference with Cognitive or Motor Performance: Because aripiprazole may have the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that aripiprazole therapy does not affect them adversely.

Heat Exposure and Dehydration: Patients should be advised regarding appropriate care in avoiding overheating and dehydration.

Alcohol:
Patients should be advised to avoid alcohol while taking ABILIFY.

Drug Interactions

Concomitant Medication
Patients should be advised 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.

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 á1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.

Potential for Other Drugs to Affect ABILIFY:
Aripiprazole is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2E1 enzymes. Aripiprazole also does not undergo direct glucuronidation. This suggests that an interaction of aripiprazole with inhibitors or inducers of these enzymes, or other factors, like smoking, is unlikely.

Both CYP3A4 and CYP2D6 are responsible for aripiprazole metabolism. Agents that induce CYP3A4 (e.g., carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (e.g., ketoconazole) or CYP2D6 (e.g., quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels.

Ketoconazole: Coadministration of ketoconazole (200 mg/day for 14 days) with a 15-mg single dose of aripiprazole increased the AUC of aripiprazole and its active metabolite by 63% and 77%, respectively. The effect of a higher ketoconazole dose (400 mg/day) has not been studied. When concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be reduced to one-half of its normal dose. Other strong inhibitors of CYP3A4 (itraconazole) would be expected to have similar effects and need similar dose reductions; weaker inhibitors (erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.

Quinidine: Coadministration of a 10-mg single dose of aripiprazole with quinidine (166 mg/day for 13 days), a potent inhibitor of CYP2D6, increased the AUC of aripiprazole by 112% but decreased the AUC of its active metabolite, dehydro-aripiprazole, by 35%. Aripiprazole dose should be reduced to one-half of its normal dose when concomitant administration of quinidine with aripiprazole occurs. Other significant inhibitors of CYP2D6, such as fluoxetine or paroxetine, would be expected to have similar effects and, therefore, should be accompanied by similar dose reductions. When the CYP2D6 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.

Carbamazepine: Coadministration of carbamazepine (200 mg BID), a potent CYP3A4 inducer, with aripiprazole (30 mg QD) resulted in an approximate 70% decrease in Cmax and AUC values of both aripiprazole and its active metabolite, dehydro-aripiprazole. When carbamazepine is added to aripiprazole therapy, aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. When carbamazepine is withdrawn from the combination therapy, aripiprazole dose should then be reduced.

No clinically significant effect of famotidine, valproate, or lithium was seen on the pharmacokinetics of aripiprazole (see CLINICAL PHARMACOLOGY: Drug-Drug Interactions).

Potential for ABILIFY to Affect Other Drugs:
Aripiprazole is unlikely to cause clinically important pharmacokinetic interactions with drugs metabolized by cytochrome P450 enzymes. In in vivo studies, 10- to 30-mg/day doses of aripiprazole had no significant effect on metabolism by CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin), and CYP3A4 (dextromethorphan) substrates. Additionally, aripiprazole and dehydro-aripiprazole did not show potential for altering CYP1A2- mediated metabolism in vitro (see CLINICAL PHARMACOLOGY: Drug-Drug Interactions).

Alcohol: There was no significant difference between aripiprazole coadministered with ethanol and placebo coadministered with ethanol on performance of gross motor skills or stimulus response in healthy subjects. As with most psychoactive medications, patients should be advised to avoid alcohol while taking ABILIFY.

BEFORE USING THIS MEDICINE: INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. Inform your doctor of any other medical conditions, allergies, pregnancy, or breast-feeding.

Adverse Reactions

Aripiprazole has been evaluated for safety in 5592 patients who participated in multipledose, premarketing trials in schizophrenia, bipolar mania, and dementia of the Alzheimer’s type, and who had approximately 3639 patient-years of exposure. A total of 1887 aripiprazole-treated patients were treated for at least 180 days and 1251 aripiprazole-treated patients had at least 1 year of exposure.

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.

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 aripiprazole was administered in doses ranging from 2 to 30 mg/day.

Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo- Controlled Trials
Overall, there was no difference in the incidence of discontinuation due to adverse events between aripiprazole-treated (7%) and placebo-treated (9%) patients. The types of adverse events that led to discontinuation were similar between the aripiprazole and placebotreated patients.

