Olanzapine and Fluoxetine 12 mg; 25 mg Capsule, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Serotonin Reuptake Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder. It is also used along with olanzapine to treat depression and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal mo...
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A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
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FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
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A synthetic red dye used to color medications and make them easier to identify. It serves as a colorant in tablets, capsules, and liquid formulations.
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Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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A blue colorant derived from indigo dye. It's added to tablets and capsules to provide color identification and improve the appearance of the medication.
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Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
13 inactive ingredients listed in the exact product block matched to this NDC.
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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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Olanzapine and Fluoxetine 12 mg/1; 25 mg 00093-5506-56 | Teva | 30 capsules | $9.813 | AB | Availability likely | — |
| Olanzapine and Fluoxetine 12 mg/1; 25 mg 49884-0252-11 | Par | 30 capsules | $9.813 | AB | Availability likely | — |
| Olanzapine and Fluoxetine 12 mg/1; 25 mgthis 42291-0655-30 | AvKARE | 30 capsules | — | AB | 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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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 42291-0655-30 You're viewing this | 30 CAPSULE in 1 BOTTLE (42291-655-30) | 2014-01-21 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNINGS: SUICIDAL THOUGHTS AND BEHAVIORS; AND INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Suicidal Thoughts and Behaviors — Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and emergence of suicidal thoughts and behaviors.
Advise families and caregivers of the need for close observation and communication with the prescriber. Olanzapine and fluoxetine capsules are not approved for use in children less than 10 years of age [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) , and Patient Counseling Information (17.2) ]. 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.
Olanzapine and fluoxetine capsules are not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.2) ]. WARNINGS: SUICIDAL THOUGHTS AND BEHAVIORS; AND INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.
Olanzapine and fluoxetine capsules are not approved for use in children less than 10 years of age (5.1 , 8.4 , 17.2 ). Monitor for worsening and emergence of suicidal thoughts and behaviors (5.1 , 17.2 ). Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Olanzapine and fluoxetine capsules are not approved for the treatment of patients with dementia-related psychosis (5.2 , 5.21 , 17.3 ).
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Olanzapine and fluoxetine capsules are indicated for the treatment of: Acute depressive episodes in Bipolar I Disorder [see Clinical Studies (14.1) ]. Treatment resistant depression (Major Depressive Disorder in patient who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) [see Clinical Studies (14.2) ]. Olanzapine and fluoxetine capsules combine olanzapine, an atypical antipsychotic and fluoxetine, a selective serotonin reuptake inhibitor, indicated for treatment of: Acute Depressive Episodes Associated with Bipolar I Disorder (1) Treatment Resistant Depression (1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Adult Starting Dose: 6 mg olanzapine with 25 mg fluoxetine (6 mg/25 mg, once daily in the evening) (2.1 , 2.2 ) Adult Maximum Dose: 12 mg/50 mg once daily (2.1 , 2.2 ). Pediatric Bipolar Depression Starting Dose: 3 mg/25 mg once daily (for ages 10 to 17 years) (2.1) . Pediatric Bipolar Depression Maximum Dose: 12 mg/50 mg (2.1) Starting dose in patients predisposed to hypotensive reactions, hepatic impairment, or with potential for slowed metabolism: 3 mg/25 mg to 6 mg/25 mg.
Escalate dose cautiously (2.3)
2.1Depressive Episodes Associated with Bipolar I Disorder Adults – Administer olanzapine and fluoxetine capsules once daily in the evening, generally beginning with the 6 mg/25 mg (mg olanzapine/mg equivalent fluoxetine) capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of olanzapine and fluoxetine capsules has not been studied. Make dosage adjustments, if indicated, according to efficacy and tolerability.
Antidepressant efficacy was demonstrated with olanzapine and fluoxetine capsules in a dose range of olanzapine 6 mg to 12 mg and fluoxetine 25 mg to 50 mg [see Clinical Studies (14.1) ]. The safety of doses above 18 mg of olanzapine and 75 mg of fluoxetine has not been evaluated in adult clinical studies. Periodically reexamine the need for continued pharmacotherapy.
Children and Adolescents (10 to 17 years of age) — Administer olanzapine and fluoxetine capsules once daily in the evening, generally beginning with the 3 mg/25 mg capsule, without regard to meals, with a recommended target dose within the approved dosing range (6/25; 6/50; 12/25; 12/50 mg) [see Clinical Studies ( (14.1) ]. The safety of doses above 12 mg of olanzapine and 50 mg of fluoxetine has not been evaluated in pediatric clinical studies. Periodically reexamine the need for continued pharmacotherapy.
2.2Treatment Resistant Depression Administer olanzapine and fluoxetine capsules once daily in the evening, generally beginning with the 6 mg/25 mg capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of olanzapine and fluoxetine capsules has not been studied. Adjust dosage, if indicated, according to efficacy and tolerability.
