olanzapine
Zyprexa, Zyprexa Zydis

Available forms
Available by prescription only
Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg
Tablets (orally disintegrating): 5 mg, 10 mg, 15 mg, 20 mg

Indications and dosages
 Short-term treatment of acute manic episodes associated with bipolar I disorder. Adults: Initially, 10 to 15 mg P.O. daily. Adjust dosage as needed by increments of 5 mg daily at intervals of 24 hours or more. Maximum dose is 20 mg P.O. daily. Duration of treatment is 3 to 4 weeks.
 Long-term treatment of schizophrenia. Adults: Initially, 5 to 10 mg P.O. daily. Goal is 10 mg P.O. daily within several days of starting therapy. Dosage may be increased weekly in increments of 5 mg daily to a maximum of 20 mg daily. However, clinical assessment is recommended for dosages that exceed 10 mg daily.
≡ Dosage adjustment. The recommended starting dose is 5 mg P.O. in patients who are debilitated, predisposed to hypotensive reactions, exhibit risk factors for slow metabolism of olanzapine (nonsmoking women older than age 65), or who may be more pharmacodynamically sensitive to olanzapine. Increase dosage cautiously in these patients.

Pharmacodynamics
Antipsychotic action: Unknown. Drug acts as an antagonist at dopamine (D_1-4) and serotonin (5-HT_2A/2C) receptors; it also may exhibit antagonist-binding at adrenergic, cholinergic, and histaminergic receptors.

Pharmacokinetics
Absorption: Food doesn’t affect rate or extent of absorption. About 40% of dose is eliminated by first-pass metabolism.
Distribution: Distributes extensively throughout the body, with a volume of distribution of about 1,000 L. Drug is 93% protein-bound, primarily to albumin and alpha₁-acid glycoprotein.
Metabolism: Metabolized by direct glucuronidation and cytochrome P-450-mediated oxidation.
Excretion: About 57% appears in urine and 30% in feces as metabolites. Only 7% of dose is recovered in urine unchanged. Elimination half-life ranges from 21 to 54 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with heart disease, cerebrovascular disease, conditions that predispose to hypotension (gradual dosage adjustment minimizes the risk), history of seizures or conditions that could lower the seizure threshold, and hepatic impairment. Also use cautiously in elderly patients, patients at risk for aspiration pneumonia, and patients with a history of paralytic ileus, significant prostatic hypertrophy, or angle-closure glaucoma.

Interactions
Drug-drug. Antihypertensives, diazepam: May potentiate hypotensive effects. Monitor blood pressure closely.
Carbamazepine, omeprazole, rifampin: May increase olanzapine clearance. Monitor patient for drug effect.
Dopamine agonists, levodopa: May antagonize effects of these drugs. Use together cautiously.
Fluvoxamine: May inhibit olanzapine elimination. Monitor patient for toxicity.
Drug-herb. Nutmeg: May reduce symptom control or interfere with existing therapy for psychiatric illnesses. Discourage use together.
Drug-lifestyle. Alcohol use: May potentiate hypotensive effects. Discourage alcohol use.

Adverse reactions
CNS: somnolence, agitation, insomnia, headache, nervousness, hostility, parkinsonism, dizziness, anxiety, personality disorder, akathisia, hypertonia, tremor, amnesia, articulation impairment, euphoria, stuttering, dystonic or dyskinetic events, tardive dyskinesia, neuroleptic malignant syndrome, suicide attempt, fever.
CV: orthostatic hypotension, tachycardia, chest pain, hypotension, edema.
EENT: amblyopia, blepharitis, corneal lesion, rhinitis, pharyngitis.
GI: constipation, dry mouth, abdominal pain, increased appetite, increased salivation, nausea, vomiting, thirst.
GU: premenstrual syndrome, hematuria, metrorrhagia, urinary incontinence, urinary tract infection.
Hematologic: eosinophilia.
Metabolic: weight gain or loss.
Musculoskeletal: joint pain, limb pain, back pain, neck rigidity, twitching.
Respiratory: increased cough, dyspnea.
Skin: vesiculobullous rash.
Other: intentional injury, flu syndrome.

Effects on lab test results
• May increase AST, ALT, GGT, CK, and serum prolactin levels.
• May increase eosinophil count.

Overdose and treatment
Signs and symptoms of overdose may include drowsiness and slurred speech.
 There’s no specific antidote to olanzapine; treatment should be symptomatic. Monitor patient for hypotension, circulatory collapse, obtundation, seizures, or dystonic reactions. Gastric lavage with activated charcoal and sorbitol may be effective. Drug isn’t removed by dialysis. Avoid epinephrine, dopamine, or other sympathomimetics with beta-agonist activity.

Special considerations
 ALERT Don’t confuse Zyprexa, an antipsychotic, with Zyrtec, an antihistamine. The two drugs look alike, sound alike, and have similar dosing. Store separately.
• Monitor patient for signs of neuroleptic malignant syndrome (hyperpyrexia, muscle rigidity, altered mental status, autonomic instability), a rare but frequently fatal adverse reaction that can occur with antipsychotic drug therapy. Stop drug immediately if this syndrome occurs, and monitor and treat patient.
• Monitor baseline and periodic liver function test results.
Breast-feeding patients
• Drug appears in breast milk. Advise breast-feeding women to use an alternative to breast-feeding during therapy.
Pediatric patients
• Safety and efficacy in children younger than age 18 haven’t been established.
Geriatric patients
• Drug may be started at lower dose because clearance may be decreased in elderly patients. Half-life is 1 1/2 times longer in this population.

Patient education
• Warn patient to avoid hazardous tasks until adverse CNS effects of drug are known.
• Caution patient against exposure to extreme heat; drug may impair ability of the body to reduce core temperature.
• Advise patient to avoid alcohol.
• Tell patient to rise slowly to avoid orthostatic hypotension.
• Advise patient to use ice chips or sugarless candy or gum to relieve dry mouth.
• Inform patient not to take prescription or OTC drugs without medical approval because of potential drug interactions.
• Inform patient or family that it may take several weeks to obtain full therapeutic effect.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use