aripiprazole

Action

Unclear. Thought to exert partial agonist activity at central dopamine D₂ and type 1A serotonin (5-HT_1A) receptors and antagonistic activity at serotonin 5-HT_2A receptors. Also has alpha-adrenergic and histamine₁-blocking properties.

Availability

Injection: 9.75 mg/1.3 ml (7.5 mg/ml)

Oral solution: 1 mg/ml

Tablets: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg

Tablets (orally disintegrating): 10 mg, 15 mg

Indications and dosages

➣ Schizophrenia

Adults: 10 to 15 mg P.O. daily. If needed, increase to 30 mg daily after 2 weeks.

Adolescents ages 13 to 17: Initially, 2 mg P.O. daily; increase to 5 mg P.O. after 2 days. Then increase to 10 mg P.O. after 2 additional days. Subsequent dosage intervals should occur in increments no greater than 5 mg, up to a maximum of 30 mg.

➣ To maintain stability in schizophrenic patients

Adults: 15 mg P.O. daily. Therapy may continue for up to 26 weeks with periodic evaluations.

Adolescents ages 13 to 17: General recommendation, continue responding patients beyond the acute response but at the lowest dosage needed to maintain remission.

➣ Acute manic and mixed episodes associated with bipolar disorder

Adults: 30 mg P.O. daily for up to 3 weeks

➣ Agitation associated with schizophrenia or bipolar mania

Adults: Usual dosage, 5.25 to 15 mg I.M. as single dose. Recommended dosage is 9.75 mg I.M. as single dose. No additional benefit was demonstrated for 15 mg compared to 9.75 mg. Lower dosage of 5.25 mg may be considered when clinical factors warrant. If agitation warranting second dose persists following initial dose, cumulative dosages up to total of 30 mg/day may be given. However, efficacy of repeated doses in agitated patients hasn't been systematically evaluated in controlled clinical trials. Also, safety of total daily doses greater than 30 mg or injections given more frequently than every 2 hours hasn't been adequately evaluated in clinical trials. If ongoing aripiprazole therapy is clinically indicated, oral aripiprazole ranging from 10 to 30 mg/day P.O. should replace aripiprazole injection as soon as possible.

➣ Adjunctive treatment of major depressive disorder

Adults: Initially, 2 to 5 mg P.O. daily. May increase up to 15 mg daily at increments of up to 5 mg/day at intervals of no less than 1 week.

Dosage adjustment

• Concurrent use of potent CYP3A4 inhibitors (such as ketoconazole), CYP2D6 inhibitors (such as fluoxetine, paroxetine, quinidine), or CYP3A4 inducers (such as carbamazepine)

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:

• cerebrovascular disease, hypotension, seizure disorder, suicidal ideation

• high risk for aspiration pneumonia

• neuroleptic malignant syndrome, tardive dyskinesia, diabetes mellitus

• leukopenia, neutropenia, agranulocytosis

• pregnant or breastfeeding patients

• elderly patients (with dementia-related psychosis)

• children, adolescents, and young adults with major depressive disorder

Administration

• Give with or without food.

• Don't administer with grapefruit juice.

• Be aware that oral solution may be substituted for tablets on a mg-to-mg basis up to 25-mg dose. Patients receiving 30 mg of tablets should receive 25 mg of oral solution.

Adverse reactions

CNS: dizziness, insomnia, akathisia, agitation, anxiety, headache, light-headedness, drowsiness, tremor, tardive dyskinesia, seizures, neuroleptic malignant syndrome, increased suicide risk

CV: orthostatic hypotension, hypertension, peripheral edema, chest pain, bradycardia, tachycardia

EENT: rhinitis

GI: nausea, vomiting, diarrhea, constipation, jaundice, abdominal pain, esophageal motility disorders, dysphagia

GU: urinary incontinence

Respiratory: cough

Skin: rash

Other: fever, hypersensitivity reactions (including anaphylaxis)

Interactions

Drug-drug. CNS depressants: increased sedation

Drugs that induce CYP3A4: decreased aripiprazole effect

Drugs that inhibit CYP3A4 or CYP2D6: serious toxic effects

Other antipsychotic agents: increased extrapyramidal effects

Drug-diagnostic tests. Granulocytes, leukocytes, neutrophils: decreased values

Serum glucose: increased level

Drug-herbs. Kava: increased CNS depression

Drug-behaviors. Alcohol use: increased sedation

Patient monitoring

☞ Watch for signs and symptoms of depression, and evaluate patient for suicidal ideation.

• Monitor neurologic status closely. Watch for tardive dyskinesia.

☞ Evaluate patient for neuroleptic malignant syndrome (fever, altered mental status, rigid muscles, arrhythmia, tachycardia, sweating). Stop drug and notify prescriber if these signs and symptoms occur.

• Monitor blood pressure, pulse, CBC with differential, and weight.

☞ Monitor blood glucose level closely; be aware that in patients with diabetes mellitus or risk factors for diabetes, serious hyperglycemia possibly associated with coma or death may occur.

Patient teaching

☞ Instruct patient to immediately contact prescriber if he experiences depression or has suicidal thoughts, altered mental status, rigid muscles, irregular heart beat, excessive sweating, rash, itching, difficulty breathing, or excessive thirst or urination.

• Inform patient that symptoms will subside slowly over several weeks.

• Tell patient he may take drug with or without food.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell patient that drug may cause urinary incontinence.

• Caution patient to avoid strenuous exercise and hot environments whenever possible.

• Instruct patient to move slowly when rising to avoid dizziness from sudden blood pressure decrease.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, herbs, and behaviors mentioned above.