Antidepressant efficacy was demonstrated with olanzapine and fluoxetine capsules in a dose range of olanzapine 6 mg to 18 mg and fluoxetine 25 mg to 50 mg [see Clinical Studies (14.2) ]. The safety of doses above 18 mg/75 mg has not been evaluated in clinical studies. Periodically reexamine the need for continued pharmacotherapy.
2.3Specific Populations Start olanzapine and fluoxetine capsules at 3 mg/25 mg or 6 mg/25 mg in patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine and fluoxetine capsules (female gender, geriatric age, nonsmoking status) or those patients who may be pharmacodynamically sensitive to olanzapine. Titrate slowly and adjust dosage as needed in patients who exhibit a combination of factors that may slow metabolism.
Olanzapine and fluoxetine capsules have not been systematically studied in patients >65 years of age or in patients <10 years of age [see Warnings and Precautions (5.21) , Use in Specific Populations (8.5) , and Clinical Pharmacology (12.3 , 12.4 )]. Treatment of Pregnant Women — When treating pregnant women with fluoxetine, a component of olanzapine and fluoxetine capsules, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalizations, respiratory support, and tube feeding [see Use in Specific Populations (8.1) ].
2.4 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Inte…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capsules (mg olanzapine, USP/mg equivalent fluoxetine): 3 mg/25 mg 6 mg/25 mg 6 mg/50 mg 12 mg/25 mg 12 mg/50 mg Capsules: 3 mg olanzapine/25 mg fluoxetine, 6 mg olanzapine/25 mg fluoxetine, 6 mg olanzapine/50 mg fluoxetine, 12 mg olanzapine/25 mg fluoxetine, and 12 mg olanzapine/50 mg fluoxetine (mg equivalent olanzapine/mg equivalent fluoxetine) (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Monoamine Oxidase Inhibitors (MAOI) : Because of the risk of serotonin syndrome, do not use MAOIs intended to treat psychiatric disorders with olanzapine and fluoxetine capsules or within 5 weeks of stopping treatment with olanzapine and fluoxetine capsules. Do not use olanzapine and fluoxetine capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start olanzapine and fluoxetine capsules in a patient who is being treated with linezolid or intravenous methylene blue.
(4.1) Pimozide : Do not use. Risk of QT interval prolongation (4.2 , 5.20 , 7.7 , 7.8 ) Thioridazine : Do not use. Risk of QT interval prolongation.
Do not use thioridazine within 5 weeks of discontinuing olanzapine and fluoxetine capsules (4.2 , 5.20 , 7.7 , 7.8 )
4.1Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with olanzapine and fluoxetine capsules or within 5 weeks of stopping treatment with olanzapine and fluoxetine capsules is contraindicated because of an increased risk of serotonin syndrome. The use of olanzapine and fluoxetine capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.4) and Warnings and Precautions (5.6) ]. Starting olanzapine and fluoxetine capsules in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.5) and Warnings and Precautions (5.6) ].
4.2Other Contraindications Pimozide [see Warnings and Precautions (5.20) and Drug Interactions (7.7 , 7.8) ] Thioridazine [see Warnings and Precautions (5.20) and Drug Interactions (7.7 , 7.8) ] Pimozide and thioridazine prolong the QT interval. Olanzapine and fluoxetine capsules can increase the levels of pimozide and thioridazine through inhibition of CYP2D6. Olanzapine and fluoxetine capsules can also prolong the QT interval.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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. Monitor for symptoms of hyperglycemia.
Perform fasting blood glucose testing before beginning, and periodically during treatment. (5.5) Dyslipidemia : Appropriate clinical monitoring is recommended, including fasting blood lipid testing before beginning, and periodically during, treatment (5.5) Weight gain : Consider potential consequences of weight gain. Monitor weight regularly (5.5) Serotonin Syndrome : Serotonin syndrome has been reported with SSRIs and SNRIs, including olanzapine and fluoxetine capsules, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St.
John's Wort). If such symptoms occur, discontinue olanzapine and fluoxetine capsules and initiate supportive treatment. If concomitant use of olanzapine and fluoxetine capsules with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases (5.6) Angle-Closure Glaucoma : Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.7) Allergic Reactions and Rash : Discontinue upon appearance of rash or allergic phenomena (5.8) Activation of Mania/Hypomania : Screen for Bipolar Disorder and monitor for activation of mania/hypomania (5.9) Tardive Dyskinesia : Discontinue if clinically appropriate (5.10) Orthostatic Hypotension : Can be associated with bradycardia and syncope.
Risk is increased during initial dose titration. Use caution in patients with cardiovascular disease or cerebrovascular disease, and those conditions that could affect hemodynamic responses (5.11) Leukopenia, Neutropenia, and Agranulocytosis : Has been reported with antipsychotics, including olanzapine and fluoxetine capsules. 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.
Consider discontinuing olanzapine and fluoxetine capsules at the first sign of a clinically significant decline in WBC in the absence of other causative factors (5.13) Seizures : Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold (5.15) Abnormal Bleeding : SSRIs increase the risk of bleeding. Use with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding (5.16) Hyponatremia : Can occur in association with syndrome of inappropriate antidiuretic hormone (SIADH).
Consider discontinuing olanzapine and fluoxetine capsules if symptomatic hyponatremia occurs (SIADH) (5.17) Potential for Cognitive and Motor Impairment : Has potential to impair judgment, thinking, and motor skills. Caution patients about operating machinery (5.18) QT Prolongation : QT prolongation and ventricular arrhythmia including Torsade de Pointes have been reported with fluoxetine. Use with caution in conditions that predispose to arrhythmias or increased fluoxetine exposure.
Use cautiously in patients with risk factors for QT prolongation (4.2 , 5.20 ) Hyperprolactinemia : May elevate prolactin levels (5.22) Long Elimination Half-Life of Fluoxetine : Changes in dose will not be fully reflected in plasma for several w…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see Boxed Warning and Warnings and Precautions (5.1) ] Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.2) ] Neuroleptic Malignant syndrome (NMS) [see Warnings and Precautions (5.3) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4) ] Hyperglycemia [see Warnings and Precautions (5.5) ] Dyslipidemia [see Warnings and Precautions (5.5) ] Weight Gain [see Warnings and Precautions (5.5) ] Serotonin Syndrome [see Warnings and Precautions (5.6) ] Angle-Closure Glaucoma [see Warnings and Precautions (5.7) ] Allergic Reactions and Rash [see Warnings and Precautions (5.8) ] Activation of Mania/Hypomania [see Warnings and Precautions (5.9) ] Tardive Dyskinesia [see Warnings and Precautions (5.10) ] Orthostatic Hypotension [see Warnings and Precautions (5.11) ] Falls [see Warnings and Precautions (5.12) ] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.13) ] Dysphagia [see Warnings and Precautions (5.14) ] Seizures [see Warnings and Precautions (5.15) ] Abnormal Bleeding [see Warnings and Precautions (5.16) ] Hyponatremia [see Warnings and Precautions (5.17) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.18) ] Body Temperature Dysregulation [see Warnings and Precautions (5.19) ] QT Prolongation [see Warnings and Precautions (5.20) ] Hyperprolactinemia [see Warnings and Precautions (5.22) ] Discontinuation Adverse Reactions [see Warnings and Precautions (5.25) ] Most common adverse reactions (≥5% and at least twice that for placebo) in adults: sedation, weight increased, appetite increased, dry mouth, fatigue, edema, tremor, disturbance in attention, blurred vision.
Children and adolescents: sedation, weight increased, appetite increased, tremor, triglyceride increased, hepatic enzymes increased (6.1) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE, Inc. at 1-855-361-3993 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. The data in the tables represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
Adults — The information below is derived from a clinical study database for olanzapine and fluoxetine capsules consisting of 2547 patients with treatment resistant depression, depressive episodes associated with Bipolar I Disorder, Major Depressive Disorder with psychosis, or sexual dysfunction with approximately 1085 patient-years of exposure. The conditions and duration of treatment with olanzapine and fluoxetine capsules 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 long-term exposure.
Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Controlled Studies Including Depressive Episodes Associated with Bipolar I Disorder and Treatment Resistant Depression — Overall, 11.3% of the 771 patients in the olanzapine and fluoxetine capsule group discontinued due to adverse reactions compared with 4.4% of the 477 patients for placebo. Adverse reactions leading to discontinuation associated with the use of olanzapine and fluoxetine capsules (incidence of at least 1% for olanzapine and fluoxetine capsules and grea…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS The risks of using olanzapine and fluoxetine capsules in combination with other drugs have not been extensively evaluated in systematic studies. The drug-drug interactions sections of fluoxetine and olanzapine are applicable to olanzapine and fluoxetine capsules. As with all drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility.
