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Liraglutide 6 mg/mL Injection, Solution — NDC 00480-7250-46 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Liraglutide 6 mg/mL Injection, Solution — NDC 0480-7250-46 (Billing 00480-7250-46)

by Teva Pharmaceuticals, Inc. · 5 SYRINGE, PLASTIC in 1 CARTON / 3 mL in 1 SYRINGE, PLASTIC

This is a package of Liraglutide 6 mg/mL Injection, Solution from Teva Pharmaceuticals, Inc., marketed since Aug 2025 and currently FDA-listed, this package's marketing is listed to end Sep 2027; retail pharmacies pay about $49.25 per mL (NADAC). It is this product's only package size.

NDC 00480-7250-46
🏷️ FDA NDC (as labeled) 0480-7250-46 billing pads the labeler segment with a zero
Rx only Generic On market Non-controlled ⚠ On shortage ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 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

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

⚠️
Active FDA shortage. Liraglutide Injection is currently reported in shortage by the FDA. Shortage details →
⚠️
Other active recalls for Liraglutide (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Apr 24, 2026 — Presence of particulate matter: a white thread-like structure in the cartridge (Lupin Pharmaceuticals Inc.) · FDA recall D-0541-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0480-7250-46
Product NDC 0480-7250
11-digit billing NDC 00480725046
NCPDP billing unit ML — per mL (volume)
RxCUI 2735350
UNII 839I73S42A
Application # ANDA214568
SPL Set ID 625ac780-70a9-41e4-a892-bcba0f803f1c
Established class (EPC) GLP-1 Receptor Agonist
Mechanism of action Glucagon-like Peptide-1 (GLP-1) Agonists
Chemical class Glucagon-Like Peptide 1
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-08-28
Marketing end 2027-09-30
Route SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance LIRAGLUTIDE
TE code (Orange Book) AP2 · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 073258
GCN 37637
HICL code 036436
Ingredient (HICL) Liraglutide
HIC1 code J
Therapeutic class — broad (HIC1) Autonomic Nervous System
HIC2 code J8
Therapeutic class — intermediate (HIC2) Anti-Obesity - Anorexics
HIC3 code J8E
Therapeutic class — specific (HIC3) Anti-Obesity Glucagon-Like Peptide-1 Recep Agonist
AHFS code 28:20.08.92
AHFS class Anorexigenic Agents, Miscellaneous
FDB label name LIRAGLUTIDE 5-PAK 18 MG/3 ML
FDB brand name Liraglutide
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 073258
  • GCN: 37637
  • HICL (First Databank): 036436
  • AHFS class code: 28:20.08.92
  • RxCUI (RxNorm): 2735350
Why two NDCs? The FDA registers this code as 0480-7250-46 — a 4-4-2 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 labeler segment → 00480-7250-46. 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 GLP-1 Receptor Agonist class.

Pharmacologic class GLP-1 Receptor Agonist
Drug family (ATC) Insulins and analogues for injection, long-acting, Glucagon-like peptide-1 (GLP-1) analogues
How it works Glucagon-like Peptide-1 (GLP-1) Agonists
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.

Clinical

Label name LIRAGLUTIDE 5-PAK 18 MG/3 ML Ingredient Liraglutide
📖 What it is MedlinePlus · NLM

Liraglutide injection is used for the following: to control blood sugar levels in certain patients with type 2 diabetes (condition in which blood sugar is too high because the body does not make or use insulin normally). to reduce the risk of a heart attack, stroke, or death in adults with type 2 diabetes and heart and blood vessel disease. to assist with weight loss in certain people who are obese or overweight and have weight-related medical problems. Liraglutide injection is in a class of medications called incretin mimetics. It works by helping the pancreas to release the right amount...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Saxenda, which contains liraglutide, helps with chronic weight management along with a lower-calorie diet and more activity. It is for adults with obesity, or overweight with a wei...
  • You inject it under the skin once a day, in your belly, thigh or upper arm. Any time of day works, with or without food. You start low and go up weekly to help your stomach adjust....
  • Stomach problems are the most common, like nausea, diarrhea, constipation and vomiting. Headache, dizziness, tiredness and injection site reactions can also happen. Call us if you...
  • Tell us everything you take. If you use insulin or a sulfonylurea, your blood sugar could drop too low, so your doctor may adjust those doses. It can also slow how fast pills are a...
📖 Read our full Liraglutide Injection guide →
1
Nutrient depletion considerations

Liraglutide may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Liraglutide nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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.

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 mLPer package
Retail pharmacies payNADAC · weekly $49.248 $738.72 / 15 ml
Medicaid paysCMS SDUD · 12 mo $68.89 $1,033.32 / 15 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
NADAC price history (per mL) — tap or hover for the price & month
Dec 2025 Mar 2026 Jun 2026 Sep 2026 $73.739 $47.695
▼ Down 31% over the last 10 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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
00480-7250-46 You're viewing this Main listing 5 SYRINGE, PLASTIC in 1 CARTON / 3 mL in 1 SYRINGE, PLASTIC 2025-08-28 Sep 30, 2027 Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Liraglutide 6 mg/mL 71288-0563-84 Meitheal 3 syringes $30.632 AP1 Availability likely save 38%
Liraglutide 6 mg/mL 00143-9144-02 Hikma 2 syringes $31.406 AP1 Availability likely save 36%
Liraglutide 6 mg/mL 70748-0346-02 Lupin 2 syringes $31.406 AP1 Availability likely save 36%
Liraglutide 6 mg/mL 70377-0094-52 Biocon 2 syringes $31.406 AP1 Availability likely save 36%
Liraglutide 6 mg/mL 72603-0745-02 NorthStar 2 syringes $31.406 AP1 Availability likely save 36%
Liraglutide 6 mg/mL 69097-0920-67 Cipla 2 syringes $31.406 AP1 Availability likely save 36%
Liraglutide 6 mg/mL 00480-3667-20 Teva 2 syringes $31.406 AP1 Availability likely save 36%
Liraglutide 6 mg/mLthis 00480-7250-46 Teva 5 syringes $49.248 AP2 Availability likely —
liraglutide 6 mg/mL 69097-0910-55 Cipla 5 syringes $49.248 AP2 Availability likely —
Saxenda 6 mg/mL 00169-2800-15 Novo 5 syringes $87.126 AP2 Availability likely +77%
Victoza 6 mg/mL 00169-4060-12 Novo 2 syringes $87.748 AP1 Availability likely +78%
Saxenda 6 mg/mL 50090-4257-00 A-S 5 syringes — AP2 FDA listed —
Liraglutide 6 mg/mL 70377-0095-52 Biocon 3 syringes — AP2 FDA listed —
liraglutide 6 mg/mL 81607-0019-01 Orbicular 3 syringes — AP2 FDA listed —
Victoza 6 mg/mL 50090-2853-00 A-S 3 syringes — AP1 FDA listed —
Victoza 6 mg/mL 50090-4503-00 A-S 3 syringes — AP1 FDA listed —
Liraglutide 6 mg/mL 50090-7501-00 A-S 3 syringes — AP1 FDA listed —
Liraglutide 6 mg/mL 81607-0018-01 Orbicular 3 syringes — AP1 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

