Rx Update: March 2003

Aripiprazole

Mary Ross, R.Ph., M.B.A., Joan Murhammer, R.Ph., Kevin Bebout, R. Ph.
First Published: March 2003
Last Revised: March 2003

Peer Review Status: Internally Reviewed


Aripiprazole (Abilify®) is an antipsychotic agent indicated for the treatment of schizophrenia. The mechanism of action for aripiprazole is not known, but it is postulated that its efficacy for schizophrenia is related to its partial agonist activity at dopamine D2 and serotonin 5-HT1 receptors and antagonist activity at serotonin 5-HT2 receptors.

The most common adverse events reported with aripiprazole therapy include headache, anxiety, insomnia, nausea, vomiting, lightheadedness, somnolence, constipation, and akathisia. Aripiprazole has the potential to cause neuroleptic malignancy syndrome, tardive dyskinesia, disruption in body temperature regulation, esophageal dysmotility and aspiration as do other antipsychotic agents. Aripiprazole has been associated with orthostatic hypotension and should be use with caution in patients with cardiovascular disease, cerebrovascular disease, or conditions which would predispose patents to hypotension. Aripiprazole can potentiate the effects of antihypertensive medications. It should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold; seizures have occurred in 0.1% of patients treated with aripiprazole.

The recommended starting dose of aripiprazole is 10 to 15 mg orally once daily. It can be given without regard to meals. The dosage range that has been studied in clinical trials is 10 to 30 mg once daily. Dosage does not need to be adjusted based on renal or liver impairment. Aripiprazole dosing does need to be adjusted when administered concomitantly with medications that affect the cytochrome P450 system. Aripiprazole dosing should be reduced by one-half of the normal dose (5 to 7.5 mg daily) when administered with medications that inhibit the CYP3A4 (e.g., ketoconazole) or CYP2D6 (e.g., quinidine, fluoxetine, paroxetine) enzyme systems. Aripiprazole dosing should be doubled (20 to 30 mg daily) when administered concomitantly with medications that induce CYP3A enzyme system (e.g., carbamazepine). Dosage needs to be adjusted if these medications are subsequently discontinued during aripiprazole therapy.

Aripiprazole is available in 10, 15, 20, and 30 mg tablets.


Safety Reminder: Don't Give Sterile Water IV

The need to provide free water (water not associated with organic or inorganic ions) rapidly to patients with severe electrolyte imbalances (e.g., hypernatremia) and/or hyperglycemia can be challenging, especially in patients with preexisting conditions such as congestive heart failure. In such situations, physicians may not want the patient to receive any infusions containing sodium or dextrose and may thus be tempted to order sterile water for injection to be administered intravenously. However, this practice can have disastrous consequences for patients. Extremely rapid correction of hypernatremia may lead to cerebral edema, seizures and possibly death. Sterile water for injections should never be given IV without additives to normalize tonicity, or hemolysis of blood cells may occur. When indicated clinically, water can be replaced orally.

Pharmacy will not dispense sterile water for injection without additives to be infused intravenously. Treatment of severe hypernatremia generally consists of infusions that contain lower concentrations of sodium (e.g., 0.2% or 0.45%) to reduce blood sodium levels slowly. Alternatives may also include D5 1/4 NS or D5 1/2 NS. If there are concerns about using dextrose solutions, elevated blood sugars can be treated with insulin. If there are concerns about fluid volume, patients can be given diuretics. If an order for sterile water is received, it should immediately be clarified with the physician.

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