Insulin Aspart

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Fiasp: 100 units/mL (10 mL) [contains metacresol, phenol]

NovoLOG: 100 units/mL (10 mL) [contains metacresol, phenol]

Generic: 100 units/mL (10 mL)

Solution Cartridge, Subcutaneous:

Fiasp PenFill: 100 units/mL (3 mL) [contains metacresol, phenol]

NovoLOG PenFill: 100 units/mL (3 mL) [contains metacresol, phenol]

Generic: 100 units/mL (3 mL)

Solution Pen-injector, Subcutaneous:

Fiasp FlexTouch: 100 units/mL (3 mL) [contains metacresol, phenol]

NovoLOG FlexPen: 100 units/mL (3 mL) [contains metacresol, phenol]

Generic: 100 units/mL (3 mL)

Pharmacology

Mechanism of Action

Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.

Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; it also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.

Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulin aspart differs from human insulin by containing aspartic acid at position B28 in comparison to the proline found in human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin aspart is a rapid-acting insulin analog.

Pharmacokinetics/Pharmacodynamics

Excretion

Urine; Clearance: Adults: 1.22 L/hour/kg

Onset of Action

SubQ: ~0.2 to 0.3 hours; onset of glucose-lowering effect occurred ~5 minutes earlier with Fiasp compared to conventional insulin aspart (Heise 2017).

Peak effect: SubQ: Fiasp: ~1.5 to 2.2 hours; the peak glucose-lowering effect occurred ~10 minutes earlier with Fiasp compared to conventional insulin aspart (Heise 2017); NovoLOG: 1 to 3 hours.

Time to Peak

Plasma: SubQ:

Fiasp: ~63 minutes; peak plasma concentration occurred 7.3 minutes earlier with Fiasp compared to conventional insulin aspart (Heise 2017).

NovoLOG: 40 to 50 minutes.

Duration of Action

SubQ: Fiasp: ~5 to 7 hours; NovoLOG: 3 to 5 hours.

Half-Life Elimination

SubQ: Fiasp: 1.1 hours; NovoLOG: 81 minutes.

Protein Binding

<10%

Use in Specific Populations

Special Populations Note

Obesity: NovoLOG clearance is reduced 28% in patients with a BMI >32 kg/m² compared with patients with a BMI l<23 kg/m².

Use: Labeled Indications

Diabetes mellitus, types 1 and 2: Treatment of type 1 diabetes mellitus and type 2 diabetes mellitus to improve glycemic control

Use: Off Label

Diabetic ketoacidosis (mild to moderate)byes

Data from a prospective, randomized open label trial in a limited number of patients with uncomplicated diabetic ketoacidosis comparing the use of subcutaneous insulin aspart to a standard low-dose IV infusion protocol of regular insulin supports the use of insulin aspart in the treatment of mild to moderate diabetic ketoacidosis Umpierrez 2004.

Based on a consensus statement from the American Diabetes Association (ADA) for the treatment of patients with hyperglycemic crises in adult patients with diabetes, the use of rapid-acting insulin analogues (eg, insulin aspart) is an effective alternative to intravenous regular insulin in the management of diabetic ketoacidosis.

Gestational diabetes mellitusyes

Based on the American College of Obstetricians and Gynecologists (ACOG) practice bulletin for the management of gestational diabetes mellitus (GDM) and the American Diabetes Association standards of medical care for the management of diabetes in pregnancy, insulin may be used to treat GDM when nutrition and exercise therapy are not effective ACOG 190 2018, ADA 2019. The Endocrine Society Clinical Practice guideline on diabetes and pregnancy as well as ACOG recommend the use of rapid-acting insulin analogs lispro and aspart in preference to regular insulin in pregnant patients with diabetes ACOG 190 2018, Blumer 2013.

Hyperglycemia during critical illnessayes

Data from 2 prospective, randomized, controlled trials in the ICU population supports the use of insulin in the management of hyperglycemia in this patient population Van den Berghe 2001, Van den Berghe 2006. However, more recent data suggest that intensive glucose control is not associated with reduced mortality or morbidity in the general critically ill adult patient or may even increase mortality and rate of severe hypoglycemia NICE-SUGAR Study Investigators 2009, Wiener 2008.

The 2011 American College of Physicians clinical practice guideline for the management of glycemic control in hospitalized patients recommends against the use of intensive insulin therapy in non-surgical ICU/medical ICU patients which includes patients suffering a myocardial infarction.