🏛️
2025
First FDA approval
Aug 2025
📍
2026
Currently FDA-listed
1 year 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.

🛡️ Latest patent/protection date listed: The latest listed FDA patent/protection lapsed Feb 2026 — those protections no longer apply, though a generic still needs FDA approval and a manufacturer to market it.
📅 FDA approved Aug 27, 2025 AP2 TE-rated RLD RS

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
Exclusivity PC
2025
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

FDA exclusivity
CodeWhat it grantsExpires
PCPediatric Exclusivity (+6 months)Feb 24, 2026
Common questions
Is there a generic version of LIRAGLUTIDE 5-PAK 18 MG/3 ML?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for LIRAGLUTIDE 5-PAK 18 MG/3 ML. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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.

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 QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • 5.5 mg / 1 mL UNII 339NCG44TV
    Phenol is a chemical compound derived from coal tar or petroleum. It serves as a preservative and antimicrobial agent in medicines, helping prevent bacterial and fungal growth to keep the product stable and safe during storage.
  • 14 mg / 1 mL 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 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • 1.42 mg / 1 mL UNII 94255I6E2T
    Sodium phosphate dibasic dihydrate is a salt that helps control the acidity level of a medicine. It acts as a buffer and pH regulator to keep the medication stable and effective.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

6 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 DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

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.

Manufacturer & labeler

LabelerTeva Pharmaceuticals, Inc.
Application holderTEVA PHARMACEUTICALS DEVELOPMENT INC
FDA applicationANDA214568 (ANDA)
Labeler code00480
First marketedAug 2025
Product typeHuman Prescription Drug
Portfolio166 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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). 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 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📖 Instructions for Use 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~1 min read ▾

WARNING: RISK OF THYROID C-CELL TUMORS Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13.1 )] . Liraglutide is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Counsel patients regarding the potential risk of MTC with use of liraglutide and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with liraglutide [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )]. WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning.

Liraglutide causes thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined ( 5.1 ). Liraglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Counsel patients regarding the potential risk of MTC and the symptoms of thyroid tumors ( 4 , 5.1 , 13.1 ).

🎯 Indications and Usage 215 words ▾

1 INDICATIONS AND USAGE Liraglutide injection is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: Adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity. Adults with overweight in the presence of at least one weight-related comorbid condition. Limitations of Use Liraglutide injection contains liraglutide.

Coadministration with other liraglutide-containing products or with any other glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended. The safety and effectiveness of liraglutide injection in pediatric patients with type 2 diabetes have not been established. Liraglutide injection is a glucagon like peptide-1 (GLP-1) receptor agonist indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: Adults and pediatric patients aged 12 years and older with body weight greater than 60 kg and obesity.

( 1 ) Adults with overweight in the presence of at least one weight-related comorbid condition. ( 1 ) Limitations of Use: Coadministration with other liraglutide-containing products or with any other GLP-1 receptor agonist is not recommended. ( 1 ) The safety and effectiveness of liraglutide injection in pediatric patients with type 2 diabetes have not been established.

( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Inject liraglutide injection subcutaneously in the abdomen, thigh, or upper arm once daily at any time of day, without regard to the timing of meals. ( 2.1 ) The recommended dose of liraglutide injection is 3 mg daily. ( 2.2 ) Initiate at 0.6 mg per day for one week.

In weekly intervals, increase the dose until a dose of 3 mg is reached. ( 2.2 ) If pediatric patients do not tolerate an increased dose during dose escalation, the dose may also be lowered to the previous level. Dose escalation for pediatric patients may take up to 8 weeks.

( 2.2 ) Pediatric patients who do not tolerate 3 mg daily may have their dose reduced to 2.4 mg daily. ( 2.2 ) Adult patients with type 2 diabetes should monitor blood glucose prior to starting liraglutide injection and during liraglutide injection treatment. ( 2.2 )

2.1Important Administration Instructions Prior to initiation of liraglutide injection, train patients on proper injection technique. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations. Inspect liraglutide injection visually prior to each injection.

Only use if solution is clear, colorless, and contains no particles. Administer liraglutide injection in combination with a reduced-calorie diet and increased physical activity. Inject liraglutide injection subcutaneously once daily at any time of day, without regard to the timing of meals.

Inject liraglutide injection subcutaneously in the abdomen, thigh, or upper arm. No dosage adjustment is needed if changing the injection site and/or timing. Rotate injection sites within the same region in order to reduce the risk of cutaneous amyloidosis [see Adverse Reactions ( 6.2 )] .

If a dose is missed, resume the once-daily regimen as prescribed with the next scheduled dose. Do not administer an extra dose or increase the dose to make up for the missed dose. If more than 3 days have elapsed since the last liraglutide injection dosage, reinitiate liraglutide injection at 0.6 mg daily and follow the dosage escalation schedule in Table 1 , to reduce the risk of gastrointestinal adverse reactions associated with reinitiation of treatment.

2.2Dosage in Adults and Pediatric Patients Aged 12 Years and Older Initiate liraglutide injection with a dose of 0.6 mg daily for one week. Then follow the dosage escalation schedule in Table 1 to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions (5.7), Adverse Reactions ( 6.1 )] . Table 1.

