Agitation Associated With Schizophrenia or Bipolar Mania
Adults:IM Recommended dose is 9.75 mg. A lower dose of 5.25 mg may be considered based on clinical factors. If agitation persists, cumulative dosages of up to 30 mg/day may be given. The safety of total daily doses greater than 30 mg or injections given more frequently than every 2 h has not been adequately evaluated.
Adults:PO Recommended starting and target dose is 15 mg as monotherapy or adjunctive therapy with lithium or valproate given once daily. The dosage can be increased to 30 mg/day based on clinical response.
Children 10 to 17 yr of age:PO Start with 2 mg/day, then titrate to 5 mg/day after 2 days and to the target dosage of 10 mg/day after 2 additional days. Subsequent dose increases should be in 5 mg/day increments up to 30 mg/day.
Irritability Associated With Autistic Disorder
Children 6 to 17 yr of age:PO Start with 2 mg/day and increase to 5 mg/day, with subsequent increases to 10 or 15 mg/day if needed. Dosage adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 wk.
Major Depressive Disorder
Adults:PO Recommended starting dosage for patients already receiving an antidepressant is 2 to 5 mg/day. Gradually make dose adjustments of up to 5 mg/day at intervals of no less than 1 wk. Efficacy of adjunctive therapy was established within the range of 2 to 15 mg/day.
Adults:PO Start with 10 or 15 mg/day once a day. The effective dose range is 10 to 30 mg/day. Do not increase dosage before 2 wk.
Children 13 to 17 yr of age:PO Start with 2 mg/day, then titrate to 5 mg/day after 2 days and to a target dose of 10 mg after 2 additional days. Subsequent dose increases should be in 5 mg/day increments up to 30 mg/day. 30 mg/day was not shown to be more efficacious than 10 mg/day.
Because of the increased risk of CNS depression, advise patients to avoid alcohol while taking aripiprazole.
Because of its alpha-adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents. Monitor the patient and adjust the dose of the antihypertensive agent as needed.
Centrally acting drugs
Because of the increased risk of CNS depression, use with caution.
May elevate aripiprazole plasma levels, increasing the pharmacologic effects and adverse reactions. During coadministration, reduce the aripiprazole dose to 50% of the normal dose. When the CYP2D6 inhibitor is discontinued, increase the dose of aripiprazole. In addition, coadministration increased plasma concentrations of fluoxetine and decreased paroxetine concentrations.
CYP3A4 inducers (eg, carbamazepine)
May reduce aripiprazole plasma levels, decreasing the therapeutic effect and necessitating dosage adjustments. For example, when carbamazepine is added to aripiprazole therapy, double the aripiprazole dose. Additional aripiprazole dose increases should be based on clinical evaluation of the patient. When the CYP3A4 inducer is discontinued, decrease the dose of aripiprazole.
Aripiprazole plasma concentrations may be elevated, increasing the pharmacologic and adverse reactions. With coadministration, reduce the aripiprazole dose to 50% of the normal dose. When the CYP3A4 inhibitor is discontinued, increase the dose of aripiprazole
Protein Binding: aripiprazole and dehydro-aripiprazole —>99%.
Metabolism/Excretion: Mostly metabolized by the liver (CYP3A4 and CYP2D6 enzymes); one metabolite (dehydro-aripiprazole) has antipsychotic activity. 18% excreted unchanged in feces; <1% excreted unchanged in urine. A small percentage of patients are poor metabolizers and may need smaller doses.