Olanzapine

Trade Names:
Zyprexa
- Tablets 2.5 mg
- Tablets 5 mg
- Tablets 7.5 mg
- Tablets 10 mg
- Tablets 15 mg
- Tablets 20 mg

Trade Names:
Zyprexa Zydis
- Tablets, orally disintegrating 5 mg
- Tablets, orally disintegrating 10 mg
- Tablets, orally disintegrating 15 mg
- Tablets, orally disintegrating 20 mg

Trade Names:
Zyprexa
- IM Powder for injection 10 mg

Pharmacology

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Unknown. May control psychotic symptoms through antagonism of selected dopamine and serotonin receptors in the CNS.

Pharmacokinetics

Absorption

Readily absorbed orally and IM. C _max is approximately 6 h (oral) and 15 to 45 min (IM). Steady state is approximately 1 wk.

Distribution

Extensively distributed throughout the body. Vd is approximately 1,000 L; 93% is protein bound.

Metabolism

In liver by glucuronidation and CYP-450–mediated oxidation; major circulating metabolites are inactive.

Elimination

Elimination is 57% in urine (7% unchanged); 30% eliminated in feces. The half-life is 21 to 54 h. Plasma Cl is 12 to 47 L/h.

Special Populations

Pharmacokinetics are similar in patients with severe renal impairment compared with healthy subjects. Dosage adjustment in patients with renal impairment is not necessary.

Impaired liver function in patients with cirrhosis had little effect on olanzapine pharmacokinetics.

The half-life increases 1.5 times. Use caution when dosing.

Cl is approximately 30% lower in women.

Drug exposure is similar among white, Chinese, and Japanese patients. Dosing adjustment based on race is not recommended.

Dosage adjustments may be necessary in certain patients based upon combined effects; for example, clearance in a young smoking male may be 3 times greater than in an elderly nonsmoking female.

Cl is approximately 40% higher in patients who smoke.

Indications and Usage

Treatment of schizophrenia (oral); treatment of acute mixed or manic episodes with bipolar I disorder (oral); in combination with lithium or valproate for short-term treatment of acute mixed or manic episodes associated with bipolar I disorder (oral); agitation associated with schizophrenia and bipolar I mania (IM). Maintenance treatment of bipolar patients on monotherapy after achieving a responder status for an average duration of 2 wk.

Unlabeled Uses

Treatment of delusional parasitosis; treatment of stuttering.

Contraindications

Standard considerations.

Dosage and Administration

IM Recommended dose is 10 mg; a lower dose of 5 to 7.5 mg may be considered. If agitation persists, subsequent doses of up to 10 mg may be given. Safety of total daily doses greater than 30 mg, or 10 mg given more frequently than 2 h after initial dose, and 4 h after second dose has not been evaluated.

PO Start with 10 to 15 mg/day and adjust at 5 mg increments or decrements in intervals no less than 24 h (safety of dosages more than 20 mg/day not evaluated). When administered in combination with lithium or valproate, oral olanzapine dosing should generally begin with 10 mg daily without regard to meals.

PO Start with 5 to 10 mg/day and adjust dosage at 5 mg increments or decrements in intervals of no less than 1 wk (safety of dosages more than 20 mg/day not evaluated).

PO Start with 5 mg/day. IM 5 mg (eg, elderly); a lower dose of 2.5 mg may be considered.

PO While there are no data as to how long patients should remain on therapy, schizophrenic patients receiving olanzapine 10 to 20 mg/day have been followed for up to 8 mo.

General Advice

• Administer prescribed dose once daily without regard to meals.
• Administer with food if GI upset occurs.
• Administer orally disintegrating tablet by peeling back foil on blister pack (do not push tablet through foil) and, using dry hands, remove tablet from foil and place in patient's mouth; tablet will disintegrate with or without liquid.
• Do not administer orally disintegrating tablet to patient with phenylketonuria without discussing it first.

• Injection
• For IM administration only. Not for intradermal, subcutaneous, IV, or intra-arterial administration.
• Reconstitute powder for injection using 2.1 mL of sterile water for injection. Resulting solution contains approximately 5 mg/mL.
• Do not mix with other medications or use other diluents.
• Do not administer if particulate matter or cloudiness is noted. Solution should be clear and yellow.
• Administer within 1 h of reconstitution.
• Administer by slow, deep injection into muscle mass.
• Discard any unused solution. Do not save unused solution for later administration.

Storage/Stability

Store tablets and orally disintegrating tablets at controlled room temperature (68° to 77°F). Protect from light and moisture. Store powder for injection at controlled room temperature (68° to 77°F). Protect from light and freezing. Following reconstitution, the injection can be stored for up to 1 h at controlled room temperature if necessary.

Drug Interactions

May reduce olanzapine plasma levels, decreasing the pharmacologic effects.

May elevate olanzapine plasma levels, increasing the risk of adverse reactions.

Olanzapine may enhance hypotensive effects.

Olanzapine Cl increases 50%, resulting in lower plasma levels.

May reduce C _max and AUC of oral olanzapine about 60%; therefore, charcoal may be useful in treating olanzapine overdosage.

Olanzapine plasma levels may be increased slightly.

Additive CNS depression, and motor and cognitive impairment.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Postural hypotension (5%); tachycardia (3%); hypertension, hypotension (2%); deep venous thrombosis, pulmonary edema (postmarketing).

CNS

Somnolence (39%); akathisia (27%); dizziness (18%); asthenia (15%); parkinsonism (14%); insomnia (12%); personality disorder (8%); tremor (7%); abnormal gait (6%); dyskinetic reaction (4%); hypertonia (3%); articulation impairment (2%); abnormal dreams, amnesia, delusions, emotional lability, euphoria, manic reaction, paresthesia, schizophrenic reaction (at least 1%).

