Pronunciation:

(IN su lin prep a RAY shuns)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Use - Unlabeled/Investigational:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

In type 1 diabetes mellitus (insulin dependent, IDDM), insulin lispro (Humalog®) and insulin glulisine (Apidra™) should be used in combination with a long-acting insulin. However, in type 2 diabetes mellitus (noninsulin dependent, NIDDM), insulin lispro (Humalog®) may be used without a long-acting insulin when used in combination with a sulfonylurea.

Insulin aspart (Apidra™, NovoLog®, NovoLog® Mix 70/30): Safety and efficacy of use in children have not been established

Adverse Reactions:

Cardiovascular: Palpitation, tachycardia, pallor

Central nervous system: Fatigue, mental confusion, loss of consciousness, headache, hypothermia

Dermatologic: Urticaria, redness

Endocrine & metabolic: Hypoglycemia

Gastrointestinal: Hunger, nausea, numbness of mouth

Local: Itching, edema, stinging, pain or warmth at injection site; atrophy or hypertrophy of SubQ fat tissue

Neuromuscular & skeletal: Muscle weakness, paresthesia, tremor

Ocular: Transient presbyopia or blurred vision

Miscellaneous: Diaphoresis, anaphylaxis, local allergy, systemic allergic symptoms

Overdosage/Toxicology:

Drug Interactions:

Drugs which DECREASE hypoglycemic effect of insulin:

Contraceptives (oral), corticosteroids, dextrothyroxine, diltiazem, dobutamine, epinephrine, niacin, smoking, thiazide diuretics, thyroid hormone

Drugs which INCREASE hypoglycemic effect of insulin:

Alcohol, alpha-blockers, anabolic steroids, beta-blockers*, clofibrate, fenfluramine, guanethidine, MAO inhibitors, pentamidine, phenylbutazone, salicylates, sulfinpyrazone, tetracyclines

*Nonselective beta-blockers may delay recovery from hypoglycemic episodes and mask signs/symptoms of hypoglycemia. Cardioselective agents may be alternatives.

Ethanol/Nutrition/Herb Interactions:

Ethanol: Caution with ethanol (may increase hypoglycemia).

Food: Insulin shifts potassium from extracellular to intracellular space. Decreases potassium serum concentration.

Herb/Nutraceutical: Use caution with chromium, garlic, gymnema (may increase hypoglycemia).

Stability:

Newer neutral formulation of regular insulin is stable at room temperature up to one month (studies indicate up to 24-30 months)

Insulin aspart (NovoLog®) and insulin glulisine (Apidra™): Can be infused SubQ by external insulin pump; do not dilute or mix with other insulins when used in an external pump for SubQ infusion; insulin in reservoir should be replaced every 48 hours. Do not expose to temperatures 37°C (98.6°F).

Insulin glargine (Lantus®): When refrigeration is unavailable, 10 mL vials may be stored at room temperature for up to 28 days; solution not used within this time must be discarded.

Insulin lispro (Humalog®): Prior to use, store in refrigerator; do not use if it has been frozen. If not refrigerated, use within 28 days and protect from heat and light. Once opened (in-use), vials may be stored in refrigerator or for up to 28 days at room temperature. Cartridges/pens should be stored at room temperature and used within 28 days.

Freezing causes more damage to insulin than room temperatures up to 100°F. Avoid direct sunlight.

Compatibility of insulin preparations:

Rapid-acting:

Insulin injection (regular): Compatible mixed with all types insulin

Lispro (Humalog®): Compatible mixed with Ultralente® / NPH

Insulin aspart (NovoLog®): Compatible mixed with NPH human insulin

Intermediate-acting: Isophane insulin suspension (NPH): Compatible mixed with regular insulin

Long-acting: When mixing with NPH insulin in any proportion, the excess protamine may combine with regular insulin and may reduce or delay activity of regular insulin (does not appear to be clinically significant); phosphate-buffered regular insulins bind with Lente® insulins forming short-acting insulin; excess protamine in PZI combines with regular insulin and prolongs its action, therefore, should not be mixed; administer as a separate injection; insulin glargine (Lantus®) cannot be diluted or mixed with any other insulin or solution

Stability of parenteral admixture of regular insulin at room temperature (25°C) and at refrigeration temperature (4°C): 24 hours

Standard diluent for regular insulin: 100 units/100 mL NS

Comments: All bags should be prepared fresh; tubing should be flushed 30 minutes prior to administration to allow adsorption as time permits

Compatibility:

Insulin (regular): Variable stability (consult detailed reference) in NS, TPN

Y-site administration: Compatible: Alatrofloxacin, amiodarone, ampicillin, ampicillin/sulbactam, aztreonam, cefazolin, cefotetan, clarithromycin, dobutamine, esmolol, famotidine, gentamicin, heparin, heparin with hydrocortisone sodium succinate, imipenem/cilastatin, indomethacin, magnesium sulfate, meperidine, meropenem, midazolam, milrinone, morphine, nitroglycerin, oxytocin, pentobarbital, potassium chloride, propofol, ritodrine, sodium bicarbonate, sodium nitroprusside, tacrolimus, terbutaline, ticarcillin, ticarcillin/clavulanate potassium, tobramycin, vancomycin, vitamin B complex with C. Incompatible: Dopamine, nafcillin, norepinephrine, ranitidine. Variable (consult detailed reference): Digoxin, diltiazem, labetalol, levofloxacin, TPN

Compatibility in syringe: Compatible: Metoclopramide

Compatibility when admixed: Compatible: Bretylium, cimetidine, lidocaine, meropenem, verapamil. Incompatible: Aminophylline, amobarbital, chlorothiazide, cytarabine, dobutamine, methylprednisolone sodium succinate, octreotide, pentobarbital, phenobarbital, phenytoin, thiopental. Variable (consult detailed reference): Ranitidine

Mechanism of Action:

Pharmacodynamics/Kinetics:

Onset of action and duration: Biosynthetic NPH human insulin shows a more rapid onset and shorter duration of action than corresponding porcine insulins; human insulin and purified porcine regular insulin are similarly efficacious following SubQ administration. The duration of action of highly purified porcine insulins is shorter than that of conventional insulin equivalents. Duration depends on type of preparation and route of administration as well as patient-related variables. In general, the larger the dose of insulin, the longer the duration of activity.

Absorption: Biosynthetic regular human insulin is absorbed from the SubQ injection site more rapidly than insulins of animal origin (60-90 minutes peak vs 120-150 minutes peak respectively) and lowers the initial blood glucose much faster. Human Ultralente® insulin is absorbed about twice as quickly as its bovine equivalent, and bioavailability is also improved. Human Lente® insulin preparations are also absorbed more quickly than their animal equivalents. Insulin glargine (Lantus®) is designed to form microprecipitates when injected subcutaneously. Small amounts of insulin glargine are then released over a 24-hour period, with no pronounced peak. Insulin glargine (Lantus®) for the treatment of type 1 diabetes (insulin dependent, IDDM) and type 2 diabetes mellitus (noninsulin dependent, NIDDM) in patients who require basal (long-acting) insulin.

Bioavailability: Medium-acting SubQ Lente®-type human insulins did not differ from the corresponding porcine insulins

Insulin aspart (NovoLog®):

Onset: 0.17-0.33 hours; Peak effect: 1-3 hours; Duration: 3-5 hours

Insulin lispro (Humalog®), insulin glulisine (Apidra™):

Onset: 0.25 hours; Peak effect: 0.5-1.5 hours; Duration: 6-8 hours

Insulin, regular (Novolin® R):

Onset: 0.5-1 hours; Peak effect: 2-3 hours; Duration: 8-12 hours

Isophane insulin suspension (NPH) (Novolin® N):

Onset: 1-1.5 hours; Peak effect: 4-12 hours; Duration: 24 hours

Insulin zinc suspension (Lente®):

Onset: 1-2.5 hours; Peak effect: 8-12 hours; Duration: 18-24 hours

Isophane insulin suspension and regular insulin injection (Novolin® 70/30):

Onset: 0.5 hours; Peak effect: 2-12 hours; Duration: 24 hours

Extended insulin zinc suspension (Ultralente®):

Onset: 4-8 hours; Peak effect: 16-18 hours; Duration: >36 hours

Insulin glargine (Lantus®):

Duration: 24 hours

Dosage:

Diabetes mellitus: The number and size of daily doses, time of administration, and diet and exercise require continuous medical supervision. In addition, specific formulations may require distinct administration procedures (see Administration).

Children and Adults: 0.5-1 unit/kg/day in divided doses

Adolescents (growth spurts): 0.8-1.2 units/kg/day in divided doses

Adjust dose to maintain premeal and bedtime blood glucose of 80-140 mg/dL (children <5 years: 100-200 mg/dL)

Insulin glargine (Lantus®): SubQ:

Type 2 diabetes (patient not already on insulin): 10 units once daily, adjusted according to patient response (range in clinical study 2-100 units/day)

Patients already receiving insulin: In clinical studies, when changing to insulin glargine from once-daily NPH or Ultralente® insulin, the initial dose was not changed; when changing from twice-daily NPH to once-daily insulin glargine, the total daily dose was reduced by 20% and adjusted according to patient response

Hyperkalemia (unlabeled use): Administer dextrose at 0.5-1 mL/kg and regular insulin 1 unit for every 4-5 g dextrose given

Diabetic ketoacidosis: Children and Adults: Regular insulin: I.V. loading dose: 0.1 unit/kg, then maintenance continuous infusion: 0.1 unit/kg/hour (range: 0.05-0.2 units/kg/hour depending upon the rate of decrease of serum glucose - too rapid decrease of serum glucose may lead to cerebral edema).

Optimum rate of decrease (serum glucose): 80-100 mg/dL/hour

Note: Newly-diagnosed patients with IDDM presenting in DKA and patients with blood sugars <800 mg/dL may be relatively "sensitive" to insulin and should receive loading and initial maintenance doses approximately ¹/2 of those indicated above.

Dosing adjustment in renal impairment (regular): Insulin requirements are reduced due to changes in insulin clearance or metabolism

Clcr 10-50 mL/minute: Administer at 75% of normal dose

Clcr<10 mL/minute: Administer at 25% to 50% of normal dose and monitor glucose closely

Hemodialysis: Because of a large molecular weight (6000 daltons), insulin is not significantly removed by either peritoneal or hemodialysis

Supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

Continuous arteriovenous or venovenous hemofiltration effects: Supplemental dose is not necessary

Administration:

SubQ administration: Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen, with sites rotated. When mixing regular insulin with other preparations of insulin, regular insulin should be drawn into syringe first. Buffered insulin (Velosulin® BR) should not be mixed with any other form of insulin.

Insulin lispro (Humalog®): May be administered within 15 minutes before or immediately after a meal.

Insulin glulisine (Apidra™): Should be administered within 15 minutes before or within 20 minutes after start of meal. Can be infused SubQ by external insulin pump; do not dilute or mix with other insulins when used in an external pump for SubQ infusion; should replace insulin in reservoir every 48 hours.

Insulin aspart (NovoLog®): Should be administered immediately before a meal (within 5-10 minutes of the start of a meal). Can be infused SubQ by external insulin pump; do not dilute or mix with other insulins when used in an external pump for SubQ infusion; should replace insulin in reservoir every 48 hours.

Human regular insulin: Should be administered within 30-60 minutes before a meal.

Intermediate-acting insulins (such as NPH): May be administered 1-2 times/day.

Long-acting insulins (such as Ultralente®, Lantus®): May be administered once daily.

Insulin glargine (Lantus®): Should be administered once daily, at any time of day, but should be administered at the same time each day. Cannot be diluted or mixed with any other insulin or solution.

Regular insulin may be administered by SubQ, I.M., or I.V. routes

I.V. administration (requires use of an infusion pump): Only regular insulin may be administered I.V.

I.V. infusions: To minimize adsorption problems to I.V. solution bag:

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 line should be flushed with the insulin solution. The nurse should then wait 30 minutes, then flush the line again with the insulin solution prior to initiating the infusion

If insulin is required prior to the availability of the insulin drip, regular insulin should be administered by I.V. push injection

Because of adsorption, the actual amount of insulin being administered could be substantially less than the apparent amount. Therefore, adjustment of the insulin drip rate should be based on effect and not solely on the apparent insulin dose. Furthermore, the apparent dose should not be used as the basis for determining the subsequent insulin dose upon discontinuing the insulin drip. Dose requires continuous medical supervision.

To be ordered as units/hour

Example: Standard diluent of regular insulin only: 100 units/100 mL NS (can be administered as a more diluted solution, ie, 100 units/250 mL NS)

Insulin rate of infusion (100 units regular/100 mL NS)

1 unit/hour: 1 mL/hour

2 units/hour: 2 mL/hour

3 units/hour: 3 mL/hour

4 units/hour: 4 mL/hour

5 units/hour: 5 mL/hour, etc

Monitoring Parameters:

Reference Range:

Therapeutic, serum insulin (fasting): 5-20 IU/mL (SI: 35-145 pmol/L)

Glucose, fasting:

Newborns: 60-110 mg/dL

Adults: 60-110 mg/dL

Elderly: 100-180 mg/dL

Dietary Considerations:

Patient Education:

Additional Information:

Anesthesia and Critical Care Concerns/Other Considerations:

Cardiovascular Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

RAPID-ACTING:

Injection, solution, aspart, human:

NovoLog®: 100 units/mL (10 mL vial)

NovoLog® [InnoLet®]: 100 units/mL (3 mL prefilled syringe)

NovoLog® [PenFill®]: 100 units/mL (3 mL cartridge)

Injection, solution, lispro, human (Humalog®): 100 units/mL (1.5 mL cartridge [DSC], 3 mL disposable pen, 10 mL vial)

Injection, solution, glulisine (Apidra™): 100 units/mL (10 mL vial)

SHORT-ACTING:

Injection, solution, regular, human:

Humulin® R: 100 units/mL (10 mL vial)

Novolin® R: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial)

Novolin® R [PenFill®]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

Injection, solution, regular, human, buffered (Velosulin® BR) [DSC]: 100 units/mL (10 mL vial)

Injection, solution, regular, human, concentrate (Humulin® R U-500): 500 units/mL (20 mL vial)

Injection, solution, regular, purified pork (Regular Iletin® II): 100 units/mL (10 mL vial)

INTERMEDIATE-ACTING:

Injection, suspension, lente, human [zinc] (Humulin® L, Novolin® L [DSC]): 100 units/mL (10 mL vial)

Injection, suspension, lente, purified pork [zinc] (Lente® Iletin® II): 100 units/mL (10 mL vial) [DSC]

Injection, suspension, NPH, human [isophane]:

Humulin® N: 100 units/mL (3 mL disposable pen, 10 mL vial)

Novolin® N: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial)

Novolin® N [PenFill®]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

Injection, suspension, NPH, purified pork [isophane] (NPH Iletin® II): 100 units/mL (10 mL vial)

LONG-ACTING:

Injection, suspension, Ultralente®, human [zinc] (Humulin U Ultralente®): 100 units/mL (10 mL vial)

Injection, solution, glargine, human (Lantus®): 100 unit/mL (10 mL vial)

COMBINATION, INTERMEDIATE-ACTING:

Injection, aspart protamine human suspension 70% and rapid-acting aspart human solution 30% (NovoLog® Mix 70/30): 100 units/mL (3 mL cartridge, 3 mL prefilled syringe)

Injection, lispro protamine human suspension 75% and rapid-acting lispro human solution 25% (Humalog® Mix 75/25™): 100 units/mL (3 mL disposable pen, 10 mL vial)

Injection, NPH human insulin suspension 50% and short-acting regular human insulin solution 50% (Humulin® 50/50): 100 units/mL (10 mL vial)

Injection, NPH human insulin suspension 70% and short-acting regular human insulin solution 30%:

Humulin® 70/30: 100 units/mL (3 mL disposable pen, 10 mL vial)

Novolin® 70/30: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial)

Novolin® 70/30 [PenFill®]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

International Brand Names: