Home › NDC Lookup › Ingredients › Olanzapine And Samidorphan L-Malate › 65757-0654-40

olanzapine and samidorphan l-malate 20 mg; 10 mg Tablet, Film Coated, 7-count

by Alkermes, Inc. · 1 BOTTLE in 1 CARTON (65757-654-40) / 7 TABLET, FILM COATED in 1 BOTTLE

NDC 65757-0654-40

🏷️ FDA NDC (as labeled) 65757-654-40 billing pads the product segment with a zero

This package

Contains7-count Cost per ea$55.05 NADAC Per package$385.32 / 7 tablets Pack sizes5 compare ↓

Also comes in: 7 tablets 65757-0654-41 30 tablets 65757-0654-42 90 tablets 65757-0654-44 128205 tablets 65757-0654-04

Discontinued Non-controlled ⚠ Discontinued by firm

🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm

📋 All sources & update times →

This page is curated, coded, and maintained by Dr. Brian Staiger, PharmD

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️

Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

🆔 Identity & classification

FDA NDC (as labeled) 65757-654-40

Product NDC 65757-654

11-digit billing NDC 65757065440

NCPDP billing unit EA — each (per item)

SPL Set ID 32ffddd1-4e2b-45d9-9b36-bb730167ec80

DEA schedule Non-controlled

Marketing category DRUG FOR FURTHER PROCESSING

Marketing status Discontinued

FDA listing status Discontinued by firm

Marketing start 2021-05-28

Dosage form TABLET, FILM COATED

Substance OLANZAPINE; SAMIDORPHAN L-MALATE

GPI-14 62994802500340

GPI class Lybalvi

GCN Seq No 082347

GCN 49739

HICL code 047406

Ingredient (HICL) Olanzapine/Samidorphan Malate

HIC1 code H

Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)

HIC2 code H7

Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 1)

HIC3 code H7T

Therapeutic class — specific (HIC3) Antipsychotic,Atypical,Dopamine,Serotonin Antagnst

AHFS code 28:16.08.04

AHFS class Atypical Antipsychotics

FDB label name LYBALVI 20-10 MG TABLET

FDB brand name Lybalvi

Legend status F — Federal legend — prescription drug or device

Why two NDCs? The FDA registers this code as 65757-654-40 — 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 → 65757-0654-40. 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.

🏭 Manufacturer & labeler

LabelerAlkermes, Inc.

Labeler code65757

First marketedMay 2021

Product typeDrug For Further Processing

Portfolio16 products on file

🔎 All NDCs from Alkermes, Inc.

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 LYBALVI 20-10 MG TABLET Ingredient Olanzapine/Samidorphan Malate

📗 Our plain-language guide HelloPharmacist

Great question. Olanzapine is the antipsychotic — it's been used for years to treat schizophrenia and bipolar disorder by helping balance dopamine and serotonin activity in the bra...
Why does Lybalvi have two drugs in it? What does each one do?
This is really important — you cannot take opioid pain medicines (like oxycodone, hydrocodone, morphine, or codeine) while you're on Lybalvi. Because Lybalvi contains an opioid blo...
Can I take any pain medications while I'm on Lybalvi?

📖 Read our full Olanzapine and Samidorphan guide →

Patient education

📘 MedlinePlus patient leaflet ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →

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 yellow / orange / blue / pink

ShapeCapsule

ImprintOS;20

Size13 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.

Where does this data come from?

Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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 system	Per ea	Per package
Retail pharmacies payNADAC · weekly	$55.046	$385.32 / 7 tablets
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.

NADAC price history (per ea) — tap or hover for the price & month

▲ Up 14% over the last 6 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

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
olanzapine and samidorphan l-malate 20 mg/1; 10 mgthis 65757-0654-40	Alkermes,	7 tablets	$55.046	—	Discontinued	—

About this product: other versions of the same ingredient, strength and form are listed above, least expensive first, with FDA equivalence ratings where available.

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

🏛️

2021

On the market since

May 2021

📍

2026

Currently FDA-listed

5 years listed

🔒

No generic listed yet

brand only

ℹ️No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route.

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 by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.

30 tablets65757-0654-42 36,412 Rx · $56,948,000

7 tablets this page65757-0654-40 No Medicaid data

7 tablets65757-0654-41 No Medicaid data

90 tablets65757-0654-44 No Medicaid data

128205 tablets65757-0654-04 No Medicaid data

Drug total (last 4 qtrs): 36,412 Rx · 1,083,279 units · $56,948,000 gross reimbursed

Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Olanzapine and samidorphan l-malate — the ingredient across all brands.

Top reported reactions

Contraindicated Product Administered108

Dizziness86

Weight Increased85

Insomnia71

Weight Decreased67

Nausea64

Vomiting61

Age at onset

Infant1

Child1

Adolescent3

Adult60

Elderly10

Reporter sex

Serious outcomes

Hospitalization169

Life-threatening30

Death16

Disabling5

Reports over time (by year) — tap or hover for the count & year

Most recent year is provisional (FAERS lags ~3 months).

Where does this data come from?

Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDC	Description	Per unit	Per pack	Marketing start	Status
65757-0654-40 You're viewing this	1 BOTTLE in 1 CARTON (65757-654-40) / 7 TABLET, FILM COATED in 1 BOTTLE	$55.05 / ea	$385.32	2021-09-20	Discontinued by firm
65757-0654-41	1 BOTTLE in 1 CARTON (65757-654-41) / 7 TABLET, FILM COATED in 1 BOTTLE	—	—	2021-09-20	Active
65757-0654-42	1 BOTTLE in 1 CARTON (65757-654-42) / 30 TABLET, FILM COATED in 1 BOTTLE	$55.05 / ea	$1,651.43	2021-09-20	Active
65757-0654-44	1 BOTTLE in 1 CARTON (65757-654-44) / 90 TABLET, FILM COATED in 1 BOTTLE	$50.08 / ea	$4,506.75	2021-09-20	Discontinued by firm
65757-0654-04	128205 TABLET, FILM COATED in 1 CONTAINER (65757-654-04)	—	—	—	Active

Per ea, this pack runs about 10% above the cheapest pack (NDC 65757-0654-44, $50.08 vs $55.05 NADAC).

This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 65757-0654-40?

NDC 65757-0654-40 is a 7-count package — 1 bottle in 1 carton / 7 tablet, film coated in 1 bottle.

