Home › NDC Lookup › Ingredients › Insulin Aspart › 50090-4959-00
💉image loading
(from DailyMed)

.Insulin Aspart Protamine and Insulin 100 [iU]/mL Injection, Suspension — NDC 50090-4959-0 (Billing 50090-4959-00)

by A-S Medication Solutions · 5 SYRINGE, PLASTIC in 1 CARTON / 3 mL in 1 SYRINGE, PLASTIC

This is a package of .Insulin Aspart Protamine and Insulin 100 [iU]/mL Injection, Suspension from A-S Medication Solutions, marketed since Sep 2002 and currently FDA-listed. It is this product's only package size.

NDC 50090-4959-00
🏷️ FDA NDC (as labeled) 50090-4959-0 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 →

This page is curated, coded, and maintained by

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 50090-4959-0 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
50090 labeler · 4959 product · 0 package
Package marketed since
Mar 12, 2020
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 5009049590 4
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 50090-4959-0
Product NDC 50090-4959
11-digit billing NDC 50090495900
NCPDP billing unit ML — per mL (volume)
RxCUI 847191
UNII D933668QVX
Application # BLA021172
SPL Set ID 14499781-b90e-47d5-a7de-006965439b94
Established class (EPC) Insulin Analog
Chemical class Insulin
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2002-09-11
Route SUBCUTANEOUS
Dosage form INJECTION, SUSPENSION
Substance INSULIN ASPART
Biologic (Purple Book) 351(a)

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

GCN Seq No 050134
GCN 17075
HICL code 023400
Ingredient (HICL) Insulin Aspart Prot/Insuln Asp
HIC1 code C
Therapeutic class — broad (HIC1) Electrolyte Balance/Metabolism/Nutrition
HIC2 code C4
Therapeutic class — intermediate (HIC2) Antihyperglycemics
HIC3 code C4G
Therapeutic class — specific (HIC3) Insulins
AHFS code 68:20.08.00
AHFS class Insulins
FDB label name INSULIN ASPART PRO MIX70-30 PN
FDB brand name Insulin Aspart Prot Mix 70-30
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 050134
  • GCN: 17075
  • HICL (First Databank): 023400
  • AHFS class code: 68:20.08.00
  • RxCUI (RxNorm): 847191
Why two NDCs? The FDA registers this code as 50090-4959-0 — 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 → 50090-4959-00. 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.

Clinical

Label name INSULIN ASPART PRO MIX70-30 PN Ingredient Insulin Aspart Prot/Insuln Asp
1
Nutrient depletion considerations

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

🧪 Full Insulin Aspart 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 Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
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
50090-4959-00 You're viewing this Main listing 5 SYRINGE, PLASTIC in 1 CARTON / 3 mL in 1 SYRINGE, PLASTIC 2020-03-12 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
NovoLog Mix 70/30 100 [iU]/mL 00169-3685-12 Novo 1 vial $6.929 — Availability likely —
Insulin Aspart Protamine and Insulin Aspart Mix 70/30 100 [iU]/mL 73070-0200-11 Novo 1 vial $6.955 — Availability likely —
Fiasp 100 [iU]/mL 00169-3206-15 Novo 5 cartridges $8.569 — Availability likely —
Insulin Aspart Protamine and Insulin Aspart Mix 70/30 100 [iU]/mL 73070-0203-15 Novo 5 syringes $8.935 — Availability likely —
NovoLog Mix 70/30 100 [iU]/mL 00169-3696-19 Novo 5 syringes $8.937 — Availability likely —
NovoLog Mix 70/30 100 [iU]/mL 00169-2201-25 Novo 5 syringes — — FDA listed —
NovoLog Mix 70/30 100 [iU]/mL 50090-2272-00 A-S 5 syringes — — FDA listed —
Novolog Mix 70/30 100 [iU]/mL 50090-4085-00 A-S 5 syringes — — Discontinued —
.Insulin Aspart Protamine and Insulin Aspart 100 [iU]/mLthis 50090-4959-00 A-S 5 syringes — — FDA listed —
NovoLog Mix 70/30 100 [iU]/mL 70518-2119-00 REMEDYREPACK 5 syringes — — FDA listed —
Insulin Aspart Protamine and Insulin Aspart Mix 70/30 100 [iU]/mL 70518-3236-00 REMEDYREPACK 5 syringes — — FDA listed —
NovoLog Mix 70/30 100 [iU]/mL 00169-2200-11 Novo 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

🏛️
2000
First FDA approval
Jun 2000
📍
2026
Currently FDA-listed
26 years listed
🔓
2026
Biosimilars listed
2 FDA-licensed
🧬FDA-licensed biosimilars listed

1 biosimilar and 1 interchangeable are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Fiaspinsulin aspart Novologinsulin aspart
Interchangeable 1
Kirstyinsulin aspart-xjhz
Biosimilars 1
Meriloginsulin aspart-szjj
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.