Adverse Events Occurring at an Incidence of 2% or More Among Aripiprazole-Treated Patients and Greater than Placebo in Short-Term Placebo-Controlled Trials
Table 1 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy (up to 6 weeks), including only those events that occurred in 2% or more of patients treated with aripiprazole (doses=2 mg/day) and for which the incidence in patients treated with aripiprazole was greater than the incidence in patients treated with placebo.

Table 1: Treatment-Emergent Adverse Events in Short-Term, Placebo-Controlled Trials
	Percentage of Patients Reporting Event(a)
Body System Adverse Event	Aripiprazole (n=926)	Placebo (n=413)
Body as a Whole Headache Asthenia Fever Digestive System Nausea Vomiting Constipation Nervous System Anxiety Insomnia Lightheadedness Somnolence Akathisia Tremor Respiratory System Rhinitis Coughing Skin and Appendages Rash Special Senses Blurred vision	32 7 2 14 12 10 25 24 11 11 10 3 4 3 Skin and Appendages 6 Special Senses 3	25 5 1 10 7 8 24 19 7 8 7 2 3 2 Skin and Appendages 5 Special Senses 1
(a) Events reported by at least 2% of patients treated with aripiprazole, except the following events, which had an incidence equal to or less than placebo: abdominal pain, accidental injury, back pain, dental pain, dyspepsia, diarrhea, dry mouth, myalgia, agitation, psychosis, extrapyramidal syndrome, hypertonia, pharyngitis, upper respiratory tract infection, dysmenorrhea, vaginitis.

An examination of population subgroups did not reveal any clear evidence of differential adverse event incidence on the basis of age, gender, or race.

Dose-Related Adverse Events: Dose response relationships for the incidence of treatment-emergent adverse events were evaluated from four trials comparing various fixed doses (2, 10, 15, 20, and 30 mg/day) of aripiprazole to placebo. This analysis, stratified by study, indicated that the only adverse event to have a possible dose response relationship, and then most prominent only with 30 mg, was somnolence (placebo, 7.7%; 15 mg, 8.7%; 20 mg, 7.5%; 30 mg, 15.3%).

Extrapyramidal Symptoms: In the short-term, placebo-controlled trials the incidence of reported EPS for aripiprazoletreated patients was 6% vs. 6% for placebo. Objectively collected data from those trials on the Simpson Angus Rating Scale (for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of Involuntary Movement Scales (for dyskinesias) also did not show a difference between aripiprazole and placebo, with the exception of the Barnes Akathisia Scale (aripiprazole, 0.08; placebo, -0.05).

Weight Gain: In short-term trials, there was a slight difference in mean weight gain between aripiprazole and placebo patients (+0.7 kg vs. -0.05 kg, respectively), and also a difference in the proportion of patients meeting a weight gain criterion of >7% of body weight [aripiprazole (8%) compared to placebo (3%)]. The following table provides the weight change results from a long-term (52-week) study of aripiprazole, both mean change from baseline and proportions of patients meeting a weight gain criterion of >7% of body weight relative to baseline, categorized by BMI at baseline:

Table 2: Weight Change Results Categorized by BMI at Baseline
	BMI<23	BMI 23-27	BMI>27
Mean change from baseline (kg)	2.6	1.4	-1.2
% with >7% increase BW	30%	19%	8

ECG Changes: Between group comparisons for pooled, placebo-controlled trials revealed no significant differences between aripiprazole and placebo in the proportion of patients experiencing potentially important changes in ECG parameters; in fact, within the dose range of 10 to 30 mg/day, aripiprazole tended to slightly shorten the QTc interval. Aripiprazole was associated with a median increase in heart rate of 4 beats per minute compared to a 1 beat per minute increase among placebo patients.

Other Adverse Events: Events are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring in at least 1/100 patients (only those not already listed in the tabulated results from placebocontrolled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

Body as a Whole:
Frequent – flu syndrome, peripheral edema, chest pain, neck pain, neck rigidy;
Infrequent – pelvic pain, suicide attempt, face edema, malaise, photosensitivity, arm rigidity, jaw pain, chills, bloating, jaw tightness, enlarged abdomen, chest tightness;
Rare – throat pain, back tightness, head heaviness, moniliasis, throat tightness, leg rigidity, neck tightness, Mendelson’s syndrome, heat stroke.