What is the difference between NDC 65757-0654-40 and NDC 65757-0654-41?

Both are olanzapine and samidorphan l-malate 20 mg; 10 mg Tablet, Film Coated — the drug itself is identical. NDC 65757-0654-40 is the 7-count package, while NDC 65757-0654-41 is the 7 tablets package.

What NDC number is used to bill for this package of olanzapine and samidorphan l-malate 20 mg; 10 mg Tablet, Film Coated?

Bill NDC 65757-0654-40 — the 11-digit billing format is 65757065440. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

🧭 About this NDC listing & data coverage

Listed for further processing / repackaging No longer marketed (per FDA listing data)

What "drug for further processing" means

FDA lists this package under the "drug for further processing" marketing category: Alkermes, Inc. supplies it to other companies for further processing or repackaging (blister cards that are later repackaged or co-packaged are a common example). The units themselves are a finished dosage form — which is why pricing or Medicaid data can still appear — but this exact package code may not be the presentation a retail pharmacy dispenses.

What data is (and isn’t) available for this NDC — tap to expand

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)	— Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS)	✓ Available
Orange Book / therapeutic-equivalence data	— Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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.

“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Is this NDC FDA-approved?

An NDC listing does not by itself establish FDA approval — the NDC Directory records that a product is listed with FDA, not that it was reviewed and approved. This listing's marketing category is "Drug For Further Processing". Products approved under an application carry an NDA, ANDA, or BLA number.

What does the discontinued status mean for this NDC?

The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.

Is the NDC printed on the package the same as the 11-digit billing NDC?

Yes, they identify this exact package in different formats. The FDA registers it as 65757-654-40, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 65757-0654-40, written without dashes as 65757065440. The Identity section at the top of this page lists every form of this code.

What do the three segments of this NDC mean?

In 65757-0654-40, the first segment (65757) is the labeler code FDA assigned to Alkermes, Inc.; the middle segment (0654) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (40) identifies this exact package size and type. Together they name one specific package of one specific product.

Does this product come in other package sizes?

Yes — the FDA directory lists 4 other package presentations of this same product, including 7 tablets (65757-0654-41), 30 tablets (65757-0654-42), 90 tablets (65757-0654-44). Each has its own NDC and its own page — see the package list near the top of this page.

Who lists this product with the FDA?

Alkermes, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.

This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.

Where does this data come from?

Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full FDA label FDA SPL

The complete FDA label for this product, verbatim, section by section. Jump with a chip, search within the label, or expand everything.

🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide

🚨 Boxed Warning 93 words ▾

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LYBALVI is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1 )] . WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LYBALVI is not approved for the treatment of patients with dementia-related psychosis. ( 5.1 )

🎯 Indications and Usage 90 words ▾

1 INDICATIONS AND USAGE LYBALVI is indicated for the treatment of: Schizophrenia in adults Bipolar I disorder in adults Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate Maintenance monotherapy treatment LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist, indicated for the treatment of: Schizophrenia in adults ( 1 ) Bipolar I disorder in adults ( 1 ) Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate Maintenance monotherapy treatment

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Indication Recommended Starting Dose (olanzapine/samidorphan) Recommended Dose (olanzapine/samidorphan) Schizophrenia ( 2.2 ) 5 mg/10 mg or 10 mg/10 mg 10 mg/10 mg 15 mg/10 mg 20 mg/10 mg Bipolar I disorder (manic or mixed episodes) ( 2.3 ) 10 mg/10 mg or 15 mg/10 mg 5 mg/10 mg 10 mg/10 mg 15 mg/10 mg 20 mg/10 mg Bipolar I disorder adjunct to lithium or valproate ( 2.3 ) 10 mg/10 mg 10 mg/10 mg 15 mg/10 mg 20 mg/10 mg See the full prescribing information for the recommended titration and maximum recommended dosage.

( 2.2 , 2.3 ) Administer LYBALVI once daily with or without food. Do not divide tablets or combine strengths. ( 2.4 ) Recommended starting dosage is 5 mg/10 mg once daily in patients who have a predisposition to hypotensive reactions, have potential for slower metabolism of olanzapine, or may be more pharmacodynamically sensitive to olanzapine.

( 2.5 )

2.1LYBALVI Initiation In Patients Using Opioids LYBALVI is contraindicated in patients using opioids or undergoing acute opioid withdrawal. In patients who use opioids, delay initiation of LYBALVI for a minimum of 7 days after last use of short-acting opioids and 14 days after last use of long-acting opioids [see Warnings and Precautions ( 5.3 )].

2.2Recommended Dosage in Schizophrenia Initiate LYBALVI at 5 mg/10 mg (contains 5 mg of olanzapine and 10 mg of samidorphan) or 10 mg/10 mg (contains 10 mg of olanzapine and 10 mg of samidorphan) orally once daily. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg (contains 15 mg of olanzapine and 10 mg of samidorphan), or 20 mg/10 mg (contains 20 mg of olanzapine and 10 mg of samidorphan) once daily. Dosage may be adjusted at weekly intervals of 5 mg (based on the olanzapine component of LYBALVI) depending upon clinical response and tolerability, up to the maximum recommended dosage of 20 mg/10 mg once daily.

2.3Recommended Dosage in Bipolar I Disorder (Manic or Mixed Episodes) Monotherapy: Initiate LYBALVI at 10 mg/10 mg or 15 mg/10 mg once daily. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg once daily. The maximum recommended dosage is 20 mg/10 mg once daily.

Dosage adjustments should occur at intervals of not less than 24 hours. When dosage adjustments are necessary, dose increments/decrements of 5 mg (based on the olanzapine component of LYBALVI) are recommended. Maintenance Monotherapy: Administer LYBALVI at 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg once daily.

Adjunctive to lithium or valproate: Initiate LYBALVI at 10 mg/10 mg once daily. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg or 20 mg/10 mg, once daily. Dosage may be adjusted at weekly intervals of 5 mg (based on the olanzapine component of LYBALVI), depending upon clinical response and tolerability, up to the maximum recommended dosage of 20 mg/10 mg once daily.

2.4Administration Information Administer LYBALVI orally once daily with or without food as a single tablet. Do not divide tablets or combine strengths.

