Brand name: NovoLOG
Drug class: Rapid-acting Insulins
ATC class: A10AB01
VA class: HS501
Chemical name: B28-Asp-insulin (human)
Molecular formula: C₂₅₆H₃₈₁N₆₅O₇₉S₆
CAS number: 116094-23-6

Medically reviewed by Drugs.com on Nov 21, 2024. Written by ASHP.

Introduction

Antidiabetic agent; rapid-acting human insulin analog prepared using recombinant DNA technology and genetically modified Saccharomyces cerevisiae.^{1 2 3 15}

Uses for Insulin Aspart

Diabetes Mellitus

Treatment of type 1 (previously called insulin-dependent) or type 2 (previously called noninsulin-dependent) diabetes mellitus in adults who require a rapid-acting insulin for glycemic control.¹

Generally used to provide prandial glycemic control in conjunction with an intermediate- or long-acting insulin preparation (e.g., isophane [NPH] insulin human, insulin aspart protamine [as the fixed combination Novolog Mix 70/30]) for basal insulin needs.^{1 15 18 19}

May provide greater convenience in timing of insulin injections in relation to meals.^{1 2 3 4 5 10 11}

Used by IV infusion in appropriately monitored patients with diabetes mellitus,¹ but American Diabetes Association (ADA) states that insulin aspart offers no advantage over regular crystalline insulin in patients who require IV insulin.^{c s}

Insulin Aspart Dosage and Administration

General

• Monitor blood glucose determinations regularly and carefully individualize dosage to attain optimum therapeutic effect.^{1 6 15 16 18} Glucose monitoring is particularly important for patients receiving insulin via an external infusion pump.¹

Transferring from Therapy with Other Insulins

• Make any change in insulin preparations cautiously and only under medical supervision.^{1 6} Changes in insulin strength, manufacturer, type, and/or species source (animal-source insulins no longer commercially available in the US) or method of manufacture may necessitate a change in dosage.¹

• When switching from isophane insulin alone or from a biphasic insulin preparation (e.g., premixed isophane and regular insulin) in patients with adequate glycemic control, use the previous insulin dosage as the initial dosage of insulin aspart/insulin aspart protamine fixed-combination preparation.^{18 19} Subsequent dosage adjustments may be required.^{18 19}

• Patients who previously were inadequately controlled with isophane insulin may require increases of 10–20% in the dosage of the insulin aspart/insulin aspart protamine fixed combination during the first week.¹⁹

• In patients receiving a multiple-daily-dose regimen consisting of an intermediate-acting (e.g., isophane) insulin and a rapid- or short-acting insulin at mealtimes, use the previous intermediate-acting insulin dosage as the initial dosage of the insulin aspart protamine component of the fixed combination.¹⁹

Administration

Insulin aspart: Administer by sub-Q injection, continuous sub-Q infusion, or IV infusion.^{1 10}

Insulin aspart/insulin aspart protamine fixed combination: Administer by sub-Q injection.¹⁵ Do notadminister IV or by continuous sub-Q infusion.¹⁵

Sub-Q Injection (Insulin Aspart or Insulin Aspart/Insulin Aspart Protamine)

For solution and drug compatibility information, see Compatibility under Stability.

Before inserting the Novolog PenFill cartridge into a compatible delivery device, roll the cartridge between the palms 10 times.¹⁵ Turn the cartridge upside down so that the glass ball inside the cartridge moves the length of the cartridge.¹⁵ Repeat rolling and turning of the cartridge ≥10 times or until the suspension appears to be uniformly white and cloudy.¹⁵ Inject immediately after resuspension, and repeat the rolling and turning of the cartridge before each subsequent injection.¹⁵

Similarly, roll the Novolog FlexPen between the palms 10 times.¹⁵ Turn the injection pen upside down so that the glass ball inside the pen moves from one end of the reservoir to the other.¹⁵ Repeat rolling and turning procedure ≥10 times or until the suspension appears uniformly white and cloudy.¹⁵ Inject immediately after resuspension, and repeat the rolling and turning of the FlexPen before each subsequent injection.¹⁵

Administer by sub-Q injection immediately (i.e., ≤5–10 minutes) prior to a meal using a conventional insulin syringe, an insulin injection pen (e.g., NovoPen 3 PenMate, Novolog FlexPen), or a compatible insulin delivery device (Innovo, InDuo).^{1 10 15 26 28} NovoLog or Novolog Mix 70/30 PenFill cartridges are intended for use with NovoPen 3 PenMate or a compatible insulin delivery device (Innovo, InDuo).^{1 15 26 28}