  • 16 mg / 1 mL UNII PDC6A3C0OX
    Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
  • 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.
  • 1.72 mg / 1 mL UNII GGO4Y809LO
    Metacresol is a preservative derived from coal tar or petroleum. It prevents bacterial and fungal growth in liquid medicines, helping keep the product safe and stable during storage.
  • 1.5 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.
  • 0.32 mg / 1 mL UNII 0DE9724IHC
    Protamine sulfate is a protein derived from fish sperm that acts as a binder and stabilizer in medications. It helps hold tablet ingredients together and can improve the stability of certain drug formulations.
  • 0.877 mg / 1 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 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.
  • 1.25 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.
  • 19.6 ug / 1 mL UNII J41CSQ7QDS
    A mineral element that strengthens tablet structure and acts as a processing aid. Zinc helps bind ingredients together and may improve the medicine's stability during manufacturing and storage.

9 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

LabelerA-S Medication Solutions
FDA applicationBLA021172 (BLA)
Labeler code50090
First marketedSep 2002
Product typeHuman Prescription Drug
Portfolio2,811 products on file

More NDCs from A-S Medication Solutions labeler code 50090

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 🔄 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 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 156 words ▾

1 INDICATIONS AND USAGE Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is a mixture of insulin aspart protamine and insulin aspart indicated to improve glycemic control in adult patients with diabetes mellitus. Limitations of Use: • Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is not recommended for the treatment of diabetic ketoacidosis. • The proportions of rapid-acting and long-acting insulins in Insulin Aspart Protamine and Insulin Aspart Mix 70/30 are fixed and do not allow for basal versus prandial dose adjustments.

Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is a mixture of insulin aspart protamine, an intermediate-acting human insulin analog, and insulin aspart, a rapid-acting human insulin analog, indicated to improve glycemic control in adult patients with diabetes mellitus. Limitations of Use: • Not recommended for the treatment of diabetic ketoacidosis. • The proportions of rapid-acting and long-acting insulins are fixed and do not allow for basal versus prandial dose adjustments (1) .

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Inspect visually before use. Appearance should be uniformly white and cloudy. Do not use it if it looks clear or if it contains solid particles ( 2.1 ). • Insulin Aspart Protamine and Insulin Aspart Mix 70/30 must be resuspended immediately before use.

Resuspension is easier when the insulin has reached room temperature ( 2.1 ). • Inject Insulin Aspart Protamine and Insulin Aspart Mix 70/30 subcutaneously in the abdominal region, buttocks, thigh, or upper arm (2.1). • Administer the dose within 15 minutes before meal initiation. For patients with type 2 diabetes, the dose may also be given after meal initiation ( 2.1 ). • Rotate injection sites within the same region from one injection to the next to reduce risk of lipodystrophy and localized cutaneous amyloidosis (2.1) . • Do not administer intravenously or use in insulin infusion pumps ( 2.1 ). • Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is typically dosed twice-daily (with each dose intended to cover 2 meals or a meal and a snack) (2.2) . • Individualize dosage based on metabolic needs, blood glucose monitoring results, glycemic control goal ( 2.2 ). • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness ( 2.2 ). • When switching from another insulin to Insulin Aspart Protamine and Insulin Aspart Mix 70/30, a different dosage of Insulin Aspart Protamine and Insulin Aspart Mix 70/30 may be needed ( 2.2 ).

2.1Important Preparation and Administration Instructions • Always check insulin labels before administration. This product is NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart) [see Warnings and Precautions ( 5.4 )] . • Inspect Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) visually before use. It should appear uniformly white and cloudy.

Do not use it if it looks clear or if it contains solid particles. • Insulin Aspart Protamine and Insulin Aspart must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature. • When using the: o Vial, roll the vial gently in hands in a horizontal position 10 times until the suspension appears uniformly white and cloudy. Inject immediately. o Insulin Aspart Protamine and Insulin Aspart FlexPen, roll Insulin Aspart Protamine and Insulin Aspart FlexPen gently between hands in a horizontal position 10 times.

Then, turn Insulin Aspart Protamine and Insulin Aspart FlexPen upside down so that the glass ball moves from one end of the reservoir to the other 10 times until the suspension appears uniformly white and cloudy. Inject immediately. • The Insulin Aspart Protamine and Insulin Aspart FlexPen dials in 1-unit increments. • Use Insulin Aspart Protamine and Insulin Aspart FlexPen with caution in patients with visual impairment who may rely on audible clicks to dial their dose. • Inject Insulin Aspart Protamine and Insulin Aspart subcutaneously in the abdominal region, buttocks, thigh, or upper arm. • Administer the dose within 15 minutes before meal initiation.

For patients with type 2 diabetes, the dose may also be given after meal initiation. • Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 , 6.3 )] . • Do not administer Insulin Aspart Protamine and Insulin Aspart intravenously or use in insulin infusion pumps. • Do not mix Insulin Aspart Protamine and Insulin Aspart with any other insulins.