In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status [see Clinical Pharmacology (12.3) ]. Monoamine Oxidase Inhibitor (MAOI) : (2.4 , 2.5 , 4.1 , 5.6 , 7.1 ) Drugs Metabolized by CYP2D6 : Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway (7.7) Tricyclic Antidepressants (TCAs) : Monitor TCA levels during coadministration with olanzapine and fluoxetine capsules or when olanzapine and fluoxetine capsules have been recently discontinued (5.6 , 7.7 ) CNS Acting Drugs : Caution is advised if the concomitant administration of olanzapine and fluoxetine capsules and other CNS-active drugs is required (7.2) Antihypertensive Agent : Enhanced antihypertensive effect (7.7) Levodopa and Dopamine Agonists : May antagonize levodopa/dopamine agonists (7.7) Benzodiazepines : May potentiate orthostatic hypotension and sedation (7.6 , 7.7 ) Clozapine : May elevate clozapine levels (7.7) Haloperidol : Elevated haloperidol levels have been observed (7.7) Carbamazepine : Potential for elevated carbamazepine levels and clinical anticonvulsant toxicity (7.7) Phenytoin : Potential for elevated phenytoin levels and clinical anticonvulsant toxicity (7.7) Alcohol : May potentiate sedation and orthostatic hypotension (7.7) Serotonergic Drugs : (2.4 , 2.5 , 4.1 , 5.6 , 7.3 ) Fluvoxamine : May increase olanzapine levels; a lower dose of the olanzapine component of olanzapine and fluoxetine capsules should be considered (7.6) Drugs that Interfere with Hemostasis : (e.g., NSAIDs, Aspirin, Warfarin, etc.): May potentiate the risk of bleeding (7.4) Drugs Tightly Bound to Plasma Proteins : Fluoxetine may cause shift in plasma concentrations (7.7) Drugs that Prolong the QT Interval : Do not use olanzapine and fluoxetine capsules in combination with thioridazine or pimozide.
Use olanzapine and fluoxetine capsules with caution in combination with other drugs that prolong the QT interval (4.2 , 5.20 , 7.7 , 7.8 )
7.1Monoamine Oxidase Inhibitors (MAOIs) [ See Dosage and Administration ( 2.4 , 2.5 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.6 ) ].
7.2CNS Acting Drugs Caution is advised if the concomitant administration of olanzapine and fluoxetine capsules and other CNS-active drugs is required. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status [ see Clinical Pharmacology ( 12.3 ) ].
7.3Serotonergic Drugs [ See Dosage and Administration ( 2.4 , 2.5 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.6 ) ].
7.4Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin) Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SNRIs or SSRIs are coadministered with warfarin [ see Warnings and Precautions ( 5.16 ) ].
Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics. Single doses of olanzapine did not affect the pharmacokinetics of war…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy : Olanzapine and fluoxetine capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (8.1) Nursing Mothers : Breast feeding is not recommended (8.3) Pediatric Use : Safety and efficacy of olanzapine and fluoxetine capsules for the treatment of bipolar I depression in patients under 10 years of age have not been established. Safety and efficacy of olanzapine and fluoxetine capsules for treatment resistant depression in patients under 18 years of age have not been established (8.4) Hepatic Impairment : Use a lower or less frequent dose in patients with cirrhosis (8.6)
8.1Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled clinical studies with olanzapine and fluoxetine capsules or their components (olanzapine and fluoxetine) in pregnant women. A number of published epidemiological studies assessing the risk of fluoxetine exposure during the first trimester of pregnancy have demonstrated inconsistent results. Neonates exposed to fluoxetine, a component of olanzapine and fluoxetine capsules, and other SSRIs and SNRIs late in the third trimester have developed complications arising immediately upon delivery (respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying) requiring prolonged hospitalization, respiratory support, and tube feeding.
These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture is consistent with serotonin syndrome. Neonates exposed to olanzapine, a component of olanzapine and fluoxetine capsules, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder.
These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). Olanzapine and fluoxetine capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, taking into account the risk of untreated Bipolar I Depression or Treatment Resistant Depression.
Human Data There are no adequate and well-controlled clinical studies with olanzapine and fluoxetine capsules, olanzapine or fluoxetine in pregnant women. Seven pregnancies were observed during premarketing clinical studies with olanzapine, including 2 resulting in normal births, 1 resulting in neonatal death due to a cardiovascular defect, 3 therapeutic abortions, and 1 spontaneous abortion. Results of a number of published epidemiological studies assessing the risk of fluoxetine exposure during the first trimester of pregnancy have demonstrated inconsistent results.
More than 10 cohort studies and case-control studies failed to demonstrate an increased risk for congenital malformations overall. However, one prospective cohort study conducted by the European Network of Teratology Information Services reported an increased risk of cardiovascular malformations in infants born to women (N = 253) exposed to fluoxetine during the first trimester of pregnancy compared to infants of women (N = 1359) who were not exposed to fluoxetine. There was no specific pattern of cardiovascular malformations.
Overall, however, a causal relationship has not been established. Neonates exposed to fluoxetine, a component of olanzapine and fluoxetine capsules, and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complication…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled clinical studies with olanzapine and fluoxetine capsules or their components (olanzapine and fluoxetine) in pregnant women. A number of published epidemiological studies assessing the risk of fluoxetine exposure during the first trimester of pregnancy have demonstrated inconsistent results. Neonates exposed to fluoxetine, a component of olanzapine and fluoxetine capsules, and other SSRIs and SNRIs late in the third trimester have developed complications arising immediately upon delivery (respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying) requiring prolonged hospitalization, respiratory support, and tube feeding.
