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Increlex mecasermin 40 mg/4mL Injection, Solution — NDC 15054-1040-5 (Billing 15054-1040-05)

by Ipsen Biopharmaceuticals, Inc. · 1 VIAL, MULTI-DOSE in 1 CARTON / 4 mL in 1 VIAL, MULTI-DOSE

This is a package of Increlex mecasermin 40 mg/4mL Injection, Solution from Ipsen Biopharmaceuticals, Inc., marketed since Jan 2006 and currently FDA-listed, this package's marketing is listed to end Dec 2027. It is this product's only package size.

NDC 15054-1040-05
🏷️ FDA NDC (as labeled) 15054-1040-5 billing pads the package segment with a zero
Rx only Brand On market Non-controlled ⇄ 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 →

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

NDC database record

One package, one record: these facts belong to NDC 15054-1040-5 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
15054 labeler · 1040 product · 5 package
Package marketed since
Jan 3, 2006
Package marketing ended
Dec 31, 2027
Sample package
No — commercial package
Barcode (UPC-A, from the NDC)
3 1505410405 6
Medicaid fills, this package
35 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 15054-1040-5
Product NDC 15054-1040
11-digit billing NDC 15054104005
NCPDP billing unit ML — per mL (volume)
RxCUI 604806, 615882
UNII 7GR9I2683O
Application # BLA021839
SPL Set ID a8b27a1b-a611-4f91-ad22-76d4b390c3ae
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2006-01-03
Marketing end 2027-12-31
Route SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance MECASERMIN
Biologic (Purple Book) 351(a)

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

GPI-14 30160045002020
GPI class Increlex
GCN Seq No 059704
GCN 25465
HICL code 033207
Ingredient (HICL) Mecasermin
HIC1 code P
Therapeutic class — broad (HIC1) Endocrine System
HIC2 code P7
Therapeutic class — intermediate (HIC2) Hepatic Hormones (Hormones Secreted By The Liver)
HIC3 code P7A
Therapeutic class — specific (HIC3) Insulin-Like Growth Factor-1 (Igf-1) Hormones
AHFS code 68:30.04.00
AHFS class Somatotropin Agonists
FDB label name INCRELEX 40 MG/4 ML VIAL
FDB brand name Increlex
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 059704
  • GCN: 25465
  • GPI-14 (Medi-Span): 30160045002020
  • HICL (First Databank): 033207
  • AHFS class code: 68:30.04.00
  • RxCUI (RxNorm): 604806
Why two NDCs? The FDA registers this code as 15054-1040-5 — a 5-4-1 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 package segment → 15054-1040-05. 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 Somatropin and somatropin agonists class.

Drug family (ATC) Somatropin and somatropin 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 INCRELEX 40 MG/4 ML VIAL Ingredient Mecasermin
📖 What it is MedlinePlus · NLM

Mecasermin injection is used to replace insulin-like growth factor (a natural hormone produced by your body) in children 2 years of age or older whose bodies do not make enough of this hormone and who are short for their age. Mecasermin is a human insulin-like growth factor (hIGF) analog. It works by replacing a hormone that promotes normal growth of bones and tissues.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Increlex is a man-made version of a hormone called IGF-1, which your child's body isn't making enough of on its own. IGF-1 is the signal that tells bones and tissues to grow — with...
  • What exactly is Increlex and why does my child need it?
  • Increlex is injected just under the skin — not into a vein — twice a day. The most important timing rule is that it must be given within about 20 minutes of a meal or snack. If you...
  • How do I give the injection, and does it have to be at a certain time?
📖 Read our full Mecasermin Injection guide →

Supplement & herbal interactions

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

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 Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $3,263.79 $13,055.14 / 4 ml
Medicare drug plans payPart D · Q2 2026 $4,094.26 $16,377.05 / 4 ml
Medicare Part B allowsASP · J2170 No ASP payment limit on file for J2170 this quarter.
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.

Billing & reimbursement

FDA NDC (as labeled)15054-1040-5
11-digit billing NDC15054-1040-05
Format5-4-1 as registered → padded to 5-4-2 for billing (zero added to the package segment)
HCPCS J-codeJ2170
DescriptorINJECTION, MECASERMIN, 1 MG
Billing units / pkg10 units
How the units are derivedThis package is 4 ML; the HCPCS unit is 1 MG, so one package = 10 billing units.
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
15054-1040-05 You're viewing this Main listing 1 VIAL, MULTI-DOSE in 1 CARTON / 4 mL in 1 VIAL, MULTI-DOSE 2006-01-03 Dec 31, 2027 Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Increlex 40 mg/4mLthis 15054-1040-05 Ipsen 1 vial — — FDA listed —
Increlex 40 mg/4mL 71863-0216-04 Eton 1 vial — — FDA listed —
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
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 & biosimilar status

🏛️
2005
First FDA approval
Aug 2005
📍
2026
Currently FDA-listed
21 years listed
🧬
·
Biosimilars
see Purple Book
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Increlexmecasermin
🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar 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 Q40Q9N063P
    Acetic acid is a weak organic acid commonly used in medicines as a buffer and pH adjuster. It helps maintain the proper acidity level to ensure the drug remains stable and effective in its formulation.
  • 36 mg / 4 mL UNII LKG8494WBH
    Benzyl alcohol is a clear liquid used as a preservative and solvent in medicines. It helps prevent bacterial and fungal growth and dissolves other ingredients to create uniform liquid formulations.
  • 8 mg / 4 mL UNII 7T1F30V5YH
    A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
  • 23.3 mg / 4 mL UNII 4550K0SC9B
    Sodium acetate is a salt derived from acetic acid. It acts as a buffer to help maintain the medicine's pH stability and may serve as a preservative or solubilizer in liquid formulations.
  • 23.4 mg / 4 mL UNII 451W47IQ8X
    Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
  • 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

LabelerIpsen Biopharmaceuticals, Inc.
FDA applicationBLA021839 (BLA)
Labeler code15054
First marketedJan 2006
Product typeHuman Prescription Drug
Portfolio17 products on file

More NDCs from Ipsen Biopharmaceuticals, Inc. labeler code 15054

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.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📖 Instructions for Use 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 174 words ▾

1 INDICATIONS AND USAGE INCRELEX (mecasermin) injection is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. ( 1 ) Limitations of use: INCRELEX is not a substitute to GH for approved GH indications. Severe Primary IGF-1 Deficiency (Primary IGFD) INCRELEX is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with: severe primary IGF-1 deficiency or growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Severe Primary IGF-1 deficiency (IGFD) is defined by: height standard deviation score ≤ –3.0 and basal IGF-1 standard deviation score ≤ –3.0 and normal or elevated growth hormone (GH). Limitations of use: INCRELEX is not a substitute to GH for approved GH indications. INCRELEX is not indicated for use in patients with secondary forms of IGF-1 deficiency, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory corticosteroids.

