Olanzapine (Zyprexa)

Antipsychotic agent that blocks multiple neurotransmitters: dopamine at D1, D2, D3 and D4 brain receptors, serotonin at 5-HT2A, 5-HT2c, 5-HT3 and 5-HT6 receptors, catecholamines at alpha1-adrenergic receptors, acteylcholine at muscarinic receptors, and histamine at H1 receptors.


Trade name Zyprexa

Pregnancy category C

Routes of administrationare oral, and intramuscular.

Bioavailability 87%.

Protein binding 93%.

Metabolism is by hepatic mechanisms of direct glucuronidation and CYP1A2 mediated oxidation.

Biological half-life 33 hours, and 51.8 hours in elderly.

Excretion in urine 57% and 7% as unchanged drug.

Fecal excretion 30%.

An atypical antipsychotic.

Approved for the treatment of schizophrenia and bipolar disorder.

Structurally similar to clozapine and quetiapine.

A dopamine antagonist and is classified as a thienobenzodiazepine.

A first-line psychiatric treatment for schizophrenia.

Reduces nausea and vomiting in patients with advanced cancer.

Usefulness for maintenance therapy is difficult to determine as more than half of people in trials quit before the six-week completion date.

Superior to haloperidol in providing a lower discontinuation rate, and in short-term symptom reduction, response rate, negative symptoms, depression, cognitive function, discontinuation due to poor efficacy, and long-term relapse.

Causes less extrapyramidal side effects, less akathisia than haloperidolca

Associated with significantly more weight gain, serum cholesterol increase, and triglyceride increase than haloperidol.

Among 10 atypical antipsychotics, only clozapine, olanzapine, and risperidone were better than first generation antipsychotics.

Olanzapine is effective in treating the acute exacerbations of schizophrenia.

Olanzapine is recommended as a first line therapy for the treatment of acute mania in bipolar disorder.

It is recommended in combination with fluoxetine as a first line therapy for acute bipolar depression; and as a second line treatment by itself for the maintenance treatment of bipolar disorder.

A meta analysis concluded that olanzapine plus fluoxetine is the most effective among treatments for bipolar depression.

Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks.

Evidence does not support the use of atypical antipsychotics including olanzapine in eating disorders.

It has also been used for Tourette syndrome and stuttering.

Should not be given to elderly patients with dementia because of a higher risk of stroke.

The principal side effect of olanzapine is weight gain.

May be associated with derangement in the blood lipid and blood sugar profiles.

Had the highest propensity for causing weight gain out of the 15 antipsychotic drugs.

Extrapyramidal side effects are infrequent to rare, and include tremors and muscle rigidity.

May produce hyperglycemia in patients with diabetes mellitus.

Associated with a greater risk of falls and accidental injury in the elderly.

Young males are at a at higher risk of dystonic reactions.

May disrupt the body’s natural thermoregulatory systems.

Occasionally it can provoke serious paradoxical reactions causing unusual changes in personality, thoughts or behavior.

Direct glucuronidation and cytochrome P450 mediated oxidation are primary metabolic pathways for olanzapine.

Studies suggest that CYPs 1A2 and 2D6, and the flavin-containing monooxygenase system are involved in olanzapine oxidation.

Use associated with a risk of developing hyperglycemia and diabetes, factors in the metabolic syndrome that may be related to the drugs’ ability to induce weight gain.

Of all the atypical antipsychotics, olanzapine is one of the most likely to induce weight gain, and the effect is dose dependent.

There are some reports of olanzapine-induced diabetic ketoacidosis.

May decrease insulin sensitivity, and may also increase triglyceride levels.

Is associated with the highest placental exposure of any atypical antipsychotic.

The available evidence suggests it is safe during pregnancy,

It is associated with weight gain.

Breastfeeding is advised against due to the fact that it is is secreted in breast milk.

It is recommended to have a gradual withdrawal when discontinuing anti-psychotic treatment to avoid acute withdrawal syndrome or rapid relapse, as compensatory changes at dopamine, serotonin, adrenergic and histamine receptor sites in the central nervous system can occur during abrupt or over-rapid reduction in dosage.

No specific guidelines with proven safety and efficacy for withdrawal are currently available.

After discontinuation of antipsychotics withdrawal symptoms include: nausea, vomiting, lightheadedness, diaphoresis, dyskinesia, orthostatic hypotension, tachycardia, nervousness, dizziness, headache, excessive non-stop crying, and anxiety.

The withdrawal process itself may be schizo-mimetic, producing schizophrenia-like symptoms even in previously healthy patients.

Symptoms of an overdose include:tachycardia, agitation, dysarthria, decreased consciousness and coma.

There is no known specific antidote for overdose.

Considered moderately toxic in overdose; more toxic than quetiapine, aripiprazole and the SSRIs and less toxic than the MAOIs and TCAs.

Zyprexa (olanzapine) 10 mg tablets.

Has among the highest affinity of any second-generation antipsychotic towards the P-glycoprotein.

A potent antagonist of the muscarinic M3 receptor, which may underlie its diabetogenic side effects.

Method of action of antipsychotic activity is unknown, but it may involve antagonism of dopamine and serotonin receptors.

Antagonism of dopamine receptors is associated with extrapyramidal effects such as tardive dyskinesia and with its therapeutic effects.

Antagonism of muscarinic acetylcholine receptors is associated with anticholinergic side effects such as dry mouth, and constipation.

Poses a relatively low risk of extrapyramidal side effects including tardive dyskinesia , due to its high affinity for the D1 receptor over the D2 receptor.

Metabolized by the cytochrome P450 system.

More than 40% of the oral dose is removed by the hepatic first-pass effect.

Drugs or agents that increase the activity of CYP1A2, may significantly increase hepatic first-pass clearance.

Drugs which inhibit CYP1A2 activity such as Ciprofloxacin, may reduce clearance.

Zyprexa and generic olanzapine are available as an orally-disintegrating wafers which rapidly dissolves in saliva.

Also available in 10 milligram vials for intramuscular injection.

Can be used as an antiemetic, particularly for the control of chemotherapy-induced nausea and vomiting, achieving a complete response in the acute prevention of nausea and vomiting in 100% of patients treated with moderately and highly-emetogenic chemotherapy, when used in combination with palonosetron and dexamethasone.

Common side effects sedation and weight gain.

May be associated with onset of diabetes.

When combined with dexamethasone has efficacy in chemotherapy induced nausea and vomiting.

Olanzapine 10 mg/ day times three days is effective for breakthrough nausea and vomiting in patients with chemotherapy induced nausea and vomiting.

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