Cardiovascular System:
Frequent – hypertension, tachycardia, hypotension, bradycardia;
Infrequent – palpitation, hemorrhage, myocardial infarction, prolonged QT interval, cardiac arrest, atrial fibrillation, heart failure, AV block, myocardial ischemia, phlebitis, deep vein thrombosis, angina pectoris, extrasystoles;
Rare – vasovagal reaction, cardiomegaly, atrial flutter, thrombophlebitis.

Digestive System:
Frequent – anorexia, nausea and vomiting;
Infrequent – increased appetitie, gastroenteritis, dysphagia, flatulence, gastritis, tooth caries, gingivitis, hemorrhoids, gastroesophageal reflux, gastrointestinal hemorrhage, periodontal abscess, tongue edema, fecal incontinence, colitis, rectal hemorrhage, stomatitis, mouth ulcer, cholecystitis, fecal impaction, oral moniliasis, cholelithiasis, eructation, intestinal obstruction, peptic ulcer;
Rare – esophagitis, gum hemorrhage, glossitis, hematemesis, melena, duodenal ulcer, cheilitis, hepatitis, hepatomegaly, pancreatitis, intestinal perforation.

Endocrine System:
Infrequent – hypothroidism;
Rare – goiter, hyperthyroidism.

Hemic/Lymphatic System:
Frequent – ecchymosis, anemia;
Infrequent – hypochromic anemia, leukopenia, leukocytosis, lymphadenopathy, thrombocytopenia;
Rare – eosinophilia, thrombocythemia, macrocytic anemia.

Metabolic and Nutritional Disorders:
Frequent – weight loss, creatine phosphokinase increased;
Infrequent – dehydration, edema, hypercholesteremia, hyperglycemia, hypokalemia, diabetes mellitus, SGPT increased, hyperlipemia, hypoglycemia, thirst, BUN increased, hyponatremia, SGOT increased, alkaline phosphatase increased, iron deficiency anemia, creatinine increased, bilirubinemia, lactic dehydrogenase increased, obesity;
Rare – hyperkalemia, gout, hypernatremia, cyanosis, hyperuricemia, hypoglycemic reaction.

Musculoskeletal System:
Frequent – muscle cramp;
Infrequent – arthralgia, bone pain, myasthenia, arthritis, arthrosis, muscle weakness, spasm, bursitis;
Rare – rhabdomyolysis, tendonitis, tenosynovitis, rheumatoid arthritis, myopathy.

Nervous System:
Frequent – depression, nervousness, increased salivation, hostility, suicidal thought, manic reaction, abnormal gait, confusion, cogwheel rigidity;
Infrequent – dystonia, twitch, impaired concentration, paresthesia, vasodilation, hypesthesia, extremity tremor, impotence, bradykinesia, decreased libido, panic attack, apathy, dyskinesia, hypersomnia, vertigo, dysarthria, tardive dyskinesia, ataxia, impaired memory, stupor, increased libido, amnesia, cerebrovascular accident, hyperactivity, depersonalization, hypokinesia, restless leg, myoclonus, dysphoria, neuropathy, increased reflexes, slowed thinking, hyperkinesia, hyperesthesia, hypotonia, oculogyric crisis;
Rare – delirium, euphoria, buccoglossal syndrome, akinesia, blunted affect, decreased consciousness, incoordination, cerebral ischemia, decreased reflexes, obsessive thought, intracranial hemmorage.

Respiratory System:
Frequent – dyspnea, pneumonia;
Infrequent – asthma, epistaxis, hiccup, laryngitis;
Rare – hemoptysis, aspiration pneumonia, increased sputum, dry nasal passages, pulmonary edema, pulmonary embolism, hypoxia, respiratory failure, apnea.

Skin and Appendages:
Frequent – dry skin, pruritis, sweating, skin ulcer;
Infrequent – acne, vesiculobullous rash, eczema, alopecia, psoriasis, seborrhea;
Rare – maculopapular rash, exfoliative dermatitis, urticaria.

Special Senses:
Frequent – conjunctivitus, ear pain;
Infrequent – dry eye, eye pain, tinnitus, otitis media, cataract, altered taste, blepharitis;
Rare – increased lacrimation, frequent blinking, otitis externa, amblyopia, deafness, diplopia, eye hemorrhage, photophobia.