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION INCRELEX should be administered subcutaneously. ( 2.2 ) Injection sites should be rotated to avoid lipohypertrophy. ( 2.2 ) Recommended starting dosage: 0.04 mg/kg to 0.08 mg/kg twice daily. If well-tolerated for at least one week, the dose may be increased by 0.04 mg/kg per dose, to the maximum dose of 0.12 mg/kg given twice daily. ( 2.1 )

2.1Recommended Dosage Treatment with INCRELEX should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with short stature associated with severe primary IGF-1 deficiency or with growth hormone gene deletion and who have developed neutralizing antibodies to growth hormone. The dosage of INCRELEX should be individualized for each patient. The recommended starting dose of INCRELEX is 0.04 mg/kg to 0.08 mg/kg of body weight twice daily by subcutaneous injection.

If well-tolerated for at least one week, the dose may be increased by 0.04 mg/kg of body weight per dose, to the maximum dose of 0.12 mg/kg of body weight given twice daily [see Warnings and Precautions (5.1 and 5.7) ]. Preprandial glucose monitoring is recommended at treatment initiation and until a well-tolerated dose is established. If frequent symptoms of hypoglycemia or severe hypoglycemia occur, preprandial glucose monitoring should continue, and glucose monitoring should also occur at the time of event if possible.

If hypoglycemia occurs with recommended doses despite adequate food intake, the dose should be reduced. INCRELEX should be administered shortly before or after (± 20 minutes) a meal or snack. If the patient is unable to eat shortly before or after a dose for any reason, that dose of INCRELEX should be withheld.

If one or more doses of INCRELEX is missed, do not increase the subsequent doses to make up for omitted doses.

2.2Administration Instructions INCRELEX is administered by subcutaneous injection only. Do not administer intravenously. INCRELEX injection sites should be rotated to a different site (upper arm, thigh, buttock or abdomen) with each injection to help prevent lipohypertrophy.

INCRELEX should be administered using sterile disposable syringes and needles. The syringes should be of small enough volume so that the prescribed dose can be withdrawn from the vial with accuracy. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use if the solution is cloudy or contains particulate matter. If using syringes that measure dose in units, doses in mg/kg must be converted to units using the following formula: Weight (kg) × Dose (mg/kg) × 1 mL/10 mg × 100 units/1 mL = units/injection.

💊 Dosage Forms and Strengths 36 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 40 mg/4 mL (10 mg/mL) clear and colorless solution in a multiple-dose glass vial. Injection: 40 mg/4 mL (10 mg/mL) solution supplied in a multiple-dose glass vial ( 3 )

⛔ Contraindications 102 words ▾

4 CONTRAINDICATIONS Known Hypersensitivity to mecasermin ( 4 ) Closed Epiphyses ( 4 ) Malignant Neoplasia ( 4 ) Known Hypersensitivity INCRELEX should not be used by patients who are allergic to mecasermin (rhIGF-1) or any of the inactive ingredients in INCRELEX, or who have experienced a severe hypersensitivity to INCRELEX [see Warnings and Precautions (5.2) and Adverse Reactions (6) ]. Closed Epiphyses INCRELEX should not be used for growth promotion in patients with closed epiphyses. Malignant Neoplasia INCRELEX is contraindicated in pediatric patients with malignant neoplasia or a history of malignancy [see Warnings and Precautions (5.7) and Adverse Reactions (6) ].

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Hypoglycemia: Severe hypoglycemia leading to hypoglycemic seizures has been observed with INCRELEX treatment. Administer INCRELEX shortly before or after a meal or snack, because it has insulin-like hypoglycemic effects. ( 5.1 ) Hypersensitivity and Allergic Reactions, including Anaphylaxis: A low number of cases indicative of anaphylaxis requiring hospitalization have been reported.

Parents and patients should be informed that such reactions are possible and that if a systemic allergic reaction occurs, treatment should be interrupted and prompt medical attention should be sought. ( 5.2 ) Intracranial Hypertension : Funduscopic examination is recommended at the initiation and periodically during the course of INCRELEX therapy. ( 5.3 ) Lymphoid Tissue Hypertrophy (tonsillar/adenoidal hypertrophy): Patients should have periodic examinations to rule out potential complications and receive appropriate treatment if necessary.

( 5.4 ) Slipped Capital Femoral Epiphysis (SCFE): Evaluate any child with onset of a limp or hip/knee pain for possible SCFE and osteonecrosis. ( 5.5 ) Progression of Scoliosis: Monitor any child with scoliosis for progression of the spine curve. ( 5.6 ) Malignant Neoplasia: Several cases of malignant neoplasia have been observed in pediatric patients treated with INCRELEX.

Therapy should be discontinued if evidence of malignant neoplasia develops and appropriate expert medical care sought. ( 5.7 ) Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preserved Solution: Benzyl alcohol, a preservative in INCRELEX, has been associated with serious adverse reactions, including death, in neonates and infants. Use of INCRELEX in infants is not recommended.

( 5.8 )

5.1Hypoglycemia Severe hypoglycemia leading to hypoglycemic seizures has been observed with INCRELEX treatment [see Adverse Reactions (6.1) ]. Because INCRELEX has insulin-like hypoglycemic effects it should be administered shortly before or after (± 20 minutes) a meal or snack. Glucose monitoring and INCRELEX dose titration are recommended until a well-tolerated dose is established [see Dosage and Administration (2.1) ] and subsequently as medically indicated.