2.5Dosage Recommendations in Specific Populations The recommended starting dosage of LYBALVI is 5 mg/10 mg once daily in patients who have a higher risk of hypotensive reactions, are at risk of slower olanzapine metabolism, or may be more pharmacodynamically sensitive to olanzapine [see Warnings and Precautions ( 5.9 ), Drug Interactions ( 7.2 ), Use in Specific Populations ( 8.5 ), and Clinical Pharmacology ( 12.3 )] . If dose escalation is necessary, increase the dosage slowly in these patients.

💊 Dosage Forms and Strengths 84 words ▾

3 DOSAGE FORMS AND STRENGTHS LYBALVI tablets are available in four strengths ( Table 1 ). Table 1: LYBALVI Tablet Strengths and Identifying Features Tablet Strength Tablet Color/Shape Tablet Markings 5 mg/10 mg (olanzapine/samidorphan) Yellow, capsule-shaped “OS” and “5” 10 mg/10 mg (olanzapine/samidorphan) Orange, capsule-shaped “OS” and “10” 15 mg/10 mg (olanzapine/samidorphan) Blue, capsule-shaped “OS” and “15” 20 mg/10 mg (olanzapine/samidorphan) Pink, capsule-shaped “OS” and “20” Tablets (olanzapine/samidorphan): 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg and 20 mg/10 mg.

( 3 )

⛔ Contraindications 117 words ▾

4 CONTRAINDICATIONS LYBALVI is contraindicated in patients: who are using opioids [ see Warnings and Precautions ( 5.3 , 5.4 ), Drug Interactions ( 7.3 )] . who are undergoing acute opioid withdrawal [see Warnings and Precautions ( 5.3 , 5.4 ), Drug Interactions ( 7.3 )] . If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for these products [see Warnings and Precautions ( 5.18 )] . Patients using opioids.

( 4 ) Patients undergoing acute opioid withdrawal. ( 4 ) If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for those products. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis : Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities). ( 5.2 ) Precipitation of Opioid Withdrawal in Patients Who are Dependent on Opioids : LYBALVI can precipitate opioid withdrawal in patients who are dependent on opioids. Prior to initiating LYBALVI, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids to avoid precipitation of opioid withdrawal.

( 2.1 , 5.3 ) Vulnerability to Life-Threatening Opioid Overdose : Risk of Opioid Overdose from Attempts to Overcome LYBALVI Opioid Blockade: Attempts to overcome LYBALVI opioid blockade with high or repeated doses of opioids may lead to fatal opioid intoxication, particularly if LYBALVI therapy is interrupted or discontinued. ( 5.4 ) Risk of Resuming Opioids in Patients with Prior Opioid Use : Patients with a history of chronic opioid use prior to LYBALVI treatment may have decreased opioid tolerance if LYBALVI therapy is interrupted or discontinued.

( 5.4 ) Neuroleptic Malignant Syndrome : Manage with immediate discontinuation and close monitoring. ( 5.5 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) : Discontinue if DRESS is suspected. ( 5.6 ) Metabolic Changes : Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain.

( 5.7 ) Tardive Dyskinesia : Discontinue if clinically appropriate. ( 5.8 ) Orthostatic Hypotension and Syncope : Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. ( 5.9 ) Leukopenia, Neutropenia, and Agranulocytosis : Perform complete blood counts in patients with a history of a clinically significant low white blood cell (WBC) count.

Consider discontinuation if clinically significant decline in WBC in the absence of other causative factors. ( 5.11 ) Seizures : Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. ( 5.13 ) Potential for Cognitive and Motor Impairment : Use caution when operating machinery.

( 5.14 ) Anticholinergic (Antimuscarinic) Effects: Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions. ( 5.16 ) Hyperprolactinemia : May elevate prolactin levels. ( 5.17 )

5.1Increased 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. In placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than in placebo-treated patients (3.5% vs 1.5%, respectively). Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients.

Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. LYBALVI is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.2 )].

5.2Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly pat…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-related Psychosis [see Boxed Warning , Warnings and Precautions ( 5.1 )] Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions ( 5.2 )] Precipitation of Opioid Withdrawal in Patients Who Are Dependent on Opioids [see Warnings and Precautions ( 5.3 ) ] Vulnerability to Life-Threatening Opioid Overdose [see Warnings and Precautions ( 5.4 )] Neuroleptic Malignant Syndrome [see Warnings and Precautions ( 5.5 )] Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions ( 5.6 )] Metabolic Changes [see Warnings and Precautions ( 5.7 )] Tardive Dyskinesia [see Warnings and Precautions ( 5.8 )] Orthostatic Hypotension and Syncope [see Warnings and Precautions ( 5.9 )] Falls [see Warnings and Precautions ( 5.10 )] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions ( 5.11 )] Dysphagia [see Warnings and Precautions ( 5.12 )] Seizures [see Warnings and Precautions ( 5.13 )] Potential for Cognitive and Motor Impairment [see Warnings and Precautions ( 5.14 )] Body Temperature Regulation [see Warnings and Precautions ( 5.15 )] Anticholinergic (Antimuscarinic) Effects [see Warnings and Precautions ( 5.16 )] Hyperprolactinemia [see Warnings and Precautions ( 5.17 )] Risks Associated with Combination Treatment with Lithium or Valproate [see Warnings and Precautions ( 5.18 )] Most common adverse reactions (incidence ≥5% and at least twice placebo): Schizophrenia (LYBALVI): weight increased, somnolence, dry mouth, and headache.

( 6.1 ) Bipolar I Disorder, Manic or Mixed Episodes (olanzapine): somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, tremor. ( 6.1 ) Bipolar I Disorder, Manic or Mixed Episodes, adjunct to Lithium or Valproate (olanzapine): dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-235-8008 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Patients with Schizophrenia Patient Exposure The safety of LYBALVI was evaluated in 1262 patients (18 to 67 years of age) diagnosed with schizophrenia in four double-blind, controlled studies and three long-term safety extension studies of up to 3 years of duration.

This experience corresponds to approximately 910 person-years. In these studies, there were a total of 663 patients exposed to LYBALVI for at least 6 months, and 386 patients for at least one year. Adverse Reactions in the Short-Term (4 week) Placebo-Controlled Trial in Adults with Schizophrenia The most common adverse reactions (incidence of at least 5% of patients exposed to LYBALVI and greater than twice the rate of placebo) are weight increased, somnolence, dry mouth, and headache.

