Olanzapine

Brand Name: Zyprexa

Description

Zyprexa is a thienobenzodiazepine used to treat emotional and mood disorders.

The mechanism of action of olanzapine, as with other antipsychotic drugs, is unknown. However, it has been proposed that this drug's antipsychotic activity is mediated through a combination of dopamine and serotonin type 2 antagonism.

Olanzapine is well absorbed after oral administration reaching peak plasma concentrations within 5 to 8 hours.

Indications and Usage

Olanzapine is indicated for the management of the manifestations of psychotic disorders.

In clinical trials, olanzapine was found to improve both positive and negative symptoms of schizophrenia.

Olanzapine has been shown to be effective in maintaining clinical improvement during one year of continuation therapy in patients who had shown an initial treatment response.

Contraindications

Olanzapine is contraindicated in patients with a known hypersensitivity to the product.

Warnings

Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

The management of NMS should include immediate discontinuation of all antipsychotic drugs including olanzapine, intensive monitoring of symptoms and treatment of any associated medical problems.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

Given these considerations, olanzapine should be prescribed in a manner that is most likely to minimize the risk of tardive dyskinesia. As with any antipsychotic drug, olanzapine should be reserved for patients who appear to be receiving substantial benefit from the drug. In such patients the lowest effective dose and the shortest duration of treatment should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on olanzapine, drug discontinuation should be considered. However, some patients may require treatment with olanzapine despite the presence of the syndrome.

Precautions

Orthostatic Hypotension: Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period. A more gradual titration to the target dose should be considered if hypotension occurs. Olanzapine should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications).

Seizures: During premarketing testing, seizures occurred in 0.9% (22/2500) of olanzapine treated patients. Olanzapine should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold (e.g., Alzheimer's dementia). Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

Caution should be exercised in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic drugs. Periodic assessment of transaminases is recommended in patients with significant hepatic disease.

Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing olanzapine for patients who will be experiencing conditions which may contribute to an elevation in core body temperature (e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Two olanzapine-treated patients in a study of olanzapine in Alzheimer's dementia died from aspiration pneumonia. One of these patients had experienced dysphagia prior to the development of aspiration pneumonia. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's dementia. Olanzapine and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

Suicide: The possibility of a suicide attempt is inherent in schizophrenia, and close supervision of high-risk patients should accompany drug therapy. Prescriptions for olanzapine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Cardiac: Because of the risk of orthostatic hypotension with olanzapine, caution should be observed in cardiac patients.

Usage in Children: The safety and effectiveness of olanzapine in children below the age of 18 have not been established.

Pregnancy & Nursing: The safety of olanzapine in pregnant women has not been established. Therefore, the drug is not recommended during pregnancy. Patients should be advised not to breast-feed an infant if they are taking olanzapine.

There are no adequate and well-controlled trials with olanzapine in pregnant females. Seven pregnancies were observed during clinical trials with olanzapine, including 2 resulting in normal births, 1 resulting in neonatal death due to a cardiovascular defect, 3 therapeutic abortions, and 1 spontaneous abortion. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Interference with Cognitive or Motor Performance: Since olanzapine has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that olanzapine therapy does not affect them adversely.

Drug Interactions

The risks of using olanzapine in combination with other drugs have not been extensively evaluated in systematic studies. Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol.

Because of its potential for inducing hypotension, olanzapine may enhance the effects of certain antihypertensive agents.

Olanzapine may antagonize the effects of antihypertensive agents.

BEFORE USING THIS MEDICINE: INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. This includes carbamazepine and medicines for high blood pressure. Inform your doctor of any other medical conditions including heart conditions, allergies, pregnancy, or breast-feeding.

Adverse Reactions

Side effects that should be reported to your doctor immediately: Difficulty swallowing; stiff arms or legs; trembling and shaking of hands and fingers.

Less common: Chest pain; inability to move eyes; lip smacking or puckering; muscle spasms of face, neck, and back; rapid or worm-like movements of tongue; twitching movements; uncontrolled chewing movements; uncontrolled movements of arms or legs.

Rare: Confusion; mental or physical sluggishness; swelling of face; trouble in breathing

Side effects, that may go away during treatment, include dizziness, drowsiness, constipation, weight gain, and restlessness. If they continue or are bothersome, check with your doctor. If you notice other effects not listed above, contact your doctor, nurse, or pharmacist.

Less common: Abdominal pain; fast heartbeat; increased appetite; increased cough; joint pain; loss of bladder control; low blood pressure; muscle tension; nausea; sore throat; stuttering; thirst; trouble in sleeping; trouble in speaking or slurred speech; vomiting; watering of mouth; weight loss.

Drug Abuse and Dependence: Olanzapine is not a controlled substance.

Olanzapine has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic, and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of misuse or abuse of olanzapine (e.g., development of tolerance, increases in dose, drug-seeking behavior).

Overdose

Signs and Symptoms

Symptoms of overdose may include drowsiness and slurred speech. Other symptoms may include may include somnolence, mydriasis, blurred vision, respiratory depression, hypotension, and possible extrapyramidal disturbances.

Treatment

If you or someone you know may have used more than the recommended dose of this medicine, contact your local poison control center or emergency room immediately.

There is no specific antidote to olanzapine. Therefore, appropriate supportive measures should be initiated. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. (Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of olanzapine-induced alpha blockade.) Close medical supervision and monitoring should continue until the patient recovers.

Dosage

Do not exceed the recommended dosage without checking with your doctor or take this medicine for longer than prescribed.

Follow the directions for using this medicine provided by your doctor.
Store this medicine at room temperature, in a tightly-closed container, away from heat and light.
If you miss a dose of this medicine, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do NOT take 2 doses at once.

Additional Information: Do not share this medicine with others for whom it was not prescribed. Do not use this medicine for other health conditions. Keep this medicine out of the reach of children.

IF YOU WILL BE USING THIS MEDICINE FOR AN EXTENDED PERIOD OF TIME, be sure to obtain necessary refills before your supply runs out.

Usual Dose: Olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg initially, with a target dose of 10 mg/day within several days. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/decrements of 5 mg daily are recommended.

Antipsychotic efficacy was demonstrated in a dose range of 10 to 15 mg/day in the clinical trials. However, doses above 10 mg/day were not demonstrated to be more efficacious than the 10 mg/day dose. An increase to a dose greater than target dose of 10 mg/day (i.e., to a dose of 15 mg/day or greater) is recommended only after clinical assessment. The safety of doses above 20 mg/day has not been evaluated in clinical trials.

Elderly & Debilitated Patients or those with Hypotension: The recommended starting dose is 5 mg. When indicated, dose escalation should be performed with caution in these patients.

Patients with Hepatic and/or Renal Impairment: As clinical experience is lacking in these patients the lower initial starting dose and slower titration to initial target dose should be considered. Further dose escalation, when indicated, should be conservative.

Maintenance Treatment: While there is no body of evidence available to answer the question of how long the patient treated with olanzapine should remain on it, the effectivenss of maintenance treatment is well established for many other antipsychotic drugs. It is recommended that responding patients be continued on olanzapine, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for mainentance treatment.

Usage in Children: Olanzapine is not indicated for patients under 18 years of age.

How Supplied

Zyprexa tablets are white, round, film-coated, and imprinted in blue ink with LILLY and the tablet number: 5 mg imprinted with "4115", 7.5 mg imprinted with "4116", 10 mg imprinted with "4117".

The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.