Special attention should be paid to small children because their oral intake may not be consistent. Patients should avoid engaging in any high-risk activities (e.g., driving, exercise, etc.) within 2 to 3 hours after dosing, particularly during the initiation of INCRELEX treatment until tolerability and a stable dose have been established [see Adverse Reactions (6.1) ] . INCRELEX should not be administered when the meal or snack is omitted.

The dose of INCRELEX should never be increased to make up for one or more omitted doses.

5.2Hypersensitivity and Allergic Reactions, including Anaphylaxis Allergic reactions to INCRELEX have been reported post-marketing. They range from localized (injection site) reactions to systemic reactions, including anaphylaxis requiring hospitalization. Parents and patients should be informed that such reactions are possible and that if a systemic allergic reaction occurs, treatment should be interrupted and prompt medical attention should be sought. [see Contraindications (4) and Adverse Reactions (6) ]

5.3Intracranial Hypertension Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting have occurred in patients treated with INCRELEX. IH-associated signs and symptoms resolved after interruption of dosing. Funduscopic examination is recommended at the initiation and periodically during the course of INCRELEX therapy. [see Adverse Reactions (6) ].

5.4Lymphoid Tissue Hypertrophy Lymphoid tissue (e.g., tonsillar and adenoidal) hypertrophy associated with complications, such as snoring, sleep apnea, and chronic middle-ear effusions have been reported with the use of INCRELEX. Patients should have periodic examinations to rule out such potential complications and receive appropriate treatmen… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions (5.1) ]. Hypersensitivity and Allergic Reactions, including Anaphylaxis [see Warnings and Precautions (5.2) ] Intracranial hypertension (IH) [see Warnings and Precautions (5.3) ] Tonsillar and Adenoidal Hypertrophy and related complications [see Warnings and Precautions (5.4) ] Slipped Capital Femoral Epiphysis [see Warnings and Precautions (5.5) ] Progression of Preexisting Scoliosis [see Warnings and Precautions (5.6) ] Malignant Neoplasia [see Warnings and Precautions (5.7) ] Benzyl Alcohol [see Warnings and Precautions (5.8) ] Common INCRELEX-related adverse reactions in clinical trials include: hypoglycemia, local and systemic hypersensitivity, tonsillar hypertrophy ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at 1-855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical studies of 71 subjects with Primary IGFD treated for a mean duration of 3.9 years and representing 274 subject-years, no subjects withdrew from any clinical study because of adverse reactions. Adverse reactions to INCRELEX treatment that occurred in 5% or more of these study participants are listed below by organ class.

Metabolism and Nutrition Disorders: hypoglycemia General Disorders and Administrative Site Conditions: lipohypertrophy, bruising Infections and Infestations: otitis media, serous otitis media Respiratory, Thoracic and Mediastinal Disorders: snoring, tonsillar hypertrophy Nervous System Disorders: headache, dizziness, convulsions Gastrointestinal Disorders: vomiting Ear and Labyrinth Disorders: hypoacusis, fluid in middle ear, ear pain, abnormal tympanometry Investigations: cardiac murmur Musculoskeletal and Connective Tissue Disorders: arthralgia, pain in extremity Blood and Lymphatic System Disorders: thymus hypertrophy Surgical and Medical Procedures: ear tube insertion Hypoglycemia was reported by 30 subjects (42%) at least once during their course of therapy.

Most cases of hypoglycemia were mild or moderate in severity. Five subjects had severe hypoglycemia (requiring assistance and treatment) on one or more occasions and 4 subjects experienced hypoglycemic seizures/loss of consciousness on one or more occasions. Of the 30 subjects reporting hypoglycemia, 14 (47%) had a history of hypoglycemia prior to treatment.

The frequency of hypoglycemia was highest in the first month of treatment, and episodes were more frequent in younger children. Symptomatic hypoglycemia was generally avoided when a meal or snack was consumed either shortly (i.e., 20 minutes) before or after the administration of INCRELEX. Tonsillar hypertrophy was noted in 11 (15%) subjects in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years.

Tonsillectomy or tonsillectomy/adenoidectomy was performed in 7 subjects; 3 of these had obstructive sleep apnea, which resolved after the procedure in all three cases. Intracranial hypertension occurred in three subjects. In two subjects the events resolved without interruption of INCRELEX treatment.

INCRELEX treatment was discontinued in the third subject and resumed later at a lower dose without recurrence. Mild elevations in the serum AST and LDH were found in a significant proportion of patients before and during treatment. Rise in levels of these serum enzymes did not lead to treatment discontinuation.

ALT elevations were occasionally noted during treatment. Renal and splenic lengths (measured by ultrasound) increased rapidly on INCRELEX treatment during the first years of therapy. This lengthening s… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS Pediatric Use: Safety and effectiveness has not been established in children less than 2 years of age. ( 8.4 )

8.1Pregnancy Risk Summary There are no available data on INCRELEX use in pregnant women. Exposure to INCRELEX during pregnancy is unlikely because the drug is not indicated for use after epiphyseal closure. In animal reproduction studies, there were no observed embryo-fetal development abnormalities with intravenous administration of INCRELEX to pregnant rats and rabbits during fetal organogenesis given at exposures up to 11 and 3 times the maximum recommended human dose (MRHD) of 0.24 mg/kg/day based on body surface area (BSA), respectively (see Data ) .

The estimated background risk of birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Studies to assess embryo-fetal toxicity evaluated the effects of INCRELEX during organogenesis in Sprague Dawley rats given 1, 4, and 16 mg/kg/day and in New Zealand White rabbits given 0.125, 0.5, and 2 mg/kg/day, administered intravenously.

There were no observed embryo-fetal developmental abnormalities in rats given up to 16 mg/kg/day (11 times the MRHD based on BSA comparison). In the rabbit study, the NOAEL for fetal toxicity was 0.5 mg/kg/day (approximately equivalent to the MRHD based on BSA) due to an increase in fetal death at 2 mg/kg. INCRELEX displayed no teratogenicity or maternal toxicity in rabbits given up to 2 mg/kg (3 times the MRHD based on BSA).

8.2Lactation Risk Summary There is no information available on the presence of mecasermin in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for INCRELEX and any potential adverse effects on the breast-fed child from INCRELEX or from the underlying maternal condition.