Adverse reactions associated with the use of LYBALVI (incidence of 2% or greater and greater than in placebo-treated patients) are shown in Table 2 . Table 2: Adverse Reactions Reported in ≥2% of LYBALVI-Treated Patients and Greater than Placebo in a 4-Week Schizophrenia Trial Adverse Reaction Placebo (N=134) % LYBALVI (10 mg/10 mg, 20 mg/10 mg) (N=134) % Weight increased 3 19 Somnolence 2 9 Dry mouth 1 7 Headache 3 6 Blood insulin increased 1 3 Sedation 0 2 Dizziness 1 2 Neutrophil count decreased 0 2 Adverse reactions that led to discontinuation in LYBALVI-treated patients in the short-term placebo-controlled trial in adults with schizophrenia incl…

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS Strong CYP3A4 Inducers : Not recommended. ( 7.1 ) Strong CYP1A2 Inhibitors : Consider dosage reduction of olanzapine component of LYBALVI. ( 7.1 ) CYP1A2 Inducer : Consider dosage increase of the olanzapine component of LYBALVI.

( 7.1 ) CNS Acting Drugs : May potentiate orthostatic hypotension. ( 7.1 ) Anticholinergic Drugs: Can increase risk for severe gastrointestinal adverse reactions. ( 7.1 ) Antihypertensive Agents : Monitor blood pressure.

( 7.2 ) Levodopa and Dopamine Agonists : Not recommended. ( 7.2 )

7.1Effects of Other Drugs on LYBALVI Table 4 describes clinically significant drug interactions where the concomitant use of other drugs affects LYBALVI. Table 4: Effects of Other Drugs on LYBALVI Strong CYP3A4 Inducer Clinical Implication: Coadministration of LYBALVI with a strong CYP3A4 inducer decreases AUC inf of olanzapine and samidorphan [see Clinical Pharmacology ( 12.3 )], which may reduce LYBALVI efficacy. Prevention or Management: Concomitant use of LYBALVI with strong CYP3A4 inducers is not recommended.

Strong CYP1A2 Inhibitor Clinical Implication: Concomitant use of LYBALVI with a strong CYP1A2 inhibitor increases olanzapine AUC and C max [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of LYBALVI adverse reactions. Prevention or Management: Consider reducing the dosage of the olanzapine component in LYBALVI when used concomitantly with strong CYP1A2 inhibitors. CYP1A2 Inducer Clinical Implication: Concomitant use of LYBALVI with CYP1A2 inducers decreases olanzapine exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce LYBALVI efficacy.

Prevention or Management: Consider increasing the dosage of the olanzapine component in LYBALVI when used concomitantly with CYP1A2 inducers. Diazepam, Alcohol, and Other CNS Acting Drugs Clinical Implication: Concomitant use of diazepam, alcohol, or other CNS acting drugs with LYBALVI may potentiate the orthostatic hypotension observed with olanzapine [see Warnings and Precautions ( 5.9 )] . Prevention or Management: LYBALVI should be used with caution in patients receiving concomitantly diazepam or other CNS acting drugs, or using alcohol.

Anticholinergic Drugs Clinical Implication: Concomitant treatment with olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Prevention or Management: LYBALVI should be used with caution in patients receiving medications having anticholinergic (antimuscarinic) effects [see Warnings and Precautions ( 5.16 )] .

7.2Effects of LYBALVI on Other Drugs Table 5 describes clinically significant drug interactions where concomitant use of LYBALVI affects other drugs. Table 5: Effects of LYBALVI on Other Drugs Antihypertensive Agents Clinical Implication: LYBALVI may enhance the effects of certain antihypertensive agents. Prevention or Management: Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling.

Levodopa and Dopamine Agonists Clinical Implication: LYBALVI may antagonize the effects of levodopa and dopamine agonists. Prevention or Management: Concomitant use of LYBALVI is not recommended with levodopa and dopamine agonists.

7.3Opioids LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal [see Contraindications ( 4 )]. LYBALVI increases the risk of precipitating acute opioid withdrawal in patients who are dependent on opioids. Prior to initiating LYBALVI, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.3 )] .

In emergency situations, if a LYBALVI-treated patient requires opioid treatment for anesthesia or analgesia, discontinue LYBALVI. The opioid should be administered by properly trained individual…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) Renal Impairment: Use is not recommended in patients with end-stage renal disease. ( 8.7 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including LYBALVI, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/ . Risk Summary Neonates exposed to antipsychotic drugs, including the olanzapine component of LYBALVI, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) .

Overall published epidemiologic studies of pregnant women exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ) . There are no available data on the use of samidorphan or the combination of olanzapine and samidorphan in pregnant women to determine a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including LYBALVI, during pregnancy (see Clinical Considerations ) .

LYBALVI In an animal reproduction study, oral administration of olanzapine and samidorphan to pregnant rats during the period of organogenesis produced adverse effects on embryofetal development and fetal toxicity at maternally toxic doses that are 6 times and >400 times the maximum recommended human dose (MRHD) of 20 mg/10 mg olanzapine/samidorphan in LYBALVI, respectively based on AUC. There were no adverse effects on embryofetal development at doses of olanzapine and samidorphan that are approximately 1 and 80 times, respectively, the MRHD based on AUC (see Data ) .

Olanzapine In animal reproduction studies, there was no evidence of malformations in rats or rabbits when orally administered olanzapine at doses up to 9 and 30 times the MRHD dose (20 mg) based on mg/m 2 body surface area, respectively. In an oral rat embryofetal developmental toxicity study, early resorptions and increased numbers of nonviable fetuses were observed at a dose 9 times the MRHD based on mg/m 2 body surface area and gestation was prolonged at 5 times the MRHD based on mg/m 2 body surface area. In an oral rabbit embryofetal developmental toxicity study, fetal toxicity (manifested as increased resorptions and decreased fetal weight) occurred at a maternally toxic dose of olanzapine which is 30 times the MRHD based on mg/m 2 body surface area (see Data ) .