2.2Dosage Recommendations • Insulin Aspart Protamine and Insulin Aspart is typically dosed twice-daily (with each dose intended to cover 2 meals or a meal and a snack). • Individualize… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 89 words ▾

3 DOSAGE FORMS AND STRENGTHS Injectable suspension: 100 units/mL (U-100) of Insulin Aspart Protamine and Insulin Aspart Mix 70/30, 70% insulin aspart protamine and 30% insulin aspart, is a white and cloudy suspension available as: • 10 mL multiple-dose vial • 3 mL single-patient-use FlexPen prefilled pen Injectable suspension: 100 units/mL (U-100) of Insulin Aspart Protamine and Insulin Aspart Mix 70/30, 70% insulin aspart protamine and 30% insulin aspart available as: • 10 mL multiple-dose vial ( 3 ) • 3 mL single-patient-use FlexPen prefilled pen ( 3 )

⛔ Contraindications 84 words ▾

4 CONTRAINDICATIONS Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is contraindicated: • During episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )] • In patients with hypersensitivity to Insulin Aspart Protamine and Insulin Aspart Mix 70/30 or one of its excipients [see Warnings and Precautions ( 5.5 )] • Do not use during episodes of hypoglycemia (4) . • Do not use in patients with hypersensitivity to Insulin Aspart Protamine and Insulin Aspart Mix 70/30 or one of its excipients (4) .

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Never share a Insulin Aspart Protamine and Insulin Aspart Mix 70/30 FlexPen between patients, even if the needle is changed (5.1) . • Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring (5.2) . • Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, concomitantly administered glucose lowering medications, meal pattern, physical activity; and in patients with renal or hepatic impairments and hypoglycemia unawareness (5.3) . • Medication Errors: Accidental mix-ups between insulin products can occur.

Instruct patients to check insulin labels before injection (5.4) . • Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur. Discontinue Insulin Aspart Protamine and Insulin Aspart Mix 70/30, treat, and monitor, if indicated (5.5) . • Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated (5.6) . • Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs) : Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs (5.7) .

5.1Never Share Insulin Aspart Protamine and Insulin Aspart Mix 70/30 FlexPen Between Patients Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) FlexPen should never be shared between patients, even if the needle is changed. Patients using Insulin Aspart Protamine and Insulin Aspart vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

5.2Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions ( 5.3) ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ( 6.1 , 6.3 )].

Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

5.3Hypoglycemia Hypoglycemia is the most common adverse reaction of all insulins, including Insulin Aspart Protamine and Insulin Aspart. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ( 7 )] , or in patients who experience recurrent hypoglycemia. Risk Factors for Hypoglycemia The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is hig… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere: • Hypoglycemia [see Warnings and Precautions ( 5.3 )] • Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )] • Hypersensitivity reactions [see Warnings and Precautions ( 5.5 )] • Hypokalemia [see Warnings and Precautions ( 5.6 )] Adverse reactions observed with insulin therapy include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash and pruritus (6) . To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Pharma, Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trial Experience Clinical trials are conducted under widely varying designs, therefore, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice. The data in: • Table 1 reflects the exposure of 55 patients with type 1 diabetes to Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) with a mean exposure duration of three months.

The mean age was 43 years old. Sixty-four percent were male and 100% were White. The mean body mass index (BMI) was 26.1 kg/m 2 .

The mean duration of diabetes was 15 years. • Table 2 reflects the exposure of 85 patients with type 2 diabetes to Insulin Aspart Protamine and Insulin Aspart with a mean exposure duration of three months. The mean age was 63 years old. Fifty-four percent were male and 100% were White.

The mean body mass index (BMI) was 28.1 kg/m 2 . The mean duration of diabetes was 15 years. Common adverse reactions were defined as events that occurred in ≥5%, excluding hypoglycemia, of the population studied.

Common adverse reactions that occurred for Insulin Aspart Protamine and Insulin Aspart-treated patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively. The trial was a three-month, open-label trial in patients with type 1 or type 2 diabetes who were treated twice daily (before breakfast and before supper) with Insulin Aspart Protamine and Insulin Aspart. Table 1: Adverse Reactions that Occurred in ≥ 5% of Type 1 Diabetes Mellitus Adult Patients Treated with Insulin Aspart Protamine and Insulin Aspart Insulin Aspart Protamine and Insulin Aspart (n=55) Preferred Term N % Hypoglycemia 38 69 Headache 19 35 Influenza-like symptoms 7 13 Dyspepsia 5 9 Back pain 4 7 Diarrhea 4 7 Pharyngitis 4 7 Rhinitis 3 5 Skeletal pain 3 5 Upper respiratory tract infection 3 5 Table 2: Adverse Reactions that Occurred in ≥ 5% of Type 2 Diabetes Mellitus Adult Patients Treated with Insulin Aspart Protamine and Insulin Aspart Insulin Aspart Protamine and Insulin Aspart (n=85) Preferred Term N % Hypoglycemia 40 47 Upper respiratory tract infection 10 12 Headache 8 9 Diarrhea 7 8 Neuropathy 7 8 Pharyngitis 5 6 Abdominal pain 4 5 Rhinitis 4 5 Severe Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Insulin Aspart Protamine and Insulin Aspart.