These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture is consistent with serotonin syndrome. Neonates exposed to olanzapine, a component of olanzapine and fluoxetine capsules, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder.
These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). Olanzapine and fluoxetine capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, taking into account the risk of untreated Bipolar I Depression or Treatment Resistant Depression.
Human Data There are no adequate and well-controlled clinical studies with olanzapine and fluoxetine capsules, olanzapine or fluoxetine in pregnant women. Seven pregnancies were observed during premarketing clinical studies with olanzapine, including 2 resulting in normal births, 1 resulting in neonatal death due to a cardiovascular defect, 3 therapeutic abortions, and 1 spontaneous abortion. Results of a number of published epidemiological studies assessing the risk of fluoxetine exposure during the first trimester of pregnancy have demonstrated inconsistent results.
More than 10 cohort studies and case-control studies failed to demonstrate an increased risk for congenital malformations overall. However, one prospective cohort study conducted by the European Network of Teratology Information Services reported an increased risk of cardiovascular malformations in infants born to women (N = 253) exposed to fluoxetine during the first trimester of pregnancy compared to infants of women (N = 1359) who were not exposed to fluoxetine. There was no specific pattern of cardiovascular malformations.
Overall, however, a causal relationship has not been established. Neonates exposed to fluoxetine, a component of olanzapine and fluoxetine capsules, and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery.
Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [ see Dosage and Administration ( 2.3 ) and Warnings…
🧒 Pediatric Use ▾
8.4Pediatric Use Olanzapine and fluoxetine capsules — The safety and efficacy of olanzapine and fluoxetine capsules in patients 10 to 17 years of age has been established for the acute treatment of Depressive Episodes Associated with Bipolar I Disorder in a single 8 week randomized, placebo-controlled clinical trial (N = 255) [ see Clinical Studies ( 14.1 ) ]. Patients were initiated at a dose of 3/25 mg/day and force-titrated to the maximum dose of 12/50 mg/day over two weeks. After Week 2, there was flexible dosing of olanzapine and fluoxetine capsules in the range of 6/25, 6/50, 12/25, or 12/50 mg/day.
The average dose was olanzapine 7.7 mg and fluoxetine 37.6 mg. The recommended starting dose for children and adolescents is 3/25 mg per day (lower than that for adults). Flexible dosing is recommended, rather than the forced titration used in the study [ see Dosage and Administration ( 2.1 ) ].
The types of adverse events observed with olanzapine and fluoxetine capsules in children and adolescents were generally similar to those observed in adults. However, the magnitude and frequency of some changes were greater in children and adolescents than adults. These included increases in lipids, hepatic enzymes, and prolactin, as well as increases in the QT interval [ see Warnings and Precautions ( 5.5 , 5.20 , 5.22 ), and Vital Signs and Laboratory Studies ( 6.2 ) ].
The frequency of weight gain ≥7%, and the magnitude and frequency of increases in lipids, hepatic analytes, and prolactin in children and adolescents treated with olanzapine and fluoxetine capsules were similar to those observed in adolescents treated with olanzapine monotherapy. The safety and efficacy of olanzapine and fluoxetine in combination for the treatment of bipolar I depression in patients under the age of 10 years have not been established. The safety and effectiveness of olanzapine and fluoxetine in combination for treatment resistant depression in patients less than 18 years of age have not been established.
Anyone considering the use of olanzapine and fluoxetine capsules in a child or adolescent must balance the potential risks with the clinical need [ see Boxed Warning and Warnings and Precautions ( 5.1 ) ]. Olanzapine — Safety and effectiveness of olanzapine in children <13 years of age have not been established. Compared to patients from adult clinical trials, adolescents treated with oral olanzapine were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin and hepatic aminotransferase levels.
Animal Data Fluoxetine — Juvenile animal toxicity studies were performed for fluoxetine alone. Significant toxicity on muscle tissue, neurobehavior, reproductive organs, and bone development has been observed following exposure of juvenile rats to fluoxetine from weaning through maturity. Oral administration of fluoxetine to rats from weaning postnatal day 21 through adulthood day 90 at 3, 10, or 30 mg/kg/day was associated with testicular degeneration and necrosis, epididymal vacuolation and hypospermia (at 30 mg/kg/day corresponding to plasma exposures [AUC] approximately 5 to 10 times the average AUC in pediatric patients at the MRHD of 20 mg/day), increased serum levels of creatine kinase (at AUC as low as 1 to 2 times the average AUC in pediatric patients at the MRHD of 20 mg/day), skeletal muscle degeneration and necrosis, decreased femur length/growth and body weight gain (at AUC 5 to 10 times the average AUC in pediatric patients at the MRHD of 20 mg/day).
