Olanzapine 10 mg/2mL Injection, Powder, For Solution
Other active recalls for Olanzapine (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Atypical Antipsychotic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Olanzapine extended-release injection is used to treat schizophrenia (a mental illness that affects how a person thinks, feels and behaves). Olanzapine injection is used to treat episodes of agitation in people who have schizophrenia or in people who have bipolar I disorder (a disease that causes depression, mania, and other abnormal moods). Olanzapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.
Read the full MedlinePlus article ↗- Olanzapine helps bring certain brain chemicals — mainly dopamine and serotonin — back into balance. Depending on what it's prescribed for, it can reduce symptoms of psychosis like...
- What exactly is olanzapine supposed to do for me?
- Honestly, yes — weight gain and changes in blood sugar and cholesterol are real and well-documented with olanzapine. Some people gain a significant amount of weight. Blood sugar ca...
- Will olanzapine make me gain weight or affect my blood sugar?
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Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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50 mg / 2 mL
UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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3.5 mg / 2 mL
UNII W4888I119H
Tartaric acid is a natural organic acid found in grapes and tamarinds. In medicines, it works as a buffer to control acidity, an antioxidant to prevent spoilage, and sometimes a flavoring or binding agent.
4 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $21.368 | $21.37 / 1 vial |
| Medicaid paysCMS SDUD · 12 mo | $3.90 | $3.90 / 1 vial |
| Medicare drug plans payPart D · Q2 2026 | $29.31 | $29.31 / 1 vial |
| Medicare Part B allowsASP · J2359 | $0.693 / J2359 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Olanzapine Intramuscular 10 mg/2mL 00121-1072-55 | PAI | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mLthis 00143-9199-01 | Hikma | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mL 00517-0955-01 | American | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mL 00781-3159-72 | Sandoz | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mL 00781-9105-72 | Sandoz | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mL 31722-0308-01 | Camber | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mL 39822-1800-01 | XGen | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg 55150-0308-01 | Eugia | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mL 68462-0952-10 | GLENMARK | 1 vial | $21.368 | AP | Availability likely | — |
| Olanzapine 10 mg/2mL 72603-0181-01 | NorthStar | 1 vial | $21.368 | AP | Availability likely | — |
| ZYPREXA Intramuscular 10 mg/2mL 00002-7597-01 | Eli | 1 vial | — | AP | Discontinued | — |
| ZYPREXA Intramuscular 10 mg/2mL 61269-0640-20 | H2-Pharma | 1 vial | — | AP | FDA listed | — |
| Olanzapine 10 mg/2mL 67184-0573-01 | Qilu | 1 vial | — | AP | FDA listed | — |
| Olanzapine Intramuscular 10 mg/2mL 72843-0576-01 | UBI | 1 vial | — | AP | FDA listed | — |
| Olanzapine 10 mg/2mL 83854-0003-01 | Anthea | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00143-9199-01 You're viewing this | 1 VIAL in 1 CARTON (0143-9199-01) / 2 mL in 1 VIAL | 2025-09-18 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Olanzapine for injection is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.5 ), and Patient Counseling Information ( 17 )] . WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Olanzapine for Injection is not approved for the treatment of patients with dementia-related psychosis. ( 5.1 , 8.5 , 17 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Olanzapine for Injection is an atypical antipsychotic indicated for the: Treatment of acute agitation associated with schizophrenia and bipolar I mania. ( 1.4 ) Efficacy was established in three 1-day trials in adults. ( 14.3 )
1.4Olanzapine for Injection: Agitation Associated with Schizophrenia and Bipolar I Mania Olanzapine for Injection is indicated for the treatment of acute agitation associated with schizophrenia and bipolar I mania. Efficacy was demonstrated in 3 short-term (24 hours of IM treatment) placebo-controlled trials in agitated adult inpatients with: schizophrenia or bipolar I disorder (manic or mixed episodes) [see Clinical Studies ( 14.3 )] . “Psychomotor agitation” is defined in DSM-IV as “excessive motor activity associated with a feeling of inner tension.” Patients experiencing agitation often manifest behaviors that interfere with their diagnosis and care, e.g., threatening behaviors, escalating or urgently distressing behavior, or self-exhausting behavior, leading clinicians to the use of intramuscular antipsychotic medications to achieve immediate control of the agitation.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Agitation associated with Schizophrenia and Bipolar I Mania in adults ( 2.4 ) IM: 10 mg (5 mg or 7.5 mg when clinically warranted) Assess for orthostatic hypotension prior to subsequent dosing (max. 3 doses 2-4 hrs apart) Lower starting dose recommended in debilitated or pharmacodynamically sensitive patients or patients with predisposition to hypotensive reactions.