Dosage Escalation Schedule Week Daily Dose 1 0.6 mg 2 1.2 mg 3 1.8 mg 4 2.4 mg 5 and onward 3 mg Adult Patients For adults, the recommended dosage of liraglutide injection is 3 mg daily, lower dosages are for titration only. Discontinue liraglutide injection if the patient cannot tolerate the 3 mg dosage. If patients do not tolerate an increased dose during dosage escalation, consider delaying dosage escalation for approximately one additional week.

Evaluate the change in body weight 16 weeks after initiating liraglutide injection and discontinue liraglutide injection if the patient has not lost at least 4% of baseline body weight, since it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. In adult patients with type 2 diabetes, monitor blood glucose prior to starting liraglutide injection and during liraglutide injection treatment. Pediatric Patients For pediatric patients, the recommended maintenance dosage of liraglutide injection is 3 mg daily.

Pediatric patients who do not tolerate 3 mg daily may have their maintenance dose reduced to 2.4 mg daily. Discontinue liraglutide injection if the patient cannot tolerate the 2.4 mg dose. If pediatric patients do not tolerate an increased dose during dosage escalation, the dose may also be lowered to the previous level.

Dosage escalation for pediatric patients may take up to 8 weeks. Evaluate the change in BMI after 12 weeks on the maintenance dose an… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 62 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 6 mg/mL clear, colorless solution in a 3 mL prefilled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg. Injection: 6 mg/mL solution in a 3 mL prefilled, single-patient-use pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg. ( 3 )

⛔ Contraindications 104 words ▾

4 CONTRAINDICATIONS Liraglutide injection is contraindicated in: Patients with a personal or family history of medullary thyroid carcinoma (MTC) or patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions ( 5.1 )]. Patients with a serious hypersensitivity reaction to liraglutide or to any of the excipients in liraglutide injection. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide [see Warnings and Precautions ( 5.8 )].

Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. ( 4 ) Hypersensitivity to liraglutide or any excipients in liraglutide injection. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including liraglutide. Discontinue if pancreatitis is suspected. ( 5.2 ) Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated.

( 5.3 ) Hypoglycemia: Can occur in adults when liraglutide is used with an insulin secretagogue (e.g. a sulfonylurea) or insulin. The risk may be lowered by a reduction in the dose of concomitantly administered insulin secretagogues or insulin. In the pediatric clinical trial, patients did not have type 2 diabetes.

Hypoglycemia occurred in liraglutide-treated pediatric patients. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. ( 5.4 ) Heart Rate Increase: Monitor heart rate at regular intervals.

( 5.5 ) Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.6 ) Severe Gastrointestinal Adverse Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. Liraglutide is not recommended in patients with severe gastroparesis.

( 5.7 ) Hypersensitivity Reactions: Postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema). Discontinue liraglutide and other suspect medications and promptly seek medical advice. ( 5.8 ) Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures.

Instruct patients to inform healthcare providers of any planned surgeries or procedures. ( 5.9 )

5.1Risk of Thyroid C-cell Tumors Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice [see Nonclinical Toxicology ( 13.1 )] . Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether liraglutide will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

Cases of MTC in patients treated with liraglutide have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. Liraglutide is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of liraglutide and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with liraglutide. Such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC, and patients with MTC usually have calcitonin values greater than 50 ng/L.

If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

5.2Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including liraglutide [see Adverse Reactions ( 6 )] . After initiation of liraglutide, observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected,… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: Risk of Thyroid C-Cell Tumors [see Warnings and Precautions ( 5.1 )] Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] Acute Gallbladder Disease [see Warnings and Precautions ( 5.3 )] Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy [see Warnings and Precautions ( 5.4 )] Heart Rate Increase [see Warnings and Precautions ( 5.5 )] Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.6 )] Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.7 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.8 )] Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.9 )] Most common adverse reactions, reported in greater than or equal to 5% are: nausea, diarrhea, constipation, vomiting, injection site reactions, headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, upper abdominal pain, pyrexia, and gastroenteritis.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 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 studies of another drug and may not reflect the rates observed in practice. Liraglutide was evaluated for safety in 5 double-blind, placebo controlled trials that included 3,384 overweight or obese adult patients treated with liraglutide for a treatment period up to 56 weeks (3 trials), 52 weeks (1 trial), and 32 weeks (1 trial) and one trial of 56 weeks in 125 pediatric patients with obesity aged 12 years and older [see Clinical Studies ( 14.1 , 14.2 )].

All patients received study drug in addition to a reduced-calorie diet and increased physical activity counseling. In the adult trials, patients received liraglutide for a mean treatment duration of 46 weeks (median, 56 weeks). Baseline characteristics included a mean age of 47 years, 71% female, 85% white, 39% with hypertension, 15% with type 2 diabetes, 34% with dyslipidemia, 29% with a BMI greater than 40 kg/m 2 , and 9% with cardiovascular disease.

In one of the 56-week trials, a subset of patients (with abnormal glucose measurements at randomization) [see Clinical Studies ( 14.1 )] were enrolled for a placebo-controlled 160-week period instead, followed by a 12-week off-treatment follow-up. For those participating in this 160-week period, patients received liraglutide for a mean treatment duration of 110 weeks (median, 159 weeks). For all trials, dosing was initiated and increased weekly to reach the 3 mg dose.

In adult clinical trials, 9.8% of patients treated with liraglutide and 4.3% of patients treated with placebo prematurely discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were nausea (2.9% versus 0.2% for liraglutide and placebo, respectively), vomiting (1.7% versus less than 0.1%), and diarrhea (1.4% versus 0%). Adverse reactions reported in greater than or equal to 2% of liraglutide-treated adult patients and more frequently than in placebo-treated patients are shown in Table 2 .

