HomeNDC LookupIngredientsOlanzapine And Fuoxetine › 49884-0250-11
Olanzapine and Fluoxetine olanzapine and fuoxetine 6 mg; 25 mg Capsule, 30-count — NDC 49884-0250-11 package photo

Olanzapine and Fluoxetine olanzapine and fuoxetine 6 mg; 25 mg Capsule, 30-count

by Par Health USA, LLC · 30 CAPSULE in 1 BOTTLE, PLASTIC (49884-250-11)
NDC 49884-0250-11
🏷️ FDA NDC (as labeled) 49884-250-11 billing pads the product segment with a zero
Rx only Generic On market Non-controlled
🗂️ Data synced Sep 10, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 49884-250-11
Product NDC 49884-250
11-digit billing NDC 49884025011
NCPDP billing unit EA — each (per item)
UNII N7U69T4SZR, I9W7N6B1KJ
UPC 0349884250119, 0349884251116, 0349884253110, 0349884252113 +1 more
Application # ANDA077742
SPL Set ID 2f6ceda3-3edc-4427-98a6-23e3c930c44d
Established class (EPC) Atypical Antipsychotic
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2012-11-26
Route ORAL
Dosage form CAPSULE
Substance OLANZAPINE; FLUOXETINE HYDROCHLORIDE
GPI-14 62995002500120
GPI class OLANZapine-FLUoxetine HCl
GCN Seq No 053400
GCN 20868
HICL code 025800
Ingredient (HICL) Olanzapine/Fluoxetine Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H7
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 1)
HIC3 code H7Z
Therapeutic class — specific (HIC3) Ssri-Antipsych, Atypical,Dopamine,Serotonin Antag
AHFS code 28:16.04.20
AHFS class Selective-Serotonin Reuptake Inhibitors
FDB label name OLANZAPINE-FLUOXETINE 6-25 MG
FDB brand name Olanzapine-Fluoxetine Hcl
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 49884-250-11 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 49884-0250-11. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Serotonin Reuptake Inhibitor class.

Pharmacologic class Serotonin Reuptake Inhibitor
Drug family (ATC) Selective serotonin reuptake inhibitors
How it works Serotonin Uptake Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerPar Health USA, LLC
Application holderPH HEALTH LTD
FDA applicationANDA077742 (ANDA)
Labeler code49884
First marketedNov 2012
Product typeHuman Prescription Drug
Portfolio210 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name OLANZAPINE-FLUOXETINE 6-25 MG Ingredient Olanzapine/Fluoxetine Hcl
📖 What it is MedlinePlus · NLM

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...

Read the full MedlinePlus article ↗
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color white / orange / yellow / gray / brown / red
ShapeCapsule
Imprint253;par
Size18 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII 35SW5USQ3G
    A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
  • UNII H3R47K3TBD
    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.
  • UNII L06K8R7DQK
    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.
  • UNII WZB9127XOA
    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.
  • UNII EX438O2MRT
    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.
  • UNII XM0M87F357
    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.
  • UNII 2G86QN327L
    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.
  • UNII 70097M6I30
    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.
  • UNII Y4S76JWI15
    Methyl alcohol, also called methanol, is a simple organic solvent. It helps dissolve and carry active ingredients in liquid medicines, and helps the product mix evenly.
  • UNII 6DC9Q167V3
    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.
  • UNII 46N107B71O
    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.
  • UNII O8232NY3SJ
    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.
  • 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.

