Aripiprazole

448.38500

448.39

82VFR53I78

759266

DTXSID3046083

C47403

Colorless, flake crystals from ethanol

N05AX12|N - Nervous system

2933790090

44.81000

4.6

Solid

1.263 g/cm3

109-111 °C @ Solvent: Methanol, Chloroform

646.2ºC at 760 mmHg

344.6ºC

1.593

DMSO: soluble 5mg/mL, clear (warmed)

Store in original container in a cool dark place.

1.38E-16mmHg at 25°C

TDLo ivn-dog: 0.03 mg/kg/10M TXAPA9 173,120,2001

7.6None

Henry's Law constant = 7.7X10-17 atm-cu m/mole at 25 °C (est)

7.6|pKa1 = 7.46 (amide); pKa2 = 13.51 (secondary amine) (est)

205.8 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|203.5 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 3.3X10-10 cu cm/molecule-sec at 25 °C (est)

UN 1993C 3 / PGIII

3

11-20/21/22-36

16-36/37

F,Xn

Stable under recommended storage conditions.

Missing Phrase - N15.00950417-P261-P280-P302 + P352 + P312-P304 + P340 + P312-P403 + P233

H301 + H311 + H331-H370

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.|SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Incompatible materials: Strong oxidizing agents

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including aripiprazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Swainston Harrison T, Perry CM; Aripiprazole: A Review of its Use in Schizophrenia and Schizoaffective disorder; Drugs 64 (15): 1715-36 (2004).[]

|Danger|H301 (84.55%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P301+P312, P321, P330, P405, and P501|Aggregated GHS information provided by 110 companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H226: Flammable liquid and vapor [Warning Flammable liquids]|P210, P233, P234, P240, P241, P242, P243, P260, P261, P264, P270, P271, P280, P301+P310, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P307+P311, P311, P312, P321, P322, P330, P332+P313, P337+P313, P361, P362, P363, P370+P378, P390, P403+P233, P403+P235, P404, P405, and P501

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Body Protection: Complete suit protecting against chemicals, Flame retardant antistatic protective clothing., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Skin protection: Handle with gloves.|Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. Use water spray to cool unopened containers.|Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours can accumulate in low areas.; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.|Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.

Studies on the safety and effectiveness of aripiprazole in pregnancy have not been performed, though there is currently a national pregnancy registry for mothers currently taking aripiprazole in pregnancy. In other studies of antipsychotic medication in pregnancy, children are at risk of extrapyramidal or withdrawal symptoms. In animal studies of pregnancy, aripiprazole was associated with a number of malformations and fetal death at doses higher than the maximum recommended human dose. Aripiprazole should only be prescribed in pregnancy if the benefits outweigh the risks. Neonates with third trimester exposure to aripiprazole may show extrapyramidal or withdrawal symptoms of varying severity. These symptoms may resolve in hours or require extended hospital care. Aripiprazole's effect on labor and delivery has not been investigated. Aripiprazole is present in human breast milk and so patients should either stop breastfeeding or stop taking aripiprazole depending on the risk and benefit to mother and child. Pharmacokinetic properties in patients 10-17 years of age are similar to that of adults once body weight has been corrected for. No dosage adjustment is necessary in elderly patients however aripiprazole is not approved for Alzheimer's associated psychosis. Patients calssified as CYP2D6 poor metabolizers should be prescribed half the regular dose of aripiprazole. Hepatic and renal function as well as sex, race, and smoking status do not affect dosage requirements for aripiprazole.|IDENTIFICATION AND USE: Aripiprazole is used IM for the acute management of agitation associated with schizophrenia or bipolar disorder, mixed or manic, in adults for whom treatment with aripiprazole is appropriate and who require an IM antipsychotic agent for rapid control of behaviors that interfere with diagnosis and care (e.g., threatening behaviors, escalating or urgently distressing behavior, self-exhausting behavior). Aripiprazole is used orally for the acute treatment of irritability associated with autistic disorder. Aripiprazole is used orally as an adjunct to antidepressants for the acute treatment of major depressive disorder in adults. Aripiprazole is used orally as monotherapy or as an adjunct to either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults and pediatric patients 10-17 years of age. The drug also is used orally as monotherapy or as adjunctive therapy with lithium or valproate for the maintenance treatment of bipolar I disorder in adults and pediatric patients 10-17 years of age. Aripiprazole is used orally for the acute and maintenance treatment of schizophrenia in adults and adolescents 13-17 years of age. HUMAN EXPOSURE AND TOXICITY: 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. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. ANIMAL STUDIES: In female mice, the incidences of pituitary gland adenomas and mammary gland adenocarcinomas and adenoacanthomas were increased at dietary dose of 3 to 30 mg/kg/day. Female rats were treated with oral doses of 2, 6, and 20 mg/kg/day of aripiprazole from 2 weeks prior to mating through day 7 of gestation. Estrus cycle irregularities and increased corpora lutea were seen at all doses, but no impairment of fertility was seen. Increased pre-implantation loss was seen at 6 and 20 mg/kg, and decreased fetal weight was seen at 20 mg/kg. Pregnant rabbits were treated with oral doses of 10, 30, and 100 mg/kg/day of aripiprazole during the period of organogenesis. Decreased maternal food consumption and increased abortions were seen at 100 mg/kg. Treatment caused increased fetal mortality (100 mg/kg), decreased fetal weight (30 and 100 mg/kg), increased incidence of a skeletal abnormality (fused sternebrae at 30 and 100 mg/kg) and minor skeletal variations (100 mg/kg). Aripiprazole and a metabolite (2,3-DCPP) were clastogenic in the in vitro chromosomal aberration assay in CHL cells with and without metabolic activation. The metabolite, 2,3-DCPP, produced increase in numerical aberrations in the in vitro assay in CHL cells in the absence of metabolic activation. A positive response was obtained in the in vivo micronucleus assay in mice, however,the response was shown to be due to a mechanism not considered relevant to humans.