The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for Insulin Aspart Protamine and Insulin Aspart with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice. Severe hypoglycemia requiring the assistance of another person and/or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with Insulin Aspart Protamine and Insulin Aspart.

The incidence of severe hypoglycemia in adult patients receiving subcutaneous I… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS The table below presents clinically significant drug interactions with Insulin Aspart Protamine and Insulin Aspart Mix 70/30 Table 3: Clinically Significant Drug Interactions with Insulin Aspart Protamine and Insulin Aspart Mix 70/30 Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Aspart Protamine and Insulin Aspart is concomitantly administered with these drugs.

Drugs that May Decrease the Blood Glucose Lowering Effect of Insulin Aspart Protamine and Insulin Aspart Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Aspart Protamine and Insulin Aspart is concomitantly administered with these drugs.

Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of Insulin Aspart Protamine and Insulin Aspart Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Aspart Protamine and Insulin Aspart is concomitantly administered with these drugs.

Drugs that May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine Intervention: Increased frequency of glucose monitoring may be required when Insulin Aspart Protamine and Insulin Aspart is concomitantly administered with these drugs. • Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics (7) . • Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones (7) . • Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine (7) . • Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine (7) .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are no available data with Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Available information from published randomized controlled trials with insulin aspart use during the second trimester of pregnancy have not reported an association with insulin aspart and major birth defects or adverse maternal or fetal outcomes [see Data] .

There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] . In animal reproduction studies, administration of subcutaneous insulin aspart to pregnant rats and rabbits during the period of organogenesis did not cause adverse developmental effects at exposures 8-times and equal to the human subcutaneous dose of 1 unit/kg/day, respectively. Pre- and post-implantation losses and visceral/skeletal abnormalities were seen at higher exposures, which are considered secondary to maternal hypoglycemia.

These effects were similar to those observed in rats administered regular human insulin [see Data] . The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA 1c >7% and has been reported to be as high as 20-25% in women with a HbA 1c >10%. The estimated background risk of 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. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.

Data Human Data Published data from 5 randomized controlled trials of 441 pregnant women with diabetes mellitus treated with insulin aspart during the late 2 nd trimester of pregnancy did not identify an association of insulin aspart with major birth defects or adverse maternal or fetal outcomes. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including a variable duration of treatment and small size of the majority of the trials. Animal Data Fertility, embryo-fetal and pre- and postnatal development studies have been performed with insulin aspart and regular human insulin in rats and rabbits.

In a combined fertility and embryo-fetal development study in rats, insulin aspart was administered before mating, during mating, and throughout pregnancy. Further, in a pre- and postnatal development study insulin aspart was given throughout pregnancy and during lactation to rats. In an embryo-fetal development study insulin aspart was given to female rabbits during organogenesis.

The effects of insulin aspart did not differ from those observed with subcutaneous regular human insulin. Insulin aspart, like human insulin, caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 units/kg/day (approximately 32 times the human subcutaneous dose of 1 unit/kg/day, based on human exposure equivalents) and in rabbits at a dose of 10 units/kg/day (approximately three times the human subcutaneous dose of 1 unit/kg/day, based on human exposure equivalents). No significant effects were observed in rats at a dose of 50 units/kg/day and in rabbits at a dose of 3 units/kg/day.

These doses are approximately 8 times the human subcutaneous dose of 1 unit/kg/day for rats and equal to the human subcutaneous dose of 1 unit/kg/day for rabbits, based on human exposure equivalents. The effects are considered secondary to maternal hypogly… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary There are no available data with Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Available information from published randomized controlled trials with insulin aspart use during the second trimester of pregnancy have not reported an association with insulin aspart and major birth defects or adverse maternal or fetal outcomes [see Data] .

There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] . In animal reproduction studies, administration of subcutaneous insulin aspart to pregnant rats and rabbits during the period of organogenesis did not cause adverse developmental effects at exposures 8-times and equal to the human subcutaneous dose of 1 unit/kg/day, respectively. Pre- and post-implantation losses and visceral/skeletal abnormalities were seen at higher exposures, which are considered secondary to maternal hypoglycemia.

These effects were similar to those observed in rats administered regular human insulin [see Data] . The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA 1c >7% and has been reported to be as high as 20-25% in women with a HbA 1c >10%. The estimated background risk of 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. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.

Data Human Data Published data from 5 randomized controlled trials of 441 pregnant women with diabetes mellitus treated with insulin aspart during the late 2 nd trimester of pregnancy did not identify an association of insulin aspart with major birth defects or adverse maternal or fetal outcomes. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including a variable duration of treatment and small size of the majority of the trials. Animal Data Fertility, embryo-fetal and pre- and postnatal development studies have been performed with insulin aspart and regular human insulin in rats and rabbits.