Adverse reactions reported in greater than or equal to 3% of liraglutide-treated pediatric patients and more frequently than in placebo-treated patients are shown in Table 3 . Table 2. Adverse Reactions Occurring in ≥2% of Liraglutide-treated Adult Patients and More Frequently than Placebo Placebo N=1,941 % Liraglutide N=3,384 % Nausea 13.8

39.3Diarrhea 9.9

20.9Constipation 8.5

19.4Vomiting 3.9

15.7Injection Site Reaction 1 10.5

13.9Headache 12.6

13.6Hypoglycemia in T2DM 2 6.6

12.6Dyspepsia 2.7

9.6Fatigue 4.6

7.5 Dizziness 5

6.9Abdominal Pain 3.1

5.4Increased Lipase 2.2

5.3Upper Abdomina… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 82 words ▾

7 DRUG INTERACTIONS Liraglutide delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution. ( 7 )

7.1Oral Medications Liraglutide causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, monitor for potential consequences of delayed absorption of oral medications concomitantly administered with liraglutide injection.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue liraglutide. ( 8.1 )

8.1Pregnancy Risk Summary Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy. Liraglutide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Additionally, weight loss offers no benefit to a pregnant patient and may cause fetal harm.

When a pregnancy is recognized, advise the pregnant patient of the risk to a fetus, and discontinue liraglutide (see Clinical Considerations ). Animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 3 mg/day.

In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD (see Animal Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-associated maternal and/or embryofetal risk Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who already have overweight or obesity, because of the obligatory weight gain that occurs in maternal tissues during pregnancy. Animal Data Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison.

Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison. Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly.

Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day.

Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels).

Irregular ossification and/or skeletal abnormalities occurred in… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy. Liraglutide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Additionally, weight loss offers no benefit to a pregnant patient and may cause fetal harm.

When a pregnancy is recognized, advise the pregnant patient of the risk to a fetus, and discontinue liraglutide (see Clinical Considerations ). Animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 3 mg/day.

In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD (see Animal Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-associated maternal and/or embryofetal risk Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who already have overweight or obesity, because of the obligatory weight gain that occurs in maternal tissues during pregnancy. Animal Data Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison.

Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison. Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly.

Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day.

Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels).

Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were o… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 203 words ▾

8.4Pediatric Use The safety and effectiveness of liraglutide as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management have been established in pediatric patients aged 12 years and older with body weight above 60 kg and an initial BMI corresponding to 30 kg/m 2 or greater for adults (obese) by international cut-offs. Use of liraglutide for this indication is supported by a 56-week double-blind, placebo-controlled clinical trial in 251 pediatric patients aged 12 to 17 years, a pharmacokinetic study in pediatric patients, and studies in adults with obesity [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.1 , 14.2 )].

In the pediatric clinical trial, one liraglutide-treated patient had an event of pancreatitis [see Warnings and Precautions ( 5.2 )] ; more episodes of hypoglycemia confirmed by self blood glucose monitoring occurred in liraglutide-treated patients compared to placebo [see Warnings and Precautions ( 5.4 ), Adverse Reactions ( 6.1 )] ; and mean increases in resting heart rate of 3 to 7 bpm from baseline were observed with liraglutide-treated patients [see Warnings and Precautions ( 5.5 )] . The safety and effectiveness of liraglutide have not been established in patients less than 12 years of age.

🧓 Geriatric Use 61 words ▾

8.5Geriatric Use In the liraglutide clinical trials, 232 (6.9%) of the liraglutide-treated patients were 65 years of age and over, and 17 (0.5%) of the liraglutide-treated patients were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

🆘 Overdosage 56 words ▾

10 OVERDOSAGE Overdoses have been reported in clinical trials and postmarketing use of liraglutide. Effects have included severe nausea, severe vomiting and severe hypoglycemia. In the event of overdosage, consider contacting the Poison Helpline (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment according to the patient’s clinical signs and symptoms.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Liraglutide is an acylated human GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). Like endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor, a cell-surface receptor coupled to adenylyl cyclase activation through the stimulatory G-protein, Gs. Endogenous GLP-1 has a half-life of 1.5 to 2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase 4 (DPP-4) and neutral endopeptidases (NEP).

Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once-daily administration, is a result of self-association that delays absorption, plasma protein binding, and stability against metabolic degradation by DPP-4 and NEP. GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation.

In animal studies, peripheral administration of liraglutide resulted in the presence of liraglutide in specific brain regions regulating appetite, including the hypothalamus. Although liraglutide activated neurons in brain regions known to regulate appetite, specific brain regions mediating the effects of liraglutide on appetite were not identified in rats.

12.2Pharmacodynamics Liraglutide lowers body weight through decreased calorie intake. Liraglutide does not increase 24-hour energy expenditure. As with other GLP-1 receptor agonists, liraglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner.

These effects can lead to a reduction of blood glucose. Gastric Emptying Liraglutide delays gastric emptying. Cardiac Electrophysiology (QTc) in healthy volunteers The effect of liraglutide on cardiac repolarization was tested in a QTc study.

Liraglutide at steady-state concentrations after daily doses up to 1.8 mg did not produce QTc prolongation. The maximum liraglutide plasma concentration (C max ) in overweight and obese subjects treated with liraglutide 3 mg is similar to the C max observed in the liraglutide QTc study in healthy volunteers.

12.3Pharmacokinetics Absorption - Following subcutaneous administration, maximum concentrations of liraglutide are achieved at 11 hours post dosing. The average liraglutide steady state concentration (AUCτ /24 ) reached approximately 116 ng/mL in obese (BMI 30 to 40 kg/m 2 ) subjects following administration of liraglutide. Liraglutide exposure increased proportionally in the dose range of 0.6 mg to 3 mg.

The intra-subject coefficient of variation for liraglutide AUC was 11% following single dose administration. Liraglutide exposures were considered similar among three subcutaneous injection sites (upper arm, abdomen, and thigh). Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%.

Distribution - The mean apparent volume of distribution after subcutaneous administration of liraglutide 3 mg is 20 to 25L (for a person weighing approximately 100 kg). The mean volume of distribution after intravenous administration of liraglutide is

0.07L/kg. Liraglutide is extensively bound to plasma protein (greater than 98%). Metabolism - During the initial 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide.

Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination. Elimination - Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or feces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or feces (6% and 5%, respectively).