Samidorphan In animal reproduction studies, oral administration of samidorphan to pregnant rats and rabbits during the period of organogenesis caused fetal toxicities in rats only at maternally toxic doses that are >248 times the human exposure at the MRHD of 10 mg/day based on AUC. Oral administration of samidorphan to pregnant rats during pregnancy and lactation resulted in lower pup survival and decreased pup weights at 188 times the human exposure at the MRHD based on AUC (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 defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk There is risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization and suicid…

🤰 Pregnancy ~3 min read ▾

Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/ Neonatal Risks Extra…

🧒 Pediatric Use 16 words ▾

8.4Pediatric Use The safety and effectiveness of LYBALVI have not been established in pediatric patients.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Clinical studies of LYBALVI did not include sufficient numbers of patients 65 years of age and older to determine whether they responded differently than younger adult patients. Olanzapine Of the 2,500 patients in premarketing clinical studies with orally administered olanzapine, 11% (263) were 65 years of age or over. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

LYBALVI is not approved for the treatment of patients with dementia-related psychosis [see Dosage and Administration ( 2.5 ), Warnings and Precautions ( 5.1 )] . Studies in elderly patients with dementia-related psychosis have suggested that there may be a different tolerability profile in this population compared to younger patients with schizophrenia. Elderly patients with dementia-related psychosis treated with olanzapine are at an increased risk of death compared to placebo.

In placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis, there was a higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in patients treated with olanzapine, compared to patients treated with placebo. In five placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis (n=1,184), the following adverse reactions were reported in olanzapine-treated patients at an incidence of at least 2% and significantly greater than in placebo-treated patients: falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth and visual hallucinations.

The rate of discontinuation due to adverse reactions was greater with olanzapine than with placebo (13% vs 7%). Consider a lower dosage of the olanzapine component of LYBALVI in geriatric patients who may have decreased clearance or an exaggerated pharmacodynamic response to olanzapine (e.g., oversedation) [see Dosage and Administration ( 2.5 )].

🆘 Overdosage ~1 min read ▾

10 OVERDOSAGE Human Experience There is limited clinical experience with overdose with LYBALVI. In premarketing clinical trials of LYBALVI involving 861 patients, overdose of LYBALVI was identified in 7 patients. This included 4 patients with accidental overdose, 2 with intentional overdose, and 1 due to a medication administration error.

None of the reported overdoses was associated with a fatal outcome. There was a reported ingestion of 11 tablets of LYBALVI 10 mg/10 mg (5.5 times and 11 times the maximum recommended daily dosage of the olanzapine and samidorphan components of LYBALVI, respectively). The patient was found unresponsive and admitted to the hospital.

Medical treatment included fluids, electrolytes, a diuretic, and a detoxicant; the patient stabilized within 2 days. In postmarketing reports of overdose with olanzapine, a component of LYBALVI, symptoms included agitation/aggressiveness, dysarthria, tachycardia, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma. Less commonly reported symptoms include: aspiration, cardiopulmonary arrest, cardiac arrhythmias (such as supraventricular tachycardia and 1 patient experiencing sinus pause with spontaneous resumption of normal rhythm), delirium, possible neuroleptic malignant syndrome, respiratory depression/arrest, convulsion, hypertension, and hypotension.

In 1 case of death, the amount of acutely ingested olanzapine was reported to be possibly as low as 450 mg; however, in another case, a patient was reported to survive an acute olanzapine ingestion of approximately 2,000 mg. Management of Overdose No specific antidotes for LYBALVI are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement.

If an overdose occurs, consult a certified Poison Control Center (1-800-222-1222) for additional overdosage management recommendations.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action of olanzapine is unclear; however, its efficacy in the treatment of schizophrenia or bipolar I disorder could be mediated through a combination of dopamine and serotonin type 2 (5HT 2 ) antagonism. The mechanism of action of samidorphan could be mediated through opioid receptor antagonism.

12.2Pharmacodynamics Olanzapine Olanzapine binds with high affinity to the following receptors: serotonin 5HT 2A/2C , 5HT 6 (K i =4, 11, and 5 nM, respectively), dopamine D 1-4 (K i =11–31 nM), histamine H 1 (K i =7 nM), and adrenergic α 1 receptors (K i =19 nM). Olanzapine is an antagonist with moderate affinity binding for serotonin 5HT 3 (K i =57 nM) and muscarinic M 1-5 (K i =73, 96, 132, 32, and 48 nM, respectively). Olanzapine binds with low affinity to GABA A , BZD, and β-adrenergic receptors (K i >10 μM).

Samidorphan Samidorphan binds to the mu-, kappa-, and delta-opioid receptors (K i =0.052, 0.23, and 2.7 nM, respectively). Samidorphan is an antagonist at the mu-opioid receptors with partial agonist activity at kappa- and delta-opioid receptors. The N-dealkylated major human metabolite binds to the mu-, kappa-, and delta-opioid receptors (K i =0.26, 23, and 56 nM, respectively), and functions as a mu-opioid receptor agonist.

The N-oxide major human metabolite binds to mu-, kappa-, and delta-opioid receptors (K i =8, 110, and 280 nM, respectively) and functions as a mu-opioid receptor antagonist. Cardiac Electrophysiology At doses up to 30 mg/30 mg (1.5 times and 3 times the maximum recommended daily dosage of olanzapine and samidorphan, respectively), LYBALVI does not prolong QTc interval to any clinically relevant extent.

12.3Pharmacokinetics The pharmacokinetics of both olanzapine and samidorphan are linear over the clinical dose range and there is no PK interaction between olanzapine and samidorphan after oral administration of LYBALVI. Steady-state concentrations of olanzapine and samidorphan are reached within 7 days of commencement of once-daily administration of LYBALVI. The primary pharmacological activities of LYBALVI are due to the parent drugs, olanzapine and samidorphan.

Following a single dose administration of LYBALVI (10 mg olanzapine/10 mg samidorphan), the mean AUC 0-inf and C max of olanzapine was 628 ng·h/mL and 16 ng/mL, respectively. The mean AUC 0-inf and C max of olanzapine after 10 mg single dose administration of olanzapine tablet was 610 ng·h/mL and 16 ng/mL, respectively. Pharmacokinetic properties of the components of LYBALVI are provided in Table 6 .

Table 6: Pharmacokinetic Properties of the Components of LYBALVI Parameters Olanzapine Samidorphan Abbreviations: AUC 24h =area under the concentration-time curve over the 24-hour dosing interval; C max =maximum plasma concentration; CYP=cytochrome P450; NA=not applicable; T max =time to C max ; t ½ =terminal elimination half-life; UGT=Uridine 5'-diphospho-glucuronosyltransferase. a Presented as arithmetic mean (standard deviation). b Presented as range of the median across multiple studies. c Geometric mean ratio (90% confidence interval) [high fat meal/fasting].

