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Insulin Aspart Protamine and Insulin Aspart Mix 70/30 100 [iU]/mL Injection, Suspension
🆔 Identity & classification
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Insulin Aspart — tap one for details:
Insulin Aspart may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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?
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?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $8.935 | $134.02 / 15 ml |
| Medicaid paysCMS SDUD · 12 mo | $9.24 | $138.57 / 15 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J1815 | No ASP payment limit on file for J1815 this quarter. | |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| NovoLog Mix 70/30 100 [iU]/mL 00169-3685-12 | Novo | 1 vial | $6.928 | — | Availability likely | save 22% |
| Insulin Aspart Protamine and Insulin Aspart Mix 70/30 100 [iU]/mL 73070-0200-11 | Novo | 1 vial | $6.955 | — | Availability likely | save 22% |
| Fiasp 100 [iU]/mL 00169-3206-15 | Novo | 5 cartridges | $8.573 | — | Availability likely | save 4% |
| Insulin Aspart Protamine and Insulin Aspart Mix 70/30 100 [iU]/mLthis 73070-0203-15 | Novo | 5 syringes | $8.935 | — | Availability likely | — |
| NovoLog Mix 70/30 100 [iU]/mL 00169-3696-19 | Novo | 5 syringes | $8.939 | — | Availability likely | +0% |
| 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]/mL 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 | — |
Where does this data come from?
⏳ Availability & biosimilar status
1 biosimilar and 1 interchangeable are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 73070-0203-15 You're viewing this | 5 SYRINGE, PLASTIC in 1 CARTON (73070-203-15) / 3 mL in 1 SYRINGE, PLASTIC (73070-203-10) | 2019-09-10 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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 ▾
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…
💊 Dosage Forms and Strengths ▾
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 ▾
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 ▾
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…
🤒 Adverse Reactions ▾
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…
🔄 Drug Interactions ▾
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 ▾
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…
🤰 Pregnancy ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
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 ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Insulin Aspart Protamine and Insulin Aspart Mix 70/30 (referred to as Insulin Aspart Protamine and Insulin Aspart ) is a white and cloudy injectable suspension containing 100 units/mL (U-100) of 70% insulin aspart protamine and 30% insulin aspart available as: One 10 mL multiple-dose vial per carton NDC 73070-200-11 Five 3 mL single-patient-use FlexPen prefilled pens per carton NDC 73070-203-15 The Insulin Aspart Protamine and Insulin Aspart FlexPen dials in 1-unit increments.
16.2Recommended Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Store unused Insulin Aspart Protamine and Insulin Aspart in a refrigerator between 2°C to 8°C (36°F to 46°F). Do not freeze Insulin Aspart Protamine and Insulin Aspart or use Insulin Aspart Protamine and Insulin Aspart if it has been frozen.
Do not expose Insulin Aspart Protamine and Insulin Aspart to excessive heat or light. Always remove the needle after each injection and store Insulin Aspart Protamine and Insulin Aspart FlexPen without a needle attached. The storage conditions are summarized in the following table: Table 7: Storage conditions for Insulin Aspart Protamine and Insulin Aspart Mix 70/30 vial and FlexPen Not in-use (unopened) Room Temperature (up to 30°C [86°F]) Not in-use (unopened) Refrigerated (2°C to 8°C [36°F to 46°F]) In-use (opened) Room Temperature (up to 30°C [86°F]) 10 mL multiple-dose vial 28 days Until expiration date 28 days (refrigerated/room temperature) 3 mL single-patient-use FlexPen 14 days Until expiration date 14 days (Do not refrigerate)
📋 Description ▾
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 ▾
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.
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