The majority of urine and feces radioactivity was excreted durin… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 201 words ▾

12.1Mechanism of Action Liraglutide is an acylated human GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). Like endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor, a cell-surface receptor coupled to adenylyl cyclase activation through the stimulatory G-protein, Gs. Endogenous GLP-1 has a half-life of 1.5 to 2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase 4 (DPP-4) and neutral endopeptidases (NEP).

Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once-daily administration, is a result of self-association that delays absorption, plasma protein binding, and stability against metabolic degradation by DPP-4 and NEP. GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation.

In animal studies, peripheral administration of liraglutide resulted in the presence of liraglutide in specific brain regions regulating appetite, including the hypothalamus. Although liraglutide activated neurons in brain regions known to regulate appetite, specific brain regions mediating the effects of liraglutide on appetite were not identified in rats.

📦 How Supplied / Storage and Handling 190 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Liraglutide injection: 6 mg/mL clear, colorless solution in a 3 mL single-patient-use prefilled pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg is available in the following package size: 5 x liraglutide injection pen NDC 0480-7250-46 Recommended Storage Prior to first use, liraglutide injection should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze liraglutide injection and do not use liraglutide injection if it has been frozen.

After initial use of the liraglutide injection pen, the pen can be stored for 30 days at controlled room temperature 59°F to 86°F (15°C to 30°C) or in a refrigerator 36°F to 46°F (2°C to 8°C). Keep the pen cap on when not in use. Protect liraglutide injection from excessive heat and sunlight.

Always remove and safely discard the needle after each injection and store the liraglutide injection pen without an injection needle attached. This will reduce the potential for contamination, infection, and leakage while also ensuring dosing accuracy.

📋 Description 196 words ▾

11 DESCRIPTION Liraglutide injection contains liraglutide, an analog of the fragment 7-37 of the naturally occurring human glucagon-like peptide 1 (GLP-1[7 - 37]), containing one amino acid substitution (Arg for Lys at position 34 of the GLP-1 sequence) and an additional fatty acid chain. Liraglutide is a linear peptide with 31 amino acids and a γ-glutamyl-palmitoyl residue linked to the ɛ-amino group of Lys 20 . All amino acid residues with exception of the archiral glycines are in the L-configuration.

The structural formula ( Figure 1 ) is: Figure 1. Structural Formula of liraglutide C 172 H 265 N 43 O 51 M.W. 3751.26 Daltons Liraglutide is manufactured by chemical synthesis.

Liraglutide injection is a sterile, aqueous, clear, colorless solution for subcutaneous use. Each 1 mL of liraglutide injection solution contains 6 mg of liraglutide and the following inactive ingredients: phenol, 5.5 mg; propylene glycol, 14 mg; sodium phosphate dibasic dihydrate, 1.42 mg; and water for injection. Liraglutide injection has a pH of approximately 8.15, hydrochloric acid or sodium hydroxide may be added to adjust pH.

Each prefilled pen contains a 3 mL solution of liraglutide injection equivalent to 18 mg liraglutide (free-base, anhydrous). structural formula

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Instructions Advise patients to take liraglutide injection exactly as prescribed. Instruct patients to follow the dose escalation schedule and to not take more than the recommended dose.

Instruct adult patients to discontinue liraglutide injection if they have not achieved 4% weight loss by 16 weeks of treatment. Instruct pediatric patients 12 years of age and older to discontinue liraglutide injection if they have not achieved a BMI reduction of 1% from baseline after 12 weeks on the maintenance dose. Risk of Thyroid C-cell Tumors Inform patients that liraglutide causes benign and malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding has not been determined.

Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia or dyspnea) to their health care provider [see Boxed Warning, Warnings and Precautions ( 5.1 )]. Acute Pancreatitis Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that may radiate to the back, and which may or may not be accompanied by nausea or vomiting. Instruct patients to discontinue liraglutide injection promptly and contact their healthcare provider if pancreatitis is suspected [see Warnings and Precautions ( 5.2 )] .

Acute Gallbladder Disease Inform patients of the risk of acute gallbladder disease. Advise patients that substantial or rapid weight loss can increase the risk of gallbladder disease, but that gallbladder disease may also occur in the absence of substantial or rapid weight loss. Instruct patients to contact their healthcare provider for appropriate clinical follow-up if gallbladder disease is suspected [see Warnings and Precautions ( 5.3 )] .

Hypoglycemia Inform pediatric patients of the risk of hypoglycemia and educate all patients on the signs and symptoms of hypoglycemia. Inform adult patients with type 2 diabetes mellitus on an insulin secretagogue (e.g., sulfonylurea) or insulin that they may have an increased risk of hypoglycemia when using liraglutide injection and to report signs and/or symptoms of hypoglycemia to their healthcare provider [see Warnings and Precautions ( 5.4 )] . Heart Rate Increase Inform patients to report symptoms of sustained periods of heart pounding or racing while at rest to their healthcare provider.

Discontinue liraglutide injection in patients who experience a sustained increase in resting heart rate [see Warnings and Precautions ( 5.5 )] . Acute Kidney Injury Due to Volume Depletion Inform patients of the potential risk of acute kidney injury due to dehydration associated with gastrointestinal adverse reactions. Advise patients to take precautions to avoid fluid depletion.

Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions ( 5.6 )] . Severe Gastrointestinal Adverse Reactions Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions ( 5.7 )] .

Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of liraglutide injection. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking liraglutide injection and seek medical advice promptly if such symptoms occur [see Warnings and Precautions ( 5.8 )] . Pulmonary Aspiration During General Anesthesia or Deep Sedation Inform patients that liraglutide injection may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Liraglutide (lir" a gloo' tide) Injection for subcutaneous use What is the most important information I should know about liraglutide injection? Serious side effects may happen in people who take liraglutide injection, including: Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath.

These may be symptoms of thyroid cancer. In studies with rats and mice, liraglutide injection and medicines that work like liraglutide injection caused thyroid tumors, including thyroid cancer. It is not known if liraglutide injection will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.

Do not use liraglutide injection if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). What is liraglutide injection? Liraglutide injection is an injectable prescription medicine used for adults with obesity or overweight (excess weight) who also have weight related medical problems, and children aged 12 to 17 years with a body weight above 132 pounds (60 kg) and obesity to help them lose weight and keep the weight off.

