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Pronunciation
(IN soo lin AS part)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of type 1 diabetes mellitus (insulin dependent, IDDM) and type 2 diabetes mellitus (noninsulin dependent, NIDDM) to improve glycemic control
Use: Unlabeled
Gestational diabetes mellitus (GDM); mild-to-moderate diabetic ketoacidosis (DKA); mild-to-moderate hyperosmolar hyperglycemic state (HHS)
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have generally not been observed in animal reproduction studies; therefore, the manufacturer classifies insulin aspart as pregnancy category B. When compared to regular insulin, the use of insulin aspart during pregnancy has not been found to increase the risk of adverse events to the fetus. Maternal hyperglycemia can be associated with adverse effects in the fetus, including macrosomia, neonatal hyperglycemia, and hyperbilirubinemia; the risk of congenital malformations is increased when the Hb A1c is above the normal range.Insulin requirements tend to fall during the first trimester of pregnancy and increase in the later trimesters, peaking at 28-32 weeks of gestation. Following delivery, insulin requirements decrease rapidly. Diabetes can be associated with adverse effects in the mother. Poorly-treated diabetes may cause end-organ damage that may in turn negatively affect obstetric outcomes. Physiologic glucose levels should be maintained prior to and during pregnancy to decrease the risk of adverse events in the fetus and the mother. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy. Insulin aspart has been demonstrated to be as safe and effective as regular human insulin when used during pregnancy and may have advantages over regular insulin during pregnancy.
Lactation
Excretion in breast milk unknown/compatible
Breast-Feeding Considerations
It is not known if insulin aspart is found in breast milk. Endogenous insulin can be found in breast milk. Plasma glucose concentrations in the mother affect glucose concentrations in breast milk. The gastrointestinal tract destroys insulin when administered orally; therefore, insulin is not expected to be absorbed intact by the breast-feeding infant. All types of insulin are safe for use while breast-feeding. Due to increased calorie expenditure, women with diabetes may require less insulin while nursing.
Contraindications
Hypersensitivity to insulin aspart or any component of the formulation; during episodes of hypoglycemia
Warnings/Precautions
Concerns related to adverse effects:
• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin detemir, insulin glargine) may delay recovery from 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.
• Hypokalemia: Insulin (especially I.V. 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 I.V. use and supplement potassium when necessary.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.
• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced.
Dosage form specific issues:
• Product variation: Human insulin differs from animal-source insulin. Any change of insulin should be made cautiously; changing manufacturers, type, and/or method of manufacture may result in the need for a change of dosage.
Other warnings/precautions:
• Appropriate use: Diabetes mellitus: The general objective of exogenous insulin therapy is to approximate the physiologic pattern of insulin secretion which is characterized by two distinct phases. Phase 1 insulin secretion suppresses hepatic glucose production and phase 2 insulin secretion occurs in response to carbohydrate ingestion; therefore, exogenous insulin therapy may consist of basal insulin (eg, intermediate- or long-acting insulin or via continuous subcutaneous insulin infusion [CSII]) and/or preprandial insulin (eg, short- or rapid-acting insulin) (see Related Information: Insulin Products). Patients with type 1 diabetes do not produce endogenous insulin; therefore, these patients require both basal and preprandial insulin administration. Patients with type 2 diabetes retain some beta-cell function in the early stages of their disease; however, as the disease progresses, phase 1 insulin secretion may become completely impaired and phase 2 insulin secretion becomes delayed and/or inadequate in response to meals. Therefore, patients with type 2 diabetes may be treated with oral antidiabetic agents, basal insulin, and/or preprandial insulin depending on the stage of disease and current glycemic control. Since treatment regimens often consist of multiple agents, dosage adjustments must address the specific phase of insulin release that is primarily contributing to the patient's impaired glycemic control. Treatment and monitoring regimens must be individualized.
Due to the short duration of action of insulin aspart, a longer acting insulin or CSII via an external insulin pump is needed to maintain adequate glucose control in patients with type 1 diabetes mellitus (insulin dependent, IDDM). In both type 1 and type 2 diabetes, preprandial administration of insulin aspart should be immediately followed by a meal within 5-10 minutes.
• CSII administration: May be administered via CSII; 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.