In a combined fertility and embryo-fetal development study in rats, insulin aspart was administered before mating, during mating, and throughout pregnancy. Further, in a pre- and postnatal development study insulin aspart was given throughout pregnancy and during lactation to rats. In an embryo-fetal development study insulin aspart was given to female rabbits during organogenesis.

The effects of insulin aspart did not differ from those observed with subcutaneous regular human insulin. Insulin aspart, like human insulin, caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 units/kg/day (approximately 32 times the human subcutaneous dose of 1 unit/kg/day, based on human exposure equivalents) and in rabbits at a dose of 10 units/kg/day (approximately three times the human subcutaneous dose of 1 unit/kg/day, based on human exposure equivalents). No significant effects were observed in rats at a dose of 50 units/kg/day and in rabbits at a dose of 3 units/kg/day.

These doses are approximately 8 times the human subcutaneous dose of 1 unit/kg/day for rats and equal to the human subcutaneous dose of 1 unit/kg/day for rabbits, based on human exposure equivalents. The effects are considered secondary to maternal hypoglycemia.

🧒 Pediatric Use 23 words ▾

8.4Pediatric Use Safety and effectiveness of Insulin Aspart Protamine and Insulin Aspart have not been established in pediatric patients with diabetes mellitus.

🧓 Geriatric Use 59 words ▾

8.5Geriatric Use Clinical studies of Insulin Aspart Protamine and Insulin Aspart did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger adult patients. In geriatric patients with diabetes, the initial dosing, dose increments should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in geriatric patients.

🆘 Overdosage 81 words ▾

10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.3 , 5.6)] . Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise, may be needed.

More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The primary activity of insulin, including Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) is the regulation of glucose metabolism. Insulin and its analog lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.

12.2Pharmacodynamics A euglycemic clamp study described below assessed glucose utilization after subcutaneous dosing of Insulin Aspart Protamine and Insulin Aspart in healthy subjects (n = 24). Following a 0.3 units/kg single subcutaneous dose of Insulin Aspart Protamine and Insulin Aspart, the onset of action is between 10-20 minutes and the mean ± SD time to peak activity is 2.7 hr ± 0.9 hr. The duration of action may be as long as 24 hours (see Figure 2).

Figure 2. Pharmacodynamic Activity Profile of Insulin Aspart Protamine and Insulin Aspart in healthy subjects after a single 0.3 units/kg subcutaneous dose Figure 2

12.3Pharmacokinetics The single substitution of the amino acid proline with aspartic acid at position B28 in insulin aspart reduces the molecule’s tendency to form hexamers as observed with regular human insulin. The rapid absorption characteristics of insulin aspart are maintained by Insulin Aspart Protamine and Insulin Aspart. Absorption and Bioavailability The 30% insulin aspart in the soluble component of Insulin Aspart Protamine and Insulin Aspart is absorbed rapidly from the subcutaneous layer.

The remaining 70% is in crystalline form as insulin aspart protamine which has a prolonged absorption profile after subcutaneous injection. The relative bioavailability of Insulin Aspart Protamine and Insulin Aspart compared to insulin aspart indicates that the insulins are absorbed to similar extent. In a euglycemic clamp study in healthy subjects (n=24) after dosing with Insulin Aspart Protamine and Insulin Aspart (0.3 units/kg), a mean maximum serum concentration (C max ) of 61.3 ± 20.1 milliunits/L was reached after 85 minutes.

Serum insulin levels returned to baseline 16 to 20 hours after a subcutaneous dose of Insulin Aspart Protamine and Insulin Aspart (see Fig. 3 for pharmacokinetic profile). Figure 3.

Pharmacokinetic Profiles of Insulin Aspart Protamine and Insulin Aspart after a single 0.3 units/kg subcutaneous dose Distribution and Elimination Insulin aspart has a low binding affinity to plasma proteins (<10%), similar to that seen with regular human insulin. Figure 3

🧬 Mechanism of Action 67 words ▾

12.1Mechanism of Action The primary activity of insulin, including Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) is the regulation of glucose metabolism. Insulin and its analog lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.

📦 How Supplied / Storage and Handling 20 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-4959 NDC: 50090-4959-0 3 mL in a SYRINGE, PLASTIC / 5 in a CARTON

📋 Description 186 words ▾

11 DESCRIPTION Insulin aspart protamine and insulin aspart is a human insulin analog containing 70% insulin aspart protamine crystals and 30% soluble insulin aspart. Insulin aspart is homologous with regular human insulin with the exception of a single substitution of the amino acid proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (baker’s yeast). Insulin aspart has the empirical formula C 256 H 381 N 65 O 79 S 6 and a molecular weight of 5825.8 Da.