Liraglutide injection should be used with a reduced calorie diet and increased physical activity. Liraglutide injection is not recommended for people who also take liraglutide or other medicines called glucagon-like peptide-1 (GLP-1) receptor agonists. It is not known if liraglutide injection is safe and effective in children under 12 years of age.

It is not known if liraglutide injection is safe and effective in children aged 12 to 17 years with type 2 diabetes. Who should not use liraglutide injection? Do not use liraglutide injection if: you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). you have had a serious allergic reaction to liraglutide or any of the ingredients in liraglutide injection.

See the end of this Medication Guide for a complete list of ingredients in liraglutide injection. See “ What are the possible side effects of liraglutide injection? ” for symptoms of a serious allergic reaction. Before taking liraglutide injection, tell your healthcare provider about all of your medical conditions, including if you: have or have had problems with your pancreas. have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food. are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). are breastfeeding or plan to breastfeed.

It is not known if liraglutide passes into your breast milk. You and your healthcare provider should decide if you will use liraglutide injection or breastfeed. Tell your healthcare provider about all the medicines you take including prescription, over-the-counter medicines, vitamins, and herbal supplements.

Liraglutide injection may affect the way some medicines work and some other medicines may affect the way liraglutide injection works. Tell your healthcare provider if you take diabetes medicines, especially insulin and sulfonylurea medicines. Talk with your healthcare provider if you are not sure if you take any of these medicines.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use liraglutide injection?

Read the Instructions for Use that comes with liraglutide injection. Use liraglutide injection exactly as your healthcare provider tells you to. Your healthcare provider should show you how to use liraglutide injection before you use it for the first time.

Use liraglutide injection with a reduced-calorie diet and incr… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption - Following subcutaneous administration, maximum concentrations of liraglutide are achieved at 11 hours post dosing. The average liraglutide steady state concentration (AUCτ /24 ) reached approximately 116 ng/mL in obese (BMI 30 to 40 kg/m 2 ) subjects following administration of liraglutide. Liraglutide exposure increased proportionally in the dose range of 0.6 mg to 3 mg.

The intra-subject coefficient of variation for liraglutide AUC was 11% following single dose administration. Liraglutide exposures were considered similar among three subcutaneous injection sites (upper arm, abdomen, and thigh). Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%.

Distribution - The mean apparent volume of distribution after subcutaneous administration of liraglutide 3 mg is 20 to 25L (for a person weighing approximately 100 kg). The mean volume of distribution after intravenous administration of liraglutide is

0.07L/kg. Liraglutide is extensively bound to plasma protein (greater than 98%). Metabolism - During the initial 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide.

Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination. Elimination - Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or feces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or feces (6% and 5%, respectively).

The majority of urine and feces radioactivity was excreted during the first 6 to 8 days. The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 0.9 to

1.4L/h with an elimination half-life of approximately 13 hours, making liraglutide suitable for once daily administration. Specific Populations Elderly - Age had no effect on the pharmacokinetics of liraglutide based on a pharmacokinetic study in healthy elderly subjects (65 to 83 years) and population pharmacokinetic analyses of data from overweight and obese patients 18 to 82 years of age [see Use in Specific Populations (8.5)] . Gender - Based on the results of population pharmacokinetic analyses, females have 24% lower weight adjusted clearance of liraglutide compared to males.

Race and Ethnicity - Race and ethnicity had no effect on the pharmacokinetics of liraglutide based on the results of population pharmacokinetic analyses that included overweight and obese patients of White, Black or African American, Asian and Hispanic/Non-Hispanic Ethnic groups. Body Weight - Body weight significantly affects the pharmacokinetics of liraglutide based on results of population pharmacokinetic analyses conducted in patients with body weight range of 60 to 234 kg. The exposure of liraglutide decreases as baseline body weight increases.

Pediatric - A population pharmacokinetic analysis was conducted for liraglutide using data from 134 pediatric patients (12 to 17 years of age) with obesity. The liraglutide exposure in the pediatric patients was similar to that in adults with obesity [see Use in Specific Populations ( 8.4 )] . Renal Impairment - The single-dose pharmacokinetics of liraglutide were evaluated in patients with varying degrees of renal impairment.

Patients with mild (estimated creatinine clearance 50 to 80 mL/min) to severe (estimated creatinine clearance less than 30 mL/min) renal impairment and patients with end-stage renal disease requiring dialysis were included in the trial. Compared to healthy subjects, liraglutide AUC in mild, moderate, and severe renal impairment and in end-stage renal disease was on average 35%, 19%, 29% and 30% lower, respectively [see Use in Specific Populations (8.6)] . Hepatic Impairment - The single-dose pharmacokinetics of liraglutide were evaluated in patients with varying degrees of… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 119 words ▾

12.2Pharmacodynamics Liraglutide lowers body weight through decreased calorie intake. Liraglutide does not increase 24-hour energy expenditure. As with other GLP-1 receptor agonists, liraglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner.

These effects can lead to a reduction of blood glucose. Gastric Emptying Liraglutide delays gastric emptying. Cardiac Electrophysiology (QTc) in healthy volunteers The effect of liraglutide on cardiac repolarization was tested in a QTc study.

Liraglutide at steady-state concentrations after daily doses up to 1.8 mg did not produce QTc prolongation. The maximum liraglutide plasma concentration (C max ) in overweight and obese subjects treated with liraglutide 3 mg is similar to the C max observed in the liraglutide QTc study in healthy volunteers.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Weight Management Trials in Adults with Overweight or Obesity The safety and efficacy of liraglutide for chronic weight management in conjunction with reduced caloric intake and increased physical activity were studied in three 56-week, randomized, double-blind, placebo-controlled trials. In all studies, liraglutide was titrated to 3 mg daily during a 4-week period. All patients received instruction for a reduced-calorie diet (approximately 500 kcal/day deficit) and physical activity counseling (recommended increase in physical activity of minimum 150 mins/week) that began with the first dose of study medication or placebo and continued throughout the trial.