High fat meal defined as meal containing approximately 900-1000 calories and 50% fat content. No clinically relevant food effect. d Presented as range of the mean across multiple studies. General Steady State Exposure (20 mg olanzapine/10 mg samidorphan) C max (ng/mL) a 64.6 (28.9) 45.1 (11.4) AUC 24h (ng∙hr/mL) a 1086 (556) 364 (112) Time to Reach Steady State 7 days 5 days Accumulation at Steady State 2-fold 1.3-fold Absorption Absolute Oral Bioavailability NA 69% T max (h) b 4.5–7 1–2 Effect of Food C max Ratio c 0.88 (0.82, 0.95) 0.85 (0.76, 0.94) AUC Ratio c 0.93 (0.91, 0.96) 1.03 (1.00, 1.05) Distribution Plasma Protein Binding 93% 23% - 33% Blood-to-Plasma Ratio Not Determined

0.8Elimination t 1/2 (h) d 35–52 7–11 CL/F (L/h) d 15–22 35–45 Metabolism Primary Pathway(s) UGT1A4, CYP1A2 CYP3A4 Minor Pathway(s) CYP2D6 C…

🧬 Mechanism of Action 53 words ▾

📦 How Supplied / Storage and Handling 172 words ▾

16 HOW SUPPLIED/ STORAGE AND HANDLING How Supplied LYBALVI (olanzapine and samidorphan) tablets have markings on both sides and are available as described in Table 9 . Table 9: LYBALVI Tablet Presentations Tablet Strength(s) (olanzapine/samidorphan) Tablet Description Package Configuration NDC Number 5 mg/10 mg Yellow, capsule-shaped, debossed with “OS” on one side and “5” on the other side 30-count bottle with child resistant closure 65757-651-42 10 mg/10 mg Orange, capsule-shaped, debossed with “OS” on one side and “10” on the other side 30-count bottle with child resistant closure 65757-652-42 15 mg/10 mg Blue, capsule-shaped, debossed with “OS” on one side and “15” on the other side 30-count bottle with child resistant closure 65757-653-42 20 mg/10 mg Pink, capsule-shaped, debossed with “OS” on one side and “20” on the other side 30-count bottle with child resistant closure 65757-654-42 Storage and Handling Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Keep tightly closed and protect from moisture.

📦 Storage and Handling 35 words ▾

Storage and Handling Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Keep tightly closed and protect from moisture.

📋 Description ~1 min read ▾

11 DESCRIPTION LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan (as samidorphan L-malate), an opioid antagonist. Olanzapine is 2-methyl-4-(4-methyl-1-piperazinyl)-10 H -thieno[2,3- b ][1,5]benzodiazepine. The molecular formula of olanzapine is: C 17 H 20 N 4 S and the molecular weight is 312.44 g/mol.

It is a yellow crystalline powder and has pKa values of 7.80 and 5.44. The chemical structure is: Samidorphan L-malate is morphinan-3-carboxamide, 17-(cyclopropylmethyl)-4, 14-dihydroxy-6-oxo-, (2S)-2-hydroxybutanedioate. The molecular formula of samidorphan L-malate is C 21 H 26 N 2 O 4 • C 4 H 6 O 5 and the molecular weight is 504.54 g/mol.

It is a white to off-white crystalline powder and has pKa values of 8.3 (amine) and 10.1 (phenol). The chemical structure is: LYBALVI is intended for oral administration and is available as film-coated, bilayer tablets in the following strengths: 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, and 20 mg/10 mg of olanzapine and samidorphan (equivalent to 13.6 mg of samidorphan L-malate). Inactive ingredients include colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.

The film coating ingredients include hypromellose, titanium dioxide, triacetin, and color additives [iron oxide yellow (5 mg/10 mg); iron oxide yellow and iron oxide red (10 mg/10 mg); FD&C Blue No. 2/ indigo carmine aluminum lake (15 mg/10 mg); iron oxide red (20 mg/10 mg)]. Olanzapine Chemical Structure Samidorphan L-malate Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Concomitant Use with Opioids is Contraindicated Advise patients to inform their healthcare provider if they are taking, or plan to take any opioids for any reason, as LYBALVI is contraindicated with use of opioids or those undergoing acute opioid withdrawal [see Dosage and Administration ( 2.1 ), Contraindications ( 4 ), Warnings and Precautions ( 5.3 ), Drug Interactions ( 7.3 )] . Precipitation of Opioid Withdrawal Advise patients not to take LYBALVI when using opioids because of the risks of opioid withdrawal syndrome, sometimes requiring hospitalization.

Advise patients that they should have an opioid-free period of a minimum of 7 days after last use of short-acting opioids and 14 days from last use of long-acting opioids before initiating LYBALVI [see Contraindications ( 4 ), Warnings and Precautions ( 5.3 )] . Risk of Opioid Overdosage Advise patients that they may be at increased risk of opioid overdosage if they attempt to use high or repeated opioid doses. Inform patients of the potential consequences of trying to overcome the opioid blockade and the serious risks of taking opioids concurrently with LYBALVI or while transitioning off LYBALVI [see Warnings and Precautions ( 5.4 )] .

Risk of Resuming Opioids in Patients with Prior Opioid Use Advise patients that if they used opioids prior to LYBALVI treatment, they may have decreased opioid tolerance if they use opioids after LYBALVI discontinuation or interruption [see Warnings and Precautions ( 5.4 )] . Neuroleptic Malignant Syndrome Counsel patients about a potentially fatal adverse reaction, Neuroleptic Malignant Syndrome (NMS), that has been reported with administration of antipsychotic drugs. Advise patients, family members, or caregivers to contact the healthcare provider or to report to the emergency room if they experience signs and symptoms of NMS [see Warnings and Precautions ( 5.5 )] .

Drug Reaction with Eosinophilia and Systemic Symptoms Advise patients 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 ( 5.6 )] . Metabolic Changes Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia and diabetes mellitus, and the need for specific monitoring, including blood glucose, lipids, and weight [see Warnings and Precautions ( 5.7 )].

