Insulin Human

Class: Insulins
ATC Class: A10AB01
VA Class: HS501
Molecular Formula: C257H383N65O77S 6
CAS Number: 11061-68-0
Brands: Humulin, Humulin 70/30, Humulin 70/30 Pen, Humulin 50/50, Humulin L, Humulin N, Humulin R, Humulin U Ultralente, Novolin, Novolin 70/30, Novolin 70/30 Innolet, Novolin 70/30 PenFill, Novolin N, Novolin R

Introduction

Antidiabetic agent; a biosynthetic protein that is structurally identical to endogenous insulin secreted by the beta cells of the human pancreas.1 2 3 5 6 38 53 65 71 75 76 Available as short-acting, rapid-acting, intermediate-acting, or long-acting insulins.1 2 3 5 6 38 53 65 71 75 76

Uses for Insulin Human

Diabetes Mellitus

Replacement therapy for the management of diabetes mellitus.5 6 7 8 12 113 Human insulin manufactured using recombinant DNA technology is replacing pork insulin; future availability of animal insulins is uncertain.103

Insulin is required in all patients with type 1 diabetes mellitus, and mandatory in the treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic states.

Also used in patients with type 2 diabetes mellitus when weight reduction, proper dietary regulation, and/or oral antidiabetic agents have failed to maintain satisfactory glycemic control in both the fasting and postprandial state.

Diet should be emphasized as the primary form of treatment when initiating therapy for patients with type 2 diabetes mellitus who do not have severe symptoms; caloric restriction and weight reduction are essential in obese patients.

Slideshow: Prediabetes - Am I at Risk?

The American Diabetes Association (ADA) and many clinicians recommend the use of physiologically based, intensive insulin regimens (i.e., 3 or more insulin injections daily with dosage adjusted according to the results of multiple daily blood glucose determinations [e.g., at least 4 times daily], dietary intake, and anticipated exercise) in most type 1 and type 2 diabetic patients who are able to understand and carry out the treatment regimen, are not at increased risk for hypoglycemic episodes, and do not have other characteristics that increase risk or decrease benefit (e.g., advanced age, end-stage renal failure, advanced cardiovascular or cerebrovascular disease, other coexisting diseases that shorten life expectancy).

Goals of insulin therapy in all patients generally should include maintenance of blood glucose as close as possible to euglycemia without undue risk of hypoglycemia; avoidance of symptoms attributable to hyperglycemia, glycosuria, or ketonuria; and maintenance of ideal body weight and of normal growth and development in children.

The ADA states that human insulin is preferred for intermittent use and those initiating insulin therapy.103

Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic States

Used in the emergency treatment of diabetic ketoacidosis or hyperosmolar hyperglycemic states when rapid control of hyperglycemia is required.5 6 7 8 12 113 Regular insulin (e.g., insulin human [regular], insulin [regular]) is the insulin of choice in the treatment of such emergency conditions because of its rapid onset of action and because it can be administered IV.113

AMI

Has been used IV early in suspected AMI in combination with IV potassium chloride and dextrose (d-glucose) (referred to as glucose-insulin-potassium or GIK therapy).95 96 97 98 99

Acute Stroke

Insulin injection (e.g., insulin human) also has been used IV in combination with IV potassium chloride and dextrose (i.e., GIK therapy) in a limited number of patients with acute stroke and mild to moderate hyperglycemia.

Critical Illness

Has been used to reduce morbidity and mortality in patients with critical illness requiring intensive care.

Gestational Diabetes Mellitus

The ADA states that human insulin is preferred for use in pregnant women or women considering pregnancy.103 The ADA recommends that insulin therapy (using insulin human) be considered in patients with gestational diabetes who, despite dietary management, have fasting plasma glucose concentrations exceeding 105 mg/dL or 2-hour postprandial plasma glucose concentrations exceeding 130 mg/dL.

Insulin Human Dosage and Administration

General

  • Adjust dosage of insulin based on blood and urine glucose determinations and carefully individualize to attain optimum therapeutic effect.e

  • Because urine glucose concentrations correlate poorly with blood glucose values, urine glucose concentrations should be used only in patients who cannot (e.g., patients with severe neuropathies, severe vision impairment, Raynaud’s syndrome, paralysis, or those receiving anticoagulants) or will not test blood glucose concentrations.