8.4Pediatric Use Toxicity (Gasping Syndrome) with Benzyl Alcohol Serious adverse reactions including fatal reactions and the "gasping syndrome" occurred in premature neonates and infants in the intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 mg/kg/day to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 mmol/L to 1.378 mmol/L). INCRELEX contains 9 mg/mL benzyl alcohol as a preservative.

Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. Use of INCRELEX in infants is not recommended [see Warnings and Precautions (5.8) ] .

Safety and effectiveness in pediatric patients below the age of 2 years of age have not been established.

8.5Geriatric Use The safety and effectiveness of INCRELEX in patients aged 65 and over has not been established.

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary There are no available data on INCRELEX use in pregnant women. Exposure to INCRELEX during pregnancy is unlikely because the drug is not indicated for use after epiphyseal closure. In animal reproduction studies, there were no observed embryo-fetal development abnormalities with intravenous administration of INCRELEX to pregnant rats and rabbits during fetal organogenesis given at exposures up to 11 and 3 times the maximum recommended human dose (MRHD) of 0.24 mg/kg/day based on body surface area (BSA), respectively (see Data ) .

The estimated background risk of birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Studies to assess embryo-fetal toxicity evaluated the effects of INCRELEX during organogenesis in Sprague Dawley rats given 1, 4, and 16 mg/kg/day and in New Zealand White rabbits given 0.125, 0.5, and 2 mg/kg/day, administered intravenously.

There were no observed embryo-fetal developmental abnormalities in rats given up to 16 mg/kg/day (11 times the MRHD based on BSA comparison). In the rabbit study, the NOAEL for fetal toxicity was 0.5 mg/kg/day (approximately equivalent to the MRHD based on BSA) due to an increase in fetal death at 2 mg/kg. INCRELEX displayed no teratogenicity or maternal toxicity in rabbits given up to 2 mg/kg (3 times the MRHD based on BSA).

🧒 Pediatric Use 163 words ▾

8.4Pediatric Use Toxicity (Gasping Syndrome) with Benzyl Alcohol Serious adverse reactions including fatal reactions and the "gasping syndrome" occurred in premature neonates and infants in the intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 mg/kg/day to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 mmol/L to 1.378 mmol/L). INCRELEX contains 9 mg/mL benzyl alcohol as a preservative.

Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. Use of INCRELEX in infants is not recommended [see Warnings and Precautions (5.8) ] .

Safety and effectiveness in pediatric patients below the age of 2 years of age have not been established.

🧓 Geriatric Use 19 words ▾

8.5Geriatric Use The safety and effectiveness of INCRELEX in patients aged 65 and over has not been established.

🆘 Overdosage 101 words ▾

10 OVERDOSAGE Treatment of acute overdose should be directed at reversing hypoglycemia. Oral glucose or food should be consumed. If the overdose results in loss of consciousness, intravenous glucose or parenteral glucagon may be required to reverse the hypoglycemic effects.

A small number of overdose cases have been reported in the post-marketing experience. In one case of acute overdose, a 3-year old patient experienced hypoglycemia after receiving one 4 mg dose of INCRELEX (a 10-fold increase beyond the prescribed dose). The event resolved following treatment with IV glucose.

Long term overdosage with INCRELEX may result in signs and symptoms of acromegaly.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Insulin-like growth factor-1 (IGF-1) is a key hormonal mediator on statural growth. Under normal circumstances, growth hormone (GH) binds to its receptor in the liver, and other tissues, and stimulates the synthesis/secretion of IGF-1. In target tissues, the Type 1 IGF-1 receptor, which is homologous to the insulin receptor, is activated by IGF-1, leading to intracellular signaling which stimulates multiple processes resulting in statural growth.

The metabolic actions of IGF-1 are in part directed at stimulating the uptake of glucose, fatty acids, and amino acids so that metabolism supports growing tissues.

12.2Pharmacodynamics The following actions have been demonstrated for endogenous human IGF-1: Tissue Growth – 1) Skeletal growth occurs at the cartilage growth plates of the epiphyses of bones where stem cells divide to produce new cartilage cells or chondrocytes. The growth of chondrocytes is under the control of IGF-1 and GH. The chondrocytes become calcified so that new bone is formed allowing the length of the bones to increase.

This results in skeletal growth until the cartilage growth plates fuse at the end of puberty. 2) Cell growth: IGF-1 receptors are present on most types of cells and tissues. IGF-1 has mitogenic activities that lead to an increased number of cells in the body.

3) Organ growth: Treatment of IGF-1 deficient rats with rhIGF-1 results in whole body and organ growth. Carbohydrate Metabolism –IGF-1 suppresses hepatic glucose production and stimulates peripheral glucose utilization and therefore has a hypoglycemic potential. IGF-1 has inhibitory effects on insulin secretion.

12.3Pharmacokinetics Absorption – The absolute bioavailability of rhIGF-1 after subcutaneous administration in healthy subjects is estimated to be close to 100%. However, the absolute bioavailability of INCRELEX given subcutaneously to subjects with primary insulin-like growth factor-1 deficiency (Primary IGFD) has not been determined. Distribution – In blood, IGF-1 is bound to six IGF binding proteins, with > 80% bound as a complex with IGFBP-3 and an acid-labile subunit.

IGFBP-3 is greatly reduced in subjects with severe Primary IGFD, resulting in increased clearance of IGF-1 in these subjects relative to healthy subjects. The total IGF-1 volume of distribution after subcutaneous administration in subjects with severe Primary IGFD is estimated to be 0.257 (± 0.073) L/kg at an INCRELEX dose of 0.045 mg/kg and is estimated to increase as the dose of INCRELEX increases. Elimination – IGF-1 is metabolized by both liver and kidney.

The mean terminal t 1/2 after single subcutaneous administration of 0.12 mg/kg INCRELEX in pediatric subjects with severe Primary IGFD is estimated to be 5.8 hours. Clearance of INCRELEX is inversely proportional to IGF binding protein-3 (IGFBP-3) levels. CL/F is estimated to be

0.04L/hr/kg at 0.5 micrograms/mL of IGFBP-3, and

0.01L/hr/kg at 3 micrograms/mL IGFBP-3; the latter is the median IGFBP-3 in subjects with normal IGF-1 serum levels. Gender – In children with Primary IGFD there were no apparent differences between males and females in the pharmacokinetics of INCRELEX. Race –The effect of race on pharmacokinetics of INCRELEX has not been studied.

