Aripiprazole Odt (aripiprazole)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Aripiprazole is considered an atypical or second-generation antipsychotic agent.
Aripiprazole is a quinolinone derivative antipsychotic agent that differs chemically from other currently available antipsychotic agents (e.g., butyrophenones, phenothiazines) and has been referred to as an atypical or second-generation antipsychotic agent. The exact mechanism of action of aripiprazole in schizophrenia, bipolar disorder, major depressive disorder, irritability associated with autistic disorder, Tourette's syndrome, and agitation associated with schizophrenia or bipolar mania has not been fully elucidated but, like that of other drugs with efficacy in these conditions (e.g., olanzapine, risperidone, ziprasidone), may involve the drug's activity at dopamine D2 and serotonin type 1 (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 is well absorbed following oral administration; peak plasma concentrations following oral administration of conventional tablets occur within 3-5 hours. Following administration of aripiprazole oral film, peak plasma concentrations are attained in a median of 1.5 hours. Administration with a high-fat meal does not affect peak plasma concentration or systemic exposure of aripiprazole or dehydro-aripiprazole.
Absolute oral bioavailability of conventional tablets is 87%. Following administration of the oral solution, plasma aripiprazole concentrations are higher than those after administration of equivalent dosages of the conventional tablets. Steady-state plasma concentrations of both aripiprazole and dehydro-aripiprazole are achieved within 14 days with oral administration.
Aripiprazole is extensively metabolized in the liver principally via dehydrogenation, hydroxylation, and N-dealkylation by the cytochrome P-450 (CYP) 3A4 and 2D6 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 aripiprazole area under the concentration-time curve (AUC) in plasma. Poor CYP2D6 metabolizers have substantially increased aripiprazole and dehydro-aripiprazole exposures compared with extensive metabolizers.
Approximately 18% of an orally administered dose of aripiprazole is excreted unchanged in feces and less than 1% is excreted unchanged in urine. The mean elimination half-life of aripiprazole and dehydro-aripiprazole is approximately 75 and 94 hours, respectively. In poor metabolizers of CYP2D6, the mean elimination half-life is approximately 146 hours.
Following IM administration of extended-release aripiprazole (Abilify Maintena(R)), the low solubility of aripiprazole particles results in prolonged aripiprazole absorption. Following multiple IM doses, peak plasma aripiprazole concentrations occur after a median of 4 or 5-7 days when administered into the deltoid or gluteal muscle, respectively. Single IM injections into the deltoid result in 31% higher peak plasma concentrations compared with the gluteal site; however, aripiprazole systemic exposures and peak plasma concentrations at steady state were similar for both injection sites.
Dose-proportional increases in aripiprazole and dehydro-aripiprazole systemic exposures were observed following extended-release aripiprazole IM doses of 300 or 400 mg given every 4 weeks. Steady-state plasma concentrations of aripiprazole are achieved by the fourth dose of extended-release aripiprazole for both sites of administration. Following gluteal administration of multiple 300- or 400-mg doses of extended-release aripiprazole every 4 weeks, the mean terminal half-life of aripiprazole is 29.9 or 46.5 days, respectively.
Following gluteal injection of extended-release aripiprazole (Abilify Asimtufii(R)), the low solubility of aripiprazole particles results in prolonged aripiprazole absorption. The release profile of aripiprazole results in prolonged plasma concentrations over a 2-month period. Over the approved dosage range, extended-release aripiprazole exhibits linear pharmacokinetics.
It demonstrates a flat plasma concentration profile, with the time to maximum plasma concentrations occurring after 1-49 days. Steady-state plasma concentrations of aripiprazole are achieved by the fourth dose of extended-release aripiprazole. Steady state plasma concentrations are similar for Abilify Maintena(R) 400 mg once monthly and Abilify Asimtufii(R) 960 mg every 2 months.
Aripiprazole lauroxil is a prodrug of aripiprazole. Following IM injection, aripiprazole lauroxil is probably converted by enzyme-mediated hydrolysis to N-hydroxymethyl aripiprazole, which is then hydrolyzed to aripiprazole. Following IM administration of extended-release aripiprazole lauroxil (Aristada(R)), aripiprazole begins to appear in the systemic circulation in 5-6 days and is continually released for an additional 36 days.
Plasma concentrations of aripiprazole increase with consecutive doses and reach steady-state concentrations following the fourth monthly injection. With the addition of a single IM injection of extended-release aripiprazole lauroxil (Aristada Initio(R)) and 30 mg of oral aripiprazole at the time of the first Aristada(R) injection, aripiprazole concentrations reach therapeutic plasma levels within 4 days. A similar effect is achieved when oral aripiprazole is administered for 21 days following the first Aristada injection.