  • Some clinicians state that in some geriatric patients in whom control of hyperglycemic symptoms is the treatment goal, monitoring of urine glucose concentrations may be adequate.

  • Patients receiving conventional insulin regimens should self-monitor blood glucose concentrations with a frequency ranging from once or twice daily to several times weekly.

  • In patients receiving intensive insulin regimens, the decision to supplement or decrease the previous preprandial dose of short- or rapid-acting insulin is made on the basis of blood glucose determinations obtained before each preprandial insulin injection.

Transferring from Therapy with Other Insulins

  • Make any change in insulin preparation or dosage regimen with caution and only under medical supervision.5 6 7 8 80 88 93 94 103 Changes in purity, strength, brand, type, and/or species source or method of manufacture may necessitate a change in dosage.5 6 7 8 77 78 79 80 88 93 94

  • Not possible to clearly identify which patients will require a change in dosage when therapy with a different preparation is initiated.5 6 7 8 May need adjustments with the first dose or may occur over a period of several weeks.5 6 7 8

  • In patients who are currently controlled on purified pork insulins, no change in dosage is usually required when transferring to insulin human, except routine dosage adjustments that are necessary to maintain stable glycemic control.12 However, hypoglycemic reactions reported in patients who were transferred from pork insulin to insulin human (regular).

Administration

Insulin human (regular), isophane insulin human suspension, and insulin human zinc suspension usually are administered sub-Q.12 54 55 71 75 82 84 88

May administer insulin human (regular) IM or IV for the treatment of diabetic ketoacidosis or hyperosmolar hyperglycemia.12 113 Insulin human (regular) is the only form of insulin human that may be administered IV.54 55

Insulin human (regular) in a dry-powder formulation has been used via oral inhalation with some success in a limited number of patients to avoid the pain and inconvenience of multiple daily injections.104 105 106 107 108 109 110

Do not administer isophane insulin human suspension and insulin human zinc suspension IV.54 55

Sub-Q Administration

Administer insulin human (regular) injection, isophane insulin human suspension, and insulin human zinc suspension usually by sub-Q injection.12 55 71 75 82 84 88

Avoid excessive agitation of the vial prior to withdrawing the insulin human regular dose since loss of potency, clumping, frosting, or precipitation may occur.67 101

Since suspensions contain insulin in the precipitate, gently agitate the vial to assure a homogeneous mixture for accurate measurement of each dose.6 8 75 84 92 93 Slowly rotate and invert or carefully shake the vial several times before withdrawal of each dose.6 8 75 84 Avoid vigorous shaking since frothing may interfere with correct measurement of a dose.6 8

Administer into the thighs, upper arms, buttocks, or abdomen using a 25- to 28-gauge needle, one-half to five-eighths inch in length.e g h j

Most individuals should grasp a fold of skin lightly with the fingers at least 3 inches apart and insert the needle at a 90° angle; thin individuals or children may need to pinch the skin and inject at a 45° angle to avoid IM injection, especially in the thigh area.

Routine aspiration to check for inadvertent intravascular injection generally is not necessary.

Inject over a period of 2–4 seconds.g h j Slow sub-Q injection of insulin suspensions may result in clogging of the tip of the needle.6 8

Press injection site lightly for a few seconds after the needle is withdrawn; do not rub.e g h j

Rotate sites so that any one site is not injected more than once every 1–2 weeks.

IV Administration

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

In general, reserve IV route for use in patients with circulatory collapse, diabetic ketoacidosis, hyperosmolar hyperglycemia, or hyperkalemia.54 55 113 Has also been administered by IV infusion for metabolic modulation in AMI or hyperglycemia associated with critical illness.12 112

Dilution

For IV infusion, usually dilute insulin human (regular) injection in 0.9% sodium chloride injection.54 55 However, has been diluted in 10 or 25% dextrose injection for IV infusion as GIK therapy in AMI.95 96

Dosage

Patients receiving insulin should be monitored with regular laboratory evaluations, including blood glucose determinations and glycosylated hemoglobin (hemoglobin A1c [HbA1c]) concentrations, to determine the minimum effective dosage of insulin when used alone, with other insulins, or in combination with an oral antidiabetic agent.