Study 1 enrolled 3,731 patients with obesity (BMI greater than or equal to 30 kg/m 2 ) or with overweight (BMI 27 to 29.9 kg/m 2 ) and at least one weight-related comorbid condition such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus were excluded. Patients were randomized in a 2:1 ratio to either liraglutide or placebo. Patients were stratified based on the presence or absence of abnormal blood glucose measurements at randomization.

All patients were treated for up to 56 weeks. Those patients with abnormal glucose measurements at randomization (2,254 of the 3,731 patients) were treated for a total of 160 weeks. At baseline, mean age was 45 years (range 18 to 78), 79% were female, 85% were White, 10% were Black or African American, and 11% were Hispanic/Latino Ethnicity.

Mean baseline body weight was 106.3 kg, and mean BMI was 38.3 kg/m 2 . Study 2 was a 56-week trial that enrolled 635 patients with type 2 diabetes and with either overweight or obesity (as defined above). Patients were to have an HbA 1c of 7% to 10% and be treated with metformin, a sulfonylurea, or a glitazone as single agent or in any combination, or with a reduced-calorie diet and physical activity alone.

Patients were randomized in a 2:1 ratio to receive either liraglutide or placebo. The mean age was 55 years (range 18 to 82), 50% were female, 83% were White, 12% were Black or African American, and 10% were Hispanic/Latino Ethnicity. Mean baseline body weight was 105.9 kg and mean BMI was 37.1 kg/m 2 .

Study 3 was a 56-week trial that enrolled 422 patients with obesity (BMI greater than or equal to 30 kg/m 2 ) or with overweight (BMI 27 to 29.9 kg/m 2 ) and at least one weight-related comorbid condition such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus were excluded. All patients were first treated with a low-calorie diet (total energy intake 1,200 to 1,400 kcal/day) in a run-in period lasting up to 12 weeks. Patients who lost at least 5% of their screening body weight after 4 to 12 weeks during the run-in were then randomized, with equal allocation, to receive either liraglutide or placebo for 56 weeks.

The mean age was 46 years (range 18 to 73), 81% were female, 84% were White, 13% were Black or African American, and 7% were Hispanic/Latino Ethnicity. Mean baseline body weight was 99.6 kg and mean BMI was 35.6 kg/m 2 . The proportions of patients who discontinued study drug in the 56-week trials were 27% for the liraglutide-treated group and 35% for the placebo-treated group, and in the 160-week trial the proportions of patients who discontinued were 47% and 55%, respectively.

In the 56-week trials, approximately 10% of patients treated with liraglutide and 4% of patients treated with placebo discontinued treatment due to an adverse reaction [see Adverse Reactions ( 6.1 )] . The majority of patients who discontinued liraglutide due to adverse reactions did so during the first few months of treatment. In the 160-week trial the proportions of patients who discontinued due to an adverse reaction was 13% and 6% for liraglutide- and placebo-treated patients, respectively.

Effect of Liraglutide on Body Weight in 56-week Trials For Study 1 and Study 2, the primary efficacy parameters were m… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1, and 3 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 43-times the exposure in obese humans, respectively, at the maximum recommended human dose (MRHD) of 3 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1 and the 3 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively.

C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3 mg/kg/day group. Thyroid C-cell tumors are rare findings during carcinogenicity testing in mice.

A treatment-related increase in fibrosarcomas was seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site. The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6 mg/mL).

A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 7-times the exposure in obese humans, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively.

A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats. Studies in mice demonstrated that liraglutide-induced C-cell proliferation was dependent on the GLP-1 receptor and that liraglutide did not cause activation of the REarranged during Transfection (RET) proto-oncogene in thyroid C-cells.

Human relevance of thyroid C-cell tumors in mice and rats is unknown and has not been determined by clinical studies or nonclinical studies [see Boxed Warning, Warnings and Precautions ( 5.1 )] . Liraglutide was negative with and without metabolic activation in the Ames test for mutagenicity and in a human peripheral blood lymphocyte chromosome aberration test for clastogenicity. Liraglutide was negative in repeat-dose in vivo micronucleus tests in rats.

In rat fertility studies using subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide, males were treated for 4 weeks prior to and throughout mating and females were treated 2 weeks prior to and throughout mating until gestation day 17. No direct adverse effects on male fertility was observed at doses up to 1 mg/kg/day, a high dose yielding an estimated systemic exposure 11-times the exposure in obese humans at the MRHD, based on plasma AUC comparison. In female rats, an increase in early embryonic deaths occurred at 1 mg/kg/day.

Reduced body weight gain and food consumption were observed in females at the 1 mg/kg/day dose.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~3 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1, and 3 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 43-times the exposure in obese humans, respectively, at the maximum recommended human dose (MRHD) of 3 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1 and the 3 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively.

C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3 mg/kg/day group. Thyroid C-cell tumors are rare findings during carcinogenicity testing in mice.

A treatment-related increase in fibrosarcomas was seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site. The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6 mg/mL).

A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 7-times the exposure in obese humans, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively.

A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats. Studies in mice demonstrated that liraglutide-induced C-cell proliferation was dependent on the GLP-1 receptor and that liraglutide did not cause activation of the REarranged during Transfection (RET) proto-oncogene in thyroid C-cells.

Human relevance of thyroid C-cell tumors in mice and rats is unknown and has not been determined by clinical studies or nonclinical studies [see Boxed Warning, Warnings and Precautions ( 5.1 )] . Liraglutide was negative with and without metabolic activation in the Ames test for mutagenicity and in a human peripheral blood lymphocyte chromosome aberration test for clastogenicity. Liraglutide was negative in repeat-dose in vivo micronucleus tests in rats.

In rat fertility studies using subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide, males were treated for 4 weeks prior to and throughout mating and females were treated 2 weeks prior to and throughout mating until gestation day 17. No direct adverse effects on male fertility was observed at doses up to 1 mg/kg/day, a high dose yielding an estimated systemic exposure 11-times the exposure in obese humans at the MRHD, based on plasma AUC comparison. In female rats, an increase in early embryonic deaths occurred at 1 mg/kg/day.

Reduced body weight gain and food consumption were observed in females at the 1 mg/kg/day dose.

