Class: Antipsychotic agents, Dibenzapine derivative
- Tablets 2.5 mg
- Tablets 5 mg
- Tablets 7.5 mg
- Tablets 10 mg
- Tablets 15 mg
- Tablets 20 mg
- Injection, powder for solution 10 mg
- Injection, powder for suspension, ER 210 mg
- Injection, powder for suspension, ER 300 mg
- Injection, powder for suspension, ER 405 mg
- Tablets, orally disintegrating 5 mg
- Tablets, orally disintegrating 10 mg
- Tablets, orally disintegrating 15 mg
- Tablets, orally disintegrating 20 mg
Unknown. May control psychotic symptoms through antagonism of selected dopamine and serotonin receptors in the CNS.
Readily absorbed orally and IM. C max is approximately 6 h (oral) and 15 to 45 min (short-acting injection). Steady state is approximately 1 wk (oral). Food does not affect the rate or extent of oral olanzapine absorption.
Extensively distributed throughout the body. Vd is approximately 1,000 L; 93% is protein bound.
In liver by glucuronidation and CYP-450–mediated oxidation; major circulating metabolites are inactive.
Elimination is 57% in urine (7% unchanged); 30% eliminated in feces. The half-life is 21 to 54 h (oral, short-acting injection) and 30 days (ER injection). Plasma Cl is 12 to 47 L/h.
Special PopulationsRenal Function Impairment
Pharmacokinetics are similar in patients with severe renal impairment compared with healthy subjects. Dosage adjustment is not necessary.Hepatic Function Impairment
Impaired liver function in patients with cirrhosis had little effect on olanzapine pharmacokinetics.Elderly
The half-life increases 1.5 times. Use caution when dosing.Children
Higher average exposure, possibly because of lower average body weight and nonsmoking status.Gender
Cl is approximately 30% lower in women.Race
Drug exposure is similar among white, Chinese, and Japanese patients.Combined effects
Dosage adjustments may be necessary in certain patients based upon combined effects; for example, Cl in a young smoking man may be 3 times greater than in an elderly nonsmoking woman.Smoking
Cl is approximately 40% higher in patients who smoke; dose modifications are not routinely recommended.
Indications and UsagePO
Treatment of schizophrenia; treatment of acute mixed or manic episodes associated with bipolar I disorder; maintenance monotherapy of bipolar disorder; in combination with lithium or valproate for short-term treatment of acute mixed or manic episodes associated with bipolar I disorder; in combination with fluoxetine for the treatment of depressive episodes associated with bipolar disorder; in combination with fluoxetine for the treatment of treatment-resistant depression.IM
Treatment of schizophrenia (ER injection); treatment of agitation associated with schizophrenia and bipolar I mania (short-acting injection).
Treatment of delusional parasitosis; treatment of stuttering.
None well documented.
Dosage and AdministrationAgitation Associated With Schizophrenia and Bipolar I Mania
IM , short-acting 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 (max, 30 mg/day).Bipolar Disorder
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.Children 13 to 17 years of age
PO Start with 2.5 to 5 mg/day and adjust at 2.5 to 5 mg increments or decrements (safety of dosages more than 20 mg/day not evaluated).Depressive Episodes Associated With Bipolar Disorder; Treatment-Resistant Depression
PO Start with olanzapine 5 mg and fluoxetine 20 mg once daily in the evening. Adjust dose according to efficacy and tolerability within the dosing range of olanzapine 5 to 12.5 mg and fluoxetine 20 to 50 mg. If converting from fixed-dose combination olanzapine/fluoxetine to the individual components, the approximate equivalents are as follows: olanzapine 3 mg/fluoxetine 25 mg, use olanzapine 2.5 mg and fluoxetine 20 mg; olanzapine 6 mg/fluoxetine 25 mg, use olanzapine 5 mg and fluoxetine 20 mg; olanzapine 12 mg/fluoxetine 25 mg, use olanzapine 10 mg plus olanzapine 2.5 mg and fluoxetine 20 mg; olanzapine 6 mg/fluoxetine 50 mg, use olanzapine 5 mg and fluoxetine 40 mg plus fluoxetine 10 mg; olanzapine 12 mg/fluoxetine 50 mg, use olanzapine 10 mg plus olanzapine 2.5 mg and fluoxetine 40 mg plus fluoxetine 10 mg.Schizophrenia
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).IM , ER
Establish tolerability with oral olanzapine prior to initiating treatment with olanzapine ER injection. Usual dosage is 150 mg to 300 mg administered every 2 wk or 405 mg administered every 4 wk. For patients taking oral olanzapine 10 mg/day, use olanzapine 210 mg ER injection every 2 wk or 405 mg every 4 wk for the first 8 wk and 150 mg every 2 wk or 300 mg every 4 wk for the maintenance dose. For patients taking oral olanzapine 15 mg/day, use olanzapine 300 mg ER injection every 2 wk for the first 8 wk and 210 mg every 2 wk or 405 mg every 4 wk for the maintenance dose. For patients taking oral olanzapine 20 mg/day, use olanzapine ER injection 300 mg every 2 wk for the first 8 wk and 300 mg every 2 wk for the maintenance dose.Children 13 to 17 y of age
PO Start with 2.5 to 5 mg/day and adjust at 2.5 to 5 mg increments or decrements (safety of dosages more than 20 mg/day not evaluated).Special Populations
Adults (eg, debilitated, elderly, predisposed to hypotension, nonsmoking women 65 y of age and older) PO
Start with 5 mg/day.IM , short-acting
5 mg (eg, elderly) or 2.5 mg per injection may be considered.IM , ER
Start with 150 mg every 4 wk.