Pediatric Patients

Diabetes Mellitus
Sub-Q

Dosage must be individualized.o

In newly diagnosed children with severe diabetes mellitus, unstable diabetes mellitus, or diabetes mellitus with complications, insulin (regular) (i.e., purified pork insulin) generally is given sub-Q in a dosage of 2–4 units, 15–30 minutes before meals and at bedtime.e

In patients who are currently controlled on purified pork insulins, no change in dosage usually is required when transferring to insulin human, except routine dosage adjustments that are necessary to maintain stable glycemic control.12

Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States
IV

In children and adolescents <20 years of age, the ADA recommends initially an IV infusion of regular insulin at a rate of 0.1 units/kg per hour.113 An initial direct IV injection of regular insulin is not recommended in such patients.113

IM, then Sub-Q

If IV access is unavailable, regular insulin may be given IM in an initial dose of 0.1 units/kg, followed by 0.1 units/kg per hour sub-Q or IM until acidosis is resolved (i.e., venous pH >7.3, serum bicarbonate concentration >15 mEq/L).113

Dosage Following Resolution of Diabetic Ketoacidosis
IV, then Sub-Q

Upon resolution of ketoacidosis or the hyperosmolar state, the regular insulin IV infusion rate should be decreased to 0.05 units/kg per hour until sub-Q replacement insulin therapy is initiated.113

Initiate replacement therapy at an insulin dosage of 0.5–1 units/kg daily given sub-Q in divided doses ((2/3) of the daily dosage in the morning [(1/3) as short-acting insulin, (2/3) as intermediate-acting insulin] and (1/3) in the evening [½ as short-acting insulin, ½ as intermediate-acting insulin]).113 In pediatric patients with newly diagnosed diabetes mellitus, may administer 0.1–0.25 units/kg of regular insulin every 6–8 hours during the first 24 hours to determine insulin requirements.113

Adults

Diabetes Mellitus
Sub-Q

Dosage must be individualized.

In newly diagnosed patients with severe diabetes mellitus, unstable diabetes mellitus, or diabetes mellitus with complications, insulin (regular) (i.e., purified pork insulin) generally is given sub-Q in a dosage of 5–10 units, 15–30 minutes before meals and at bedtime.e

In patients who are currently controlled on purified pork insulins, no change in dosage usually is required when transferring to insulin human, except routine dosage adjustments that are necessary to maintain stable glycemic control.12

Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States
Mild Diabetic Ketoacidosis
IV, then Sub-Q or IM

For the treatment of mild diabetic ketoacidosis (plasma glucose >250 mg/dL with an arterial pH of 7.25–7.3 and serum bicarbonate of 15–18 mEq/L), the ADA recommends a loading dose of 0.4–0.6 units/kg of regular insulin administered in 2 doses, with 50% given by direct IV injection and 50% by sub-Q or IM injection.113 After the loading dose, administer 0.1 units/kg per hour of regular insulin sub-Q or IM.113

Moderate to Severe Diabetic Ketoacidosis
IV

For the treatment of moderate to severe diabetic ketoacidosis (plasma glucose >250 mg/dL with arterial pH ≤7–7.24 and serum bicarbonate ≤10–15 mEq/L) or hyperosmolar hyperglycemia in adults, the ADA recommends a loading dose of 0.15 units/kg of regular insulin by direct IV injection, followed by continuous IV infusion of 0.1 units/kg per hour.113

If plasma glucose concentrations do not fall by 50 mg/dL within the first hour of insulin therapy, insulin infusion rate may be doubled every hour, provided the patient is adequately hydrated, until plasma glucose decreases steadily by 50–75 mg/dL per hour.113