📚 References 25 words ▾

15 REFERENCES 1. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000;320(7244):1240-3.

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE Liraglutide (lir" a gloo' tide) Injection Read these instructions carefully before using your liraglutide injection pen. Do not use your pen without proper training from your healthcare provider. Make sure that you know how to give yourself an injection with the pen before you start your treatment.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the liraglutide injection pen . Start by checking your pen to make sure that it contains liraglutide injection, then look at the pictures below to get to know the different parts of your pen and needle.

Your pen is a prefilled, dial-a-dose, single-patient-use pen. It contains 18 mg of liraglutide, and you can select doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and 3 mg. Your pen is compatible with universal fit disposable pen needles up to a length of 8 mm, including NovoFine ® .

Compatible needles will state ISO11608-2 on the outer packaging. Your pen is not compatible with NovoTwist ® disposable needles. Pen needles are not included with your liraglutide injection pen.

Liraglutide injection pen and needle (example) Step 1. Prepare your pen with a new needle Wash your hands with soap and water. Check the name and colored label of your pen, to make sure that it contains liraglutide injection.

This is especially important if you take more than 1 type of medicine. Pull off the pen cap. Check that liraglutide injection in your pen is clear and colorless.

Look through the pen window. If liraglutide injection looks cloudy, do not use the pen. Take a new needle, and tear off the paper tab.

Push the needle straight onto the pen. Turn until it is on tight. Pull off the outer needle cap.

Do not throw it away. Pull off the inner needle cap and throw it away. A drop of liraglutide injection may appear at the needle tip.

This is normal, but you must still check the liraglutide injection flow, if you use a new pen for the first time. Always use a new needle for each injection. This will prevent contamination, infection, leakage of liraglutide injection, and blocked needles leading to the wrong dose.

Never use a bent or damaged needle. Do not attach a new needle to your pen until you are ready to take your injection. Step 2.

Check the liraglutide injection flow with each new pen. Check the liraglutide injection flow before your first injection with each new pen. If your liraglutide injection pen is already in use, go to Step 3 “Select your dose”.

Turn the dose selector until the dose counter shows the flow check symbol ( ). Hold the pen with the needle pointing up. Press and push in the dose button until the dose counter shows 0.

The black arrow indicating 0 must appear in the notch. A drop of liraglutide injection will appear at the needle tip. If no drop appears, repeat Step 2 above as shown in Figures G and H up to 6 times.

If there is still no drop, change the needle and repeat Step 2 as shown in Figures G and H 1 more time. Do not use the pen if a drop of liraglutide injection still does not appear . Contact Teva at 1-888-838-2872.

Always make sure that a drop appears at the needle tip before you use a new pen for the first time. This makes sure that liraglutide injection flows. If no drop appears, you will not inject any liraglutide injection, even though the dose counter may move.

This may mean that there is a blocked or damaged needle. A small drop may remain at the needle tip, but it will not be injected. Only check the liraglutide injection flow before your first injection with each new pen.

Step 3. Select your dose Turn the dose selector until the dose counter shows your dose (0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg). Make sure you know the dose of liraglutide injection you should use.

If you select the wrong dose, you can turn the dose selector forward or backwards to the correct dose. Always use the dose counter and the black arrow in the n… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 39 words ▾

Indications and Usage ( 1 )………………………….……………............………….5/2025 Dosage and Administration, Patient Selection ( 2.1 )..........................…(Removed) 5/2025 Contraindications, Pregnancy ( 4 )………………………………….……................……(Removed) 5/2025 Warnings and Precautions, Severe Gastrointestinal Adverse Reactions ( 5.7 )………..…................………..10/2025 Suicidal Behavior and Ideation ( 5.9 )…………..............…...……....(Removed) 2/2026

📄 Package Label / Principal Display Panel 64 words ▾

PRINCIPAL DISPLAY PANEL NDC 0480-7250-46 Liraglutide Injection 18 mg/3 mL (6 mg/mL) Single Patient Use Only Discard pen 30 days after first use REFRIGERATE – DO NOT FREEZE For Subcutaneous Use Only Compatible with universal fit disposable pen needles (e.g. NovoFine ® ) Protect from light. PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 5 x 3 mL Prefilled Pens carton-5s

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

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 this package alone, 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.
📅 Q3 2025 – Q4 2025 · 2 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
1.6K
Units reimbursed last 4 qtrs
21.7K
Gross reimbursed last 4 qtrs
$1.5M
Avg / prescription
$961.64
Avg / unit
$68.8878
Latest quarter Q4 2025
1.1KRx
Medicaid pays / mL
$68.8878
gross reimbursed
vs
NADAC / mL
$49.2481
acquisition cost
=
Spread
+$19.6397
+40% vs cost
What Medicaid paid per mL (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 ⓘ
12% FFS 88% MCO
Fee-for-service · 184 Rx Managed care · 1,373 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: 3,471 units · 60.5 per 100k residents MN Wisconsin: 1,503 units · 25.4 per 100k residents WI Michigan: 741 units · 7.4 per 100k residents MI New York: no data reported NY Vermont: no data reported VT New Hampshire: 522 units · 37.2 per 100k residents NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: 180 units · 1.5 per 100k residents OH Pennsylvania: 1,974 units · 15.2 per 100k residents PA New Jersey: no data reported NJ Massachusetts: 153 units · 2.2 per 100k residents MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 11,349 units · 130 per 100k residents VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: 837 units · 76.4 per 100k residents RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: 207 units · 7.0 per 100k residents KS Arkansas: no data reported AR Tennessee: 531 units · 7.5 per 100k residents TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: 267 units · 9.1 per 100k residents MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.5130
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 Virginia 130 /100k
2 Rhode Island 76.4 /100k
3 Minnesota 60.5 /100k
4 New Hampshire 37.2 /100k
5 Wisconsin 25.4 /100k
6 Pennsylvania 15.2 /100k
7 Mississippi 9.1 /100k
8 Tennessee 7.5 /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.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Liraglutide — the program that covers self-administered drugs. 5 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Liraglutide. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$19.11M
Claims incl. refills
44.1K
Beneficiaries
28.1K
Spend / beneficiary
$680.06
Spend / claim
$433.77
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.
← 00480-7168-98 · Teva 00480-7270-10 · Teva →
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.