A-Z Drug Facts > Olanzapine

Olanzapine

Pronouncation: (oh-LAN-za-peen)
Class: Dibenzapine derivative

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 t _½ is 21 to 54 h. Plasma Cl is 12 to 47 L/h.

Special Populations

Elderly

The t _½ increases 1.5 times. Use caution when dosing.

Gender

Cl is approximately 30% lower in women.

Smoking

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).

Contraindications

Standard considerations.

Dosage and Administration

Schizophrenia
Adults

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 doses above 20 mg/day not evaluated).

Bipolar Mania
Adults

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 doses 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.

Agitation Associated With Schizophrenia and Bipolar I Mania
Adults

IM Recommended dose is 10 mg; a lower dose of 5 to 7.5 mg may be considered. If agitation persists, subsequent doses 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.

Special Populations
Adults (eg, elderly, predisposed to hypotension, nonsmoking women at least 65 yr of age)

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

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 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 are 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 oral 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

Agents that induce CYP1A2 or glucuronyl transferase enzymes (eg, omeprazole, rifampin, ritonavir)

May reduce olanzapine plasma levels, decreasing the pharmacologic effects.

Agents that inhibit CYP1A2 (eg, fluvoxamine)

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

Antihypertensive drugs

Olanzapine may enhance hypotensive effects.

Carbamazepine

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

Fluoxetine

Olanzapine plasma levels may be increased slightly.

Sedating drugs and alcohol

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%); dizziness (18%); asthenia (15%); parkinsonism (14%); insomnia (12%); personality disorder (8%); abnormal gait, tremor (6%); akathisia (5%); dyskinetic reaction (4%); abnormal dreams, 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%).

Genitourinary

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

Metabolic

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

Respiratory

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

Miscellaneous

Accidental injury (12%); fever (6%); back pain, extremity pain, joint pain (5%); chest pain (3%); dental pain, flu-like symptoms, injection-site pain, joint stiffness and twitching, leukopenia (at least 1%); rhabdomyolysis (postmarketing).

Precautions

Warnings Elderly patients with dementia-related psychosis treated with atypical antipsychotic agents are at an increased risk of death compared with placebo. Although the causes of death are varied, most appear to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia). Olanzapine is not approved for treatment of patients with dementia-related psychosis.

Monitor Assess LFTs periodically; assess blood glucose for hyperglycemia, especially in diabetic patients.

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.

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.

Hyperprolactinemia

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

Neuroleptic malignant syndrome (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).

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.

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 change the dose or stop taking unless advised by health care provider.
• 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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