Based on the 2012 Society of Critical Care Medicine (SCCM) guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients, insulin aspart is a recommended treatment option to manage hyperglycemia in critically ill patients who are clinically stable and have low insulin requirements. The 2012 SCCM guidelines suggest a glycemic goal range of 100 to 150 mg/dL, with absolute values <180 mg/dL Jacobi 2012. The ADA recommends a target blood glucose of 140 to 180 mg/dL for the majority of critically ill patients ADA 2019. The Surviving Sepsis Campaign guidelines recommend initiating insulin dosing in patients with severe sepsis when 2 consecutive blood glucose concentrations are >180 mg/dL and to target an upper blood glucose ≤180 mg/dL Rhodes 2017.

Contraindications

Hypersensitivity to insulin aspart or any component of the formulation; during episodes of hypoglycemia

Dosage and Administration

Dosing: Adult

Note: Insulin aspart is a rapid-acting insulin analog available in a conventional formulation (eg, NovoLOG, NovoRapid [Canadian product]) and a faster-acting formulation (Fiasp), which differ in onset of action and administration instructions (Heise 2017; Matthieu 2018). These products are not interchangeable (Institute for Safe Medication Practices 2019). Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision.

Diabetes mellitus, type 1: SubQ:

Note: Insulin aspart must be used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injection regimen) or in a continuous subcutaneous insulin infusion (CSII) pump. The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.

General insulin dosing:

Initial TDD: ~0.4 to 0.5 units/kg/day; conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid the potential for hypoglycemia; higher initial doses may be required in patients who are obese, sedentary or presenting with ketoacidosis (American Association of Clinical Endocrinologists [AACE]/American College of Endocrinology [ACE] [Handelsman 2015]; American Diabetes Association [ADA] 2019).

Usual TDD maintenance range: 0.4 to 1 units/kg/day in divided doses (ADA 2019).

Division of TDD (multiple daily injections):

Basal insulin: Generally, 40 to 50% of the TDD is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (AACE/ACE [Handelsman 2015]; ADA 2019).

Prandial insulin: The remaining portion (ie, 50 to 60%) of the TDD is then divided and administered before, at, or just after mealtimes (depending on the formulation) as a rapid-acting (eg, aspart, faster aspart, glulisine, lispro, insulin for inhalation) or short-acting (regular) insulin (AACE/ACE [Handelsman 2015]; ADA 2019).

Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.

Diabetes mellitus, type 2 (AACE/ACE [Garber 2019]; ADA 2019): SubQ:

Initial: 4 to 5 units or 10% of the basal insulin dose administered before the largest meal of the day.

Note: Stepwise addition of prandial insulin starting with a single meal and progressing to 2 or more meals as needed every 3 months is associated with a lower risk of hypoglycemia and increased patient satisfaction compared with immediate introduction of a full basal-bolus regimen. Insulin aspart (ie, a rapid-acting insulin) is usually given in addition to a regimen that includes basal insulin (ie, a long-acting insulin such as glargine, degludec, or detemir; or an intermediate-acting insulin such as NPH) and metformin +/- other noninsulin agents. Consider reducing the total daily dose by 4 units or 10% of the basal insulin dose if HbA_1c is <8% when initiating prandial insulin.

Dosage adjustment:

Adjust dose by 10% to 15% or 1 to 2 units twice weekly.

For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 10% to 20%; for severe hypoglycemia (ie, requiring assistance from another person or blood glucose <40 mg/dL) reduce dose by 20% to 40%.

HbA_1c still not controlled despite titrations to reach glycemic targets: One option is to advance to ‘basal-bolus’ (ie, insulin aspart administered with ≥2 meals per day) in addition to basal insulin and usually given in addition to metformin +/- other noninsulin agents.

Patients with diabetes receiving enteral feedings (ADA 2019): Note: TDD of insulin is divided into a basal component (intermediate- or long-acting insulin) and nutritional and correctional components (regular insulin or rapid-acting insulins).

Nutritional/correctional component: SubQ: 1 unit of insulin aspart per 10 to 15 g of carbohydrate plus correctional insulin aspart (as needed for hyperglycemia) administered every 4 hours or prior to each bolus feeding.

Patients with diabetes undergoing surgery and using CSII pump (ADA 2019): On the morning of surgery or procedure, give 60% to 80% of the usual dose of pump “basal” insulin (rapid-or short-acting insulins) dose.

Diabetic ketoacidosis, mild to moderate (off-label use): Subcutaneous injection:

1-hour interval dosing: Initial: 0.3 units/kg, followed by 0.1 units/kg every hour until blood glucose <250 mg/dL, then decrease to 0.05 units/kg every hour until resolution of ketoacidosis (Umpierrez 2004).

2-hour interval dosing: Initial: 0.3 units/kg, followed by 0.2 units/kg 1 hour later and then every 2 hours thereafter until blood glucose <250 mg/dL, then decrease to 0.1 units/kg every 2 hours until resolution of ketoacidosis (Umpierrez 2004).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Insulin aspart is a rapid-acting insulin analog which is normally administered SubQ as a premeal component of the insulin regimen or as a continuous SubQ infusion and should be used with intermediate- or long-acting insulin. When compared to insulin regular, insulin aspart has a more rapid onset and shorter duration of activity. In carefully controlled clinical settings with close medical supervision and monitoring of blood glucose and potassium, insulin aspart may also be administered IV in some situations. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision. See Insulin Regular for additional information.

General insulin dosing:

Type 1 diabetes mellitus: Children and Adolescents: Note: Multiple daily doses or continuous subcutaneous infusions guided by blood glucose monitoring are the standard of diabetes care. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations combined.

Initial total insulin dose: SubQ: 0.2-0.6 units/kg/day in divided doses. Conservative initial doses of 0.2-0.4 units/kg/day are often recommended to avoid the potential for hypoglycemia. A rapidly acting insulin may be the only insulin formulation used initially.

Usual maintenance range: SubQ: 0.5-1 unit/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:

Nonobese: 0.4-0.6 units/kg/day

Obese: 0.8-1.2 units/kg/day

Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day (IDF/ISPAD, 2011)

Adjustment of dose: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.

Continuous SubQ insulin infusion (insulin pump): A combination of a "basal" continuous insulin infusion rate with preprogrammed, premeal bolus doses which are patient controlled. When converting from multiple daily SubQ doses of maintenance insulin, it is advisable to reduce the basal rate to less than the equivalent of the total daily units of longer acting insulin (eg, NPH); divide the total number of units by 24 to get the basal rate in units/hour. Do not include the total units of regular insulin or other rapid-acting insulin formulations in this calculation. The same premeal regular insulin dosage may be used.

Reconstitution

For SubQ administration:

Fiasp: Do not dilute or mix with any other insulin products or solutions.

NovoLOG: Vials may be diluted with Insulin Diluting Medium for NovoLog to a concentration of 10 units/mL (U-10) or 50 units/mL (U-50). Do not dilute insulin contained in a cartridge, prefilled pen, or if using in an external insulin pump.

For IV infusion: May be diluted in compatible fluid (eg, NS) to concentrations of 0.05 to 1 unit/mL.

Administration

Use only if solution is clear and colorless; do not use if solution contains particulate matter or is colored.

SubQ administration: Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, or abdomen; NovoLOG may also be administered in the buttocks. Rotate injection sites within the same region to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. For prefilled pen injectors, prime the needle before each injection with 2 units of insulin. Once injected, hold the pen device in the skin for a count of 6 after the dose dial has returned to 0 units before the needle is removed to ensure the full dose has been administered.

Fiasp: Inject at the beginning of or within 20 minutes after starting a meal. Do not mix with any other insulin products or solutions. Fiasp FlexTouch is designed to dial doses in 1-unit increments.

NovoLOG: Administer immediately (within 5 to 10 minutes) before a meal. NovoLOG from a vial may be mixed with insulin NPH only (do not mix with other types of insulin) but should be drawn into syringe first. Do not dilute or mix other insulin formulations with NovoLOG contained in a cartridge or prefilled pen. NovoLOG FlexPen and FlexTouch are designed to dial doses in 1-unit increments.

Continuous subcutaneous insulin infusion administration: Patients should be trained in the proper use of their external insulin pump and in intensive insulin therapy. Infusion sets and infusion set insertion sites should be changed at least every 3 days; rotate infusion sites. Insulin in reservoir should be changed at least every 6 days or according to continuous subcutaneous insulin infusion device user manual (whichever is shorter). Do not dilute or mix other insulin formulations with insulin aspart that is to be used in an external insulin pump.

IV administration: May be administered IV with close monitoring of blood glucose and serum potassium; appropriate medical supervision is required. Do not administer insulin mixtures intravenously.

IV infusions: To minimize insulin adsorption to plastic IV tubing: Although data is lacking regarding adsorption with insulin aspart, insulin regular loss has been shown to occur by adsorption to plastic (ie, polyvinyl chloride, polyethylene, polyolefin, polypropylene) IV containers and tubing (Greenwood 2012; Hirsch 1977; Hirsch 1981; Rocchio 2013; Thompson 2012). Therefore, flush the IV tubing with a priming infusion of 20 mL from the insulin infusion, whenever a new IV tubing set is added to the insulin infusion container (SCCM [Jacobi 2012]; Thompson 2012).

Note: Also refer to institution-specific protocols where appropriate.

Because of insulin adsorption to plastic IV tubing or infusion bags, the actual amount of insulin being administered via IV infusion could be substantially less than the apparent amount. Therefore, adjustment of the IV infusion rate should be based on effect and not solely on the apparent insulin dose. The apparent dose may be used as a starting point for determining the subsequent SubQ dosing regimen (Moghissi 2009); however, the transition to SubQ administration requires continuous medical supervision, frequent monitoring of blood glucose, and careful adjustment of therapy. In addition, SubQ insulin should be given 1 to 4 hours prior to the discontinuation of IV insulin to prevent hyperglycemia (Moghissi 2009).

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage

Fiasp:

Unopened vials, cartridges, and prefilled pens may be stored under refrigeration between 2°C and 8°C (36°F and 46°F) until the expiration date or at room temperature <30°C (<86°F) for 28 days; do not freeze; keep away from heat and sunlight.

Once punctured (in use), vials may be stored under refrigeration or at room temperature <30°C (<86°F); use within 28 days. Opened (in use) Fiasp FlexTouch pens may be stored at room temperatures <30°C (<86°F) or under refrigeration at 2°C to 8°C (36°F to 46°F) and should be used within 28 days. Opened (in use) Fiasp PenFill cartridges may be stored at room temperature <30°C (<86°F) and should be used within 28 days; do not refrigerate.

For continuous subcutaneous insulin infusion: Insulin aspart contained within an external insulin pump reservoir should be replaced at least every 6 days; discard if exposed to temperatures >37°C (>98.6°F).

For IV infusion: Stable in compatible fluid (eg, NS) for 24 hours at room temperature.

NovoLOG:

Unopened vials, cartridges, and prefilled pens may be stored under refrigeration between 2°C and 8°C (36°F and 46°F) until the expiration date or at room temperature <30°C (<86°F) for 28 days; do not freeze; keep away from heat and sunlight.

Once punctured (in use), vials may be stored under refrigeration or at room temperature <30°C (<86°F); use within 28 days. Cartridges and prefilled pens that have been punctured (in use) should be stored at temperatures <30°C (<86°F) and used within 28 days; do not freeze or refrigerate.

For continuous subcutaneous insulin infusion: Insulin aspart contained within an external insulin pump reservoir should be replaced at least every 6 days; discard if exposed to temperatures >37°C (>98.6°F).

Dilution for SubQ administration (vials only): Diluted insulin aspart should be stored at temperatures <30°C (<86°F) and used within 28 days.

For IV infusion: Stable in compatible fluid (eg, NS) for 24 hours at room temperature.

Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Insulins. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Monitor therapy

Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Exceptions: Liraglutide. Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification

Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Avoid combination

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. Consider therapy modification

Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Adverse Reactions

Rates of adverse reactions were defined during combination therapy with other insulins (NPH, detemir, or glargine). Adverse reactions are reported for adults, unless otherwise noted.

>10%:

Endocrine & metabolic: Severe hypoglycemia (adults, children, and adolescents: Type 1: 1% to 17%, Type 2: 3% to 10%)

Immunologic: Antibody development (adults: 3% to 28%; children and adolescents: 3%)

Nervous system: Headache (adults: 5% to 12%; children and adolescents: 6% to 10%), hyporeflexia (11%)

Respiratory: Nasopharyngitis (20% to 24%), viral respiratory tract infection (children and adolescents: 21% to 23%)

Miscellaneous: Accidental injury (11%)

1% to 10%:

Cardiovascular: Chest pain (5%)

Dermatologic: Onychomycosis (10%), dermatological disorder (5%), allergic skin rash (2%)

Gastrointestinal: Vomiting (children and adolescents: 3% to 8%), nausea (5% to 7%), abdominal pain (5%), diarrhea (3% to 5%)

Genitourinary: Urinary tract infection (6% to 8%)

Hypersensitivity: Hypersensitivity reaction (4%)

Infection: Influenza (children and adolescents: 6% to 8%)

Local: Infusion site reaction (10%), injection site reaction (children and adolescents: 4%; adults: 2%), lipoatrophy at injection site (children and adolescents: 2%; adults: <1%)

Nervous system: Abnormal sensory symptoms (9%)

Neuromuscular & skeletal: Back pain (4% to 5%)

Respiratory: Upper respiratory tract infection (children and adolescents: 8% to 12%; adults: 7% to 9%), rhinitis (children and adolescents: 4% to 6%), sinusitis (5%)

Miscellaneous: Fever (children and adolescents: 6% to 8%)

<1%: Facial edema, peripheral edema

Frequency not defined:

Endocrine & metabolic: Diabetic retinopathy, weight gain

Local: Erythema at injection site, injection site pruritus, swelling at injection site

Nervous system: Peripheral neuropathy

Ophthalmic: Error of refraction

Postmarketing: Amyloidosis (localized cutaneous at injection site), anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Glycemic control: Hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type, and/or administration method. The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content, timing of meals), changes in the level of physical activity, increased work or exercise without eating, or changes to coadministered medications. Use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long-standing diabetes, diabetic nerve disease, patients taking beta-blockers, or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.
• Hypersensitivity: Hypersensitivity reactions (serious, life-threatening and anaphylaxis) have occurred. If hypersensitivity reactions occur, discontinue administration and initiate supportive care measures.
• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium frequently with IV use and supplement potassium when necessary.

Disease-related concerns:

• Bariatric surgery:

– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2013). Insulin secretion and sensitivity may be partially or completely restored after these procedures (Korner 2009; Peterli 2012). Rates and timing of type 2 diabetes improvement and resolution vary widely by patient. Insulin dose reduction of ≥75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014). Avoid the use of bolus insulin injections or dose conservatively with close clinical monitoring in the early phases after surgery.

– Weight gain: Evaluate risk versus benefit and consider alternative therapy after gastric bypass, sleeve gastrectomy, and gastric banding; weight gain may occur (Apovian 2015).

• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones, may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Risk of hypoglycemia may be increased; more frequent monitoring and dosage adjustments may be required.
• Renal impairment: Use with caution in patients with renal impairment. Risk of hypoglycemia may be increased; more frequent monitoring and dosage adjustments may be required.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Hospitalized patients with diabetes: Exclusive use of a sliding scale insulin regimen (insulin regular) in the inpatient hospital setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin or basal plus bolus is preferred. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin, nutritional, and correction components is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia). A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2019).

Dosage form specific issues:

• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).

Other warnings/precautions:

• Continuous subcutaneous insulin infusion administration: Insulin aspart may be administered via continuous subcutaneous insulin infusion; do not dilute or mix with other insulin formulations. Rule out external pump failure if unexplained hyperglycemia or ketosis occurs; temporary SubQ insulin administration may be required until the problem is identified and corrected.
• IV administration: Insulin aspart may be administered IV in selected clinical situations to control hyperglycemia; close monitoring of blood glucose and serum potassium as well as medical supervision is required.
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.

Monitoring Parameters

Critically ill patients receiving insulin aspart infusion: Blood glucose every 1 to 2 hours. Note: Every 4 hour blood glucose monitoring is not recommended unless a low hypoglycemia rate is demonstrated with the insulin protocol used. Arterial or venous whole blood sampling is recommended for patients in shock, on vasopressor therapy, or with severe edema, and when on a prolonged insulin infusion (SCCM [Jacobi 2012]).

Diabetes mellitus: Plasma glucose (typically before meals and snacks and at bedtime; occasionally additional monitoring may be required), electrolytes, HbA_1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2019]); renal function; hepatic function, weight.

Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 190 2018).

IV administration: Close monitoring of blood glucose and serum potassium.

Pregnancy

Pregnancy Considerations

Rapid-acting insulin aspart (NovoLOG) can be detected in cord blood (Pettitt 2007).

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA_1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2020).

Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed (ACOG 190 2018; ACOG 201 2018; ADA 2020). Rapid-acting insulin aspart is one of the preferred insulins for use in pregnancy (ACOG 190 2018; ACOG 201 2018; Blumer 2013).

Maternal use of faster-acting insulin aspart (Fiasp) compared to rapid-acting insulin aspart (NovoLog) in pregnancy is under study (NCT03770767).

Females with diabetes mellitus who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2020). Rapid-acting insulin aspart is one of the preferred insulins for use in females with diabetes mellitus planning a pregnancy (Blumer 2013).

Patient Education

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

Frequently reported side effects of this drug

• Common cold symptoms
• Sore throat
• Stuffy nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Burning or numbness feeling
• Vision changes
• Chills
• Severe dizziness
• Passing out
• Mood changes
• Seizures
• Slurred speech
• Painful urination
• Blood in the urine
• Severe injection site irritation
• Injection site change in skin to thick or thin
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.