- 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.
- For IM administration only. Not for intradermal, subcutaneous, IV, or intra-arterial administration.
- Assess patients requiring subsequent injections of short-acting olanzapine for orthostatic hypotension prior to subsequent doses.
- Reconstitute short-acting powder for injection using 2.1 mL of sterile water for injection. Resulting solution contains approximately 5 mg/mL.
- ER injection should be suspended using only the supplied diluent. Refer to manufacturer's prescribing information for complete reconstitution and administration instructions.
- 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. Suspension should be yellow and opaque.
- Administer short-acting injection within 1 h of reconstitution; reconstituted ER injection is stable for up to 24 h in the vial and should be agitated immediately prior to drug withdrawal.
- Administer short-acting injection by slow, deep injection into muscle mass; administer ER injection by deep IM gluteal injection.
- Discard any unused solution. Do not save unused solution for later administration.
Store tablets and orally disintegrating tablets at 68° to 77°F. Protect from light and moisture. Store unreconstituted short-acting injection vials at 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. Store unreconstituted ER injection vials at room temperature (below 86°F). Following reconstitution, the injection can be stored for up to 24 h at controlled room temperature.
Drug InteractionsAgents that induce CYP1A2 or glucuronyl transferase enzymes (eg, carbamazepine, omeprazole, rifampin)
May reduce olanzapine plasma levels, decreasing the pharmacologic effects. Monitor the clinical response of the patient and adjust the olanzapine dose as needed.Agents that inhibit CYP1A2 (eg, estrogens, fluvoxamine)
May elevate olanzapine plasma levels, increasing the risk of adverse reactions. Monitor the clinical response of the patient and adjust the olanzapine dose as needed.Agents that inhibit CYP2D6 (eg, fluoxetine)
Olanzapine plasma concentrations may be slightly elevated. Monitor the clinical response of the patient. If an interaction is suspected, adjust the olanzapine dose as needed.Alcohol, CNS depressants (eg, diazepam)
Coadministration may lead to enhanced CNS depression. Use caution when administering olanzapine in combination with other centrally acting drugs. In addition, the coadministration of diazepam or alcohol with olanzapine potentiated the orthostatic hypotension observed with olanzapine. Monitor BP.Antihypertensive drugs
Olanzapine may enhance hypotensive effects. Monitor BP and adjust the antihypertensive dose as needed.Charcoal
May reduce C max and AUC of oral olanzapine approximately 60%; therefore, charcoal may be useful in treating olanzapine overdosage.Dopamine agonists, levodopa
Olanzapine may antagonize the effects of levodopa and dopamine agonists. Carefully monitor patients with Parkinson disease. If an interaction is suspected, it may be necessary to adjust the levodopa dose or discontinue olanzapine.Parenteral benzodiazepines
Coadministration of IM olanzapine and parenteral benzodiazepine is not recommended.Protease inhibitors (eg, ritonavir)
Olanzapine plasma concentrations may be reduced, decreasing the therapeutic effects. Monitor the clinical response of the patient and adjust the olanzapine dose as needed.Tramadol
Olanzapine may increase the risk of seizures when coadministered with tramadol. Use with caution.
Postural hypotension (5%); hypertension, tachycardia (3%); hypotension, QT interval prolongation (2%); deep venous thrombosis, pulmonary embolism (postmarketing).
Sedation/somnolence (48%); extrapyramidal reaction (32%); akathisia (27%); asthenia, parkinsonism (20%); dizziness, headache (18%); fatigue (14%); insomnia (12%); personality disorder (8%); tremor (7%); abnormal gait (6%); abnormal thinking, auditory hallucinations, dystonic events, hypertonia, restlessness (3%); abnormal dreams, articulation impairment, dysarthria, sleep disorder (2%).
Ecchymosis (5%); acne (2%).
Nasal congestion, rhinitis (7%); nasopharyngitis (6%); ear pain, pharyngitis (4%); amblyopia, epistaxis, pharyngolaryngeal pain, sinusitis (3%).
Increased appetite (29%); dry mouth (22%); constipation, dyspepsia (11%); nausea (9%); diarrhea (7%); abdominal pain, vomiting (6%); toothache, tooth infection (4%); flatulence (2%); pancreatitis (postmarketing).
Vaginal discharge (4%); urinary incontinence, UTI (2%); priapism (postmarketing).