When a plasma glucose concentration of 250 or 300 mg/dL is achieved in patients with diabetic ketoacidosis or hyperosmolar hyperglycemia, respectively, may decrease the insulin infusion rate to 0.05–0.1 units/kg per hour.113 May need to adjust the rate of insulin administration or the concentration of dextrose to maintain glucose concentration until resolution of diabetic ketoacidosis (i.e., serum glucose <200 mg/dL, venous pH >7.3, serum bicarbonate ≥18 mEq/L) or hyperosmolar hyperglycemia (i.e., patient mentally alert, serum osmolality of ≤315 mOsm/kg).b

Dosage Following Resolution of Diabetic Ketoacidosis
IV, then Sub-Q

Upon resolution of diabetic ketoacidosis (i.e., plasma glucose <200 mg/dL, venous pH >7.3, serum bicarbonate ≥18 mEq/L) or hyperosmolar hyperglycemia in patients who are unable to eat, continue IV insulin and fluid replacement; may give sub-Q regular insulin as needed every 4 hours.113 May give regular insulin sub-Q in 5-unit increments for every 50-mg/dL increase in blood glucose concentrations above 150 mg/dL, to a dose of up to 20 units of regular insulin for a blood glucose of ≥300 mg/dL.113

When the patient is able to eat, initiate a multiple-dose, sub-Q insulin regimen consisting of a short- or rapid-acting insulin and an intermediate- or long-acting insulin.113 Continue regular insulin IV for 1–2 hours after initiation of the sub-Q insulin regimen to ensure adequate plasma insulin concentrations during the transition.113 Abrupt discontinuance of IV insulin with the institution of delayed-onset sub-Q insulin may lead to worsened glycemic control.113 Patients with known diabetes mellitus may reinstitute the insulin regimen they were receiving before the onset of hyperglycemic crises, and the regimen may be adjusted further as needed for adequate glycemic control.113

Patients with newly diagnosed diabetes mellitus should receive a total daily insulin dosage of 0.5–1 units/kg as part of a multiple-dose regimen of short- and long-acting insulin, until an optimal dosage is established.113 May manage some patients with newly diagnosed type 2 diabetes mellitus with diet therapy and oral antidiabetic agents following resolution of hyperglycemic crises.113

AMI
IV

For metabolic modulation in patients with AMI, a low-dose GIK solution (containing regular insulin 20 units/L and potassium chloride 40 mEq/L in 10% dextrose injection) has been infused at a rate of 1 mL/kg per hour for 24 hours, and a high-dose solution (containing regular insulin 50 units/L and potassium chloride 80 mEq/L in 25% dextrose injection) has been infused at a rate of 1.5 mL/kg per hour for 24 hours.95 96 High-dose regimen may be more effective and is therefore preferred.95 96

Cautions for Insulin Human

Warnings/Precautions

Warnings

Hypoglycemia

Care should be taken in patients who are most at risk for the development of these effects, including patients who are fasting or those with defective counterregulatory responses (e.g., patients with autonomic neuropathy, adrenal or pituitary insufficiency, those receiving β-adrenergic blocking agents).

Reduce the potential for late postprandial hypoglycemia by altering the timing, frequency, and content of meals; altering exercise patterns; frequently monitoring blood glucose concentrations; adjusting insulin dosage; and/or switching to a more rapid-acting insulin (i.e., insulin lispro).

Use intensive insulin therapy with caution in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes. Higher target blood glucose concentrations (e.g., fasting blood glucose concentrations of 140 mg/dL and 2-hour postprandial concentrations of 200–250 mg/dL) are advisable in these patients.

Exercise extreme caution when concentrated (U-500) insulin human (regular) injection is used in patients with marked insulin resistance (i.e., daily insulin requirements >200 units).o Inadvertent overdosage may result in irreversible insulin shock.o Serious consequences may result if this concentrated injection is used without constant medical supervision.o

Sensitivity Reactions

Local reactions (e.g., pain at injection site, erythema, pruritus, swelling) reported.c Warming refrigerated insulin to room temperature prior to use will limit local irritation at the injection site.67 101

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

Insulin human is less immunogenic than purified pork insulin.34 35 45 46 59 The incidence of allergic reactions may have decreased with the availability of more purified insulin (e.g., insulin human, insulin lispro). In patients who may have selective allergic reactions to pork insulin or proteins, prevent further allergic reactions by substitution of an insulin that contains less protein (i.e., purified insulins, including insulin human). The ADA states that human insulin is preferred for use in individuals with allergies to animal-derived insulins.103

