Aripiprazole

Uses

Schizophrenia

Schizoaffective disorder

Acute manic and mixed episodes associated with Bipolar I Disorder

Maintaining efficacy in patients with Bipolar I Disorder who are stabilized

Aripiprazole is also used to associated treatment for these conditions: Agitation, Bipolar 1 Disorder, Irritability, Major Depressive Disorder (MDD), Mixed manic depressive episode, Psychosis, Psychotic Depression, Schizophrenia, Tourette's Disorder (TD), Acute Manic episode

How Aripiprazole works

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.

Dosage

Aripiprazole dosage

For Schizophrenia:

Adults-10 to 15 mg, once daily, without regard to food. Dose increment should not be made before 2 weeks, the time needed to achieve steady state.

For Bipolar mania:

Adults- 30 mg, once daily, without regard to food.

Side Effects

Headache, constipation, asthenia, nausea, dyspepsia, vomiting, coughing, abdominal pain.

Toxicity

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.

Precaution

Aripiprazole may be associated with orthostatic hypotension (orthostatic lightheadedness).

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

Seizures occurred in aripiprazole-treated patients. As with other antipsychotic drugs, aripiprazole should be used cautiously in patients with Alzheimer\\\'s dementia.

Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.

Interaction

Caution should be exercised when aripipazole is taken in combination with other centrally acting drugs and alcohol. Carbamazepine could cause an increase in aripiprazole clearance and lower blood levels. Ketoconazole, quinidine, fluoxetine or paroxetine can inhibit aripiprazole elimination and cause increased blood levels.

Food Interaction

• Avoid alcohol. Alcohol may increase CNS effects.
• Drink plenty of fluids. Drink water to avoid dehydration while taking aripiprazole.
• Take with or without food. Food does not affect absorption.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Aripiprazole Cholesterol interaction

[Moderate] Atypical antipsychotic drugs have been associated with undesirable alterations in lipid levels.

While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile.

Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.

Aripiprazole Drug Interaction

Moderate: duloxetine, duloxetine, lithium, lithium, pregabalin, pregabalin, lisdexamfetamine, lisdexamfetamineUnknown: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, vortioxetine, vortioxetine, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Aripiprazole Disease Interaction

Major: dementia, acute alcohol intoxication, CNS depression, NMS, tardive dyskinesiaModerate: depression, aspiration, seizure, hematologic abnormalities, hyperglycemia/diabetes, hypotension, lipid alterations, weight gain, anticholinergic effects, hyperprolactinemia, liver disease, parkinsonism

Volume of Distribution

404L or 4.9L/kg.

Elimination Route

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.

Half Life

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.

Clearance

0.8mL/min/kg. Other studies have reported a clearance rate of 3297±1042mL/hr.

Elimination Route

25% of a given dose will be eliminated in urine and 55% in the feces. Label,4.

Pregnancy & Breastfeeding use

Aripiprazole should not be used in pregnancy as no human trial is performed. Patients should be advised not to breast-feed an infant if they are taking aripiprazole.

Contraindication

Aripiprazole is contraindicated in patients who are hypersensitive to it or to any component of this product.

Acute Overdose

Aripiprazole at doses up to 1080 mg causes no fatalities. The signs and symptoms observed with aripiprazole overdose included nausea, vomiting, asthenia, diarrhea, and somnolence.

Interaction with other Medicine

Caution should be exercised when aripipazole is taken in combination with other centrally acting drugs and alcohol. Carbamazepine could cause an increase in aripiprazole clearance and lower blood levels. Ketoconazole, quinidine, fluoxetine or paroxetine can inhibit aripiprazole elimination and cause increased blood levels.

Innovators Monograph

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