ARIPIPRAZOLE

Aripiprazole activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D 2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma. The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active...

Efficacy of the oral formulations of aripiprazole was established in the following adequate and well-controlled trials:

• Four short-term trials and one maintenance trial in adult patients and one short-term trial in adolescents (ages 13 to 17) with schizophrenia [see Clinical Studies (14.1) ]
• Four short-term monotherapy trials and one 6-week adjunctive trial in adult patients and one short-term monotherapy trial in pediatric patients (ages 10 to 17) with manic or mixed episodes [see Clinical Studies (14.2) ]
• One maintenance monotherapy trial and in one maintenance adjunctive trial in adul...

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following adverse reactions are discussed in more detail in other sections of the labeling:

• Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning and Warnings and Precautions (5.1) ]
• Cerebrov...

Aripiprazole oral solution is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis [see Adverse Reactions (6.2) ].

• Known hypersensitivity to aripiprazole oral solution (4)

• Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities) (5.2)
• Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring (5.4)
• Tardive Dyskinesia: Discontinue if clinically appropriate (5.5)
• Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemi...

7 DRUG INTERACTIONS Dosage adjustment due to drug interactions (7.1) : Factors Dosage Adjustments for Aripiprazole oral solution Known CYP2D6 Poor Metabolizers Administer half of usual dose Known CYP2D6 Poor Metabolizers and strong CYP3A4 inhibitors Administer a quarter of usual dose Strong CYP2D6 or CYP3A4 inhibitors Administer half of usual dose Strong CYP2D6 and CYP3A4 inhibitors Administer a q...