Table 1. Summary of INCRELEX Single-Dose Pharmacokinetic Parameters in Children with Severe Primary IGFD (0.12 mg/kg, SC) C max (ng/mL) T max (hr) AUC 0-8 (hr*ng/mL) t 1/2 (hr) Vd/F (L/kg) CL/F (L/hr/kg) n 3 3 3 3 12 Data represents 3 subjects each at doses 0.015, 0.03, 0.06, and 0.12 mg/kg SC. 12 C max = maximum concentration; T max = time of maximum concentration; AUC 0-8 = area under the curve; t 1/2 = half-life; Vd/F = apparent volume of distribution; CL/F = apparent systemic clearance; SC = subcutaneous injection; CV% = coefficient of variation in %.

Male/female data combined, ages 12 to 22 years. PK parameters based on baseline adjusted plasma concentrations. Mean 234 2 2932 5.8 0.257 0.0424 CV% 23 0… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 95 words ▾

12.1Mechanism of Action Insulin-like growth factor-1 (IGF-1) is a key hormonal mediator on statural growth. Under normal circumstances, growth hormone (GH) binds to its receptor in the liver, and other tissues, and stimulates the synthesis/secretion of IGF-1. In target tissues, the Type 1 IGF-1 receptor, which is homologous to the insulin receptor, is activated by IGF-1, leading to intracellular signaling which stimulates multiple processes resulting in statural growth.

The metabolic actions of IGF-1 are in part directed at stimulating the uptake of glucose, fatty acids, and amino acids so that metabolism supports growing tissues.

📦 How Supplied / Storage and Handling 126 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied INCRELEX injection is supplied as a 40 mg/4 mL (10 mg/mL) sterile, clear, and colorless solution in multiple-dose glass vials (NDC-15054-1040-5). Storage and Handling Before Opening – Vials of INCRELEX are stable when refrigerated at 2º to 8ºC (36º to 46ºF). Avoid freezing the vials of INCRELEX.

Protect from direct light. Expiration dates are stated on the labels. After Opening – Vials of INCRELEX are stable for 30 days after initial vial entry when stored refrigerated at 2º to 8ºC (36º to 46ºF).

Avoid freezing the vials of INCRELEX. Protect from direct light. INCRELEX should not be used after its expiration date.

Keep refrigerated and use within 30 days of initial vial entry. Remaining unused material should be discarded.

📦 Storage and Handling 193 words ▾

Storage and Handling Before Opening – Vials of INCRELEX are stable when refrigerated at 2º to 8ºC (36º to 46ºF). Avoid freezing the vials of INCRELEX. Protect from direct light.

Expiration dates are stated on the labels. After Opening – Vials of INCRELEX are stable for 30 days after initial vial entry when stored refrigerated at 2º to 8ºC (36º to 46ºF). Avoid freezing the vials of INCRELEX.

Protect from direct light. INCRELEX should not be used after its expiration date. Keep refrigerated and use within 30 days of initial vial entry.

Remaining unused material should be discarded.

Before Opening – Vials of INCRELEX are stable when refrigerated at 2º to 8ºC (36º to 46ºF). Avoid freezing the vials of INCRELEX. Protect from direct light. Expiration dates are stated on the labels.

After Opening – Vials of INCRELEX are stable for 30 days after initial vial entry when stored refrigerated at 2º to 8ºC (36º to 46ºF). Avoid freezing the vials of INCRELEX. Protect from direct light. INCRELEX should not be used after its expiration date. Keep refrigerated and use within 30 days of initial vial entry. Remaining unused material should be discarded.

📋 Description 145 words ▾

11 DESCRIPTION Mecasermin is a human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology. IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. The amino acid sequence of the product is identical to that of endogenous human IGF-1.

The rhIGF-1 protein is synthesized in bacteria ( E. coli ) that have been modified by the addition of the gene for human IGF-1. INCRELEX (mecasermin) injection is a sterile, aqueous, clear and colorless solution intended for subcutaneous injection. Each multiple-dose vial of INCRELEX contains 40 mg of mecasermin in 4 mL solution, and each mL contains 10 mg mecasermin, 9 mg benzyl alcohol, 0.43 mg glacial acetic acid, 2 mg polysorbate 20, 3.51 mg sodium acetate, and 5.84 mg sodium chloride in Water for Injection, USP at a pH of approximately 5.4.

💬 Information for Patients 199 words ▾

17 PATIENT COUNSELING INFORMATION Advise patients and/or caregivers to read the FDA-approved patient labeling (Patient Information) and Instructions for Use. Counsel patients and/or parents that there have been occurrences of malignant neoplasia observed among pediatric patients who received treatment with INCRELEX. Instruct patients and/or parents to monitor for development of any new growth or symptoms of cancer and to report it immediately.

Instruct patients and/or caregivers in the proper administration of INCRELEX. Give INCRELEX shortly before or after (20 minutes on either side of) a meal or snack. Do not give INCRELEX when the meal or snack is omitted.

Do not increase the dose of INCRELEX to make up for one or more omitted doses. INCRELEX therapy will be initiated at a low dose and the dose should be increased only if no hypoglycemia episodes have occurred after at least 7 days of dosing. Educate patients and caregivers on how to recognize the signs and symptoms of hypoglycemia.

Educate patients and caregivers on the identification of signs and symptoms of serious allergic reactions to INCRELEX and the need to seek prompt medical contact should such a reaction occur. Instruct patients and caregivers to discontinue INCRELEX if a reaction occurs.

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Absorption – The absolute bioavailability of rhIGF-1 after subcutaneous administration in healthy subjects is estimated to be close to 100%. However, the absolute bioavailability of INCRELEX given subcutaneously to subjects with primary insulin-like growth factor-1 deficiency (Primary IGFD) has not been determined. Distribution – In blood, IGF-1 is bound to six IGF binding proteins, with > 80% bound as a complex with IGFBP-3 and an acid-labile subunit.

IGFBP-3 is greatly reduced in subjects with severe Primary IGFD, resulting in increased clearance of IGF-1 in these subjects relative to healthy subjects. The total IGF-1 volume of distribution after subcutaneous administration in subjects with severe Primary IGFD is estimated to be 0.257 (± 0.073) L/kg at an INCRELEX dose of 0.045 mg/kg and is estimated to increase as the dose of INCRELEX increases. Elimination – IGF-1 is metabolized by both liver and kidney.