Figure 1. Structural formula of insulin aspart Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is a uniform, white and cloudy, sterile injectable suspension for subcutaneous use. Each mL contains 100 units of insulin aspart and the inactive ingredients: disodium hydrogen phosphate dihydrate (1.25 mg), glycerol (16.0 mg), metacresol (1.72 mg), phenol (1.50 mg), protamine sulfate (0.32 mg), sodium chloride (0.877 mg), zinc (19.6 mcg), and Water for Injection, USP.

Insulin Aspart Protamine and Insulin Aspart Mix 70/30 has a pH of 7.20 - 7.44. Hydrochloric acid or sodium hydroxide may be added to adjust pH. Molecular chain of insulin aspart.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Never Share an Insulin Aspart Protamine and Insulin Aspart Mix 70/30 FlexPen between Patients Advise patients that they must never share Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) FlexPen device with another person even if the needle is changed. Advise patients using Insulin Aspart Protamine and Insulin Aspart vials not to share needles or syringes with another person.

Sharing poses a risk for transmission of blood-borne pathogens [see Warnings and Precautions ( 5.1 )] . Hyperglycemia or Hypoglycemia Inform patients that hypoglycemia is the most common adverse reaction with insulin. Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of Insulin Aspart Protamine and Insulin Aspart therapy.

Instruct patients on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals. Instruct patients on the management of hypoglycemia [see Warnings and Precautions ( 5.3 )] . Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia.

Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery. Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions ( 5.2 )] . Hypoglycemia with Medication Errors Instruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions ( 5.4 )] .

Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with Insulin Aspart Protamine and Insulin Aspart. Inform patients of the symptoms of hypersensitivity reactions [see Warnings and Precautions ( 5.5 )] . Manufactured by: Novo Nordisk Inc.

800 Scudders Mill Road Plainsboro, NJ 08536 U.S. License Number 1261 Distributed by: Novo Nordisk Pharma, Inc. (Se habla español) 1-800-727-6500 Version: 4 Novo Nordisk ® , FlexPen ® , and Novolin ® are registered trademarks of Novo Nordisk ® A/S.

Patent Information: http://novonordisk-us.com/products/product-patents.html © 2023 Novo Nordisk

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics The single substitution of the amino acid proline with aspartic acid at position B28 in insulin aspart reduces the molecule’s tendency to form hexamers as observed with regular human insulin. The rapid absorption characteristics of insulin aspart are maintained by Insulin Aspart Protamine and Insulin Aspart. Absorption and Bioavailability The 30% insulin aspart in the soluble component of Insulin Aspart Protamine and Insulin Aspart is absorbed rapidly from the subcutaneous layer.

The remaining 70% is in crystalline form as insulin aspart protamine which has a prolonged absorption profile after subcutaneous injection. The relative bioavailability of Insulin Aspart Protamine and Insulin Aspart compared to insulin aspart indicates that the insulins are absorbed to similar extent. In a euglycemic clamp study in healthy subjects (n=24) after dosing with Insulin Aspart Protamine and Insulin Aspart (0.3 units/kg), a mean maximum serum concentration (C max ) of 61.3 ± 20.1 milliunits/L was reached after 85 minutes.

Serum insulin levels returned to baseline 16 to 20 hours after a subcutaneous dose of Insulin Aspart Protamine and Insulin Aspart (see Fig. 3 for pharmacokinetic profile). Figure 3.

Pharmacokinetic Profiles of Insulin Aspart Protamine and Insulin Aspart after a single 0.3 units/kg subcutaneous dose Distribution and Elimination Insulin aspart has a low binding affinity to plasma proteins (<10%), similar to that seen with regular human insulin. Figure 3

🧬 Pharmacodynamics 102 words ▾

12.2Pharmacodynamics A euglycemic clamp study described below assessed glucose utilization after subcutaneous dosing of Insulin Aspart Protamine and Insulin Aspart in healthy subjects (n = 24). Following a 0.3 units/kg single subcutaneous dose of Insulin Aspart Protamine and Insulin Aspart, the onset of action is between 10-20 minutes and the mean ± SD time to peak activity is 2.7 hr ± 0.9 hr. The duration of action may be as long as 24 hours (see Figure 2).

Figure 2. Pharmacodynamic Activity Profile of Insulin Aspart Protamine and Insulin Aspart in healthy subjects after a single 0.3 units/kg subcutaneous dose Figure 2

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Clinical Studies in Adult Patients with Type 1 and Type 2 Diabetes In a three-month, open-label trial, adult patients with type 1 (n=104) or type 2 (n=187) diabetes mellitus were treated twice daily (before breakfast and before supper) with Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) or Novolin 70/30. Patients had received insulin for at least 24 months before the study. Oral hypoglycemic agents were not allowed within 1 month prior to the study or during the study.

The small changes in HbA 1c were comparable across the treatment groups (see Table 4). For patients with type 1 diabetes mellitus (T1DM) the mean age was 43 years old, 64% were male, 100% were White, the mean body mass index (BMI) was 26.1 kg/m 2 , and mean duration of diabetes mellitus was 15 years. For patients with type 2 diabetes mellitus (T2DM), the mean age was 63 years old, 54% were male, 100% were White, the BMI 28.1 kg/m 2 , and the mean duration of diabetes mellitus was 15 years.