• I.V. administration: Insulin aspart may be administered I.V. 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 (DSME) is essential to maximize the effectiveness of therapy.
Adverse Reactions
Primarily symptoms of hypoglycemia
Cardiovascular: Pallor, palpitation, tachycardia
Central nervous system: Fatigue, headache, hypothermia, loss of consciousness, mental confusion
Dermatologic: Redness, urticaria
Endocrine & metabolic: Hypoglycemia, hypokalemia
Gastrointestinal: Hunger, nausea, numbness of mouth
Local: Atrophy or hypertrophy of SubQ fat tissue; edema, itching, pain or warmth at injection site; stinging
Neuromuscular & skeletal: Muscle weakness, paresthesia, tremor
Ocular: Transient presbyopia or blurred vision
Miscellaneous: Anaphylaxis, diaphoresis, local and/or systemic hypersensitivity reactions
Metabolism/Transport Effects
None known.
Drug Interactions
Antidiabetic Agents (Thiazolidinedione): Insulin may enhance the fluid-retaining effect of Antidiabetic Agents (Thiazolidinedione). Risk C: Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Insulin. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy
Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy
Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Quinolone Antibiotics: Insulin may enhance the hyperglycemic effect of Quinolone Antibiotics. Insulin may enhance the hypoglycemic effect of Quinolone Antibiotics. Risk C: Monitor therapy
Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy modification
Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Refer to Insulin Regular.
Storage
Unopened vials, cartridges, and prefilled pens may be stored under refrigeration between 2°C and 8°C (36°F to 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. When used for CSII, 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 SubQ administration: NovoLog® vials: According to the manufacturer, diluted insulin should be stored at temperatures <30°C (<86°F) and used within 28 days.
For I.V. infusion: Stable for 24 hours at room temperature.
Reconstitution
For SubQ administration: 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 external insulin pump.
For I.V. infusion: May be diluted in NS, D5W, or D10W to concentrations of 0.05-1 unit/mL.
Compatibility
Stable in D5W, D10W, and NS. Note: Insulin Diluting Medium for NovoLog® is available from the manufacturer for SubQ administration.
Compatibility in syringe: Compatible: Insulin NPH. Incompatible: Insulin detemir, insulin glargine, insulin glulisine, insulin lispro, insulin regular.
Mechanism of Action
Insulin aspart is a rapid-acting insulin analog.
Refer to Insulin Regular.
Pharmacodynamics/Kinetics
Note: Rate of absorption, onset, and duration of activity may be affected by site of injection, exercise, presence of lipodystrophy, local blood supply, and/or temperature.
Onset of action: 0.2-0.3 hours
Peak effect: 1-3 hours
Duration: 3-5 hours
Protein binding: <10%
Half-life elimination: SubQ: 81 minutes
Time to peak, plasma: 40-50 minutes
Excretion: Urine
Dosage
Note: When compared to insulin regular, insulin aspart has a more rapid onset and shorter duration of activity.
SubQ:
Diabetes mellitus:
Type 1:
Children <2 years (unlabeled use): Refer to Insulin Regular
Children ≥2 years and Adults: Refer to Insulin Regular
Type 2: Children (unlabeled use) and Adults: Refer to Insulin Regular
Diabetic ketoacidosis (DKA), mild-to-moderate (unlabeled use): Refer to Insulin Regular
Gestational diabetes mellitus (unlabeled use): Refer to Insulin Regular
Hyperosmolar hyperglycemic state (HHS), mild-to-moderate (unlabeled use): Refer to Insulin Regular
I.V.: Glycemic control in selected clinical situations and under appropriate medical supervision: Adults: Refer to Insulin Regular
Dosing adjustment in renal impairment: Refer to Insulin Regular
Dosing adjustment in hepatic impairment: Refer to Insulin Regular
Administration: I.V.
Do not use if solution is viscous or cloudy; use only if clear and colorless. May be administered I.V. with close monitoring of blood glucose and serum potassium; appropriate medical supervision is required. Do not administer insulin mixtures intravenously.
Administration: Other
SubQ administration: Do not use if solution is viscous or cloudy; use only if clear and colorless. Insulin aspart should be administered immediately (within 5-10 minutes) before a meal. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites. When mixing insulin aspart with other preparations of insulin (eg, insulin NPH), insulin aspart should be drawn into syringe first. Do not dilute or mix other insulin formulations with insulin aspart contained in a cartridge or prefilled pen.
CSII administration: Do not use if solution is viscous or cloudy; use only if clear and colorless. 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. Do not dilute or mix other insulin formulations with insulin aspart that is to be used in an external insulin pump.
Administration: I.V. Detail
I.V. infusions: To minimize adsorption to I.V. solution bag: Note: Refer to institution-specific protocols where appropriate.
If new tubing is
not
needed: Wait a minimum of 30 minutes between the preparation of the solution and the initiation of the infusion
If new tubing is needed: After receiving the insulin drip solution, the administration set should be attached to the I.V. container and the entire line should be flushed with a priming infusion of 20-50 mL of the insulin solution (Goldberg, 2006; Hirsch, 2006). Wait 30 minutes, and then flush the line again with the insulin solution prior to initiating the infusion.
Because of adsorption, the actual amount of insulin being administered via I.V. infusion could be substantially less than the apparent amount. Therefore, adjustment of the I.V. 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 1-4 hours prior to the discontinuation of I.V. insulin to prevent hyperglycemia (Moghissi, 2009).
pH: 7.2-7.6
Monitoring Parameters
Diabetes mellitus: Plasma glucose, electrolytes, Hb A1c
I.V. administration: Close monitoring of blood glucose and serum potassium
Reference Range
Refer to Insulin Regular.
Dietary Considerations
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Patient Education
Do not share pens, cartridges, or needles with others. This medication is used to control diabetes; it is not a cure. It is imperative to follow other components of prescribed treatment (eg, diet and exercise regimen). With insulin aspart (NovoLog®), you must start eating within 5-10 minutes after injection. If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Monitor glucose levels as directed by prescriber. Report adverse side effects, including chest pain or palpitations; persistent fatigue, confusion, headache; skin rash or redness; numbness of mouth, lips, or tongue; muscle weakness or tremors; vision changes; respiratory difficulty; or nausea, vomiting, or flu-like symptoms.
Geriatric Considerations
Intensive glucose control (HbA1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly" to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient's functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other disease states. An HbA1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% is acceptable for frail elderly patients, those with a duration of illness >10 years, or those with comorbid conditions and requiring combination diabetes medications. Patients who are unable to accurately draw up their dose will need assistance, such as prefilled syringes. Initial doses may require considerations for renal function in the elderly with dosing adjusted subsequently based on blood glucose monitoring. For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control.
Additional Information
Refer to Insulin Regular.
Dental Health: Effects on Dental Treatment
Patients with type 1 diabetes (insulin dependent) should be appointed for dental treatment in the morning in order to minimize chance of stress-induced hypoglycemia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness or confusion
Mental Health: Effects on Psychiatric Treatment
MAO inhibitors may enhance the hypoglycemic effects of insulin; TCAs may antagonize the effects of insulin
Nursing: Physical Assessment/Monitoring
Monitor for hypoglycemia at regular intervals during therapy. Teach patient proper use, including appropriate injection technique and syringe/needle disposal, and monitoring requirements.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
NovoLOG®: 100 units/mL (10 mL) [vial]
NovoLOG® FlexPen®: 100 units/mL (3 mL)
NovoLOG® Penfill®: 100 units/mL (3 mL) [cartridge]
Pricing: U.S. (www.drugstore.com)
Solution (NovoLOG)
100 units/mL (10): $122.99
Solution (NovoLOG FlexPen)
100 units/mL (15): $239.99
References
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, "Canadian Diabetes Association 2008 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada," Can J Diabetes, 20078, 32(suppl 1):1-201.
Goldberg PA, Kedves A, Walter K, et al, “'Waste Not, Want Not': Determining Optimal Priming Volume for Intravenous Insulin Infusions,” Diabetes Technol Ther, 2006, 8(5):598-601.
Hirsch IB, “Evidence-Based Priming,” Diabetes Technol Ther, 2006, 8(5):521-2.
Moghissi ES, Korytkowski MT, DiNardo M, et al, “American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control,” Endocr Pract, 2009, 15(4):353-69.
Rodbard HW, Jellinger PS, Davidson JA, et al, “Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control,” Endocr Pract, 2009, 15(6):540-59.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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