The mean terminal t 1/2 after single subcutaneous administration of 0.12 mg/kg INCRELEX in pediatric subjects with severe Primary IGFD is estimated to be 5.8 hours. Clearance of INCRELEX is inversely proportional to IGF binding protein-3 (IGFBP-3) levels. CL/F is estimated to be

0.04L/hr/kg at 0.5 micrograms/mL of IGFBP-3, and

0.01L/hr/kg at 3 micrograms/mL IGFBP-3; the latter is the median IGFBP-3 in subjects with normal IGF-1 serum levels. Gender – In children with Primary IGFD there were no apparent differences between males and females in the pharmacokinetics of INCRELEX. Race –The effect of race on pharmacokinetics of INCRELEX has not been studied.

Table 1. Summary of INCRELEX Single-Dose Pharmacokinetic Parameters in Children with Severe Primary IGFD (0.12 mg/kg, SC) C max (ng/mL) T max (hr) AUC 0-8 (hr*ng/mL) t 1/2 (hr) Vd/F (L/kg) CL/F (L/hr/kg) n 3 3 3 3 12 Data represents 3 subjects each at doses 0.015, 0.03, 0.06, and 0.12 mg/kg SC. 12 C max = maximum concentration; T max = time of maximum concentration; AUC 0-8 = area under the curve; t 1/2 = half-life; Vd/F = apparent volume of distribution; CL/F = apparent systemic clearance; SC = subcutaneous injection; CV% = coefficient of variation in %.

Male/female data combined, ages 12 to 22 years. PK parameters based on baseline adjusted plasma concentrations. Mean 234 2 2932 5.8 0.257 0.0424 CV% 23 0 50 64 28 38 Figure 1.

Mean Total IGF-1 Concentration after a Single Subcutaneous Dose of INCRELEX in Children with Severe Primary IGFD (0.06 mg/kg and 0.12 mg/kg, n=3 per group) Figure 1 Renal impairment – No studies have been conducted in Primary IGFD children with renal impairment. Hepatic impairment – No studies have been conducted to determine the effect of hepatic impairment on the pharmacokinetics of rhIGF-1 in Primary IGFD children with hepatic impairment.

🧬 Pharmacodynamics 157 words ▾

12.2Pharmacodynamics The following actions have been demonstrated for endogenous human IGF-1: Tissue Growth – 1) Skeletal growth occurs at the cartilage growth plates of the epiphyses of bones where stem cells divide to produce new cartilage cells or chondrocytes. The growth of chondrocytes is under the control of IGF-1 and GH. The chondrocytes become calcified so that new bone is formed allowing the length of the bones to increase.

This results in skeletal growth until the cartilage growth plates fuse at the end of puberty. 2) Cell growth: IGF-1 receptors are present on most types of cells and tissues. IGF-1 has mitogenic activities that lead to an increased number of cells in the body.

3) Organ growth: Treatment of IGF-1 deficient rats with rhIGF-1 results in whole body and organ growth. Carbohydrate Metabolism –IGF-1 suppresses hepatic glucose production and stimulates peripheral glucose utilization and therefore has a hypoglycemic potential. IGF-1 has inhibitory effects on insulin secretion.

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES

14.1Effects of INCRELEX Treatment in Children with Severe Primary Insulin-like Growth Factor-1 Deficiency (Severe Primary IGFD) Five clinical studies (four open-label and one double-blind, placebo-controlled), with subcutaneous doses of INCRELEX generally ranging from 0.06 to 0.12 mg/kg (60 to 120 micrograms/kg) administered twice daily, were conducted in 71 pediatric subjects with severe Primary IGFD. Patients were enrolled in the trials on the basis of extreme short stature, slow growth rates, low IGF-1 serum concentrations, and normal growth hormone secretion.

Data from these 5 clinical studies were pooled for a global efficacy and safety analysis. Baseline characteristics for the patients evaluated in the primary and secondary efficacy analyses were (mean, SD): chronological age (years): 6.7 ± 3.8; height (cm): 84.8 ± 15.3 cm; height standard deviation score (SDS): -6.7 ± 1.8; height velocity (cm/yr): 2.8 ± 1.8; height velocity SDS: -3.3 ± 1.7; IGF-1 (ng/mL): 21.6 ± 20.6; IGF-1 SDS: -4.3 ± 1.6; and bone age (years): 4.2 ± 2.8. Sixty-one subjects had at least one year of treatment.

Fifty-three (87%) had Laron Syndrome; 7 (11%) had GH gene deletion, and 1 (2%) had neutralizing antibodies to GH. Thirty-seven (61%) of the subjects were male; forty-eight (79%) were Caucasian. Fifty-six (92%) of the subjects were pre-pubertal at baseline.

Annual results for height velocity, height velocity SDS, and height SDS are shown in Table 2. Pre-treatment height velocity data were available for 58 subjects. The height velocities at a given year of treatment were compared by paired t-tests to the pre-treatment height velocities of the same subjects completing that treatment year.

Table 2: Annual Height Results by Number of Years Treated with INCRELEX Pre-Tx Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Pre-Tx = Pre-treatment; SD = Standard Deviation; SDS = Standard Deviation Score Height Velocity (cm/yr) N 58 58 48 38 23 21 20 16 13 Mean (SD) 2.8 (1.8) 8.0 (2.2) 5.8 (1.5) 5.5 (1.8) 4.7 (1.6) 4.7 (1.6) 4.8 (1.5) 4.6 (1.5) 4.3 (1.1) Mean (SD) for change from pre-treatment +5.2 (2.6) +2.9 (2.4) +2.3 (2.4) +1.5 (2.2) +1.5 (1.8) +1.5 (1.7) +1.0 (2.1) +0.7 (2.5) P-value for change from pre-treatment P-values for comparison versus pre-treatment values are computed using paired t-tests. <0.0001 <0.0001 <0.0001 0.0045 0.0015 0.0009 0.0897 0.3059 Height Velocity SDS N 58 58 47 37 22 19 18 15 11 Mean (SD) -3.3 (1.7) 1.9 (3.0) -0.2 (1.6) -0.2 (2.0) -0.7 (2.1) -0.6 (2.1) -0.4 (1.4) -0.4 (1.9) -0.4 (1.9) Mean (SD) for change from pre-treatment +5.2 (3.1) +3.1 (2.3) +2.9 (2.3) +2.2 (2.2) +2.5 (2.2) +2.7 (1.7) +2.5 (2.1) +2.7 (2.8) Height SDS N 61 61 51 40 24 21 20 16 13 Mean (SD) -6.7 (1.8) -5.9 (1.8) -5.6 (1.8) -5.4 (1.8) -5.5 (1.9) -5.6 (1.8) -5.4 (1.8) -5.2 (2.0) -5.2 (2.0) Mean (SD) for change from pre-treatment +0.8 (0.5) +1.2 (0.8) +1.4 (1.1) +1.3 (1.2) +1.4 (1.3) +1.4 (1.2) +1.4 (1.1) +1.5 (1.1) Forty-nine subjects were included in an analysis of the effects of INCRELEX on bone age advancement.