IM injection of extended-release aripiprazole lauroxil (441 mg) into the deltoid and gluteal areas results in similar systemic exposure; therefore, these injection sites are considered interchangeable. In addition, IM administration of aripiprazole lauroxil 882 mg every 6 weeks or 1064 mg every 2 months results in plasma aripiprazole concentrations that are within the established therapeutic range for dosages of 441 and 882 mg once monthly. The mean elimination half-life of aripiprazole ranges from about 54-57 days following monthly, every 6 week, or every 2 month injections of extended-release aripiprazole lauroxil (Aristada Initio(R)) .
Aripiprazole is commercially available in the US as aripiprazole and aripiprazole lauroxil.
Generic name: aripiprazole
Pronunciation: (AR-i-PIP-ra-zole)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Aripiprazole Odt
Indications
The following indications are listed for Aripiprazole Odt:
- Bipolar Disorder
- Gilles De La Tourette Syndrome
- Infantile Autism
- Major Depressive Disorder Treatment Adjunct
- Schizophrenia
Also known as: Adjunctive Treatment Of Major Depressive Disorder, Augmentation Therapy For Major Depressive Disorder, Autism, Bipolar Affective Disorder, Bipolar Affective Illness, Bipolar Mood Disorder, Childhood Autism, Combined Vocal And Motor Tics For More Than One Year, Dementia Praecox, Gilles De La Tourette's Syndrome, Kanner's Syndrome, Major Depressive Disorder Treatment Augmentation, Manic-Depressive Illness, Parergasia, Tourette's Disorder, Tourette's Syndrome.
Dosing
Aripiprazole oral solution may be given at the same dose on a mg-per-mg basis as the tablet strengths of the medication up to a dose of 25 mg. However, if the oral solution is used in patients who were receiving aripiprazole 30 mg as tablets, a dose of 25 mg of the oral solution should be used.
Conventional tablets and orally disintegrating tablets of aripiprazole are bioequivalent; therefore, dosing for the orally disintegrating tablets is the same as for the conventional tablets.
Dosage of aripiprazole lauroxil is expressed in terms of aripiprazole lauroxil.
Extended-release aripiprazole lauroxil (Aristada(R)) doses of 441, 662, 882, and 1064 mg correspond to aripiprazole doses of 300, 450, 600, and 724 mg, respectively.
Of the available oral dosage forms of aripiprazole, aripiprazole oral film (Opipza(R)) is not indicated for use in pediatric or adult patients with manic and mixed episodes associated with bipolar I disorder.
Aripiprazole is administered orally or by IM injection. Aripiprazole lauroxil is administered only by IM injection.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to aripiprazole; hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
In adults with schizophrenia receiving oral aripiprazole in clinical trials, akathisia was the only adverse effect that occurred in >=5% of patients and at an incidence at least twice that for placebo.
Adverse effects occurring in >=5% of adolescents (13 to 17 years of age) with schizophrenia receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include extrapyramidal disorder, somnolence, and tremor.
Adverse effects occurring in >=5% of adults with bipolar mania receiving oral aripiprazole as monotherapy in clinical trials and at an incidence at least twice that of placebo include akathisia, sedation, restlessness, tremor, and extrapyramidal disorder.
Adverse effects occurring in >=5% of adults with bipolar mania receiving oral aripiprazole as adjunctive therapy with lithium or valproate in clinical trials and at an incidence at least twice that of placebo include akathisia, insomnia, and extrapyramidal disorder.
Adverse effects occurring in >=5% of pediatric patients 10 to 17 years of age with bipolar mania receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness.
Adverse effects occurring in >=5% of adults with major depressive disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.
Adverse effects occurring in >=5% of pediatric patients 6 to 17 years of age with autistic disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy.
Adverse effects occurring in >=5% of pediatric patients 6 to 18 years of age with Tourette's Disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, and increased appetite.
In clinical trials with aripiprazole tablets with sensor and other components of the digital ingestion tracking system (Abilify MyCite(R)), skin rash localized at the application site of the wearable sensor (patch) was reported in 12.4% of patients.
Adverse effects occurring in >=5% of adults receiving extended-release IM aripiprazole injection in clinical trials and at an incidence at least twice that for placebo include increased weight, akathisia, injection site pain, and sedation.
In patients receiving extended-release IM aripiprazole lauroxil injection (Aristada(R)) in clinical trials, akathisia was the only adverse effect that occurred in >=5% of patients and at an incidence at least twice that for placebo.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of oral aripiprazole have not been established in pediatric patients with major depressive disorder.
Safety and efficacy of oral aripiprazole have not been established in pediatric patients with agitation associated with schizophrenia or bipolar mania.
Safety and efficacy of extended-release IM formulations of aripiprazole and aripiprazole lauroxil have not been evaluated in pediatric patients <18 years of age.
Safety and efficacy of aripiprazole tablets with sensor have not been established in pediatric patients.
Safety and efficacy of oral aripiprazole for the acute management of schizophrenia in pediatric patients 13 to 17 years of age have been established in a placebo-controlled study of 6 weeks' duration. Although the efficacy of oral aripiprazole for maintenance treatment of schizophrenia in pediatric patients has not been systematically evaluated, the manufacturer states that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.
Safety and efficacy of oral aripiprazole monotherapy for the acute management of bipolar mania in pediatric patients 10 to 17 years of age have been established in a placebo-controlled study of 4 weeks' duration.
The efficacy of oral aripiprazole as an adjunct to lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar disorder in pediatric patients has not been systematically evaluated. However, efficacy can be extrapolated from adult data in addition to pharmacokinetic comparisons of aripiprazole between adult and pediatric populations.
Safety and efficacy of oral aripiprazole for the treatment of irritability associated with autistic disorder have been established in 2 placebo-controlled clinical trials of 8 weeks' duration in pediatric patients 6 to 17 years of age. Efficacy of the drug as maintenance therapy for irritability associated with autistic disorder was not established in a longer-term, placebo-controlled relapse prevention trial in pediatric patients 6 to 17 years of age.
Safety and efficacy of oral aripiprazole for the treatment of Tourette's syndrome have been established in one 8-week, placebo-controlled trial in pediatric patients 7 to 17 years of age and one 10-week, placebo-controlled trial in pediatric patients 6 to 18 years of age. Efficacy of the drug as maintenance therapy in pediatric patients with Tourette's syndrome has not been systematically evaluated.
The pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients 10 to 17 years of age are similar to those in adults after correcting for differences in body weight.
Mean weight gain of 1.6 kg was reported in pediatric patients with schizophrenia or bipolar disorder receiving oral aripiprazole compared with a gain of 0.3 kg in those receiving placebo in 2 short-term studies. After 24 weeks of therapy, the mean change from baseline in body weight in the aripiprazole-treated patients was 5.8 kg compared with 1.4 kg in placebo recipients. Similar gains in weight were observed in short-term studies in pediatric patients with irritability associated with autistic disorder and Tourette's syndrome.
A greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants). No suicides occurred in these pediatric trials. These findings should be carefully considered when assessing potential benefits and risks of aripiprazole in a child or adolescent for any clinical use.
Neonates exposed to antipsychotic agents during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Symptoms reported to date have included agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, and feeding disorder. Neonates exhibiting such symptoms should be monitored and managed appropriately. The complications have varied in severity; some neonates recovered within hours to days without specific treatment, while others have required prolonged hospitalization.
There is a pregnancy registry that monitors pregnancy outcomes in females exposed to atypical antipsychotics during pregnancy. Clinicians are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 and https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregi stry/atypicalantipsychotic/.
Limited data indicate that aripiprazole is present in human milk at a relative infant dose (RID) ranging from 0.7-8.3% of the maternal weight-adjusted dosage. Poor weight gain in breast-fed infants exposed to aripiprazole and inadequate milk supply in lactating women have been reported. The manufacturers of aripiprazole state that the benefit of aripiprazole therapy to the mother as well as the benefits of breast-feeding to the infant should be weighed against the potential risk to the infant resulting from exposure to the drug or from the underlying maternal condition.
No dosage adjustment is necessary in geriatric patients..
The manufacturer of extended-release IM aripiprazole (Abilify Asimtufii(R)) states that an insufficient number of patients >=65 years of age were included in clinical trials to assess differences in response compared to younger adults; however, dosage selection for elderly patients should be undertaken with caution and dosages should be initiated at the lower end of the dosage range.
The safety and efficacy of Aristada(R) or Aristada Initio(R) have not been established in patients >65 years of age.
In clinical studies, approximately 8% of over 13,000 patients treated with oral aripiprazole were >=65 years of age and approximately 6% were >=75 years of age. Experience from placebo-controlled trials with oral aripiprazole in patients with schizophrenia, bipolar mania, or major depressive disorder who are >=65 years of age is insufficient to determine whether they respond differently than younger adults.
The manufacturer of oral and extended-release IM formulations of aripiprazole states that dosage adjustment is not necessary in geriatric patients on the basis of age alone. The manufacturer of extended-release IM aripiprazole lauroxil states that the safety and efficacy of the drug have not been evaluated in patients >65 years of age and makes no specific dosage recommendations for geriatric patients.
The manufacturer of extended-release IM aripiprazole (Abilify Asimtufii(R)) states that an insufficient number of patients >=65 years of age were included in clinical trials to assess differences in response compared to younger adults; however, dosage selection for elderly patients should be undertaken with caution and dosages should be initiated at the lower end of the dosage range.
Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death. In addition, an increased incidence of adverse cerebrovascular events (cerebrovascular accidents and TIAs), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with aripiprazole in placebo-controlled studies. Aripiprazole is not approved for the treatment of dementia-related psychosis.
In pooled data analyses, a reduced risk of suicidality was observed in adults >=65 years of age with antidepressant therapy compared with placebo.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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