Urogenital System:
Frequent – urinary incontinence;
Infrequent – cystitis, urinary frequency, leukorrhea, urinary retention, hematuria, dysuria, amenorrhea, abnormal ejaculation, vaginal hemorrhage, vaginal moniliasis, kidney failure, uterus hemorrhage, menorrhagia, albuminuria, kidney calculus, nocturia, polyuria, urinary urgency;
Rare – breast pain, cervicitis, female lactation, anorgasmy, urinary burning, glycosuria, gynecomastia, urolithiasis, priapism.

DO NOT DRINK ALCOHOL while you are taking this medicine.

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 (e.g., development of tolerance, increases in dose, drug-seeking behavior).

Overdose

Human Experience

In premarketing clinical studies, involving more than 5500 patients, accidental or intentional acute overdosage of aripiprazole was identified in seven patients. In the two patients taking the largest identified amount, 180 mg, the only symptoms reported were somnolence and vomiting in one of the two patients. In the patients who were evaluated in hospital settings, including the two patients taking 180 mg, there were no observations indicating an adverse change in vital signs, laboratory assessments, or ECG. An uneventful, accidental overdose (15 mg) occurred in a non-patient, an 18-month-old child, with concomitant ingestion of ATIVAN® (2 mg).

Treatment

If you or someone you know may have used more than the recommended dose of this medicine, contact your local poison control center or emergency room immediately.

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%.

Dosage

Do not exceed the recommended dosage or take this medicine for longer than prescribed. Continue to take this medicine even if you feel better. Do not miss any doses.

The recommended starting and target dose for ABILIFY is 10 or 15 mg/day administered on a once-a-day schedule without regard to meals. ABILIFY has been systematically evaluated and shown to be effective in a dose range of 10 to 30 mg/day; however, doses higher than 10 or 15 mg/day, the lowest doses in these trials, were not more effective than 10 or 15 mg/day. Dosage increases should not be made before 2 weeks, the time needed to achieve steady state.

AT LEAST 1 TO 2 WEEKS, and sometimes up to 4 weeks, may pass before Abilify reaches its full effect.

Dosage adjustment for patients taking aripiprazole concomitantly with potential CYP3A4 inhibitors: When concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be reduced to one-half of the usual dose. When the CYP3A4 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.

Dosage adjustment for patients taking aripiprazole concomitantly with potential CYP2D6 inhibitors: When concomitant administration of potential CYP2D6 inhibitors such as quinidine, fluoxetine, or paroxetine with aripiprazole occurs, aripiprazole dose should be reduced at least to one-half of its normal dose. When the CYP2D6 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.

Dosage adjustment for patients taking potential CYP3A4 inducers: When a potential CYP3A4 inducer such as carbamazepine is added to aripiprazole therapy, the aripiprazole dose should be doubled (to 20 to 30 mg). Additional dose increases should be based on clinical evaluation. When carbamazepine is withdrawn from the combination therapy, the aripiprazole dose should be reduced to 10 to 15 mg.

Maintenance Therapy
There is no body of evidence available from controlled trials to answer the question of how long a patient treated with aripiprazole should remain on it. It is generally agreed, however, that pharmacological treatment for episodes of acute schizophrenia should continue for up to 6 months or longer. Patients should be periodically reassessed to determine the need for maintenance treatment.

Switching from Other Antipsychotics
There are no systematically collected data to specifically address switching patients with schizophrenia from other antipsychotics to ABILIFY or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

Follow the directions for using this medicine provided by your doctor.
Store this medicine at room temperature, away from heat and light.
This medicine may be taken on an empty stomach or with food.

Additional Information: Do not share this medicine with others for whom it was not prescribed. Do not use this medicine for other health conditions. Keep this medicine out of the reach of children.

IF USING THIS MEDICINE FOR AN EXTENDED PERIOD OF TIME, obtain refills before your supply runs out.

How Supplied

ABILIFY (aripiprazole) Tablets are available in bottles of 30 or blisterpaks of 100 in the following strengths:

10 mg, 15mg, 20 mg, 30 mg

Inactive ingredients include lactose monohydrate, cornstarch, microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate. Colorants include ferric oxide (yellow or red).

Links: Additional Information on Abilify

FIND OUT MORE ABOUT ABILIFY
Are you caring for someone with schizophrenia? Get help. Get information about schizophrenia and treatment, including helpful tools and caregiver support. Click here.

Home to HealthyPlace.com

Chat/Forums Communities Medications HealthyPlace Radio News
Site Events Web Tour Advertise Email Us

The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.