Dermatologic

Ecchymosis (5%); sweating (at least 1%).

EENT

Rhinitis (7%); pharyngitis (4%); amblyopia (3%); conjunctivitis (at least 1%).

GI

Dry mouth (22%); constipation, dyspepsia (11%); nausea (9%); increased appetite (6%); vomiting (4%); flatulence, increased salivation, increased thirst (at least 1%); pancreatitis (postmarketing).

Genitourinary

Urinary incontinence, UTI (2%); vaginitis (at least 1%); priapism (postmarketing).

Hematologic-Lymphatic

Neutropenia (postmarketing).

Hepatic

Jaundice (postmarketing).

Hypersensitivity

Allergic reactions including anaphylactoid reaction, angioedema, pruritus, urticaria (postmarketing).

Lab Tests

Elevated cholesterol, elevated triglyceride (postmarketing).

Local

Injection-site pain (at least 1%).

Metabolic

Weight gain (6%); peripheral edema (3%); diabetic coma (postmarketing).

Musculoskeletal

Back pain, joint pain (5%); joint stiffness and twitching (at least 1%).

Respiratory

Increased cough (6%); dyspnea (at least 1%).

Miscellaneous

Accidental injury (12%); fever (6%); extremity pain (5%); chest pain (3%); dental pain, flu-like symptoms (at least 1%); rhabdomyolysis (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hepatic Function

Use with caution.

Special Risk Patients

Use with caution in patients with clinically important prostatic hypertrophy, narrow-angle glaucoma, or a history of paralytic ileus.

Body temperature regulation

Antipsychotics disrupt the ability to reduce core body temperature. Use with caution in patients who will experience conditions that may contribute to an elevation in core body temperature (eg, concomitant anticholinergic therapy, exposure to extreme heat, strenuous exercise, subject to dehydration).

Cerebrovascular adverse reactions

Cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including fatalities, may occur.

Cognitive and motor impairment

Caution patients about operating potentially hazardous machinery (eg, cars) until they know whether the drug impairs their ability. Advise patients to avoid alcohol.

Concomitant illness

Clinical experience is limited in patients with concomitant illnesses (eg, renal and hepatic impairment).

Dysphagia

Use with caution in patients at risk for aspiration pneumonia.

Hyperglycemia and diabetes mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, may occur.

Hyperlipidemia

Undesirable alterations in lipids have been observed. Very high (eg, more than 500 mg/dL) triglyceride elevations have occurred.

Hyperprolactinemia

Olanzapine-treated patients often have elevation in prolactin levels; however, there is no evidence of increased breast tumor risk.

NMS

NMS has occurred and is potentially fatal. Signs and symptoms are altered mental status, diaphoresis, hyperpyrexia, irregular pulse, irregular BP, muscle rigidity, and tachycardia.

Orthostatic hypotension

May occur with associated symptoms of dizziness, syncope, and tachycardia. Most common during titration period and in patients with CV disease, cerebrovascular disease, and conditions that predispose to hypotension (eg, dehydration, hypovolemia, treatment with antihypertensive agents).

Phenylketonurics

Olanzapine orally disintegrating tablets contain phenylalanine; use with caution in patients with phenylketonuria.

Seizures

Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold (eg, Alzheimer dementia).

Suicide

Possible suicide attempts are inherent to schizophrenia and bipolar disorder. Closely supervise high-risk patients.

Tardive dyskinesia

Syndrome of potentially irreversible, involuntary dyskinetic movements may develop. Prevalence is highest in elderly patients, especially women.

Weight gain

There is a potential for weight gain. Approximately 22% of patients receiving olanzapine gained at least 7% of their baseline weight with a median exposure of 8 wk.

Overdosage

Symptoms

Agitation/aggressiveness, aspiration, cardiac arrhythmias (eg, supraventricular tachycardia), cardiopulmonary arrest, convulsion, death, delirium, drowsiness, dysarthria, hypertension, hypotension, possible NMS, reduced level of consciousness, respiratory depression/arrest, sedation to coma, sinus pause, slurred speech, tachycardia, various extrapyramidal symptoms.

Patient Information

• Instruct patient to take prescribed dose daily without regard to meals, but to take with food if GI upset occurs.
• Caution patient using disintegrating tablet not to open the blister until ready to take the dose.
• Caution patient using disintegrating tablet that tablets contain phenylalanine (aspartame).
• Advise patient that if a dose is missed to take it as soon as possible and then return to the normal schedule. Instruct patient not to double the dose to catch up if a dose is missed.
• Advise patient that dose will be started low and then increased until max benefit is obtained.
• Instruct patient not to stop taking olanzapine when feeling better.
• Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct patient with diabetes to monitor blood glucose more frequently when drug is started or dose is changed, and to inform health care provider of significant changes in readings.
• Tell patient to immediately report altered mental status, frequent urination, high fever, hives, irregular pulse, irritability, mood swings, muscle rigidity, racing thoughts, rash, seizures, sweating, unquenchable thirst, or unusual hunger to health care provider.
• Advise patient to notify health care provider of the following: change in personality or mood, excessive drowsiness, involuntary body or facial movements, rapid pulse, swelling in the feet or ankles, weight gain.
• Advise patient to avoid strenuous activity in high temperature or humidity.
• Instruct patient to avoid alcoholic beverages and sedatives (eg, diazepam) while taking olanzapine.
• Instruct patient to get up slowly from lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patient to report dizziness with position changes to health care provider. Caution patient that hot tubs and hot showers or baths may make dizziness worse.
• Advise patient taking antihypertensives to monitor BP at regular intervals.
• Advise patient that drug may impair judgment, thinking, or motor skills or cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

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