Insulin Resistance

Chronic insulin resistance resulting from immunity has been decreased by changing to a purified insulin preparation (e.g., insulin human). The ADA states that human insulin is preferred for use in individuals with immune resistance to animal-derived insulins.103

General Precautions

Lipodystrophy

Atrophy or hypertrophy of subcutaneous fat tissue may occur at sites of frequent insulin injections.c Rotate injection site to reduce or prevent these effects.d

Hypokalemia

Care should be taken in patients who are most at risk for the development of hypokalemia, such as those who are receiving potassium-lowering drugs.

Since diabetic ketoacidosis often is associated with hypokalemia, the possibility of potassium imbalance should be evaluated and, if present, corrected before administration of insulin as long as adequate renal function is assured.

Concurrent Illness

Illness, particularly nausea and vomiting, and changes in eating patterns may alter insulin requirements.c

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.

Most clinicians recommend initiation of intensive insulin therapy (3 or more insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) prior to conception in diabetic patients who are well controlled on oral hypoglycemic agents and who are considering pregnancy.

Geriatric Use

The safety of an intensive insulin regimen (3 or more insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) in geriatric patients has been questioned. Increased incidence of hypoglycemia associated with intensive insulin therapy may increase the probability of strokes and heart attacks in such patients.

Hypoglycemic reactions in geriatric diabetic patients may mimic a cerebrovascular accident.d An increased incidence of macrovascular disease in geriatric patients with type 2 diabetes mellitus may make such patients more vulnerable to serious consequences of hypoglycemia (e.g., fainting, seizures, falls, stroke, silent ischemia, MI, sudden death).

Common Adverse Effects

Hypoglycemia.

Interactions for Insulin Human

Specific Drugs

  • Drugs That May Potentiate Hypoglycemic Effects
  • Alcohol

  • ACE inhibitors

  • Disopyramide

  • Fibrate derivatives

  • Fluoxetine

  • Guanethidine

  • MAO inhibitors

  • Oral antidiabetic agents

  • Propoxyphene

  • Salicylates

  • Somatostatin derivatives (e.g., octreotide)

  • Sulfa anti-infectives

  • Drugs That May Antagonize Hypoglycemic Effects
  • Calcium-channel blocker

  • Corticosteroids

  • Danazol

  • Diuretics

  • Estrogens and progestins (e.g., oral contraceptives)

  • Isoniazid

  • Niacin

  • Phenothiazines

  • Somatropin

  • Sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline)

  • Thyroid hormones

  • Drugs That May Have a Variable Effect on Glycemic Control
  • Alcohol

  • β-Adrenergic blocking agents

  • Clonidine

  • Lithium salts

  • Pentamidine

  • Drugs That May Reduce or Eliminate Signs of Hypoglycemia (Sympatholytic Agents)
  • β-Adrenergic blocking agents

  • Clonidine

  • Guanethidine

  • Reserpine

Insulin Human Pharmacokinetics

Absorption

Bioavailability

Because of its protein nature, insulin is destroyed in the GI tract and usually is administered parenterally.e

Following sub-Q injection, insulin human (regular) appears to be absorbed more rapidly than purified pork insulin (regular).17 24 28 29 30 42

Following IM or IV administration, serum insulin concentrations are similar for insulin human (regular) and purified pork insulin (regular).17 18 19 31 32 43

Onset and Duration of Action of Human Insulins

Formulation

Onset (hours)

Peak (hours)

Duration (hours)

Short-Acting

 Insulin (regular) 71

0.5

2.5–5

8

Intermediate-Acting

 Insulin Zinc (Lente)

1–3

6–14

16–24+

 Isophane Insulin (NPH) humanf g

1.5

4–12

24

Long-Acting

 Insulin zinc, extended (Ultralente)

4–6

8–20

24–28

Insulin Mixtures

Insulin Human and Insulin Isophane (Humulin 50/50)

0.5–1

1.5–4.5

7.5–24

Insulin Human and Insulin Isophane (Novolin 70/30, Humulin 70/30)h q

0.5

2–12

24

In patients with diabetes mellitus, insulin human appears to have a slightly faster onset and shorter duration of action than purified pork insulin.58

Distribution

Extent

Rapidly distributed throughout extracellular fluids.e

Elimination

Metabolism

Rapidly metabolized mainly in the liver and to a lesser extent in the kidneys and muscle tissue.e

Elimination Route

Excreted in the urine principally as metabolites.e

Half-life

Insulin has a plasma half-life of a few minutes in healthy individuals.e The biologic half-life may be prolonged in diabetic patients, probably as a result of binding of the hormone to antibodies.