The mean ± SD change in chronological age was 4.9 ± 3.4 years and the mean ± SD change in bone age was 5.3 ± 3.4 years.

🧪 Nonclinical Toxicology 207 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis : INCRELEX was tumorigenic in rats in a study using doses of 0, 0.25, 1, 4, and 10 mg/kg/day by subcutaneous injection for up to 2 years. The incidence of adrenal medullary hyperplasia and pheochromocytoma increased in male rats given ≥1 mg/kg/day (below clinical exposure at the maximum recommended human dose [MRHD] based on AUC) and in female rats at all dose levels (below clinical exposure at the MRHD based on AUC). The incidence of keratoacanthoma in the skin increased in male rats given 4 and 10 mg/kg/day (approximately the clinical exposure at the MRHD based on AUC).

The incidence of mammary gland carcinoma in male rats increased in animals treated with 10 mg/kg/day (3 times the MRHD based on AUC). Only doses that exceeded the maximum tolerated dose (MTD) (based on excess mortality secondary to IGF-1 induced hypoglycemia) caused skin and mammary tumors. Mutagenesis : INCRELEX was not clastogenic in the in vitro chromosome aberration assay and the in vivo mouse micronucleus assay.

Impairment of fertility : INCRELEX had no effects on fertility in rats using intravenous doses 0.25, 1, and 4 mg/kg/day (up to 3 times the clinical exposure at the MRHD based on BSA).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 204 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis : INCRELEX was tumorigenic in rats in a study using doses of 0, 0.25, 1, 4, and 10 mg/kg/day by subcutaneous injection for up to 2 years. The incidence of adrenal medullary hyperplasia and pheochromocytoma increased in male rats given ≥1 mg/kg/day (below clinical exposure at the maximum recommended human dose [MRHD] based on AUC) and in female rats at all dose levels (below clinical exposure at the MRHD based on AUC). The incidence of keratoacanthoma in the skin increased in male rats given 4 and 10 mg/kg/day (approximately the clinical exposure at the MRHD based on AUC).

The incidence of mammary gland carcinoma in male rats increased in animals treated with 10 mg/kg/day (3 times the MRHD based on AUC). Only doses that exceeded the maximum tolerated dose (MTD) (based on excess mortality secondary to IGF-1 induced hypoglycemia) caused skin and mammary tumors. Mutagenesis : INCRELEX was not clastogenic in the in vitro chromosome aberration assay and the in vivo mouse micronucleus assay.

Impairment of fertility : INCRELEX had no effects on fertility in rats using intravenous doses 0.25, 1, and 4 mg/kg/day (up to 3 times the clinical exposure at the MRHD based on BSA).

📄 Patient Package Insert ~3 min read ▾

This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 07/2025 PATIENT INFORMATION INCRELEX ® (EENK-RUH-LEX) (mecasermin) injection for subcutaneous use Read the Patient Information that comes with INCRELEX before your child starts receiving INCRELEX and each time your child gets a refill. There may be new information.

This Patient Information leaflet does not take the place of talking with your child's doctor about your child's medical condition or treatment. What is INCRELEX? INCRELEX is a liquid that contains man-made insulin-like growth factor-1 (IGF-1).

INCRELEX is used to treat children who are very short for their age because their bodies do not make enough IGF-1. This condition is called primary IGF-1 deficiency. IGF-1 should not be used instead of growth hormone.

It is not known if INCRELEX is safe and effective in children under 2 years of age. Who should not receive INCRELEX? Your child should not receive INCRELEX if your child: is allergic to mecasermin or any of the ingredients in INCRELEX.

See the end of this Patient Information leaflet for a complete list of ingredients in INCRELEX. Check with your child's doctor if you are not sure. has finished growing (the bone growth plates are closed). has any cancerous tumors or growths; or has a history of cancer or a condition that increases the risk of cancer. Your child should never receive INCRELEX through a vein.

What should I tell my child's doctor before my child starts receiving INCRELEX? Tell your child's doctor about all of your child's medical conditions, including if your child: has diabetes. has a curved spine (scoliosis). is pregnant or you think your child might be pregnant. It is not known if INCRELEX can harm an unborn baby. is breastfeeding or plans to breastfeed.

Talk to your child's doctor about the best way for your child to feed her baby if she receives INCRELEX. Tell your child's doctor about all the medicines your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements . Especially tell your child's doctor if your child takes insulin or other anti-diabetes medicines.

A change in dose may be needed for these medicines. How should my child receive INCRELEX? Use INCRELEX exactly as prescribed for your child.

Your child's doctor or nurse should teach you how to inject INCRELEX. Do not give your child INCRELEX unless you understand all of the instructions. See the " Instructions for Use " at the end of this Patient Information leaflet.

Inject INCRELEX under your child's skin 20 minutes before or 20 minutes after a meal or snack. Skip your child's dose of INCRELEX if your child cannot eat for any reason. Do not give your child an extra dose of INCRELEX or increase the amount of your child's dose to make up for a missed dose.

What are the possible side effects of INCRELEX? INCRELEX may cause serious side effects, including: Low blood sugar (hypoglycemia) . INCRELEX may lower blood sugar levels.