Must resuspend insulin aspart in fixed combination with insulin aspart protamine (Novolog Mix 70/30) immediately before use.¹⁵ Roll the vial gently between the hands 10 times until the suspension appears to be uniformly white and cloudy.¹⁵

Administer insulin aspart in fixed combination with insulin aspart protamine (Novolog Mix 70/30) by sub-Q injection twice daily, 15 minutes before the morning and evening meal.^{15 18} Each dose is intended to optimize glycemic control during 2 meals or a meal and a snack.^{15 18}

Administer in abdominal wall, thigh, or upper arm.¹ Follow a planned rotation of injection sites within an area.^{1 6}

Sub-Q Infusion (Insulin Aspart)

Administer by continuous sub-Q infusion into the abdominal wall using an external controlled-infusion device.^{1 13} Do not use insulin aspart in fixed combination with insulin aspart protamine in infusion pumps.¹⁵

Rotate infusion sites within the same region.^{1 6 15}

Recommended for use in certain external infusion pumps (i.e., Minimed model 500 series, Disetronic H-TRON series or other equivalent pump).¹

IV Administration (Insulin Aspart)

May be administered by IV infusion under proper medical supervision in a clinical setting.¹

Dilution

For IV infusion in polypropylene infusion bags, dilute to a concentration of 0.05–1 unit/mL in 0.9% sodium chloride, 5% dextrose, or 10% dextrose injection with 40 mEq/L of potassium chloride.¹

May be diluted to a concentration of 10 or 50 units/mL with insulin-diluting medium for Novolog.^a

Dispensing and Administration Precautions

To prevent medication errors, the packaging colors for Novolog were changed to differentiate it from Novolog Mix 70/30.^{21 23} Packaging for Novolog Mix 70/30 remains white with a blue band along the left side of the package (similar to previous packaging).^{21 23} The current packaging for Novolog is now white with an orange band along the left side of the package.^{21 23} Packaging color should not be relied upon as the sole means of identifying the correct drug.²³ Use the drug name, NDC number, and other measures (e.g., matching product name on the prescription to the pharmacy-issued label, separating agents with similar names on pharmacy shelves, counseling patients) to carefully distinguish between insulin formulations when dispensing.^{21 23}

Report dispensing errors to the manufacturer (800-727-6500), the USP Medication Errors Reporting Program (800-233-7767), or the FDA MedWATCH program by phone (800-FDA-1088, 800-FDA-0178 [fax]) or online at [Web].²¹

Dosage

The potency of insulin is standardized according to its ability to lower blood glucose concentrations in normal fasting rabbits as compared to the USP Insulin Reference Standard.^d Potency is expressed in USP units per mL.^d Dosage of parenteral insulin is always expressed in USP units.^d

Pediatric Patients

Diabetes Mellitus

Sub-Q Injection

Newly diagnosed patients with type 1 diabetes mellitus: Initially, total daily insulin dosage of approximately 0.5–1 units/kg, a portion of which may be given as insulin aspart.^{1 t v} Dosage requirement may be much lower during the period of partial remission or higher with severe insulin resistance (e.g., during puberty, in obese patients).^{g t}

Type 1 diabetes mellitus in adolescents in rapid-growth phase or patients experiencing ketosis or illness: Initially, total daily insulin dosage of 1–1.5 units/kg, a portion of which may be given as insulin aspart.^{1 g n t}

Type 2 diabetes mellitus: Initially, total daily insulin dosage of 0.5–1 units/kg, a portion of which may be given as insulin aspart, recommended by some clinicians.^f Optimum dosage regimen and type of insulin for use in pediatric patients with type 2 diabetes mellitus not fully elucidated.^e

Conventional therapy: When used in a preprandial sub-Q injection treatment regimen, the manufacturer states that 50–70% of total insulin requirements may be provided by the rapid-acting insulin aspart, with the remainder provided by an intermediate- or long-acting insulin.^{1 q r s} Some clinicians suggest that preprandial insulin comprise 40–60% of the total daily insulin dosage, with the remaining 60–40% given for basal needs using an intermediate- or long-acting insulin.^{b i n o q r s}

Some patients may require more basal insulin and a greater total daily insulin dosage to prevent preprandial hyperglycemia when using insulin aspart than when using insulin human (regular).¹

Intensive therapy: Generally ≥3 doses of rapid- or short-acting insulin daily administered by subcutaneous injection, or continuous subcutaneous infusion via insulin pump; adjust dosage according to results of frequent (e.g., at least 3–4 times daily) self-monitored blood glucose determinations and anticipated dietary intake and exercise.^{i j k l m p}

Adults

Diabetes Mellitus

Sub-Q Injection

Type 1 diabetes mellitus: Initially, total daily insulin dosage of approximately 0.5–1 units/kg, a portion of which may be given as insulin aspart.^{1 i n o p t v} Dosage requirement may be much lower during the period of partial remission (newly diagnosed patients) or higher with severe insulin resistance (e.g., obese patients).^{g t}

Type 2 diabetes mellitus: Initially, total daily insulin dosage ranges from 0.2–0.4 units/kg, a portion of which may be given as insulin aspart; some clinicians suggest an average initial total insulin dosage of 0.6 units/kg daily.^{29 h}

Conventional therapy: When used in a preprandial sub-Q injection treatment regimen, the manufacturer states that 50–70% of total insulin requirements may be provided by the rapid-acting insulin aspart, with the remainder provided by an intermediate- or long-acting insulin.^{1 q r s} Some clinicians suggest that preprandial insulin comprise 40–60% of the total daily insulin dosage, with the remaining 60–40% given for basal needs using an intermediate- or long-acting insulin.^{b i n o q r s u}

Some patients may require more basal insulin and a greater total daily insulin dosage to prevent preprandial hyperglycemia when using insulin aspart than when using insulin human (regular).¹

Intensive therapy: Generally ≥3 doses of rapid- or short-acting insulin daily administered by subcutaneous injection, or continuous subcutaneous infusion via insulin pump; adjust dosage according to results of frequent (e.g., at least 3–4 times daily) self-monitored blood glucose determinations and anticipated dietary intake and exercise.^{i j k l m p}

Sub-Q Infusion

When used in external infusion pumps, initial programming of the pump is based on the total daily insulin dosage previously used.¹

Although there is substantial interpatient variability, preprandial administration of insulin aspart injection via sub-Q infusion comprises approximately 50% of the total daily insulin dosage, with remainder given as basal infusion.^{1 25} Adjustments in basal insulin injections or higher basal infusion rates may be necessary.¹

Fixed-Combination Insulin Aspart/Insulin Aspart Protamine Therapy

Sub-Q Injection

When the fixed combination is used as monotherapy, initially, 0.4–0.6 units/kg daily given in 2 divided doses (before the morning and evening meal) has been recommended.^{18 19} Titrate subsequent dosage in increments of 2–4 units daily every 3–4 days to achieve the target fasting plasma glucose concentration.^{18 19}

When the fixed combination is used in combination with oral antidiabetic agents, initially, 0.2–0.3 unit/kg daily has been recommended.^{18 19} Titrate subsequent dosage to target glycemic goals.^{18 19}

Special Populations

Hepatic Impairment

Dosage requirements may be reduced.^{1 15} Careful monitoring of blood glucose and adjustment of dosage may be necessary.^{1 10 15}

Renal Impairment

Dosage requirements may be reduced.^{1 15} Careful monitoring of blood glucose and adjustment of dosage may be necessary.^{1 10}

Geriatric Patients

Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹⁵ Initiate dosage at lower end of the usual range.¹⁵

Cautions for Insulin Aspart

Contraindications

• Known hypersensitivity to insulin aspart or any ingredient in the formulation.¹

• Hypoglycemic episodes.¹

Warnings/Precautions

Warnings

Formulation Considerations

More rapid onset and shorter duration of action than insulin human (regular).^{1 2 3 4 5 10 11} Patients with type 1 diabetes mellitus generally require a longer-acting insulin to maintain adequate glycemic control.¹

Hypoglycemia

Most common adverse effect of insulins.^{1 6 7} Monitor blood glucose concentrations.^{1 6 7 15}

Rapid changes in serum glucose concentrations may precipitate manifestations of hypoglycemia, regardless of glucose concentrations.¹ Early warning signs of hypoglycemia may differ or be less pronounced in patients with a longer duration of diabetes, diabetic neuropathy, and/or those receiving concomitant therapy with β-adrenergic blocking agents or intensive insulin therapy.¹ Possible severe hypoglycemia and loss of consciousness prior to patient awareness of hypoglycemia.¹

Insulin Pumps

Risk of hyperglycemia and ketosis in a short time period with pump or infusion set malfunctions or insulin degradation.¹

Because of rapid absorption and short duration of action, such effects may occur when patients are switched from multiple injection therapy or infusion with buffered regular insulin.¹ Prompt identification and correction of hyperglycemia or ketosis is necessary.¹ May require interim therapy with intermittent sub-Q injections.¹

Sensitivity Reactions

Hypersensitivity Reactions

Localized allergic reactions (e.g., pruritus, erythema, swelling) at injection site reported.^{1 15} Such reactions usually resolve within a few days to a few weeks, but occasionally may require discontinuance of insulin aspart.^{1 15}

Generalized hypersensitivity reactions (e.g., rash, pruritus, shortness of breath, wheezing, hypotension, tachycardia, diaphoresis) reported less frequently than localized reactions, but may be life-threatening.¹

Localized reactions and generalized myalgias reported with use of cresol, an excipient in the NovoLog and NovoLog Mix 70/30 formulations.^{1 15}

Antibody Formation

Can stimulate transient formation of antibodies to insulin that may cross react with insulin aspart or insulin human.^{1 3 24} No consistent relationship between antibody formation and glycemic control (as measured by HbA_1c) observed, and dosage adjustments not necessary to maintain glycemic control.^{1 24} Clinical importance unknown.^{1 3}

General Precautions

Hypoglycemia and Hypokalemia

Care should be taken in patients most at risk for development of hypoglycemia and hypokalemia, such as those who are fasting, have autonomic neuropathy, or are taking potassium-lowering drugs or drugs sensitive to serum potassium concentrations.¹

Rapid onset of action of IV insulin aspart necessitates increased attention to potential hypoglycemia and hypokalemia.¹ Monitor closely serum glucose and potassium concentrations during IV administration of insulin to avoid potentially fatal hypoglycemia or hypokalemia.¹

Dispensing and Administration Precautions

To prevent medication errors, the packaging colors for Novolog have been changed to differentiate it from Novolog Mix 70/30.^{21 23} (See Dispensing and Administration Precautions under Dosage and Administration.)

Lipodystrophy

Atrophy or hypertrophy of sub-Q fat tissue may occur at sites of frequent insulin injections; ^{1 6 10} injection site rotation may reduce or prevent these effects.^{1 6 10}

Concurrent Illness

Insulin requirements may be altered during illness, emotional disturbances, or stress.¹

Specific Populations

Pregnancy

Category B for insulin aspart.¹ Category C for insulin aspart in fixed combination with insulin aspart protamine.¹⁵

Lactation

Not known whether insulin aspart is distributed into milk.¹ Use caution.¹

Pediatric Use

Safety and efficacy of insulin aspart in fixed combination with insulin aspart protamine not established in children.¹⁵

The safety and efficacy of insulin aspart were comparable to that of insulin human in several clinical studies in children and adolescents 2–18 years of age with type 1 diabetes mellitus.^{1 8}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether safety differs from younger adults.¹ Efficacy (as measured by HbA_1c) similar to that in younger adults, particularly in patients with type 2 diabetes mellitus.¹ (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Hypoglycemia, hypersensitivity reactions, lipodystrophy, pruritus, rash, injection site reactions.¹

Drug Interactions

Many drugs affect glucose metabolism; if such drugs are used concomitantly, insulin aspart dosage adjustment and careful monitoring may be required.¹

Specific Drugs1

Insulin Aspart Pharmacokinetics

Absorption

Bioavailability

Following sub-Q injection, absorption of insulin aspart is rapid and faster than that of regular human insulin.¹ When administered in fixed combination with insulin aspart protamine, absorption of insulin aspart protamine is prolonged, while rapid-absorption characteristics of insulin aspart are maintained.¹⁵

Onset

Following sub-Q injection of insulin aspart, maximum hypoglycemic effect occurs in 1–3 hours.¹

Following sub-Q injection of insulin aspart in fixed combination with insulin aspart protamine, maximum hypoglycemic effect occurs in 1–4 hours.¹⁵

Insulin aspart has a more rapid onset than insulin human in children (6–17 years of age) and adults.^{1 9}

Substantial interindividual and intraindividual variation may occur based on site of injection, tissue blood supply, temperature, and physical activity.^{1 15}

Duration

Following sub-Q injection of insulin aspart, duration of hypoglycemic action is 3–5 hours.¹

Following sub-Q injection of insulin aspart in fixed combination with insulin aspart protamine, duration of hypoglycemic action may be up to 24 hours.¹⁵

Insulin aspart has a shorter duration of action than insulin human in children (6–17 years of age) and adults.^{1 9}

Special Populations

Renal impairment: No effect on peak serum drug concentrations or AUC.¹

Hepatic impairment (Child-Pugh score ≤12): No effect on pharmacokinetics.¹

Distribution

Extent

Not known whether insulin aspart is distributed into milk.¹

Plasma Protein Binding

0–9%.¹

Elimination

Half-life

Insulin aspart: Averages 81 minutes.¹

Fixed-combination insulin aspart/insulin aspart protamine: About 8–9 hours.¹⁵

Stability

Storage

Parenteral

Injection, for Sub-Q Use

2–8°C; do not freeze.¹ Do not use if has been frozen or exposed to temperatures >37°C.¹

After puncture of vial, prefilled syringe, or cartridge, may keep unrefrigerated for up to 28 days away from direct heat and sunlight at temperature <30°C.¹ Open vials may be refrigerated.¹

Do not refrigerate cartridges after insertion into NovoPen 3 delivery device.¹

IV solutions containing 10 or 50 units/mL prepared using insulin-diluting medium for Novolog are stable for 28 days at <30ºC.¹ IV solutions in polypropylene infusion bags containing 0.05–1 units/mL prepared using 0.9% sodium chloride, 5% dextrose, or 10% dextrose injection with 40 mEq/L of potassium chloride are stable at room temperature for 24 hours.¹ Discard infusion sets (reservoirs, tubing, catheters) and drug in the reservoir after ≤48 hours of use or after exposure to temperatures >37°C.¹

Injectable Suspension

2–8°C; do not freeze.¹⁵ Do not use if has been frozen.¹⁵

If refrigeration is not possible after puncture of vial, may keep unrefrigerated for up to 28 days away from direct heat and sunlight at temperature <30°C.¹⁵

Once a cartridge or prefilled syringe is punctured, may use for up to 14 days if kept away from direct heat and sunlight at temperature <30°C.¹⁵ Must not store cartridges or prefilled syringes in use under refrigeration.¹⁵ May store unpunctured cartridges or prefilled syringes under refrigeration until expiration date printed on label; store prefilled syringes or unused cartridges in carton to keep clean and protect from light.¹⁵

Compatibility

Parenteral

If mixed with isophane insulin human for sub-Q injection, draw insulin aspart into syringe first to avoid transfer of isophane insulin human into the insulin vial.^{1 10} Use immediately after mixing; do not administer IV.¹

Effect of mixing insulin aspart with crystalline zinc insulin formulations, insulins of animal source, or preparations produced by other manufacturers not studied.¹ Do not mix insulin aspart with these preparations.¹

When used in an external infusion pump, do not mix insulin aspart with other insulins or diluent.¹

Do not mix fixed-combination insulin aspart/insulin aspart protamine with any other insulin.¹⁵

Actions

• Pharmacologic effects comparable to those of insulin human;¹ stimulates peripheral glucose uptake by tissues (e.g., skeletal muscle, fat), inhibits hepatic glucose production, inhibits lipolysis, and enhances protein synthesis.^{1 15 d}

• In biological assays in animals, has the same glucose-lowering effect as human insulin (regular).¹⁵

• More rapid onset and shorter duration of action than insulin human (regular); thus, associated with greater relative reductions in postprandial blood glucose concentrations than insulin human (regular).^{1 2 3 4 5 10 11}

Advice to Patients

• Provide copy of manufacturer’s patient information.¹

• Provide information regarding the potential risks and advantages of insulin aspart-containing therapy.^{1 15}

• Provide instructions regarding the use of sub-Q insulin infusion devices (e.g., infusion pumps and accessories) and intensive insulin therapy with multiple injections.¹

• Provide instructions regarding self-monitoring of blood glucose, insulin storage and injection technique, adherence to meal planning, regular physical exercise, periodic HbA_1c monitoring, and management of hypoglycemia or hyperglycemia.^{1 6 7 15}

• Importance of not mixing insulin aspart with crystalline zinc insulin preparations, insulins of animal source, or preparations produced by other manufacturers.¹ Importance of using insulin aspart only if solution is clear and colorless with no particles visible; resuspended insulin aspart in fixed combination with insulin aspart protamine must appear uniformly white and cloudy.^{1 15}

• Importance of not mixing insulin aspart with other insulins or diluent when used in external sub-Q infusion pumps.¹

• Importance of administering insulin aspart or the fixed combination of insulin aspart and insulin aspart protamine within 5–10 minutes or within 15 minutes, respectively, of the start of a meal.^{1 15}

• Discuss potential for alterations in insulin requirements in special situations (e.g., illness, emotional disturbances or other stresses) or as a result of changes in physical activity or usual meal plan, missed doses, or inadvertent administration of incorrect doses.^{1 15 16}

• Importance of patient informing clinician if skin reactions (erythema, pruritus, thickened skin) develop at infusion sites if using insulin infusion pumps.¹ Importance of selection of a new infusion site, as continued infusion may increase skin reactions and/or alter absorption.¹

• Importance of resumption of sub-Q insulin injection therapy and of contacting a clinician if pump malfunctions occur and cannot be corrected promptly.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 4}

• Importance of informing patients of other important precautionary information.^{1 15} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Biological Products Related to insulin aspart

Find detailed information on biosimilars for this medication.

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