1 Star2 Stars3 Stars4 Stars5 Stars (No Ratings Yet)
blankLoading...

Aripiprazole

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

INNs in other languages (French, Latin, and Spanish): Anpiprazol; Anpiprazolum; OPC-31; OPC-14597.

Adverse Effects, Treatment, and Precautions

Although aripiprazole may share some of the adverse effects seen with the classical antipsychotics (see Chlorpromazine), the incidence and severity of such effects may vary. Common adverse effects with aripiprazole include gastrointestinal disorders such as constipation, dyspepsia, nausea, and vomiting, headache, anxiety, insomnia, lightheadedness, and drowsiness. Weight gain has been reported however, this appears to be slight. The incidence of extrapyramidal effects with aripiprazole is low with akathisia being most commonly reported. Tardive dyskinesia has been reported infrequently and there have been a few cases of neuroleptic malignant syndrome. Tachycardia and orthostatic hypotension are uncommon with aripiprazole treatment bradycardia, ventricular arrhythmias, cardiac arrest, and sudden unexplained death have been reported very rarely as have QT prolongation and torsade de pointes. Nonetheless aripiprazole should be used with caution in patients with cardiovascular or cerebrovascular disease, or in those with conditions that would predispose to hypotension.

Seizures are rare with aripiprazole but it should be used with care in those with a history of seizures or with conditions that lower the seizure threshold. When aripiprazole is used as an adjunct in depression, patients should be closely monitored during early therapy until significant improvement in depression is observed because suicide is an inherent risk in depressed patients. For further details, see under Depression.

Aripiprazole may affect the performance of skilled tasks including driving.

 

aripiprazole_5mg

Dementia. The FDA has issued advice against the use of atypical antipsychotics in the treatment of behavioural problems in elderly patients with dementia after analysis of placebo-controlled studies showed an increased risk of mortality with certain drugs of this class, including aripiprazole most of the deaths appeared due to cardiovascular events or infection. See also under Risperidone.

The manufacturer subsequently also included a warning in the licensed product information for aripiprazole about evidence of a dose-response relationship between cerebrovascular adverse events and the use of aripiprazole in elderly patients with psychosis associated with Alzheimer’s disease.

Effects on body-weight. The increased risk of weight gain with some atypical antipsychotics is discussed under Adverse Effects of Clozapine.

Effects on carbohydrate metabolism. The increased risk of glucose intolerance and diabetes mellitus with some atypical antipsychotics, and recommendations on monitoring, are discussed under Adverse Effects of Clozapine.

Effects on lipid metabolism. The increased risk of hyperlip-idaemia with some atypical antipsychotics is discussed under Adverse Effects of Chlorpromazine. See also Effects on Carbohydrate Metabolism under Adverse Effects of Clozapine.

Overdosage. The manufacturer has reported that patients have taken estimated overdoses of up to 1080 mg of aripiprazole with no fatalities. Signs and symptoms have included nausea, vomiting, asthenia, diarrhoea, and somnolence. In one report a 27-year-old woman who ingested 330 mg of aripiprazole with cyclobenzaprine 10 mg and quetiapine 25 mg was found to be drowsy but easily rousable 50 minutes later. Initial treatment consisted of oral activated charcoal recovery was subsequently uneventful. Serum concentrations of aripiprazole and its main metabolite dehydro-aripiprazole, measured 195 minutes after in-gestion, were 596 nanograms/mL and 120 nanograms/mL respectively. In another report a 2/ -year-old child vomited and became lethargic within 1 hour of taking 195 mg of aripiprazole (17.1 mg/kg). Activated charcoal was given 3 hours after inges-tion but she subsequently became unconscious. However, respiratory support was not required and the child gradually regained consciousness over the next 24 hours. Symptoms of somnolence, ataxia and tremulousness resolved over 7 days. The serum concentration of aripiprazole plus dehydro-aripiprazole was found to be 1873 nanograms/mL 10 hours after ingestion.

Pregnancy. For comments on the use of some atypical antipsy-chotics, including aripiprazole, during pregnancy, see under Precautions of Clozapine.

Licensed product information states that aripiprazole showed possible teratogenic effects in some animals it was noted that there are no adequate and well-controlled studies in human pregnancy. Aripiprazole should only be used if the benefits to the mother outweigh the risks to the fetus.

aripiprazole_30mg

Interactions

The central effects of other CNS depressants including alcohol may be enhanced by aripiprazole. Aripiprazole may also enhance the effects of antihypertensive drugs. It should be used with caution in patients also receiving drugs that prolong the QT interval or cause electrolyte imbalance.

Aripiprazole is metabolised by the cytochrome P450 isoenzymes CYP3A4 and CYP2D6. Ketoconazole, a potent CYP3A4 inhibitor, can increase aripiprazole plasma concentrations by about 60% licensed product information states that the dose of aripiprazole should be reduced by half when given with ketoconazole. Similarly, the dose of aripiprazole should be halved when given with quinidine, a potent inhibitor of CYP2D6. Conversely, plasma concentrations of aripiprazole may decrease by about 70% when given with carbamazepine, a potent CYP3 A4 inducer the dose of aripiprazole should be doubled if carbamazepine is added to aripiprazole treatment. Similar effects may occur with other potent inhibitors or inducers of these isoenzymes and a reduced or increased dose of aripiprazole, respectively, in such combinations is recommended.

Antiepileptics. For a report of Stevens-Johnson syndrome occurring on use of aripiprazole with lamotrigine.

Pharmacokinetics

Aripiprazole is well absorbed from the gastrointestinal tract after oral doses with peak plasma concentrations reached in about 3 to 5 hours. Following intramuscular injection, peak plasma concentrations are reached between 1 to 3 hours. The absolute bioavailability is reported to be 87% with tablet formulations and 100% with the intramuscular injection it is widely distributed. Aripiprazole is metabolised mainly in the liver and pathways involved include dehydrogenation and hydroxylation, via the cytochrome P450 isoenzymes CYP3A4 and CYP2D6, and N-dealkylation, via CYP3 A4. The major metabolite, dehydro-aripiprazole, is also active and represents about 40% of the plasma levels of aripiprazole. The mean elimination half-lives of aripiprazole and dehydro-aripiprazole are about 75 and 95 hours, respectively in a minority of poor metabolisers the half-life of aripiprazole may be extended to about 146 hours. Protein binding of aripiprazole and its major metabolite is about 99%, mainly to albumin. Elimination is mostly in the faeces (about 55%), with about 25% of a dose appearing in the urine, mainly in the form of metabolites. On the basis of studies in rats, it is thought to be distributed into breast milk.

Uses and Administration

Aripiprazole is an atypical antipsychotic that has serotonin 5-HT1A-receptor partial agonist and 5-HT2A-re-ceptor antagonist properties as well as being a partial agonist at dopamine D2 receptors. It is used in the management of schizophrenia and in acute manic or mixed episodes associated with bipolar disorder. Aripiprazole is also used as an adjunct in the treatment of depression.

For the treatment of schizophrenia, aripiprazole is given in an initial oral dose of 10 or 15 mg once daily. The usual maintenance dose is 15 mg once daily although the dose may be adjusted at intervals of not less than 2 weeks up to a maximum of 30 mg daily.

Aripiprazole is also used for the treatment of mania associated with bipolar disorder. In the USA, it is given in an initial oral dose of 30 mg once daily, this may subsequently be decreased to 15 mg once daily according to tolerance. Similar doses are licensed in the UK although licensed product information recommends an initial dose of 15 mg once daily.

Aripiprazole may be given by deep intramuscular injection for acute agitation in patients with schizophrenia or bipolar mania. The recommended initial dose is 9.75 mg although some patients may only need 5.25 mg and others up to 15 mg. If necessary, further doses may be given after at least 2 hours, up to a maximum total daily dose of 30 mg. Patients should be switched to oral therapy as soon as possible if ongoing treatment is required.

Aripiprazole is used as adjunctive therapy in depression. US licensed product information recommends an initial oral dose of 2 to 5 mg once daily, which may be adjusted in increments of up to 5 mg at intervals of not less than 1 week to a maximum of 15 mg daily. The usual recommended dose is 5 to 10 mg once daily.

Dose adjustments of aripiprazole may be necessary in patients also taking potent inhibitors or inducers of cytochrome P450 isoenzymes. See Interactions, above for further details.

For details of uses and associated doses in children, see below.

Aripiprazole_group

Administration in children. In the USA, aripiprazole may be used for the treatment of schizophrenia in adolescents aged 13 to 17 years and for the treatment of acute manic or mixed episodes associated with bipolar disorder in those aged 10 to 17 years. For both indications, the recommended initial oral dose is 2 mg daily increased to 5 mg daily after 2 days and then to the target dose of lOmg daily after another 2 days subsequent dose increases should be made in 5-mg increments up to a total maximum dose of 30 mg daily.

Dose adjustments of aripiprazole may be necessary in patients also taking potent inhibitors or inducers of cytochrome P450 isoenzymes. See Interactions, above for further details.

Psychiatric disorders. Aripiprazole is used in the management of schizophrenia and bipolar disorder. Although data are scanty, systematic reviews’ have concluded that aripiprazole does not have significant advantages over other atypical and classical antipsychotics in the treatment of schizophrenia. However, it was found to have a lower risk for hyperpro-lactinaemia and QT interval prolongation compared with other atypical antipsychotics, and a higher risk for insomnia compared with classical antipsychotics. Aripiprazole is also used as an adjunct in the treatment of depression.

 

Preparations

Proprietary Preparations

Argentina: Arlemide Graven Irazem Siblix

Australia: Abilify

Belgium: Abilify

Brazil: Abilify

Chile: Abilify Azymol Viza

Czech Republic: Abilify

Denmark: Abilify

Finland: Abilify

France: Abilify

Germany: Abilify

Greece: Abilify

Hong Kong: Abilify

Hungary: Abilify

India: Real One

Indonesia: Abilify

Ireland: Abilify

Italy: Abilify

Malaysia: Abilify

Mexico: Abilify

The Netherlands: Abilify

Norway: Abilify

New Zealand: Abilify

Philippines: Abilify

Portugal: Abilify

South Africa: Abilify

Singapore Abilify

Spain: Abilify

Sweden: Abilify

Switzerland: Abilify

Thailand: Abilify

UK: Abilify

USA: Abilify

Venezuela: Abilify

Leave a Reply

  Subscribe  
Notify of