14 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 systemPer eaPer package
Retail pharmacies payNADAC · weekly $4.028 $120.84 / 30 capsules
Medicaid paysCMS SDUD · 12 mo $5.36 $160.77 / 30 capsules
Medicare drug plans payPart D · Q2 2026 $8.74 $262.24 / 30 capsules
NADAC price history (per ea) — tap or hover for the price & month
Feb 2021 Nov 2022 Mar 2026 Aug 2026 $7.883 $4.028
▼ Down 49% over the last 16 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Olanzapine and Fluoxetine 6 mg/1; 25 mg 00093-5504-56 Teva 30 capsules $4.028 AB Availability likely
Olanzapine and Fluoxetine 6 mg/1; 25 mgthis 49884-0250-11 Par 30 capsules $4.028 AB Availability likely
Olanzapine and Fluoxetine 6 mg/1; 25 mg 42291-0653-30 AvKARE 30 capsules AB FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2012
On the market since
Nov 2012
📍
2026
Currently FDA-listed
14 years listed
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 49884-0250-11, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
1K
Units reimbursed last 4 qtrs
32.7K
Gross reimbursed last 4 qtrs
$175.3K
Avg / prescription
$171.67
Avg / unit
$5.3590
Latest quarter Q4 2025
230Rx
Medicaid pays / ea
$5.3590
gross reimbursed
vs
NADAC / ea
$4.0280
acquisition cost
=
Spread
+$1.3310
+33% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care
63% FFS 37% MCO
Fee-for-service · 645 Rx Managed care · 376 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 4,637 units · 46.2 per 100k residents MI New York: 6,428 units · 32.8 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 3,270 units · 77.3 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: 687 units · 21.4 per 100k residents IA Illinois: no data reported IL Indiana: no data reported IN Ohio: 3,031 units · 25.7 per 100k residents OH Pennsylvania: no data reported PA New Jersey: 2,681 units · 28.9 per 100k residents NJ Massachusetts: no data reported MA California: 3,060 units · 7.9 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: 799 units · 12.9 per 100k residents MO Kentucky: 1,057 units · 23.4 per 100k residents KY West Virginia: no data reported WV Virginia: 693 units · 8.0 per 100k residents VA Maryland: no data reported MD Connecticut: 3,287 units · 90.9 per 100k residents CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 1,634 units · 15.1 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 1,443 units · 4.7 per 100k residents TX Florida: no data reported FL
Units reimbursed · per 100k residents
4.790.9
gray = no data reported
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Connecticut 90.9 /100k
2 Oregon 77.3 /100k
3 Michigan 46.2 /100k
4 New York 32.8 /100k
5 New Jersey 28.9 /100k
6 Ohio 25.7 /100k
7 Kentucky 23.4 /100k
8 Iowa 21.4 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
49884-0250-11 You're viewing this 30 CAPSULE in 1 BOTTLE, PLASTIC (49884-250-11) 2012-11-26 Active

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning ~1 min read

WARNING: 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 healthcare provider. 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 )] . 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 )] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS and INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS S e e full prescribing information for complete boxed warning. I ncreased 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. Monitor for worsening and emergence of suicidal thoughts and behaviors (5.1, 8.4). El derly 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).

🎯 Indications and Usage 96 words

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 combines 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 ~3 min read

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 have 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 have 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 Use in Specific Populations (8.5) and Clinical Pharmacology (12.3, 12.4)] .

2.4Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with olanzapine and fluoxetine capsules. Conversely, at least 5 weeks should be allowed after stopping olanzapine and fluoxetine capsules before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)] .

2.5 Use of Olanzapine and Fluoxetine Capsules with Other MAOIs su…

💊 Dosage Forms and Strengths 47 words

3 DOSAGE FORMS AND STRENGTHS Capsules (mg olanzapine/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/25 mg, 6 mg/25 mg, 6 mg/50 mg, 12 mg/25 mg, and 12 mg/50 mg (mg olanzapine/mg equivalent fluoxetine) (3)

Contraindications ~1 min read

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) P imozide : 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 ~3 min read

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 ) H y perg lycemia 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 ) D ys l ipidemia : Appropriate clinical monitoring is recommended, including fasting blood lipid testing before beginning, and periodically during, treatment ( 5.5 ) W e ight 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.

If such symptoms occur, discontinue olanzapine and fluoxetine capsules and serotonergic agents 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) Increased Risk of 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) Anticholinergic (antimuscarinic) Effects : Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, history of paralytic ileus or related conditions (5.21) Hyperprolactinemia : May…

🤒 Adverse Reactions ~2 min read

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)] Increased Risk of 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)] Anticholinergic (antimuscarinic) Effects [see Warnings and Precautions (5.21)] Hyperprolactinemia [see Warnings and Precautions (5.22)] Discontinuation Adverse Reactions [see Warnings and Precautions (5.25)] Sexual Dysfunction [see Warnings and Precautions (5.26)] 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 Endo at 1-800-828-9393 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 capsules group discontinued due to adverse reactions compared with 4.4% of the 477 patients for placebo. Adverse reactions leading to discontinuation associated with the…

🔄 Drug Interactions ~3 min read

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) CN S Acting Drugs : Caution is advised if the concomitant administration of olanzapine and fluoxetine capsules and other CNS-active drugs is required (7.2) A n t ihypertensive Agent : Enhanced antihypertensive effect (7.7) Le v odopa and Dopa m ine Agonists : May antagonize levodopa/dopamine agonists (7.7) B e n z od iazepines : May potentiate orthostatic hypotension and sedation (7.6, 7.7) C lozapine : May elevate clozapine levels (7.7) Ha loperidol : Elevated haloperidol levels have been observed (7.7) Carba m a z ep ine : Potential for elevated carbamazepine levels and clinical anticonvulsant toxicity (7.7) P hen yt o in : Potential for elevated phenytoin levels and clinical anticonvulsant toxicity (7.7) A lcohol : May potentiate sedation and orthostatic hypotension (7.7) S ero t onerg ic 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 t hat 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 t hat 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)] .

7.3Other Serotonergic Drugs The concomitant use of serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) with olanzapine and fluoxetine capsules increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases.

