Medical and Pharmacy Editor: Jay W. Marks, MD

GENERIC NAME: olanzapine

BRAND NAME: Zyprexa, Zydis

DRUG CLASS AND MECHANISM: Olanzapine is a medication that is used to treat schizophrenia and acute manic episodes associated with bipolar I disorder. Olanzapine belongs to a drug class known as atypical antipsychotics. Other members of this class include clozapine (Clozaril), risperidone (Risperdal), aripiprazole (Abilify) and ziprasidone (Geodon). The exact mechanism of action of olanzapine is not known. It may work by blocking receptors for several neurotransmitters (chemicals that nerves use to communicate with each other) in the brain. It binds to alpha-1, dopamine, histamine H-1, muscarinic, and serotonin type 2 (5-HT2) receptors. Olanzapine was approved by the FDA in 1996.

PRESCRIPTION: Yes

GENERIC AVAILABLE: No

PREPARATIONS: Tablets: 2.5, 5, 7.5, 10, 15, 20 mg. Intramuscular Injection: 10 mg vial.

STORAGE: Tablets should be kept at room temperature, 20-25°C (68-77°F).

PRESCRIBED FOR: Olanzapine is used for treating schizophrenia and acute mixed, or manic episodes associated with bipolar disorder. It also is used as maintenance therapy for bipolar disorder and treating agitation due to schizophrenia or bipolar disorder.

DOSING: The usual oral dose for treating schizophrenia is 10 mg once daily. Therapy is initiated with 5-10 mg/day and the dose may be increased by 5 mg a day in weekly intervals. Doses greater than 10 mg daily have not been shown to be more effective than 10 mg daily. The safety and efficacy of doses greater than 20 mg daily have not been evaluated.

Treatment of bipolar disorder usually is initiated with oral doses of 10-15 mg once daily. The dose may be increased by 5 mg daily at 24 hour intervals. Doses greater than 20 mg daily have not been evaluated. In clinical trials, doses of 5-20 mg daily were effective.

The usual dose for treating agitation due to schizophrenia or bipolar disorder is 10 mg administered by intramuscular injection. Additional 10 mg doses may be administered, but the efficacy of total daily doses greater than 30 mg daily have not been adequately evaluated.

DRUG INTERACTIONS: Carbamazepine (Tegretol) can reduce blood concentrations of olanzapine, possibly necessitating higher doses of olanzapine. Other drugs that also may reduce blood levels of olanzapine are omeprazole (Prilosec) and rifampin. Smoking may also reduce blood concentrations of olanzapine. Ciprofloxacin (Cipro), diltiazem (Cardizem; Dilacor; Tiazac), erythromycin, and fluvoxamine (Luvox) may have the opposite effect, that is, they may increase blood levels, and the dose of olanzapine may need to be reduced. Olanzapine can cause orthostatic hypotension, a drop in blood pressure upon rising that may cause dizziness or even fainting. Taking olanzapine with either diazepam (Valium), other related benzodiazepines or alcohol can exaggerate the orthostatic hypotension caused by olanzapine.

PREGNANCY: There are no adequate studies of olanzapine in pregnant women. Olanzapine should only be administered to pregnant women if the benefits justify the unknown risks.

NURSING MOTHERS: Olanzapine is excreted into breast milk. Therefore, it is recommended that olanzapine not be used by nursing mothers.

SIDE EFFECTS: Side effects seen with olanzapine include akathisia (an inability to sit still), constipation, dizziness, drowsiness, insomnia, dry mouth, orthostatic hypotension (see DRUG INTERACTIONS), tremor, and weight gain.

Several disorders of movement also may occur with olanzapine, for example, extrapyramidal effects (sudden, often jerky, involuntary motions of the head, neck, arms, body, or eyes). Tardive dyskinesia (involuntary movements of the mouth, tongue, jaw, or eyelids) also may occur in 1 in 100 patients receiving olanzapine. Some cases can be irreversible. The likelihood of developing tardive dyskinesia increases with prolonged treatment.

There may be an increased risk of increased blood sugar levels and diabetes with olanzapine as well as the other antipsychotic medications in its class. Patients should be tested during treatment for elevated blood sugar. Additionally, persons with risk factors for diabetes, including obesity or a family history of diabetes, should have their fasting levels of blood sugar tested before starting treatment and periodically throughout treatment to detect the onset of diabetes. Any patient developing symptoms that suggest diabetes during treatment should be tested for diabetes

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