The high dose of 30 mg/kg/day exceeded a maximum tolerated dose. When animals were evaluated after a drug-free period (up to 11 weeks after cessation of dosing), fluoxetine was associated with neurobehavioral abnormalities (decreased reactivity at AUC as low as approximately 0.1 to 0.2 times the average AUC in pediatric patients at the MRHD and learning deficit at the high dose), and reproductive functiona…
🧓 Geriatric Use ▾
8.5Geriatric Use Olanzapine and fluoxetine capsules — Clinical studies of olanzapine and fluoxetine capsules did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [ see Dosage and Administration ( 2.3 ) ].
Olanzapine — Of the 2500 patients in premarketing clinical studies with olanzapine, 11% (263 patients) were ≥65 years of age. In patients with Schizophrenia, there was no indication of any different tolerability of olanzapine in the elderly compared with younger patients. Studies in patients with dementia-related psychosis have suggested that there may be a different tolerability profile in this population compared with 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 reactions (e.g., stroke, transient ischemic attack) in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of patients with dementia-related psychosis [ see Boxed Warning , Dosage and Administration ( 2.3 ), and Warnings and Precautions ( 5.2 ) ].
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. Fluoxetine — U.S. fluoxetine clinical studies included 687 patients ≥65 years of age and 93 patients ≥75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
SNRIs and SSRIs, including olanzapine and fluoxetine capsules, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [ see Warnings and Precautions ( 5.17 ) ].
🆘 Overdosage ▾
10 OVERDOSAGE Olanzapine and fluoxetine capsules — During premarketing clinical studies of olanzapine and fluoxetine in combination, overdose of both fluoxetine and olanzapine were reported in 5 study subjects. Four of the 5 subjects experienced loss of consciousness (3) or coma (1). No fatalities occurred.
Adverse reactions involving overdose of fluoxetine and olanzapine in combination, and olanzapine and fluoxetine capsules, have been reported. An overdose of combination therapy is defined as confirmed or suspected ingestion of a dose of >20 mg olanzapine in combination with a dose of >80 mg fluoxetine. Adverse reactions associated with these reports included somnolence (sedation), impaired consciousness (coma), impaired neurologic function (ataxia, confusion, convulsions, dysarthria), arrhythmias, lethargy, essential tremor, agitation, acute psychosis, hypotension, hypertension, and aggression.
Fatalities have been confounded by exposure to additional substances including alcohol, thioridazine, oxycodone, and propoxyphene. Olanzapine — 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 as well as a patient that experienced sinus pause with spontaneous resumption of normal rhythm), delirium, possible neuroleptic malignant syndrome, respiratory depression/arrest, convulsion, hypertension, and hypotension. Reports of fatality in association with overdose of olanzapine alone have been received. 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.
Fluoxetine — Worldwide exposure to fluoxetine is estimated to be over 38 million patients (circa 1999). Of the 1578 cases of overdose involving fluoxetine, alone or with other drugs, reported from this population, there were 195 deaths. Among 633 adult patients who overdosed on fluoxetine alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdose, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, erectile dysfunction, movement disorder, and hypomania.
The remaining 206 patients had an unknown outcome. The most common signs and symptoms associated with non-fatal overdose were seizures, somnolence, nausea, tachycardia, and vomiting. The largest known ingestion of fluoxetine in adult patients was 8 grams in a patient who took fluoxetine alone and who subsequently recovered.
However, in an adult patient who took fluoxetine alone, an ingestion as low as 520 mg has been associated with lethal outcome, but causality has not been established. Among pediatric patients (ages 3 months to 17 years), there were 156 cases of overdose involving fluoxetine alone or in combination with other drugs. Six patients died, 127 patients completely recovered, 1 patient experienced renal failure, and 22 patients had an unknown outcome.
One of the 6 fatalities was a 9-year-old boy who had a history of OCD, Tourette’s Syndrome with tics, attention deficit disorder, and fetal alcohol syndrome. He had been receiving 100 mg of fluoxetine daily for 6 months in addition to clonidine, methylphenidate, and promethazine. Mixed-drug ingestion or other methods of suicide complicated all 6 overdoses in children that resulted in fatalities.
The largest ingestion in pediatric patients was 3 grams, which w…
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Although the exact mechanism of olanzapine and fluoxetine capsules is unknown, it has been proposed that the activation of 3 monoaminergic neural systems (serotonin, norepinephrine, and dopamine) is responsible for its enhanced antidepressant effect. In animal studies, olanzapine and fluoxetine in combination has been shown to produce synergistic increases in norepinephrine and dopamine release in the prefrontal cortex compared with either component alone, as well as increases in serotonin.
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 to 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 weakly to GABA A , BZD, and β-adrenergic receptors (K i >10 μM).
Fluoxetine is an inhibitor of the serotonin transporter and is a weak inhibitor of the norepinephrine and dopamine transporters. Antagonism at receptors other than dopamine and 5HT 2 may explain some of the other therapeutic and side effects of olanzapine. Olanzapine’s antagonism of muscarinic M 1-5 receptors may explain its anticholinergic-like effects.
