Jane S. Ricciuti, RPh, MS

Disclosures

December 27, 2002

In This Article

Psychotropic Agents

Abilify
(aripiprazole) Tablets

Manufacturer: Otsuka Pharmaceutical Co, Ltd.

Drug Approval Classification: Original New Drug Application (Approval Date: 11/15/02)

Indication: Abilify (aripipazole) is indicated for the treatment of schizophrenia. The efficacy of Abilify in the treatment of schizophrenia was established in short-term (4- and 6-week) controlled trials of schizophrenic inpatients. The long-term efficacy of aripiprazole in the treatment of schizophrenia has not been established. The physician who elects to use Abilify for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Dosing: The recommended starting and target dose for Abilify is 10 or 15 mg/day administered on a once-a-day schedule without regard to meals. In clinical trials, doses higher than 10 or 15 mg/day did not demonstrate greater efficacy than doses in the range of 10 or 15 mg/day. Dosage increases should not be made before 2 weeks, the time needed to achieve steady state. Duration of treatment has not been evaluated in a clinical trial.

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 aripiprazole occurs, aripiprazole dose should be reduced to one half the usual dose. When the CYP3A4 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.

Dosage adjustment for patients taking aripiprazole concomitantly with potential CYP2D6 inhibitors: When concomitant administration of potential CYP2D6 inhibitors such as quinidine, fluoxetine, or paroxetine with aripiprazole occurs, aripiprazole dose should be reduced at least to one half its normal dose. When the CYP2D6 inhibitor is withdrawn from the combination therapy, the aripiprazole dose should then be increased.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 aripiprazole therapy, the aripiprazole dose should be doubled (to 20 or 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 When carbamazepine is withdrawn from the combination therapy, the aripiprazole dose should be reduced to 10 to 15 mg.

Available strengths include 10 mg, 15 mg, 20 mg, and 30 mg oral tablets.

Clinical Summary: Aripiprazole, also known as 7-[4-[4-(2,3-dichlorophenyl)-1-iperazinyl]butoxy]-3,4-dihydrocarbostyril, is classified as a psychotropic drug. 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 is unknown. The proposed 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.

Abilify was studied in more than 1300 patients in 4 short-term (4- and 6-week), placebo-controlled/active-controlled (risperidone) trials of acutely relapsed inpatients who predominantly met DSM-III/IV criteria for schizophrenia. Three of the clinical studies were positive for Abilify, but 1 study did not demonstrate an effect compared with placebo.

There were 4 scales used to determine primary end points to assess for psychiatric signs and symptoms:

The Positive and Negative Syndrome Scale (PANSS)

  • The PANSS positive subscale

  • The PANSS negative subscale

  • The Clinical Global Impression (CGI) assessment

  • In both the 4-week and 6-week trials, patients treated with Abilify showed clinical improvement superior to that seen with placebo or risperidone.

    Adverse Effects: The most common adverse events experienced during clinical trials with Abilify are listed in the Table .

    Two possible cases of neuroleptic malignant syndrome (NMS) have been reported in association with aripiprazole. Signs and symptoms of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia).

    Caution is advised in using aripiprazole in patients with a history of seizures. Seizures occurred in 0.1% (1/926) of aripiprazole-treated patients. Caution is also advised in patients with Alzheimer's disease.

    Pharmacokinetics: The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole (major metabolite), respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties. Elimination of aripiprazole is mainly through hepatic metabolism involving isozymes CYP2D6 and CYP3A4.

    Peak plasma concentrations occur 3 to 5 hours post oral administration.

    Drug Interactions: Agents that induce CYP3A4 (eg, carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (eg, ketoconazole, itraconazole) or CYP2D6 (eg, quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels.

    Specific aripiprazole drug interactions studies were conducted for:

    Ketoconazole: When concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be reduced to one half its normal dose.

  • Quinidine: Aripiprazole dose should be reduced to one half its normal dose when concomitant administration of quinidine with aripiprazole occurs.

  • Carbamazepine: When carbamazepine is added to aripiprazole therapy, aripiprazole dose should be doubled.

  • Reference

    Abilify (aripiprazole) Tablets labeling

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