Tardive Dyskinesia Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their healthcare provider if these abnormal movements occur [see Warnings and Precautions ( 5.8 )]. Orthostatic Hypotension and Syncope Educate patients about the risk of orthostatic hypotension and syncope, especially early in treatment, and also at times of re-initiating treatment [see Warnings and Precautions ( 5.9 ), Drug Interactions ( 7.2 )] . Leukopenia/Neutropenia Advise patients with a pre-existing low WBC or a history of drug induced leukopenia/ neutropenia that they should have their CBC monitored while taking LYBALVI [see Warnings and Precautions ( 5.11 )].

Potential for Cognitive and Motor Impairment Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that LYBALVI therapy does not affect them adversely [see Warnings and Precautions ( 5.14 )] . Concomitant Medication Advise patients to inform their healthcare providers if they are taking, or plan to take any other olanzapine containing medication. Advise patients to inform their healthcare providers of any changes to their current prescription or over-the-counter medications because there is a potential for interactions [see Drug Interactions ( 7.1 , 7.2 , 7.3 )] .

Body Temperature Dysregulation Educate patients regarding appropriate care in av…

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 1/2024 MEDICATION GUIDE LYBALVI ® (lee bawl' vee) (olanzapine and samidorphan) tablets, for oral use If your healthcare provider prescribes LYBALVI in combination with valproate or lithium, also read the Medication Guide that comes with those medicines. What is the most important information I should know about LYBALVI?

LYBALVI may cause serious side effects, including: Increased risk of death in elderly people with dementia related psychosis. LYBALVI increases the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). LYBALVI is not approved for the treatment of people with dementia-related psychosis.

What is LYBALVI? LYBALVI is a prescription medicine which contains 2 medicines (olanzapine and samidorphan) used in adults: to treat schizophrenia alone for short-term (acute) or maintenance treatment of manic or mixed episodes that happen with bipolar I disorder in combination with valproate or lithium to treat manic or mixed episodes that happen with bipolar I disorder It is not known if LYBALVI is safe or effective in children. Do not take LYBALVI if you are taking opioids or are experiencing acute opioid withdrawal.

See “ What are the possible side effects of LYBALVI. ” Before taking LYBALVI, tell your healthcare provider about all of your medical conditions, including if you: have or had heart problems or a stroke use or abuse street (illegal) drugs have or had low or high blood pressure have kidney problems have diabetes or high blood sugar or a family history of diabetes or high blood sugar have or have had high levels of total cholesterol, LDL cholesterol, or triglycerides or low levels of HDL cholesterol have or had a low white blood cell count have problems swallowing have or had seizures (convulsions) have or had problems with urination or prostate problems have or had breast cancer have or had constipation or a bowel obstruction have or had high prolactin levels are pregnant or plan to become pregnant.

Talk to your healthcare provider about the risks to you and your unborn or newborn baby if you take LYBALVI during pregnancy. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with LYBALVI. If you become pregnant during treatment with LYBALVI, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics.

You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ are breastfeeding or plan to breastfeed. LYBALVI passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with LYBALVI.

Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. LYBALVI and other medicines may affect each other causing possible serious side effects. LYBALVI may affect the way other medicines work, and other medicines may affect how LYBALVI works.

Especially tell your healthcare provider if you: take opioids or have stopped taking opioids in the past 14 days take or plan to take other olanzapine containing medicines Your healthcare provider can tell you if it is safe to take LYBALVI with your other medicines. Do not start or stop any medicines while taking LYBALVI without first talking to your healthcare provider. Tell your healthcare provider if you take a urine drug screening test because LYBALVI may affect your test results.

Tell those giving the drug screening test that you are taking LYBALVI. Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine.

How should I take LYBALVI? Take LYBALVI exactly as your healthcare provider tells you to take it. Do not change the dose or stop…

Glossary — plain-language definitions of medical terms used in this label:

contraindicated: Should not be used in that situation, because the risk is considered too high.

Absorption: How a medicine moves from where it is taken, such as the stomach or gut, into the bloodstream.

abuse: Using a medicine in a way it was not meant to be used, such as taking more than prescribed to feel a high.

accumulation: A buildup of a medicine in the body when new doses are taken before earlier ones are fully removed.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

agitation: A state of feeling restless and upset and being unable to relax, sometimes with pacing or fidgeting.

agonist: A substance that switches on a specific target in the body to produce an effect, the way a key turns a lock.

agranulocytosis: A severe drop in a certain type of infection-fighting white blood cell, greatly raising the risk of serious infections.

animal reproduction studies: Tests in pregnant animals used to check whether a medicine might harm a developing baby.

antagonist: A substance that blocks a target in the body so a natural signal or another medicine cannot produce its usual effect.

asthenia: Unusual weakness or lack of physical strength and energy.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

Bioavailability: The share of a dose that actually reaches the bloodstream and is able to have an effect.

Boxed Warning: The strongest safety warning the FDA can require, set inside a bold black border because the risk it describes can be very serious.

CBC: A common blood test that measures red blood cells, white blood cells, and platelets.

clearance: How quickly the body removes a medicine from the blood, usually through the liver and kidneys.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Clinical Studies: The label section summarizing the research trials used to show that a medicine works and is acceptably safe.

confidence interval: A range of numbers that likely contains the true result, showing how sure researchers can be about a study's finding.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

convulsion: Uncontrolled, rapid shaking of the body caused by muscles rapidly tightening and relaxing, often during a seizure.

CYP1A2: A liver enzyme that breaks down certain medicines and whose activity can be changed by cigarette smoke.

CYP2D6: A liver enzyme that breaks down many medicines; people inherit different versions, so it works faster in some and slower in others.

CYP3A4: One of the most important liver and gut enzymes, responsible for breaking down a large share of all medicines.

cytochrome P450: A large family of enzymes, mostly in the liver, that break down many medicines so the body can remove them.

depression: A lasting low mood with loss of interest that affects everyday life.

Distribution: How a medicine spreads from the blood into the body's tissues and organs after it is absorbed.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

double-blind: A study in which neither the patients nor their doctors know who is getting the real medicine and who is getting the dummy.