Table 4: Glycemic Parameters at the End of Treatment [Mean ± SD (n subjects)] Insulin Aspart Protamine and Insulin Aspart Novolin 70/30 Type 1, n=104 Fasting Blood Glucose (mg/dL) 174 ± 64 (48) 142 ± 59 (44)

1.5 Hour Post Breakfast (mg/dL) 187 ± 82 (48) 200 ± 82 (42)

1.5Hour Post Dinner (mg/dL) 162 ± 77 (47) 171 ± 66 (41) HbA 1c (%) Baseline 8.4 ± 1.2 (51) 8.5 ± 1.1 (46) HbA 1c (%) Week 12 8.4 ± 1.1 (51) 8.3 ± 1.0 (47) Type 2, n=187 Fasting Blood Glucose (mg/dL) 153 ± 40 (76) 152 ± 69 (93)

1.5 Hour Post Breakfast (mg/dL) 182 ± 65 (75) 200 ± 80 (92)

1.5Hour Post Dinner (mg/dL) 168 ± 51 (75) 191 ± 65 (93) HbA 1c (%) Baseline 8.1 ± 1.2 (82) 8.2 ± 1.3 (98) HbA 1c (%) Week 12 7.9 ± 1.0 (81) 8.1 ± 1.1 (96) The significance, with respect to the long-term clinical sequelae of diabetes, of the differences in postprandial hyperglycemia between treatment groups has not been established.

14.2Clinical Studies in Adult Patients with Type 2 Diabetes with Insulin and Oral Antidiabetic Agents Trial 1: In a 34-week, open-label trial (Trial 1), insulin-naïve patients with type 2 diabetes mellitus currently treated with 2 oral antidiabetic agents were switched to treatment with metformin and pioglitazone. The mean age of the trial population was 53 years old and mean duration of diabetes was 9.2 years. Forty-six percent were male.

Eighty-five percent were White, 12% were Black and 3% were Asian. The mean BMI was approximately 32.4 kg/m 2 . During an 8-week optimization period metformin and pioglitazone were increased to 2500 mg per day and 30 or 45 mg per day, respectively.

After the optimization period, patients were randomized to receive either Insulin Aspart Protamine and Insulin Aspart twice daily added on to the metformin and pioglitazone regimen or continue the current optimized metformin and pioglitazone therapy. Insulin Aspart Protamine and Insulin Aspart was started at a dose of 6 international units twice daily (before breakfast and before supper). Insulin doses were titrated to a pre-meal glucose goal of 80-110 mg/dL.

The total daily insulin dose at the end of the study was 56.9 ± 30.5 international units. Table 5: Combination Therapy with Metformin and Pioglitazone in Patients with Type 2 Diabetes Mellitus [Mean (SD)] (Trial 1) Treatment duration 24-weeks Insulin Aspart Protamine and Insulin Aspart + Metformin + Pioglitazone Metformin + Pioglitazone HbA 1c Baseline mean ± SD (n) 8.1 ± 1.0 (102) 8.1 ± 1.0 (98) End-of-study mean ± SD (n) - LOCF 6.6 ± 1.0 (93) 7.8 ± 1.2 (87) Adjusted Mean change from baseline ± SE (n)* -1.6 ± 0.1 (93) -0.3 ± 0.1 (87) Treatment difference mean ± SE* 95% CI* -1.3 ± 0.1 (-1.6, -1.0) Percentage of subjects reaching HbA 1c <7.0% 76% 24% Percentage of subjects reaching HbA 1c ≤6.5% 59% 12% Fasting Blood Glucose (mg/dL) Baseline Mean ± SD (n) 173 ± 39.8 (93) 163 ± 35.4 (88) End of Study Mean ± SD (n) - LOCF 130 ± 50.0 (90) 162 ± 40.8 (84) Adjusted Mean change from b… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 201 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of Insulin Aspart Protamine and Insulin Aspart Mix 70/30. In 52-week studies, Sprague-Dawley rats were dosed subcutaneously with insulin aspart, the rapid-acting component of Insulin Aspart Protamine and Insulin Aspart Mix 70/30, at 10, 50, and 200 units/kg/day (approximately 2, 8, and 32 times the human subcutaneous dose of 1.0 unit/kg/day, based on units/body surface area, respectively).

At a dose of 200 units/kg/day, insulin aspart increased the incidence of mammary gland tumors in females when compared to untreated controls. The relevance of these findings to humans is not known. Insulin aspart was not genotoxic in the following tests: Ames test, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice, and in ex viv o UDS test in rat liver hepatocytes.