Elevated AST (28%); elevated ALT (12%); elevated GGT (10%); liver enzymes increased (8%); elevated CPK; cholestatic or mixed liver injury, hepatitis, jaundice (postmarketing).
Allergic reactions (including anaphylactoid reaction, angioedema, pruritus, and/or urticaria) (postmarketing).
Elevated prolactin (34%); elevated cholesterol, elevated triglycerides (postmarketing).
Injection-site reaction (including buttock pain, induration, injection-site mass, and injection-site pain) (4%).
Weight gain (31%); peripheral edema (3%); diabetic coma, diabetic ketoacidosis (postmarketing).
Back pain, joint pain (5%); musculoskeletal stiffness (4%); arthralgia, muscle spasms (3%).
Cough (9%); upper respiratory tract infection (4%); respiratory tract infection (3%); sneezing (2%).
Fever, pain in extremity (6%); chest pain, pain (3%); viral infection (2%); discontinuation reactions (including diaphoresis, nausea, or vomiting), rhabdomyolysis (postmarketing).
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared with those taking placebo. 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. Olanzapine is not approved for treatment of dementia-related psychosis.Postinjection delirium/sedation syndrome
Adverse reactions with signs and symptoms consistent with olanzapine overdose, in particular sedation (including coma) and/or delirium, have been reported following administration of olanzapine ER injection. Olanzapine ER injection must be administered in a registered health care facility with ready access to emergency response services. Patients must be observed at the facility by a health care provider for at least 3 h after each injection. Health care provider, health care facility, patient, and dispensing pharmacy must be enrolled in the Zyprexa Relprevv Patient Care Program. Olanzapine ER injection is available only through a restricted distribution program.
Assess LFTs periodically; monitor blood glucose for hyperglycemia, and assess patient for symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia), especially in patients with diabetes. 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.
Category C .
Excreted in breast milk.
Safety and efficacy not established for treatment of bipolar disorder or schizophrenia in children younger than 13 y of age. Safety and efficacy not established for use in combination with fluoxetine or for the injection formulations in patients younger than 18 y of age.
Consider a lower starting dose.
Use with caution.
Special Risk Patients
Use with caution in patients with clinically important prostatic hypertrophy, cerebrovascular disease, conditions that predispose patients to hypotension (eg, dehydration, hypovolemia), CV disease, 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, were reported in elderly patients with dementia-related psychosis.
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.
Use with caution in patients at risk for aspiration pneumonia.
Observe patients continuously for at least 3 h after each injection. Confirm that the patient is alert, oriented, and absent of any signs/symptoms of postinjection delirium/sedation syndrome prior to releasing patient. All patients must be accompanied to their destination upon leaving the health care facility. Patient should not be allowed to drive or operate heavy machinery for the remainder of the day of each injection.
Leukopenia/neutropenia has been reported temporally related to antipsychotic agents, including olanzapine. Agranulocytosis has also been reported.
Hyperglycemia and diabetes mellitus
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, may occur.
Undesirable alterations in lipids have been observed. Very high (eg, more than 500 mg/dL) triglyceride elevations have occurred.
Olanzapine-treated patients often have elevation in prolactin levels.
NMS has occurred and is potentially fatal. Signs and symptoms include altered mental status, diaphoresis, hyperpyrexia, irregular BP, irregular pulse, muscle rigidity, and tachycardia.
May occur with associated symptoms of dizziness, syncope, and tachycardia.
Olanzapine orally disintegrating tablets contain phenylalanine; use with caution in patients with phenylketonuria.
Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold (eg, Alzheimer dementia).
Possible suicide attempts are inherent to schizophrenia and bipolar disorder. Closely supervise high-risk patients.
Syndrome of potentially irreversible, involuntary dyskinetic movements may develop. Prevalence is highest in elderly patients, especially women.
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.
Agitation/aggressiveness, altered gait, aspiration, cardiac arrhythmias (eg, supraventricular tachycardia), cardiopulmonary arrest, confusion, convulsion, death, delirium, difficulty ambulating, disorientation, dizziness, dysarthria, hypertension, hypotension, possible NMS, reduced consciousness ranging from sedation to coma, respiratory depression/arrest, sinus pause, slurred speech, tachycardia, various extrapyramidal symptoms, weakness.
- Instruct patient to take prescribed dose daily without regard to meals, but to take with food if GI upset occurs.
- Caution patient using orally disintegrating tablet not to open the blister until ready to take the dose.
- Caution patient using orally disintegrating tablet that tablets contain phenylalanine.
- Advise patient that dose will be started low and then increased until maximum benefit is obtained.
- Instruct patient not to stop taking olanzapine when feeling better.
- Advise patients of the risk of postinjection delirium/sedation syndrome each time they receive an olanzapine ER injection. Advise patients that after each injection they must be observed at the health care facility for at least 3 h and must be accompanied to their destination upon leaving the facility.
- Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
- Counsel patients that hyperglycemia, hyperlipidemia, and weight gain can occur with olanzapine use
- Instruct patients 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 judgement, 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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