Drug Interactions: The label section listing other medicines, foods, or substances that can change how a medicine works or raise the chance of side effects.

dysarthria: Slurred or slow speech caused by weakness or poor control of the muscles used for speaking.

dyskinesia: Involuntary, uncontrolled movements of the face, arms, legs, or body.

dyslipidemia: Unhealthy levels of fats, such as cholesterol and triglycerides, in the blood.

dyspepsia: Discomfort, fullness, or a burning feeling in the upper belly, commonly called indigestion.

dysphagia: Trouble or discomfort swallowing food, liquids, or pills.

edema: Swelling caused by extra fluid trapped in the body's tissues.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

Elimination: The overall removal of a medicine from the body by breaking it down and passing it out.

end-stage renal disease: The most advanced, permanent stage of kidney failure, usually needing dialysis or a kidney transplant.

eosinophilia: A higher-than-normal level of eosinophils, a type of white blood cell often linked to allergies or drug reactions.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

extrapyramidal symptoms: Movement problems caused by certain medicines, such as stiffness, tremor, restlessness, or unusually slow movements.

food effect: A change in how much or how fast a medicine is absorbed when it is taken with food.

Full Prescribing Information: The complete, detailed label for a prescription medicine that follows the summary highlights.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

heart failure: A condition in which the heart cannot pump blood as well as it should, causing tiredness, breathlessness, and swelling.

hyperglycemia: High blood sugar, meaning there is more glucose (sugar) in the blood than normal.

hyperprolactinemia: A higher-than-normal level of prolactin, a hormone, in the blood, which can affect fertility and breast milk.

hypertension: Blood pressure that stays higher than normal, commonly called high blood pressure.

hypotension: Blood pressure that is lower than normal, which can cause dizziness or fainting.

ileus: A slowdown or stop in the normal movement of the intestines, so food and waste do not pass through.

incidence: How often a new event, such as a side effect, happens in a group of people over a set period of time.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

inducer: A substance that speeds up an enzyme, which can lower the levels of drugs that enzyme breaks down.

inhibitor: A substance that blocks an enzyme or transporter, which can raise the levels of drugs it normally handles.

lactation: The making and release of milk from a mother's breasts after giving birth.

lethargy: A state of tiredness and sluggishness, often with slowed thinking or movement.

leukopenia: A low level of white blood cells, the cells that help the body fight off infections.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Medication Guide: An FDA-approved handout written for patients that explains important safety information about certain medicines in plain language.

Metabolism: How the body chemically changes a medicine, usually in the liver, into other substances.

metabolite: A new substance formed when the body breaks a medicine down.

monotherapy: Treatment using a single medicine by itself.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

neonatal: Relating to a newborn baby during its first four weeks of life.

neuroleptic malignant syndrome: A rare but serious reaction to certain medicines causing high fever, severe muscle stiffness, confusion, and an unstable heartbeat.

neutropenia: A low level of neutrophils, a type of white blood cell that fights infection, which can make it easier to catch infections.

neutrophil: A type of white blood cell that is one of the body's main defenders against infection.

organogenesis: The early stage of pregnancy when the developing baby's organs are first forming.

orthostatic hypotension: A drop in blood pressure when you stand up from sitting or lying down, which can cause brief dizziness.

Overdosage: The label section describing what can happen if too much of a medicine is taken and how it may be treated.

paresthesia: A tingling, prickling, or "pins and needles" feeling in the skin, often in the hands or feet.

partial agonist: A substance that switches on a body target only part way, giving a weaker effect than a full activator would.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

peripheral edema: Swelling, usually in the feet, ankles, or legs, caused by extra fluid building up in the tissues.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

placebo: An inactive treatment with no real medicine in it, such as a sugar pill, used for comparison in a study.

placebo-controlled: Describes a study that compares people taking the real medicine against people taking a dummy pill with no active ingredient.

plasma concentration: The amount of medicine measured in the liquid part of the blood at a given time.

potentiate: To make the effect of one medicine stronger by taking another substance along with it.

Pregnancy Exposure Registry: A study that collects health information from women who took a medicine while pregnant to learn how safe it is.

Prescribing Information: The official, detailed document approved by the FDA that tells health professionals how to use a prescription medicine.

preterm birth: Birth of a baby earlier than usual, before 37 weeks of pregnancy.

protein binding: How much of a medicine sticks to proteins in the blood instead of moving freely through the body.

psychosis: A state of losing touch with reality, such as seeing or hearing things that are not there or holding false beliefs.

pyrexia: A raised body temperature; a fever.

QTc: A number from a heart tracing (ECG) that measures the heart's electrical recovery time, adjusted for the heart rate.

receptor: A special docking spot on a cell that a medicine or natural body chemical attaches to in order to trigger an effect.

relapse: The return of a cancer after a period of improvement or disappearance.

renal impairment: Reduced kidney function, meaning the kidneys do not filter waste and fluid from the blood as well as normal.

respiratory depression: Breathing that becomes too slow or too shallow to move enough air, so the body may not get enough oxygen.

sedation: A calm, sleepy, slowed-down state caused by a medicine that relaxes the brain and body.

seizure: A sudden burst of abnormal electrical activity in the brain that can cause shaking, staring, confusion, or loss of awareness.

somnolence: Feeling very sleepy or drowsy, with trouble staying awake during the day.

steady state: The point where the amount of medicine going in equals the amount leaving, so blood levels stay fairly even.

syncope: The medical term for fainting, a brief loss of consciousness from a temporary drop in blood flow to the brain.

tachycardia: A faster-than-normal heart rate, usually over 100 beats per minute.

tardive dyskinesia: Involuntary, repetitive movements—often of the face, mouth, or tongue—that can develop after long-term use of certain medicines.

titration: Slowly adjusting a medicine's dose up or down in small steps to find the amount that works best with the fewest side effects.

tolerance: When the body gets used to a medicine over time, so a larger dose is needed to get the same effect.

transient ischemic attack: A brief, stroke-like episode from a temporary drop in blood flow to the brain, with symptoms that go away.

tremor: Shaking or trembling of part of the body, such as the hands, that a person cannot control.

trimester: One of the three roughly three-month stages that a pregnancy is divided into.

UGT: A family of enzymes that attach a sugar-like molecule to a drug, making it easier for the body to remove.

urinary retention: Being unable to empty the bladder fully or at all.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

withdrawal: Uncomfortable physical or mental symptoms that appear when a medicine the body has gotten used to is reduced or stopped.

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

← 65757-0653-40 · Alkermes, 65757-0725-00 · Alkermes, →

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.

olanzapine and samidorphan l-malate 20 mg; 10 mg Tablet, Film Coated, 7-count

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