It is important to only give your child INCRELEX 20 minutes before or 20 minutes after a meal or snack to reduce the chances of low blood sugar. Do not give your child INCRELEX if your child cannot eat. Signs of low blood sugar include: dizziness tiredness restlessness hunger irritability trouble concentrating sweating nausea fast or irregular heartbeat Severe hypoglycemia may cause unconsciousness, seizures, or death.

If your child receives INCRELEX, they should avoid participating in high risk activities (e.g. driving, exercise, etc.) within 2 to 3 hours after the INCRELEX injection, especially at the beginning of INCRELEX treatment. Before beginning treatment with INCRELEX your child's doctor or nurse will explain to you how to treat hypoglycemia. Your child should always have a source of sugar such as orange juice, glucose gel, candy, or milk available in case symptoms of hypoglycemia happen.

For severe hypoglycemia, if your child is not responsive and cannot drink sugar-containi… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE INCRELEX ® (EENK-RUH-LEX) (mecasermin) injection for subcutaneous use Read this Instructions for Use before you start using INCRELEX and each time you get a refill. There may be new information. This information does not take the place of talking to your child's doctor about your child's medical condition or treatment.

Do not share your child's needles and syringes with another person. Your child may give another person an infection or your child could get an infection from them. Important : Inject INCRELEX exactly as your child's doctor or nurse has shown you.

Follow your doctor's instructions for the type of syringe and needle to use to prepare and inject your child's dose of INCRELEX . Always use a new, unopened needle and syringe for each injection. Only use single-use, disposable needles and syringes.

Never reuse disposable needles and syringes. Throw away used needles and syringes in a puncture-resistant, disposable sharps container as soon as you finish giving the injection. See step 5 " How should I throw away (dispose of) used needles and syringes? " at the end of these instructions.

Supplies needed to give the injection: 1 vial of INCRELEX 1 alcohol swab 1 gauze or cotton ball alcohol (to clean the skin at the injection site) 1 sharps container for throwing away (disposing of) used needles and syringes. See step 5 " How should I throw away (dispose of) used needles and syringes? " at the end of these instructions. Preparing the Dose: Wash your hands before getting INCRELEX ready for your child's injection.

Check the liquid to make sure it is clear and colorless. Do not use if it is cloudy or if you see particles. Check the expiration date printed on the label of the vial.

Do not use INCRELEX if the expiration date has passed. If you are using a new vial, remove the protective cap. Do not remove the rubber top (see Figure 1 ).

Figure 1: Remove the protective cap Wipe the rubber top on the vial with an alcohol swab (see Figure 2 ). Figure 2: Wipe rubber top with alcohol swab Before putting the needle into the vial, pull back on plunger to draw air into the syringe equal to the INCRELEX dose. Put the needle through the rubber top of the vial and push the plunger to inject air into the vial (see Figure 3 ).

Figure 3: Inject air into vial Leave the syringe in the vial and turn both upside down. Hold the syringe and vial firmly (see Figure 4 ). Figure 4: Prepare to withdraw liquid Make sure the tip of the needle is in the liquid (see Figure 5 ).

Pull the plunger to withdraw the correct dose into the syringe (see Figure 6 ). Figure 5: Tip in liquid Figure 6: Withdraw correct dose Before you take the needle out of the vial, check the syringe for air bubbles. If bubbles are in the syringe, hold the vial and syringe with needle straight up and tap the side of the syringe until the bubbles float to the top.

Push the bubbles out with the plunger and draw liquid back in until you have the correct dose (see Figure 7 ). Figure 7: Remove air bubbles and refill syringe Remove the needle from the vial. Do not let the needle touch anything.

You are now ready to inject (see Figure 8 ). Figure 8: Ready to inject Injecting the Dose: Inject INCRELEX exactly as your child's doctor or nurse has shown you. Do not give the INCRELEX injection if your child is unable to eat within 20 minutes before or after the injection .

1. Choose an injection site – upper arm, upper leg (thigh), buttocks, or stomach area (abdomen) (see below). The injection site should be changed (rotated) for each injection.

Upper arm Thigh Buttock Abdomen 2. Use alcohol to clean the skin where you are going to inject your child. The injection site should be dry before you inject.

Do not fan or blow on the cleaned skin. Do not touch the injection site again before giving the injection. 3.

Lightly pinch the skin. Insert the needle into the pinched skin as instructed by your child's doctor or nurse (see Figure A ). Release the pinched skin.

Figure A: Light… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 11 words ▾

Warning and Precautions, Slipped Capital Femoral Epiphysis ( 5.5 ) 05/2025

📄 Package Label / Principal Display Panel 36 words ▾

PRINCIPAL DISPLAY PANEL - 4 mL Vial Carton IPSEN Rx only increlex ® (mecasermin) injection 40 mg/4 mL (10 mg/mL) For subcutaneous use only 4 mL multiple-dose vial PRINCIPAL DISPLAY PANEL - 4 mL Vial Carton

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.
📅 Q1 2025 – Q3 2025 · 3 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
35
Units reimbursed last 4 qtrs
320
Gross reimbursed last 4 qtrs
$1.04M
Avg / prescription
$29,840.32
Avg / unit
$3,263.79
Latest quarter Q3 2025
0Rx
Fee-for-service vs managed care ⓘ
100% FFS
Fee-for-service · 35 Rx Managed care · 0 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 320 units · 1.6 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported 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: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported 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: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 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: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.61.6
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 New York 1.6 /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.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Increlex (this brand).

Top reported reactions

Headache68
Hypoglycaemia62
Vomiting44
Injection Site Pain41
Blood Glucose Decreased36
Pyrexia36
Tonsillar Hypertrophy36

Age at onset

Infant3
Child62
Adolescent43
Adult11

Reporter sex

809 reports
Male · 66%
Female · 34%

Serious outcomes

Hospitalization219
Death24
Life-threatening22
Disabling6
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 45 10
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page it is currently marketed — but Ipsen Biopharmaceuticals, Inc. has reported a marketing end date of 2027-12-31, after which this package is expected to stop being marketed. The directory data on this page refreshes weekly.
Who lists this product with the FDA?
Ipsen Biopharmaceuticals, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J2170 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 15054-0530-06 · Ipsen 15054-1060-04 · Ipsen →
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.