2.4Olanzapine for Injection: Agitation Associated with Schizophrenia and Bipolar I Mania Dose Selection for Agitated Adult Patients with Schizophrenia and Bipolar I Mania — The efficacy of intramuscular olanzapine for injection in controlling agitation in these disorders was demonstrated in a dose range of 2.5 mg to 10 mg. The recommended dose in these patients is 10 mg. A lower dose of 5 or 7.5 mg may be considered when clinical factors warrant [see Clinical Studies ( 14.3 )] .
If agitation warranting additional intramuscular doses persists following the initial dose, subsequent doses up to 10 mg may be given. However, the efficacy of repeated doses of intramuscular olanzapine for injection in agitated patients has not been systematically evaluated in controlled clinical trials. Also, the safety of total daily doses greater than 30 mg, or 10 mg injections given more frequently than 2 hours after the initial dose, and 4 hours after the second dose have not been evaluated in clinical trials.
Maximal dosing of intramuscular olanzapine (e.g., 3 doses of 10 mg administered 2-4 hours apart) may be associated with a substantial occurrence of significant orthostatic hypotension [see Warnings and Precautions ( 5.7 )] . Thus, it is recommended that patients requiring subsequent intramuscular injections be assessed for orthostatic hypotension prior to the administration of any subsequent doses of intramuscular olanzapine for injection. The administration of an additional dose to a patient with a clinically significant postural change in systolic blood pressure is not recommended.
If ongoing olanzapine therapy is clinically indicated, oral olanzapine may be initiated in a range of 5-20 mg/day as soon as clinically appropriate. Intramuscular Dosing in Special Populations — A dose of 5 mg/injection should be considered for geriatric patients or when other clinical factors warrant. A lower dose of 2.5 mg/injection should be considered for patients who otherwise might be debilitated, be predisposed to hypotensive reactions, or be more pharmacodynamically sensitive to olanzapine [see Warnings and Precautions ( 5.14 ), Drug Interactions ( 7 ), and Clinical Pharmacology ( 12.3 )] .
Administration of Olanzapine for Injection — Olanzapine for Injection is intended for intramuscular use only. Do not administer intravenously or subcutaneously. Inject slowly, deep into the muscle mass.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Directions for Preparation of Olanzapine for Injection with Sterile Water for Injection — Dissolve the contents of the vial using 2.1 mL of Sterile Water for Injection to provide a solution containing approximately 5 mg/mL of olanzapine. The resulting solution should appear clear and yellow.
Olanzapine for Injection reconstituted with Sterile Water for Injection should be used immediately (within 1 hour) after reconstitution. Discard any unused portion. The following table provides injection volumes for delivering various doses of intramuscular olanzapine for injection reconstituted with Sterile Water for Injection.
Dose, mg Olanzapine Volume of Injection, mL 10 Withdraw total contents of vial 7.5 1.5 5 1 2.5
0.5Physical Incompatibility Information — Olanzapine for Injection should be reconstituted only with Sterile Water for Injection. Olanzapine for Injection should not be combined in a syringe with diazepam injection because precipitation occurs when these products are mixed. Lorazepam injection should not be used to…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Olanzapine for Injection is available as single-dose 10 mg vial (1s). Intramuscular Injection: 10 mg single-dose vial. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None with olanzapine monotherapy. For specific information about the contraindications of lithium or valproate, refer to the Contraindications section of the package inserts for these other products. None with olanzapine monotherapy. ( 4 ) When using olanzapine in combination with lithium or valproate, refer to the Contraindications section of the package inserts for those products. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Elderly Patients with Dementia-Related Psychosis: Increased risk of death and increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack). ( 5.1 ) Suicide: The possibility of a suicide attempt is inherent in schizophrenia and in bipolar I disorder, and close supervision of high-risk patients should accompany drug therapy. ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring.
( 5.3 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue if DRESS is suspected. ( 5.4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. ( 5.5 ) Hyperglycemia and Diabetes Mellitus: In some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking olanzapine.
Patients taking olanzapine should be monitored for symptoms of hyperglycemia and undergo fasting blood glucose testing at the beginning of, and periodically during, treatment. ( 5.5 ) Dyslipidemia: Undesirable alterations in lipids have been observed. Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of, and periodically during, treatment.
( 5.5 ) Weight Gain: Potential consequences of weight gain should be considered. Patients should receive regular monitoring of weight. ( 5.5 ) Tardive Dyskinesia: Discontinue if clinically appropriate.
( 5.6 ) Orthostatic Hypotension: Orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, may occur especially during initial dose titration. Use caution in patients with cardiovascular disease, cerebrovascular disease, and those conditions that could affect hemodynamic responses. ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Has been reported with antipsychotics, including olanzapine.
Patients with a history of a clinically significant low white blood cell count (WBC) or drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of olanzapine should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors. ( 5.9 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold.
( 5.11 ) Potential for Cognitive and Motor Impairment: Has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery. ( 5.12 ) Anticholinergic (antimuscarinic) Effects: Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions.
( 5.14 ) Hyperprolactinemia: May elevate prolactin levels. ( 5.15 ) Use in Combination with Lithium or Valproate: Also refer to the package inserts for lithium, or valproate. ( 5.16 ) Laboratory Tests: Monitor fasting blood glucose and lipid profiles at the beginning of, and periodically during, treatment.
( 5.17 )
5.1Elderly Patients with Dementia-Related Psychosis Increased Mortality — Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Olanzapine for injection is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Use in Specific Populations ( 8.5 ), and Patient Counseling Information ( 17 )] . In placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than placebo-treated patients (3.5% vs 1.5%, respectively).
Cerebrovascular Adverse Events (CVAE), Including Stroke — Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (≥5% and at least twice that for placebo) associated with: Combination of Olanzapine and Lithium or Valproate: Manic or Mixed Episodes, Bipolar I Disorder (Adults) – dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia. ( 6.1 ) Olanzapine for Injection: Agitation with Schizophrenia and Bipolar I Mania (Adults) – somnolence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice. Clinical Trials in Adults The information below for olanzapine is derived from a clinical trial database for olanzapine consisting of 10,504 adult patients with approximately 4765 patient-years of exposure to olanzapine plus 722 patients with exposure to intramuscular olanzapine for injection.
This database includes: (1) 2500 patients who participated in multiple-dose oral olanzapine premarketing trials in schizophrenia and Alzheimer's disease representing approximately 1122 patient-years of exposure as of February 14, 1995; (2) 182 patients who participated in oral olanzapine premarketing bipolar I disorder (manic or mixed episodes) trials representing approximately 66 patient-years of exposure; (3) 191 patients who participated in an oral olanzapine trial of patients having various psychiatric symptoms in association with Alzheimer's disease representing approximately 29 patient-years of exposure; (4) 5788 additional patients from 88 oral olanzapine clinical trials as of December 31, 2001; (5) 1843 additional patients from 41 olanzapine clinical trials as of October 31, 2011; and (6) 722 patients who participated in intramuscular olanzapine for injection premarketing trials in agitated patients with schizophrenia, bipolar I disorder (manic or mixed episodes), or dementia.
Also included below is information from the premarketing 6-week clinical study database for olanzapine in combination with lithium or valproate, consisting of 224 patients who participated in bipolar I disorder (manic or mixed episodes) trials with approximately 22 patient-years of exposure. The conditions and duration of treatment with olanzapine varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or longer-term exposure.
Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analytes, ECGs, chest x-rays, and results of ophthalmologic examinations. Certain portions of the discussion below relating to objective or numeric safety parameters, namely, dose-dependent adverse reactions, vital sign changes, weight gain, laboratory changes, and ECG changes are derived from studies in patients with schizophrenia and have not been duplicated for bipolar I disorder (manic or mixed episodes) or agitation.
However, this information is also generally applicable to bipolar I disorder (manic or mixed episodes) and agitation. Adverse reactions during exposure were obtained by spontaneous report and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized reaction categories.
In the tables and tabulations that follow, MedDRA and COSTART Dictionary terminology has been used to classify reported adverse reactions. The stated frequenc…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS The risks of using olanzapine in combination with other drugs have not been extensively evaluated in systematic studies. Diazepam: May potentiate orthostatic hypotension. ( 7.1 , 7.2 ) Alcohol: May potentiate orthostatic hypotension.
( 7.1 ) Carbamazepine: Increased clearance of olanzapine. ( 7.1 ) Fluvoxamine: May increase olanzapine levels. ( 7.1 ) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs and alcohol.
( 7.2 ) Antihypertensive Agents: Enhanced antihypertensive effect. ( 7.2 ) Levodopa and Dopamine Agonists: May antagonize levodopa/dopamine agonists. ( 7.2 ) Lorazepam (IM): Increased somnolence with IM olanzapine.
( 7.2 ) Other Concomitant Drug Therapy: When using olanzapine in combination with lithium or valproate, refer to the Drug Interactions sections of the package insert for those products. ( 7.2 )
7.1Potential for Other Drugs to Affect Olanzapine Diazepam — The co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions ( 7.2 )] . Cimetidine and Antacids — Single doses of cimetidine (800 mg) or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine. Inducers of CYP1A2 — Carbamazepine therapy (200 mg bid) causes an approximately 50% increase in the clearance of olanzapine.
This increase is likely due to the fact that carbamazepine is a potent inducer of CYP1A2 activity. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. Alcohol — Ethanol (45 mg/70 kg single dose) did not have an effect on olanzapine pharmacokinetics.
The co-administration of alcohol (i.e., ethanol) with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions ( 7.2 )] . Inhibitors of CYP1A2 Fluvoxamine: Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine Cmax following fluvoxamine of 54% in female nonsmokers and 77% in male smokers.
The mean increase in olanzapine AUC is 52% and 108%, respectively. Lower doses of olanzapine should be considered in patients receiving concomitant treatment with fluvoxamine. Inhibitors of CYP2D6 Fluoxetine: Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance.
The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. Warfarin — Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics [see Drug Interactions ( 7.2 )] . Inducers of CYP1A2 or Glucuronyl Transferase — Omeprazole and rifampin may cause an increase in olanzapine clearance.
Charcoal — The administration of activated charcoal (1 g) reduced the Cmax and AUC of oral olanzapine by about 60%. As peak olanzapine levels are not typically obtained until about 6 hours after dosing, charcoal may be a useful treatment for olanzapine overdose. Anticholinergic Drugs — Concomitant treatment with olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility.
Olanzapine should be used with caution in patients receiving medications having anticholinergic (antimuscarinic) effects [see Warnings and Precautions ( 5.14 )] .
7.2Potential for Olanzapine to Affect Other Drugs CNS Acting Drugs — Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol. Antihypertensive Agents — Olanzapine, because of its potential for inducing hypotension, may enhance the effects of certain antihypertensive agents. Levodopa and Dopamine Agonists — Olanzapine may antagonize the effects of levodopa and dopamine…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) Pediatric Use: Safety and effectiveness of olanzapine in children <13 years of age have not been established. ( 8.4 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including olanzapine, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including olanzapine, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations) .
Overall available data from published epidemiologic studies of pregnant women exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including olanzapine, during pregnancy (see Clinical Considerations) . Olanzapine was not teratogenic when administered orally to pregnant rats and rabbits at doses that are 9- and 30-times the daily oral maximum recommended human dose (MRHD), based on mg/m 2 body surface area; some fetal toxicities were observed at these doses (see Data) .
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and embryo/fetal risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors.
Fetal/Neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including olanzapine, during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Placental passage has been reported in published study reports; however, the placental passage ratio was highly variable ranging between 7% to 167% at birth following exposure during pregnancy. The clinical relevance of this finding is unknown.
Published data from observational studies, birth registries, and case reports that have evaluated the use of atypical antipsychotics during pregnancy do not establish an increased risk of major birth defects. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. Animal Data In oral reproduction studies in rats at doses up to 18 mg/kg/day and in rabbits at doses up to 30 mg/kg/day (9 and 30 times the daily oral MRHD based on mg/m 2 body surface area, respectively), no evidence of teratogenicity was observed.
In an oral rat teratology study, early resorptions and increased numbers of nonviable fetuses were obser…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including olanzapine, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including olanzapine, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations) .
Overall available data from published epidemiologic studies of pregnant women exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including olanzapine, during pregnancy (see Clinical Considerations) . Olanzapine was not teratogenic when administered orally to pregnant rats and rabbits at doses that are 9- and 30-times the daily oral maximum recommended human dose (MRHD), based on mg/m 2 body surface area; some fetal toxicities were observed at these doses (see Data) .
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and embryo/fetal risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors.
Fetal/Neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including olanzapine, during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Placental passage has been reported in published study reports; however, the placental passage ratio was highly variable ranging between 7% to 167% at birth following exposure during pregnancy. The clinical relevance of this finding is unknown.
Published data from observational studies, birth registries, and case reports that have evaluated the use of atypical antipsychotics during pregnancy do not establish an increased risk of major birth defects. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. Animal Data In oral reproduction studies in rats at doses up to 18 mg/kg/day and in rabbits at doses up to 30 mg/kg/day (9 and 30 times the daily oral MRHD based on mg/m 2 body surface area, respectively), no evidence of teratogenicity was observed.
In an oral rat teratology study, early resorptions and increased numbers of nonviable fetuses were observed at a dose of 18 mg/kg/day (9 times the daily oral MRHD based on mg/m 2 body surface area), and gestation was prolonged at 10 mg/kg/day (5 times the daily oral MRHD based on mg/m 2 body surface area). In an oral rabbit teratology study, fetal toxicity manifes…
🧒 Pediatric Use ▾
8.4Pediatric Use Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin and hepatic aminotransferase levels [see Warnings and Precautions ( 5.5 , 5.15 , 5.17 ) and Adverse Reactions ( 6.1 )] . When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia.
Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents. Safety and effectiveness of olanzapine in children <13 years of age have not been established [see Patient Counseling Information ( 17 )] .
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 2500 patients in premarketing clinical studies with oral olanzapine, 11% (263) were 65 years of age or over. In patients with schizophrenia, there was no indication of any different tolerability of olanzapine in the elderly compared to younger patients. Studies in elderly patients with dementia-related psychosis have suggested that there may be a different tolerability profile in this population compared to younger patients with schizophrenia.
Elderly patients with dementia-related psychosis treated with olanzapine are at an increased risk of death compared to placebo. In placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis, there was a higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in patients treated with olanzapine compared to patients treated with placebo. In 5 placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis (n=1184), the following adverse reactions were reported in olanzapine-treated patients at an incidence of at least 2% and significantly greater than placebo-treated patients: falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth and visual hallucinations.
The rate of discontinuation due to adverse reactions was greater with olanzapine than placebo (13% vs 7%). Elderly patients with dementia-related psychosis treated with olanzapine are at an increased risk of death compared to placebo. Olanzapine is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions ( 5.1 ), and Patient Counseling Information ( 17 )] .
Olanzapine is not approved for the treatment of patients with dementia-related psychosis. Also, the presence of factors that might decrease pharmacokinetic clearance or increase the pharmacodynamic response to olanzapine should lead to consideration of a lower starting dose for any geriatric patient [see Boxed Warning , and Warnings and Precautions ( 5.1 )] .
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Human Experience In premarketing trials involving more than 3100 patients and/or normal subjects, accidental or intentional acute overdosage of olanzapine was identified in 67 patients. In the patient taking the largest identified amount, 300 mg, the only symptoms reported were drowsiness and slurred speech. In the limited number of patients who were evaluated in hospitals, including the patient taking 300 mg, there were no observations indicating an adverse change in laboratory analytes or ECG.
Vital signs were usually within normal limits following overdoses. In postmarketing reports of overdose with olanzapine alone, symptoms have been reported in the majority of cases. In symptomatic patients, symptoms with ≥10% incidence included agitation/aggressiveness, dysarthria, tachycardia, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma.
Among less commonly reported symptoms were the following potentially medically serious reactions: aspiration, cardiopulmonary arrest, cardiac arrhythmias (such as supraventricular tachycardia and 1 patient experiencing sinus pause with spontaneous resumption of normal rhythm), delirium, possible neuroleptic malignant syndrome, respiratory depression/arrest, convulsion, hypertension, and hypotension. Company has received reports of fatality in association with overdose of olanzapine alone. In 1 case of death, the amount of acutely ingested olanzapine was reported to be possibly as low as 450 mg of oral olanzapine; however, in another case, a patient was reported to survive an acute olanzapine ingestion of approximately 2 g of oral olanzapine.
10.2Management of Overdose There is no specific antidote to an overdose of olanzapine. The possibility of multiple drug involvement should be considered. Establish and maintain an airway and ensure adequate oxygenation and ventilation.
Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. Contact a Certified Poison Control Center for the most up to date information on the management of overdosage (1-800-222-1222). For specific information about overdosage with lithium or valproate, refer to the Overdosage section of the prescribing information for those products.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action of olanzapine, in the listed indications is unclear. However, the efficacy of olanzapine in schizophrenia could be mediated through a combination of dopamine and serotonin type 2 (5HT 2 ) antagonism.
12.2Pharmacodynamics Olanzapine binds with high affinity to the following receptors: serotonin 5HT 2A/2C , 5HT 6 (K i =4, 11, and 5 nM, respectively), dopamine D 1-4 (K i =11-31 nM), histamine H 1 (K i =7 nM), and adrenergic α 1 receptors (K i =19 nM). Olanzapine is an antagonist with moderate affinity binding for serotonin 5HT 3 (K i =57 nM) and muscarinic M 1-5 (K i =73, 96, 132, 32, and 48 nM, respectively). Olanzapine binds with low affinity to GABA A , BZD, and β-adrenergic receptors (K i >10 μM).
12.3Pharmacokinetics Oral Administration, Monotherapy — Olanzapine is well absorbed and reaches peak concentrations in approximately 6 hours following an oral dose. It is eliminated extensively by first pass metabolism, with approximately 40% of the dose metabolized before reaching the systemic circulation. Food does not affect the rate or extent of olanzapine absorption.
Pharmacokinetic studies showed that Zyprexa tablets and Zyprexa Zydis dosage forms of olanzapine are bioequivalent. Olanzapine displays linear kinetics over the clinical dosing range. Its half-life ranges from 21 to 54 hours (5th to 95th percentile; mean of 30 hr), and apparent plasma clearance ranges from 12 to 47 L/hr (5th to 95th percentile; mean of 25 L/hr).
Administration of olanzapine once daily leads to steady-state concentrations in about 1 week that are approximately twice the concentrations after single doses. Plasma concentrations, half-life, and clearance of olanzapine may vary between individuals on the basis of smoking status, gender, and age. Olanzapine is extensively distributed throughout the body, with a volume of distribution of approximately 1000 L.
It is 93% bound to plasma proteins over the concentration range of 7 to 1100 ng/mL, binding primarily to albumin and α 1 -acid glycoprotein. Metabolism and Elimination — Following a single oral dose of 14 C labeled olanzapine, 7% of the dose of olanzapine was recovered in the urine as unchanged drug, indicating that olanzapine is highly metabolized. Approximately 57% and 30% of the dose was recovered in the urine and feces, respectively.
In the plasma, olanzapine accounted for only 12% of the AUC for total radioactivity, indicating significant exposure to metabolites. After multiple dosing, the major circulating metabolites were the 10-N-glucuronide, present at steady state at 44% of the concentration of olanzapine, and 4′-N-desmethyl olanzapine, present at steady state at 31% of the concentration of olanzapine. Both metabolites lack pharmacological activity at the concentrations observed.
Direct glucuronidation and cytochrome P450 (CYP) mediated oxidation are the primary metabolic pathways for olanzapine. In vitro studies suggest that CYPs 1A2 and 2D6, and the flavin-containing monooxygenase system are involved in olanzapine oxidation. CYP2D6 mediated oxidation appears to be a minor metabolic pathway in vivo, because the clearance of olanzapine is not reduced in subjects who are deficient in this enzyme.
Intramuscular Administration — Olanzapine for Injection results in rapid absorption with peak plasma concentrations occurring within 15 to 45 minutes. Based upon a pharmacokinetic study in healthy volunteers, a 5 mg dose of intramuscular olanzapine for injection produces, on average, a maximum plasma concentration approximately 5 times higher than the maximum plasma concentration produced by a 5 mg dose of oral olanzapine. Area under the curve achieved after an intramuscular dose is similar to that achieved after oral administration of the same dose.
The half-life observed after intramuscular administration is similar to that observed after oral dosing. The pharmacokinetics are linear over the clinical dosing range. Metaboli…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism of action of olanzapine, in the listed indications is unclear. However, the efficacy of olanzapine in schizophrenia could be mediated through a combination of dopamine and serotonin type 2 (5HT 2 ) antagonism.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Olanzapine for Injection is available in: NDC 0143-9199-01 – 10 mg single-dose vial (1s)
16.2Storage and Handling Store Olanzapine for Injection vials (before reconstitution) at controlled room temperature, 20° to 25°C (68° to 77°F) [ see USP Controlled Room Temperature]. Reconstituted Olanzapine for Injection may be stored at controlled room temperature, 20° to 25°C (68° to 77°F) [ see USP Controlled Room Temperature] for up to 1 hour if necessary. Discard any unused portion of reconstituted Olanzapine for Injection.
The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses. Protect Olanzapine for Injection from light, do not freeze.
16.1How Supplied Olanzapine for Injection is available in: NDC 0143-9199-01 – 10 mg single-dose vial (1s)
📦 Storage and Handling ▾
16.2Storage and Handling Store Olanzapine for Injection vials (before reconstitution) at controlled room temperature, 20° to 25°C (68° to 77°F) [ see USP Controlled Room Temperature]. Reconstituted Olanzapine for Injection may be stored at controlled room temperature, 20° to 25°C (68° to 77°F) [ see USP Controlled Room Temperature] for up to 1 hour if necessary. Discard any unused portion of reconstituted Olanzapine for Injection.
The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses. Protect Olanzapine for Injection from light, do not freeze.
📋 Description ▾
11 DESCRIPTION Olanzapine is an atypical antipsychotic that belongs to the thienobenzodiazepine class. The chemical designation is 2-methyl-4-(4-methyl-1-piperazinyl)-10 H -thieno[2,3- b ] [1,5]benzodiazepine. The molecular formula is C 17 H 20 N 4 S, which corresponds to a molecular weight of 312.44.
The chemical structure is: Olanzapine is a yellow crystalline solid, which is practically insoluble in water. Olanzapine for injection is intended for intramuscular use only. Each single-dose vial provides for the administration of 10 mg (32 μmol) olanzapine with inactive ingredients 50 mg lactose monohydrate and 3.5 mg tartaric acid.
Diluted hydrochloric acid and/or sodium hydroxide may have been added during manufacturing to adjust pH. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking olanzapine as monotherapy. If you do not think you are getting better or have any concerns about your condition while taking olanzapine, call your doctor. Elderly Patients with Dementia-Related Psychosis: Increased Mortality and Cerebrovascular Adverse Events (CVAE), Including Stroke Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with olanzapine had a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) compared with placebo. Olanzapine is not approved for elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions ( 5.1 )] . Neuroleptic Malignant Syndrome (NMS) Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs, including olanzapine.
Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see Warnings and Precautions ( 5.3 )] . Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Patients should be advised to report to their health care provider at the earliest onset of any signs and symptoms that may be associated with drug reaction with eosinophilia and systemic symptoms (DRESS) [see Warnings and Precautions ( 5.4 )] .
Hyperglycemia and Diabetes Mellitus Patients should be advised of the potential risk of hyperglycemia-related adverse reactions. Patients should be monitored regularly for worsening of glucose control. Patients who have diabetes should follow their doctor's instructions about how often to check their blood sugar while taking olanzapine [see Warnings and Precautions ( 5.5 )] .
Dyslipidemia Patients should be counseled that dyslipidemia has occurred during treatment with olanzapine. Patients should have their lipid profile monitored regularly [see Warnings and Precautions ( 5.5 )] . Weight Gain Patients should be counseled that weight gain has occurred during treatment with olanzapine.
Patients should have their weight monitored regularly [see Warnings and Precautions ( 5.5 )] . Orthostatic Hypotension Patients should be advised of the risk of orthostatic hypotension, especially during the period of initial dose titration and in association with the use of concomitant drugs that may potentiate the orthostatic effect of olanzapine, e.g., diazepam or alcohol [see Warnings and Precautions ( 5.7 ) and Drug Interactions ( 7 )] . Patients should be advised to change positions carefully to help prevent orthostatic hypotension, and to lie down if they feel dizzy or faint, until they feel better.
Patients should be advised to call their doctor if they experience any of the following signs and symptoms associated with orthostatic hypotension: dizziness, fast or slow heartbeat, or fainting. Potential for Cognitive and Motor Impairment Because olanzapine has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that olanzapine therapy does not affect them adversely [see Warnings and Precautions ( 5.12 )] .
Body Temperature Regulation Patients should be advised regarding appropriate care in avoiding overheating and dehydration. Patients should be advised to call their doctor right away if they become severely ill and have some or all of these symptoms of dehydration: sweating too much or not at all, dry mouth, feeling very hot, feeling thirsty,…