In fertility studies in male and female rats, insulin aspart at subcutaneous doses up to 200 units/kg/day (approximately 32 times the human subcutaneous dose, based on units/body surface area) had no direct adverse effects on male and female fertility, or on general reproductive performance of animals.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 198 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of Insulin Aspart Protamine and Insulin Aspart Mix 70/30. In 52-week studies, Sprague-Dawley rats were dosed subcutaneously with insulin aspart, the rapid-acting component of Insulin Aspart Protamine and Insulin Aspart Mix 70/30, at 10, 50, and 200 units/kg/day (approximately 2, 8, and 32 times the human subcutaneous dose of 1.0 unit/kg/day, based on units/body surface area, respectively).

At a dose of 200 units/kg/day, insulin aspart increased the incidence of mammary gland tumors in females when compared to untreated controls. The relevance of these findings to humans is not known. Insulin aspart was not genotoxic in the following tests: Ames test, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice, and in ex viv o UDS test in rat liver hepatocytes.

In fertility studies in male and female rats, insulin aspart at subcutaneous doses up to 200 units/kg/day (approximately 32 times the human subcutaneous dose, based on units/body surface area) had no direct adverse effects on male and female fertility, or on general reproductive performance of animals.

📄 Patient Package Insert ~3 min read ▾

PATIENT INFORMATION Insulin Aspart Protamine and Insulin Aspart Mix 70/30 injectable suspension, for subcutaneous use This product is NovoLog Mix 70/30 (insulin aspart protamine and insulin aspart). Do not share your Insulin Aspart Protamine and Insulin Aspart Mix 70/30 FlexPen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

What is Insulin Aspart Protamine and Insulin Aspart Mix 70/30? • Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is a man-made insulin that is used to control high blood sugar in people with diabetes mellitus. • It is not known if Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is safe and effective in children. Who should not take Insulin Aspart Protamine and Insulin Aspart Mix 70/30? Do not take Insulin Aspart Protamine and Insulin Aspart Mix 70/30 if you: • are having an episode of low blood sugar (hypoglycemia). • have an allergy to Insulin Aspart Protamine and Insulin Aspart Mix 70/30 or any of the ingredients in Insulin Aspart Protamine and Insulin Aspart Mix 70/30.

Before taking Insulin Aspart Protamine and Insulin Aspart Mix 70/30, tell your healthcare provider about all your medical conditions including, if you are: • pregnant, planning to become pregnant, or are breastfeeding. • taking new prescription or over-the-counter medicines, vitamins, or herbal supplements. Before you start taking Insulin Aspart Protamine and Insulin Aspart Mix 70/30, talk to your healthcare provider about low blood sugar and how to manage it. How should I take Insulin Aspart Protamine and Insulin Aspart Mix 70/30? • Read the Instructions for Use that come with your Insulin Aspart Protamine and Insulin Aspart Mix 70/30. • Take Insulin Aspart Protamine and Insulin Aspart Mix 70/30 exactly as your healthcare provider tells you to. • Insulin Aspart Protamine and Insulin Aspart Mix 70/30 starts acting fast.

If you have Type 1 diabetes, inject it up to 15 minutes before you eat a meal. Do not inject Insulin Aspart Protamine and Insulin Aspart Mix 70/30 if you are not planning to eat within 15 minutes. If you have Type 2 diabetes, you may inject Insulin Aspart Protamine and Insulin Aspart Mix 70/30 up to 15 minutes before or after starting your meal. • Do not mix Insulin Aspart Protamine and Insulin Aspart Mix 70/30 with other insulin products or use in an insulin pump. • Know the type and strength of insulin you take.

Do not change the type of insulin you take unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you take different types of insulin. • Check your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels. • Do not reuse or share your needles or syringes with other people.

You may give other people a serious infection or get a serious infection from them. • Insulin Aspart Protamine and Insulin Aspart Mix 70/30 is injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs, or upper arms. • Change (rotate) your injection sites within the same area you choose with each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites. o Do not use the exact same spot for each injection. o Do not inject where skin has pits, is thickened, or has lumps. o Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.

What should I avoid while taking Insulin Aspart Protamine and Insulin Aspart Mix 70/30? While taking Insulin Aspart Protamine and Insulin Aspart Mix 70/30 do not: • Drive or operate heavy machinery, until you know how Insulin Aspart Protamine and Insulin Aspart Mix 70/30 affects you. • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. What are the possible side effe… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 4 words ▾

insulin aspart Label Image

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

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

Medicare Part D (outpatient prescription) spending for Novolog Flexpen (matched by generic name) — the program that covers self-administered drugs. 2 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 Novolog Flexpen. CMS lists 6 products for this generic; we show the highest-spend one. 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
$101.37M
Claims incl. refills
519.5K
Beneficiaries
359.6K
Spend / beneficiary
$281.88
Spend / claim
$195.13
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.

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 — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

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: this package is listed as actively marketed, with no marketing end date reported by A-S Medication Solutions. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
A-S Medication Solutions 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.
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.
← 50090-4956-00 · A-S 50090-4968-00 · A-S →
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.