Olanzapine
Pronunciation: (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 half-life is 21 to 54 h. Plasma Cl is 12 to 47 L/h.
Special Populations
Renal Function ImpairmentPharmacokinetics are similar in patients with severe renal impairment compared with healthy subjects. Dosage adjustment in patients with renal impairment is not necessary.
Hepatic Function ImpairmentImpaired liver function in patients with cirrhosis had little effect on olanzapine pharmacokinetics.
ElderlyThe half-life increases 1.5 times. Use caution when dosing.
GenderCl is approximately 30% lower in women.
RaceDrug exposure is similar among white, Chinese, and Japanese patients. Dosing adjustment based on race is not recommended.
Combined effectsDosage 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.
SmokingCl 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
Agitation Associated With Schizophrenia and Bipolar I ManiaAdults
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.
Bipolar ManiaAdults
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.
SchizophreniaAdults
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).
Special PopulationsAdults (eg, debilitated, elderly, predisposed to hypotension, nonsmoking women 65 yr of age and older)
PO Start with 5 mg/day. IM 5 mg (eg, elderly); a lower dose of 2.5 mg may be considered.
Maintenance TreatmentAdults
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
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 drugsOlanzapine may enhance hypotensive effects.
CarbamazepineOlanzapine Cl increases 50%, resulting in lower plasma levels.
CharcoalMay reduce C max and AUC of oral olanzapine about 60%; therefore, charcoal may be useful in treating olanzapine overdosage.
FluoxetineOlanzapine plasma levels may be increased slightly.
Sedating drugs and alcoholAdditive 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
WarningsIncreased mortalityElderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared with those taking placebo. Over a course of a 10-wk controlled trial, the rate of death in drug-treated patients was about 4.5% compared with 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. |
MonitorAssess LFTs periodically; assess blood glucose for hyperglycemia, especially in diabetic patients. In patients receiving treatment for extended time, periodically reevaluate the long-term usefulness of continued therapy. Monitor baseline and follow-up lipid levels. Regularly monitor patient's weight. |
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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Zyprexa Zydis Orally Disintegrating Tablets
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