Yes

Antidiabetic Agent (Insulin); Antidote

Treatment of insulin-dependent diabetes mellitus, also noninsulin-dependent diabetes mellitus unresponsive to treatment with diet and/or oral hypoglycemics; to assure proper utilization of glucose and reduce glucosuria in nondiabetic patients receiving parenteral nutrition whose glucosuria cannot be adequately controlled with infusion rate adjustments or those who require assistance in achieving optimal caloric intakes; hyperkalemia (regular insulin only; use with glucose to shift potassium into cells to lower serum potassium levels)

B; C (insulin glargine [Lantus®]; insulin aspart [NovoLog™])

Clinical effects on the fetus: Does not cross the placenta. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy. There are no well-controlled studies using insulin glargine (Lantus®) during pregnancy; use during pregnancy only if clearly needed.

Breast-feeding/lactation: The gastrointestinal tract destroys insulin when administered orally and therefore would not be expected to be absorbed intact by the breast-feeding infant.

Hypoglycemia is the most common adverse effect of insulin. The timing of hypoglycemia differs among various insulin formulations. 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; human insulin differs from animal-source insulin; regular insulin is the only insulin to be used I.V.; hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (insulin glargine, Ultralente®, insulin U) may delay recovery from hypoglycemia

Use with caution in renal or hepatic impairment

Insulin aspart (NovoLog™): Safety and efficacy of use in children has not been established

1% to 10%:

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 S.C. fat tissue

Neuromuscular & skeletal: Muscle weakness, paresthesia, tremors

Ocular: Transient presbyopia or blurred vision

Miscellaneous: Diaphoresis, anaphylaxis

Symptoms of overdose include tachycardia, anxiety, hunger, tremors, pallor, headache, motor dysfunction, speech disturbances, sweating, palpitations, coma, death

Antidote is glucose and glucagon, if necessary

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.

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

Insulin glargine (Lantus®): When refrigeration is unavailable, 10 mL vials and 3 mL cartridges may be stored at room temperature for up to 28 days, 5 mL vials may be stored at room temperature for 14 days; solution not used within these times must be discarded

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:

Protamine zinc insulin suspension (PZI): Compatible mixed with regular insulin

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: 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

The principal hormone required for proper glucose utilization in normal metabolic processes; it is obtained from beef or pork pancreas or a biosynthetic process converting pork insulin to human insulin; insulins are categorized into 3 groups related to promptness, duration, and intensity of action

Onset and duration of hypoglycemic effects depend upon preparation administered:

Lispro (Humalog®):

Onset 0.25 hours; peak 0.5-1.5 hours; duration 6-8 hours

Insulin aspart (NovoLog™):

Onset 0.5 hours; peak 1-3 hours; duration 3-5 hours

Insulin, regular (Novolin® R):

Onset 0.5-1 hours; peak 2-3 hours; duration 8-12 hours

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

Onset 1-1.5 hours; peak 4-12 hours; duration 24 hours

Insulin zinc suspension (Lente®):

Onset 1-2.5 hours; peak 8-12 hours; duration 18-24 hours

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

Onset 0.5 hours; peak 2-12 hours; duration 24 hours

Prompt zinc insulin suspension (PZI):

Onset 4-8 hours; peak 14-24 hours; duration 36 hours

Extended insulin zinc suspension (Ultralente®):

Onset 4-8 hours; peak 16-18 hours; duration >36 hours

Insulin glargine (Lantus®):

Duration 24 hours

Onset 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 S.C. 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 S.C. 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 and type 2 diabetes mellitus in patients who require basal (long-acting) insulin to control hypoglycemia.

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

Dose requires continuous medical supervision; may administer I.V. (regular), I.M., S.C.

Lispro should be given within 15 minutes before or immediately after a meal

Human regular insulin should be given within 30-60 minutes before a meal.

Intermediate-acting insulins may be administered 1-2 times/day.

Long-acting insulins may be administered once daily.

Insulin glargine (Lantus®) should be administered subcutaneously once daily at bedtime. Maintenance doses should be administered subcutaneously and sites should be rotated to prevent lipodystrophy.

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®):

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: Administer calcium gluconate and NaHCO₃ first then 50% dextrose at 0.5-1 mL/kg and 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

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

Cl_cr <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

Alcohol: Increase in hypoglycemic effect of insulin; monitor blood glucose concentration; avoid or limit use

Food:

Potassium: Shifts potassium from extracellular to intracellular space. Decreases potassium serum concentration; monitor potassium serum concentration.

Sodium: SIADH; water retention and dilutional hyponatremia may occur. Patients at greatest risk are those with CHF or hepatic cirrhosis. Monitor sodium serum concentration and fluid status.

Buffered insulin (Velosulin® BR) should not be mixed with any other form of insulin

Insulin glargine (Lantus®): Cannot be diluted or mixed with any other insulin or solution; should be administered S.C. only; use only if solution is clear and colorless

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

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

S.C. 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

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 given 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

Urine sugar and acetone, serum glucose, electrolytes

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

Glucose, fasting:

Newborns: 60-110 mg/dL

Adults: 60-110 mg/dL

Elderly: 100-180 mg/dL

May cause drowsiness or confusion

MAOIs may enhance the hypoglycemic effects of insulin; TCAs may antagonize the effects of insulin

No information available to require special precautions

Type 1 diabetics (insulin-dependent) should be appointed for dental treatment in the morning in order to minimize chance of stress-induced hypoglycemia

This medication is used to control diabetes; it is not a cure. Other components of treatment plan are important: follow prescribed diet, medication, and exercise regimen. Take exactly as directed. Do not change dose or discontinue unless so advised by prescriber. Inform prescriber of all other prescription or OTC medications you are taking; do not introduce new medication without consulting prescriber. If you experience hypoglycemic reaction, contact prescriber immediately. Maintain regular dietary intake and exercise routine and always carry quick source of sugar with you. 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; changes in vision; difficulty breathing; or nausea, vomiting, or flu-like symptoms. With insulin aspart (NovoLog™), you must start eating within 5-10 minutes after injection.

Patients using human insulin may be less likely to recognize hypoglycemia than if they use pork insulin, patients on pork insulin that have low blood sugar exhibit hunger and sweating; regular insulin is the only form for I.V. use. Patients who are unable to accurately draw up their dose will need assistance such as prefilled syringes. Patients using insulin aspart (NovoLog™) must start eating within 5-10 minutes following injection.

All insulins are 100 units/mL (10 mL) except where indicated:

Insulin lispro rDNA origin: Humalog®[ Lilly] (1.5 mL, 10 mL)

Insulin aspart injection: NovoLog™[ Novo Nordisk] (3 mL, 10 mL)

Insulin injection (Regular Insulin)

Beef and pork: Regular Iletin® I [ Lilly]

Human:

rDNA: Humulin® R [ Lilly], Novolin® R [ Novo Nordisk]

Semisynthetic: Velosulin® Human [ Novo Nordisk]

rDNA Human, Buffered: Velosulin® BR

Pork: Regular Insulin [ Novo Nordisk]

Purified pork:

Pork Regular Iletin® II [ Lilly], Regular Purified Pork Insulin [ Novo Nordisk]

Regular (Concentrated) Iletin® II U-500 ( Lilly): 500 units/mL

INTERMEDIATE-ACTING:

Insulin zinc suspension (Lente)

Beef and pork: Lente® Iletin® I [ Lilly]

Human, rDNA: Humulin® L [ Lilly], Novolin® L [ Novo Nordisk]

Purified pork: Lente® Iletin® II [ Lilly], Lente® L [ Novo Nordisk]

Isophane insulin suspension (NPH)

Beef and pork: NPH Iletin® I [ Lilly]

Human, rDNA: Humulin® N [ Lilly], Novolin® N [ Novo Nordisk]

Purified pork: Pork NPH Iletin® II [ Lilly], NPH-N [ Novo Nordisk]

LONG-ACTING:

Insulin zinc suspension, extended (Ultralente®)

Human, rDNA: Humulin® U [Lilly]

Insulin glargine, rDNA: Lantus®[ Avantis Pharmaceuticals Inc]

COMBINATIONS:

Isophane insulin suspension and insulin injection

Isophane insulin suspension (50%) and insulin injection (50%) human (rDNA): Humulin® 50/50 [ Lilly]

Isophane insulin suspension (70%) and insulin injection (30%) human (rDNA): Humulin® 70/30 [ Lilly], Novolin® 70/30 [ Novo Nordisk]

Insulin lispro protamine suspension and insulin lispro injection

Insulin lispro protamine suspension (50%) and insulin lispro injection (50%) (rDNA): Humalog® Mix 50/50™[ Lilly]

Insulin lispro protamine suspension (75%) and insulin lispro injection (25%) (rDNA): Humalog® Mix 75/25™[ Lilly]

The term "purified" refers to insulin preparations containing no more than 10 ppm proinsulin (purified and human insulins are less immunogenic). Buffering agent in Velosulin® BR may alter the activity of other insulin products.

Campbell IW and Ratcliffe JG, "Suicidal Insulin Overdosage Managed Exclusively by Excision of Insulin Injection Site," Br Med J (Clin Res Ed), 1982, 285(6339):408-9.

Hopkins DF, Cotton SJ, and Williams G, "Effective Treatment of Insulin-Induced Edema Using Ephedrine," Diabetes Care, 1993, 16(7):1026-8.

Levine DF and Bulstrode C, "Managing Suicidal Insulin Overdose," Br Med J (Clin Res Ed), 1982, 285(6346):974-5.

Morley JE and Perry HM 3d, "The Management of Diabetes Mellitus in Older Individuals," Drugs, 1991, 41(4):548-65.

Mueller-Schoop J, "Accidental Intravenous Self-Injection With Insulin Pen," Lancet, 1993, 341(8849):894.

Nathan DM, "Insulin Treatment in the Elderly Diabetic Patient," Clin Geriatr Med, 1990, 6(4):923-31.

Pickup J, "Human Insulin: Problems With Hypoglycaemia in a Few Patients," BMJ, 1989, 299(6706):991-3.

Roberge RJ, Martin TG, and Delbridge TR, "Intentional Massive Insulin Overdose: Recognition and Management," Ann Emerg Med, 1993, 22(2):228-34.

Simeon PS, Geffner ME, Levin SR, et al, "Continuous Insulin Infusions in Neonates: Pharmacologic Availability of Insulin in Intravenous Solutions," J Pediatr, 1994, 124(5 Pt 1):818-20.