Liver test abnormalities have not been reported to occur in patients on long term therapy with aripiprazole, but most studies have not provided information on serum enzyme results. Despite its widescale use, there have been no published reports of clinically apparent acute liver injury attributable to aripiprazole. The product label for aripiprazole mentions that hepatitis and jaundice have been reported in less than 1:1000 patients, but no specific details are given. Thus, acute liver injury from aripiprazole must be rare if it occurs at all.|Liver test abnormalities were reported to occur in ~1% of patients on long term therapy with brexpiprazole, but similar rates occurred in patients on placebo or with comparator agents. There have been no published reports of clinically apparent acute liver injury due to brexpiprazole and only rare instances have been reported with the much more frequently used aripiprazole. Thus, liver injury due to brexpiprazole must be rare, if it occurs at all.

Substrates of Hepatic Microsomal Enzymes: Substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4; pharmacokinetic interaction unlikely.|Hypotensive Agents: Potential pharmacologic interaction (additive hypotensive effects)|Famotidine: Coadministration of aripiprazole (given in a single dose of 15 mg) with a 40-mg single dose of the H2 antagonist famotidine, a potent gastric acid blocker, decreased the solubility of aripiprazole and, hence, its rate of absorption, reducing by 37% and 21% the Cmax of aripiprazole and dehydro-aripiprazole, respectively, and by 13% and 15%, respectively, the extent of absorption (AUC). No dosage adjustment of aripiprazole is required when administered concomitantly with famotidine.|Valproate: When valproate (500-1500 mg/day) and aripiprazole (30 mg/day) were coadministered at steady state, the C max and AUC of aripiprazole were decreased by 25%. No dosage adjustment of aripiprazole is required when administered concomitantly with valproate.|For more Interactions (Complete) data for ARIPIPRAZOLE (12 total), please visit the HSDB record page.

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of adjunctive ABILIFY or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. ABILIFY is not approved for use in pediatric patients with depression. /Included in label/|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.|Seizures have occurred in 0.1% of adults treated with oral aripiprazole, in 0.2% of pediatric patients 6-17 years of age, and in 0.2% of adults treated with parenteral aripiprazole. Aripiprazole should be used with caution in patients with a history of seizures or other conditions that may lower the seizure threshold (e.g., dementia of the Alzheimer's type); conditions that lower the seizure threshold may be more prevalent in geriatric patients 65 years of age or older.|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).

>99%.

Aripiprazole's production and administration as a medication(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+4(SRC), determined from a structure estimation method(2), indicates that aripiprazole is expected to be immobilein soil(SRC). The estimated pKa1 of aripiprazole is 7.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species of aripiprazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.7X10-17 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Aripiprazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2015).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+4(SRC), determined from a structure estimation method(2), indicates that aripiprazole is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.7X10-17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 1500(SRC), from an estimated log Kow of 5.30(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Biodegradation data in water were not available(SRC, 2015).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), aripiprazole, which has an estimated vapor pressure of 3.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase aripiprazole may be removed from the air by wet and dry deposition(SRC). Aripiprazole contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Aripiprazole is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Aripiprazole contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Based on UV spectra of other amino chlorobenzenes(2), aripiprazole may absorb light at wavelengths >290 nm(SRC).

An estimated BCF of 1500 was calculated in fish for aripiprazole(SRC), using an estimated log Kow of 5.30(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of aripiprazole can be estimated to be 2.5X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that aripiprazole is expected to be immobile in soil. The estimated pKa of aripiprazole is 7.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for aripiprazole is estimated as 7.7X10-17 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that aripiprazole is expected to be essentially nonvolatile from water and moist soil surfaces(2). Aripiprazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-13 mm Hg(SRC), determined from a fragment constant method(3).

While data specific to aripiprazole were not located(SRC, 2015), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are, therefore, discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Aripiprazole is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Occupational exposure to aripiprazole may occur through inhalation and dermal contact with this compound at workplaces where aripiprazole is produced or used. Exposure to aripiprazole among the general population may be limited to those administered the drug, an antipsycholtic. (SRC)

Aripiprazole is indicated for manic and mixed episodes associated with bipolar I disorder, irritability associated with autism spectrum disorder, treatment of schizophrenia, treatment of Tourette's disorder, and as an adjunctive treatment of major depressive disorder. An injectable formulation of aripiprazole is indicated for agitation associated with schizophrenia or bipolar mania.|FDA Label|Aripiprazole Accord is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older., , Aripiprazole Accord is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment., , Aripiprazole Accord is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.,|Aripiprazole Mylan Pharma is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older.Aripiprazole Mylan Pharma is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment.Aripiprazole Mylan Pharma is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.|Abilify is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older., , Abilify is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment., , Abilify is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.,|Aripiprazole Zentiva is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older.Aripiprazole Zentiva is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment.Aripiprazole Zentiva is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.|Aripiprazole Sandoz is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older.Aripiprazole Sandoz is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment.Aripiprazole Sandoz is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.|Maintenance treatment of schizophrenia in adult patients stabilised with oral aripiprazole.|Treatment of bipolar affective disorder, Treatment of schizophrenia

Aripiprazole is an atypical antipsychotic used in the treatment of schizophrenia and bipolar illness. Aripiprazole therapy has not been associated consistently with serum aminotransferase elevations and has yet to be linked to cases of clinically apparent acute liver injury.|Brexpiprazole is an atypical antipsychotic used in the treatment of schizophrenia and major depressive disorders. Brexpiprazole has been associated with a low rate of serum aminotransferase elevations during therapy, but has not been linked to instances of clinically apparent acute liver injury.

Antipsychotic Agents

Antipsychotic Agents|Aripiprazole is used IM for the acute management of agitation associated with schizophrenia or bipolar disorder, mixed or manic, in adults for whom treatment with aripiprazole is appropriate and who require an IM antipsychotic agent for rapid control of behaviors that interfere with diagnosis and care (e.g., threatening behaviors, escalating or urgently distressing behavior, self-exhausting behavior).|Aripiprazole is used orally for the acute treatment of irritability associated with autistic disorder.|Aripiprazole is used orally as an adjunct to antidepressants for the acute treatment of major depressive disorder in adults.|For more Therapeutic Uses (Complete) data for ARIPIPRAZOLE (6 total), please visit the HSDB record page.

/BOXED WARNING/ WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death 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. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. ABILIFY (aripiprazole) is not approved for the treatment of patients with dementia-related psychosis. /Included in label/|/BOXED WARNING/ WARNING: INCREASED SUICIDALTHOUGHTS AND BEHAVIORS. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of adjunctive ABILIFY or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. ABILIFY is not approved for use in pediatric patients with depression. /Included in label/|Contraindications: Known hypersensitivity reaction to aripiprazole or any ingredient in the formulation; such reactions have ranged from pruritus/urticaria to anaphylaxis.|Safety and effectiveness in pediatric patients with bipolar mania were established in a 4-week, placebo-controlled clinical trial in 197 pediatric patients aged 10 to 17 years. The incidence of discontinuation due to adverse reactions between aripiprazole-treated and placebo-treated pediatric patients (10 to 17 years) was 7% and 2%, respectively. Commonly observed adverse reactions associated with the use of aripiprazole in pediatric patients with bipolar mania (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness. Although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.|For more Drug Warnings (Complete) data for ARIPIPRAZOLE (27 total), please visit the HSDB record page.

Aripiprazole has high affinity for serotonin type 2 (5HT2), dopamine type 2 (D2), alpha1 and 2 adrenergic, and H1 histaminergic receptors. It also acts on a number of other receptors with lower affinity. The exact method by which aripiprazole's action on these receptors translates to a clinically relevant effect is not yet known.

Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. (See all compounds classified as Antidepressive Agents.)|Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.)|Compounds and drugs that bind to and inhibit or block the activation of DOPAMINE D2 RECEPTORS. (See all compounds classified as Dopamine D2 Receptor Antagonists.)|Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes. (See all compounds classified as Serotonin 5-HT1 Receptor Agonists.)|Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes. (See all compounds classified as Serotonin 5-HT2 Receptor Antagonists.)|Drugs that bind to and activate dopamine receptors. (See all compounds classified as Dopamine Agonists.)

Aripiprazole tablets are 87% bioavailable and reach peak plasma concentrations in 3 to 5 hours. These tablets can be taken with or without food, but a high fat meal can delay the time to max concentration by 3 hours and up to 12 hours for the active metabolite.|25% of a given dose will be eliminated in urine and 55% in the feces. <1% of a dose is eliminated in the urine as unmetabolized aripiprazole and approximately 18% of a dose will be eliminated in the feces unmetabolized.|404L or 4.9L/kg.|0.8mL/min/kg. Other studies have reported a clearance rate of 3297±1042mL/hr.|Oral availability 87%. Aripiprazole is well absorbed and can be administered with or without food. Administration with a high fat meal did not affect the Cmax or AUC, but delayed Tmax by 3 hours for aripiprazole, and 12 hours for dehydro-aripiprazole.|Time to peak concentration: Peak plasma concentrations: within 3 to 5 hours.|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.|There was dose-dependent D2-receptor occupancy indicating brain penetration of aripiprazole in healthy human volunteers administered 0.5 to 30 mg per day.|For more Absorption, Distribution and Excretion (Complete) data for ARIPIPRAZOLE (8 total), please visit the HSDB record page.

Metabolism of aripiprazole is predominantly hepatic, mediated mostly by cytochrome P450 (CYP)3A4 and CYP2D6. These enzymes perform dehydrogenation and hydroxylation while CYP3A4 alone performs N-dealkylation. At any given time, the active metabolite dehydro-aripiprazole is approximately 40% of the drug available in plasma.|Aripiprazole is extensively metabolized in the liver principally via dehydrogenation, hydroxylations, and N-dealkylation by the cytochrome P-450 (CYP) 2D6 and 3A4 isoenzymes. The major active metabolite of aripiprazole, dehydro-aripiprazole, exhibits affinity for D2 receptors similar to that of the parent compound and represents approximately 40% of the aripiprazole area under the concentration-time curve (AUC) in plasma. Steady-state plasma concentrations of both aripiprazole and dehydro-aripiprazole are achieved within 14 days.|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.|Aripiprazole has known human metabolites that include 2,3-dichlorophenylpiperazine, 4-Hydroxyaripiprazole, 4-[(2-oxo-3,4-dihydro-1H-quinolin-7-yl)oxy]butanal, and dehydro-aripiprazole.

The half life of aripiprazole is 75 hours while the half life of the active metabolite is 94 hours. For populations that are poor CYP2D6 metabolizers, the half life of aripiprazole is 146 hours and these patients should be treated with half the normal dose. Other studies have reported a half life of 61.03±19.59 hours for aripiprazole and 279±299 hours for the active metabolite.|The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively.

The antipsychotic action of aripiprazole is likely due to the agonism of D2 and 5-HT1A receptors though the exact mechanism has not been defined. Some adverse effects may be due to action on other receptors. For example, orthostatic hypotension may be explained by antagonism of the adrenergic alpha1 receptors.|The exact mechanism of antipsychotic action of aripiprazole has not been fully elucidated but, like that of other atypical antipsychotic agents (e.g.,olanzipine, risperidone, ziprasidon), may involve the drug's activity at dopamine D2 and serotonin type (5-HT1A) and type 2 (5-HT2A) receptors. However, aripiprazole appears to differ from other atypical antipsychotic agents because the drug demonstrates partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Antagonism at other receptors (e.g., alpha1-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence) observed with aripiprazole.|...Aripiprazole exhibits typical antagonism at dopamine (D2) receptors in the mesolimbic pathway, as well as having unique partial agonist activity at D2 receptors in the mesocortical pathway. As exemplified by other atypical antipsychotics, it displays strong 5-HT(2a) receptor antagonism and is similar to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among the atypical antipsychotics, aripiprazole displays the lowest affinity for alpha(1)adrenergic (alpha(1)), histamine (H1) and muscarinic (M1) receptors. This combination of effects may be responsible for its efficacy in positive and negative symptoms of schizophrenia and in bipolar disorder. ...Other early data suggest that aripiprazole may induce reductions in plasma prolactin, as well as in plasma glucose and lipid profiles ...

Emergency and supportive measures: 1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. 2. Treat coma, seizures, hypotension, and hyperthermia if they occur. 3. Monitor vital signs ECG for at least 6 hours and admit the patient for at least 24 hours if there are signs of significant intoxication. Children with antipsychotic intoxication should be evaluated for possible intentional abuse. /Antipsychotic drugs/|Specific drugs and antidotes. There is no specific antidote.1. Dystonic reactions. Give diphenhydramine ... or benztropine ... . 2. QRS interval prolongation: treat quinidine-like cardiotoxic effects with bicarbonate ... . 3. Hypotension from these drugs probably involves vasodilation caused by alpha-1 receptor blockade. Treat with iv fluids and, if needed a vasoconstrictor such as norepinephrine or phenylephrine. Theoretically, drugs with beta-2 activity (eg, epinephrine, isoproterenol) may worsen hypotension. 4. QT prolongation and torsade may respond to magnesium infusion or overdrive pacing. /Antipsychotic drugs/|Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antipsychotic drugs/|Enhanced elimination. Owing to extensive tissue distribution, these drugs are not effectively removed by dialysis or hemoperfusion. Repeat-dose activated charcoal has not been evaluated. /Antipsychotic drugs/|For more Antidote and Emergency Treatment (Complete) data for ARIPIPRAZOLE (7 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ 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.|/SIGNS AND SYMPTOMS/ Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported in patients receiving antipsychotic agents, including rare cases associated with aripiprazole therapy.|/SIGNS AND SYMPTOMS/ A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) may occur 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) 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.|/SIGNS AND SYMPTOMS/ 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.|For more Human Toxicity Excerpts (Complete) data for ARIPIPRAZOLE (7 total), please visit the HSDB record page.

7-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone

Table: Aripiprazole Preparations [Table#6922]

Information available in 2005 indicated that Aripiprazole was used in the manufacture of pharmaceutical preparations in the following countries: Australia, Germany, Mexico, Switzerland, United Kingdom, United States (1,2)

LC-MS/MS determination in plasma.

Human drugs -> Aripiprazole Accord -> EMA Drug Category|Psycholeptics -> Human pharmacotherapeutic group|Human drugs -> Aripiprazole Mylan Pharma (previously Aripiprazole Pharmathen) -> EMA Drug Category|Human drugs -> Abilify -> EMA Drug Category|Human drugs -> Aripiprazole Zentiva -> EMA Drug Category|Human drugs -> Aripiprazole Sandoz -> EMA Drug Category|Human drugs -> Abilify Maintena -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients