Abilify

Abilify Information

Generic Name: Aripiprazole

Abilify (aripiprazole) is a psychotropic drug that is available as tablets for oral administration.

Abilify (aripiprazole) is indicated for the treatment of schizophrenia.

Abilify Ingredients and Composition

How Does Abilify Work?

Pharmacodynamics

Aripiprazole, the active ingredient in Abilify, 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 sero-tonin 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, the active ingredient in Abilify, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that the efficacy of aripiprazole 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.

How To Take Abilify and Abilify Dosage and Administration

Usual Dose

The recommended starting and target dose for Abilify (aripiprazole) 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.

Dosage in Special Populations

Abilify dosage adjustments are not routinely indicated on the basis of age, gender, race, or renal or hepatic impairment status.

Dosage adjustment for patients taking aripiprazole concomitantly with potential CYP3A4 inhibitors: When concomitant administration of ketoconazole with Abilify (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 Abilify (aripiprazole) concomitantly with potential CYP2D6 inhibitors: When concomitant administration of potential CYP2D6 inhibitors such as Ativan, 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 Abilify (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 Abilify (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 anti-psychotic 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.

If you suspect a Abilify Overdose

Human Experience

In premarketing clinical studies, involving more than 5500 patients, accidental or intentional acute overdosage of Abilify (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).

Management of Overdosage

No specific information is available on the treatment of overdose with Abilify (aripiprazole). An elec-trocardiogram 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%.

Hemodialysis:

Although there is no information on the effect of hemodialysis in treating an overdose with Abilify (aripiprazole), hemodialysis is unlikely to be useful in overdose management since aripiprazole is highly bound to plasma proteins.

Abilify Side Effects

Abilify Precautions and Contraindications

Because Abilify (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.

General Orthostatic Hypotension

Abilify (aripiprazole) may be associated with orthostatic hypotension, perhaps due to its a1-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).

Abilify (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 Abilify-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 anti-psychotics, 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 such as Abilify. 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. Abilify (aripiprazole) and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

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.