If serotonin syndrome occurs, consider discontinuation of olanzapine and fluoxetine and/or concomitant serotonergic drugs [see 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…

👥 Use in Specific Populations ~2 min read

8 USE IN SPECIFIC POPULATIONS P regnan c y : SSRI use, particularly later in pregnancy, may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, irritability, tremor) in the neonate. Olanzapine may cause extrapyramidal symptoms and/or withdrawal symptoms in neonates with third trimester exposure (8.1) P ed iatric 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) Hepa t ic Impairment : Use a lower or less frequent dose in patients with cirrhosis (8.6)

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including olanzapine and fluoxetine capsules, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.16) and Clinical Considerations].

Neonates exposed to antipsychotic drugs, including the olanzapine component of olanzapine and fluoxetine capsules, 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 and postmarketing reports of pregnant women exposed to olanzapine or fluoxetine have not established a drug-associated increased risk of major birth defects or miscarriage (see Data). Some studies in pregnant women exposed to fluoxetine have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship (see Data).

There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension (PPHN) (see Data) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, during pregnancy (see Clinical Considerations). Neonates exposed to antipsychotic drugs, including the olanzapine component of olanzapine and fluoxetine capsules, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations).

In animal studies, administration of the combination of olanzapine and fluoxetine during the period of organogenesis resulted in adverse effects on development (decreased fetal body weights in rats and rabbits and retarded skeletal ossification in rabbits) at maternally toxic doses greater than those used clinically. When administered to rats throughout pregnancy and lactation, an increase in early postnatal mortality was observed at doses similar to those used clinically (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, miscarriage, or another 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/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants.

This finding is from a prospective, longitudinal study t…

🤰 Pregnancy ~2 min read

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including olanzapine and fluoxetine capsules, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.16) and Clinical Considerations].

Neonates exposed to antipsychotic drugs, including the olanzapine component of olanzapine and fluoxetine capsules, 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 and postmarketing reports of pregnant women exposed to olanzapine or fluoxetine have not established a drug-associated increased risk of major birth defects or miscarriage (see Data). Some studies in pregnant women exposed to fluoxetine have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship (see Data).

There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension (PPHN) (see Data) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, during pregnancy (see Clinical Considerations). Neonates exposed to antipsychotic drugs, including the olanzapine component of olanzapine and fluoxetine capsules, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations).

In animal studies, administration of the combination of olanzapine and fluoxetine during the period of organogenesis resulted in adverse effects on development (decreased fetal body weights in rats and rabbits and retarded skeletal ossification in rabbits) at maternally toxic doses greater than those used clinically. When administered to rats throughout pregnancy and lactation, an increase in early postnatal mortality was observed at doses similar to those used clinically (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, miscarriage, or another 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/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants.

This finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of olanzapine and fluoxetine capsules in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.16)].

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 va…

🧒 Pediatric Use ~3 min read

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 (6.1)] .

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.

Juvenile Animal Toxicity 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 functio…

🧓 Geriatric Use ~2 min read

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 elderly patients with dementia-related psychosis have suggested that there may be a different tolerability profile in this population compared with younger patients with Schizophrenia.

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. 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 significantly 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 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 ~2 min read

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. There have been 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.

Fluoxetine — The following have been reported with fluoxetine overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, Torsade de Pointes, and cardiac arrest. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol.

Serotonin syndrome (patients with a multiple drug overdosage with other pro-serotonergic drugs may have a higher risk).

10.1Management of Overdose For current information on the management of olanzapine and fluoxetine capsules overdose, consider contacting a Certified Poison Control Center (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. In managing overdose, consider the possibility of multiple drug involvement. Establish and maintain an airway and ensure adequate ventilation.

Commence cardiovascular monitoring immediately and include continuous electrocardiographic monitoring to detect possible arrhythmias. A specific precaution involves patients who are taking or have recently taken olanzapine and fluoxetine capsules and may have ingested excessive quantities of a TCA (tricyclic antidepressant). In such cases, accumulation of the parent TCA and/or an active metabolite increases the possibility of serious sequelae and extends the time needed for close medical observation.

Due to the large volume of distribution of olanzapine and fluoxetine, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidote for either fluoxetine or olanzapine overdose is known.

🧬 Clinical Pharmacology ~3 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action of olanzapine and fluoxetine in the listed indications, is unclear. However, the combined effect of olanzapine and fluoxetine at the monoaminergic neural systems (serotonin, norepinephrine, and dopamine) could be responsible for the pharmacological effect.

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.

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 have 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 dose metabolized before reaching the systemic circulation.

Fluoxetine — Following a single oral 40 mg dose, peak plasma concentrations of fluoxetine from 15 to 55 ng/mL are observed after 6 to 8 hours. Food does not appear to affect the systemic bioavailability of fluoxetine given as Prozac, although it may delay its absorption by 1 to 2 hours, which is probably not clinically significant. Distribution Olanzapine and fluoxetine capsules — The in vitro binding to human plasma proteins of olanzapine and fluoxetine in combination is similar to the binding of the individual components.

Olanzapine — 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…

🧬 Mechanism of Action 42 words

12.1Mechanism of Action The mechanism of action of olanzapine and fluoxetine in the listed indications, is unclear. However, the combined effect of olanzapine and fluoxetine at the monoaminergic neural systems (serotonin, norepinephrine, and dopamine) could be responsible for the pharmacological effect.

📦 How Supplied / Storage and Handling 204 words

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Olanzapine and Fluoxetine Capsules, USP are supplied in 3/25 mg, 6/25 mg, 6/50 mg, 12/25 mg, and 12/50 mg (mg olanzapine/mg equivalent fluoxetine a ) strengths. Olanzapine and Fluoxetine Capsules CAPSULE STRENGTH 3 mg/25 mg 6 mg/25 mg 6 mg/50 mg 12 mg/25 mg 12 mg/50 mg Color white opaque body & orange opaque cap rich yellow opaque body and cap light grey opaque body & rich yellow opaque cap dark tan opaque body & red opaque cap light grey opaque body & red opaque cap Imprintings ‘277’ on body and ‘par’ on cap in black ink ‘par’ on body and ‘250’ on cap in black ink ‘251’ on body and ‘par’ on cap in black ink ‘252’ on body and ‘par’ on cap in black ink ‘253’ on body and ‘par’ on cap in black ink NDC Codes Bottle of 30 49884-277-11 49884-250-11 49884-251-11 49884-252-11 49884-253-11 a Fluoxetine base equivalent.

16.2Storage and Handling Store olanzapine and fluoxetine capsules at room temperature, between 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. Keep container tightly closed and protect from moisture.

📦 Storage and Handling 45 words

16.2Storage and Handling Store olanzapine and fluoxetine capsules at room temperature, between 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. Keep container tightly closed and protect from moisture.

📋 Description ~2 min read

11 DESCRIPTION Olanzapine and Fluoxetine Capsules, USP combines an atypical antipsychotic and a selective serotonin reuptake inhibitor, olanzapine (the active ingredient in Zyprexa, and Zyprexa Zydis) and fluoxetine hydrochloride (the active ingredient in Prozac and Sarafem). Olanzapine 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. Fluoxetine hydrochloride 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 molecular formula is C 17 H 18 F 3 NO•HCl, which corresponds to a molecular weight of 345.79. The chemical structures are: Olanzapine is a yellow crystalline solid, which is practically insoluble in water. Fluoxetine hydrochloride 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 3 6 6 12 12 Fluoxetine base equivalent 25 25 50 25 50 Each capsule consists of gelatin, magnesium stearate, partially pregelatinized starch, titanium dioxide, and yellow iron oxide. In addition, the 3 mg/25 mg capsule also contains red iron oxide; the 6 mg/50 mg capsule also contains FD&C blue No. 2, FD&C red No.

3, and FD&C yellow No. 6; the 12 mg/25 mg capsule also contains D&C red No. 28, FD&C blue No.

1, FD&C red No. 40, and red iron oxide; and the 12 mg/50 mg capsule also contains D&C red No. 28, FD&C blue No.

1 FD&C blue No. 2, FD&C red No. 3, FD&C red No.

40, and FD&C yellow No. 6. The capsules also have printing in edible black ink which contains the following ingredients: D&C yellow No.

10, ethanol, FD&C blue No. 1, FD&C blue No. 2, FD&C red No.

40, iron oxide black, methanol, n-Butyl alcohol, propylene glycol, and shellac glaze in alcohol. This is the structure

💬 Information for Patients ~3 min read

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Patients should be advised of the following issues and asked to alert their healthcare provider if these occur while taking olanzapine and fluoxetine capsules. Information on Medication Guide Healthcare providers 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 its appropriate use.

A patient Medication Guide is available for olanzapine and fluoxetine capsules. The healthcare providers 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.

Suicidal 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 healthcare provider, 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)] . 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 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)] . 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, 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)] . 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 and caregivers should be counseled that metabolic changes have occurred during treatment with olanzapine and fluoxetine capsules.

Patients who have diabetes should follow their doctor's instructions about ho…

💬 Medication Guide ~3 min read

Medication Guide Olanzapine and Fluoxetine (oh-LAN-za-peen and floo-OX-e-teen) Capsules Read the Medication Guide that comes with olanzapine and fluoxetine capsules before you start taking it 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: 1.

Suicidal thoughts or actions. 2. Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis).

3. High blood sugar (hyperglycemia). 4.

High fat levels in your blood (increased cholesterol and triglycerides), especially in children and adolescents age 10 to 17. 5. 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.…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.