The antagonism of histamine H 1 receptors by olanzapine may explain the somnolence observed with this drug. The antagonism of α 1 -adrenergic receptors by olanzapine may explain the orthostatic hypotension observed with this drug. Fluoxetine has relatively low affinity for muscarinic, α 1 -adrenergic, and histamine H 1 receptors.
12.3Pharmacokinetics Olanzapine and fluoxetine capsules — Fluoxetine (administered as a 60 mg single dose or 60 mg daily for 8 days) caused a small increase in the mean maximum concentration of olanzapine (16%) following a 5 mg dose, an increase in the mean area under the curve (17%) and a small decrease in mean apparent clearance of olanzapine (16%). In another study, a similar decrease in apparent clearance of olanzapine of 14% was observed following olanzapine doses of 6 or 12 mg with concomitant fluoxetine doses of 25 mg or more.
The decrease in clearance reflects an increase in bioavailability. The terminal half-life is not affected, and therefore the time to reach steady state should not be altered. The overall steady-state plasma concentrations of olanzapine and fluoxetine when given as the combination in the therapeutic dose ranges were comparable with those typically attained with each of the monotherapies.
The small change in olanzapine clearance, observed in both studies, likely reflects the inhibition of a minor metabolic pathway for olanzapine via CYP2D6 by fluoxetine, a potent CYP2D6 inhibitor, and was not deemed clinically significant. Therefore, the pharmacokinetics of the individual components is expected to reasonably characterize the overall pharmacokinetics of the combination. Absorption and Bioavailability Olanzapine and fluoxetine capsules — Following a single oral 12 mg/50 mg dose of olanzapine and fluoxetine capsules, peak plasma concentrations of olanzapine and fluoxetine occur at approximately 4 and 6 hours, respectively.
The effect of food on the absorption and bioavailability of olanzapine and fluoxetine capsules has not been evaluated. The bioavailability of olanzapine given as Zyprexa ® , and the bioavailability of fluoxetine given as Prozac ® were not affected by food. It is unlikely that there would be a significant food effect on the bioavailability of olanzapine and fluoxetine capsules.
Olanzapine — Olanzapine is well absorbed and reaches peak concentration approximately 6 hours following an oral dose. Food does not affect the rate or extent of olanzapine absorption when olanzapine is given as Zyprexa ® . It is eliminated extensively by first pass metabolism, with approximately 40% of the d…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Although the exact mechanism of olanzapine and fluoxetine capsules is unknown, it has been proposed that the activation of 3 monoaminergic neural systems (serotonin, norepinephrine, and dopamine) is responsible for its enhanced antidepressant effect. In animal studies, olanzapine and fluoxetine in combination has been shown to produce synergistic increases in norepinephrine and dopamine release in the prefrontal cortex compared with either component alone, as well as increases in serotonin.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Olanzapine and fluoxetine capsules USP are supplied as follows: 3 mg/25 mg strength: Capsules with opaque buff body and cap with "TEVA" imprinted on the cap and "5503" imprinted on the body, in bottles of 30. (NDC 42291-652-30) 6 mg/25 mg strength: Capsules with opaque orange body and cap with "TEVA" imprinted on the cap and "5504" imprinted on the body, in bottles of 30. (NDC 42291-653-30) 6 mg/50 mg strength: Capsules with opaque white body and cap with "TEVA" imprinted on the cap and "5505" imprinted on the body, in bottles of 30.
(NDC 42291-654-30) 12 mg/25 mg strength: Capsules with opaque yellow body and cap with "TEVA" imprinted on the cap and "5506" imprinted on the body, in bottles of 30. (NDC 42291-655-30) 12 mg/50 mg strength: Capsules with opaque maroon body and cap with "TEVA" imprinted on the cap and "5507" imprinted on the body, in bottles of 30. (NDC 42291-656-30)
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) with excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from light and moisture. Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
16.1How Supplied Olanzapine and fluoxetine capsules USP are supplied as follows: 3 mg/25 mg strength: Capsules with opaque buff body and cap with "TEVA" imprinted on the cap and "5503" imprinted on the body, in bottles of 30. (NDC 42291-652-30) 6 mg/25 mg strength: Capsules with opaque orange body and cap with "TEVA" imprinted on the cap and "5504" imprinted on the body, in bottles of 30. (NDC 42291-653-30) 6 mg/50 mg strength: Capsules with opaque white body and cap with "TEVA" imprinted on the cap and "5505" imprinted on the body, in bottles of 30.
(NDC 42291-654-30) 12 mg/25 mg strength: Capsules with opaque yellow body and cap with "TEVA" imprinted on the cap and "5506" imprinted on the body, in bottles of 30. (NDC 42291-655-30) 12 mg/50 mg strength: Capsules with opaque maroon body and cap with "TEVA" imprinted on the cap and "5507" imprinted on the body, in bottles of 30. (NDC 42291-656-30)
📦 Storage and Handling ▾
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) with excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from light and moisture. Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
📋 Description ▾
11 DESCRIPTION Olanzapine and Fluoxetine Capsules USP combine an atypical antipsychotic and a selective serotonin reuptake inhibitor, olanzapine, USP (the active ingredient in Zyprexa ® , and Zyprexa ® Zydis ® ) and fluoxetine hydrochloride, USP (the active ingredient in Prozac ® , Prozac ® Weekly ™ , and Sarafem ® ). Olanzapine, USP 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.
Fluoxetine hydrochloride, USP is a selective serotonin reuptake inhibitor (SSRI). The chemical designation is (±)-N-methyl-3-phenyl-3-[(α,α,α-trifluoro- p -tolyl)oxy]propylamine hydrochloride. The chemical structures are: C 17 H 20 N 4 S M.W.
312.44 C 17 H 18 F 3 NO•HCl M.W. 345.79 Olanzapine, USP is a yellow crystalline solid, which is practically insoluble in water. Fluoxetine hydrochloride, USP is a white to off-white crystalline solid with a solubility of 14 mg/mL in water.
Olanzapine and Fluoxetine Capsules USP are available for oral administration in the following strength combinations: 3 mg/25 mg 6 mg/25 mg 6 mg/50 mg 12 mg/25 mg 12 mg/50 mg Olanzapine, USP 3 6 6 12 12 fluoxetine base equivalent 25 25 50 25 50 Each capsule also contains D&C yellow #10 aluminum lake, FD&C blue #1 aluminum lake, FD&C blue #2 aluminum lake, FD&C red #40 aluminum lake, gelatin, iron oxide black, magnesium stearate, pregelatinized corn starch, propylene glycol, shellac glaze, and titanium dioxide. Additionally, the 3 mg/25 mg capsule contains D&C yellow #10 and FD&C yellow #6; both the 6 mg/25 mg and 12 mg/25 mg capsules contain ferric oxide yellow; the 6 mg/25 mg capsule contains ferric oxide red; and the 12 mg/50 mg capsule contains D&C red #28, FD&C blue #1, and FD&C red #40. olanzapine structural formula fluoxetine hydrochloride structural formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-approved Medication Guide. Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking olanzapine and fluoxetine capsules.
17.1Information on Medication Guide Prescribers or other health professionals should inform patients, their families, and their caregivers about the potential benefits and potential risks associated with treatment with olanzapine and fluoxetine capsules and should counsel them in their appropriate use. A patient Medication Guide is available for olanzapine and fluoxetine capsules. The prescribers or other health professionals should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents.
Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have.
17.2Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt.
Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [ see Boxed Warning and Warnings and Precautions ( 5.1 ) ].
17.3Elderly 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 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 and fluoxetine capsules are not approved for elderly patients with dementia-related psychosis [ see Boxed Warning and Warnings and Precautions ( 5.2 ) ].
17.4Neuroleptic 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, a component of olanzapine and fluoxetine capsules. 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 ) ].
17.5Drug 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 ) ].
17.6Hyperglycemia 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 and caregivers should be counseled that metabolic changes have occurred during treatment with olanzapine and fluoxetine capsules. Patients who have diabetes shoul…
💬 Medication Guide ▾
Medication Guide Olanzapine (oh-LAN-zah-peen) and Fluoxetine (floo-OX-eh-teen) Capsules Read the Medication Guide that comes with olanzapine and fluoxetine capsules before you start taking them and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment.
Talk with your doctor or pharmacist if there is something you do not understand or you want to learn more about olanzapine and fluoxetine capsules. What is the most important information I should know about olanzapine and fluoxetine capsules? Olanzapine and fluoxetine capsules may cause serious side effects, including: Suicidal thoughts or actions.
Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis). High blood sugar (hyperglycemia). High fat levels in your blood (increased cholesterol and triglycerides), especially in children and adolescents age 10 to 17.
Weight gain, especially in children and adolescents age 10 to 17. These serious side effects are described below. 1.
Suicidal thoughts or actions. Antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions: Talk to your, or your family member's, healthcare provider about: all risks and benefits of treatment with antidepressant medicines. all treatment choices for depression or other serious mental illness. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member? Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying attempts to commit suicide new or worse depression new or worse anxiety feeling very agitated or restless panic attacks trouble sleeping (insomnia) new or worse irritability acting aggressive, being angry, or violent acting on dangerous impulses an extreme increase in activity and talking (mania) or other unusual changes in behavior or mood.
What else do I need to know about antidepressant medicines? Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member. Antidepressant medicines can interact with other medicines.
Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start…