Special Populations

In patients with renal impairment, the biologic half-life may be prolonged as a result of altered degradation/decreased clearance.

Stability

Storage

Parenteral

Solution for Injection

With unopened vials or cartridges of insulin human injections than have not been placed in a delivery device, 2–8°C; do not freeze.5 7 53 64 67 71 82 89 93 100 101 c j Vials in use, below 30°C; protect from excessive heat or cold and light.67 c

Novolin PenFill 3-mL cartridges of insulin human (regular) injection assembled in a delivery device are stable for 28 days at room temperature.71 Discard unrefrigerated Novolin Penfill cartridges not used within this time period.67 Protect from excessive heat or cold and light.71

Discard insulin human (regular) injection exhibiting discoloration, turbidity, or unusual viscosity,5 7 71 82 88 89 since these changes indicate deterioration or contamination.5 7 101

Suspension for Injection

With unopened vials, pens, prefilled syringes, or cartridges containing insulin human zinc or isophane insulin human suspensions, 2–8°C in the original container; do not freeze.6 8 53 64 65 80 84 92 93 100 101 f g h i k l m p q With vials in use, below 30°C; protect from heat and light.80 g h i k l m r Freezing will cause isophane insulin human and insulin human zinc to resuspend improperly, preventing accurate measurement of a dose.54 55 In addition, agglomeration of particles may occur, altering absorption from the injection site.54 55

Preparations of insulin isophane suspension available with a delivery device (Novolin N PenFill cartridges, Humulin N pen) are stable below 30°C for 14 days.67 f m Protect from excessive heatf m or coldf and light.f m

Preparations of insulin human and isophane insulin human suspensions available with a delivery device (Novolin 70/30 PenFill 3-mL cartridges assembled in a delivery device, Novolin 70/30 Innoletprefilled syringes, Humulin 70/30 pen) are stable below 30°C for 10 days.67 f p q Should discard unrefrigerated insulin after 10 days.p Protect from excessive heat and light.p

Should discard isophane insulin human and insulin human zinc if the suspensions are clear, if they remain clear after the vial is rotated, if the precipitate has become clumped or granular in appearance, or if solid particles have adhered to the wall of the vial.6 8 64 65 75 76 80 83 84 90 92 93 101

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID (Human Insulin Regular)

10% insulin loss in 1 hour in PVC container; 35–45% loss in 24 hours in polyolefin container.

Variable

Sodium chloride 0.9%

Drug Compatibility (Human Insulin Regular)
Admixture CompatibilityHID

Compatible

Meropenem

Incompatible

Cytarabine

Octreotide acetate

Ranitidine HCl

Y-Site CompatibilityHID

Compatible

Amiodarone HCl

Ampicillin sodium

Ampicillin sodium-sulbactam sodium

Aztreonam

Caspofungin acetate

Cefazolin sodium

Cefepime HCl

Cefotetan disodium

Ceftaroline fosamil

Ceftazidime

Dobutamine HCl

Doripenem

Doxapram HCl

Esmolol HCl

Famotidine

Gentamicin sulfate

Heparin sodium

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Imipenem-cilastatin sodium

Indomethacin sodium trihydrate

Magnesium sulfate

Meperidine HCl

Meropenem

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nitroglycerin

Oxytocin

Pantoprazole sodium

Pentobarbital sodium

Propofol

Sodium bicarbonate

Sodium nitroprusside

Tacrolimus

Terbutaline sulfate

Ticarcillin disodium-clavulanate potassium

Tobramycin sulfate

Vancomycin HCl

Vasopressin

Incompatible

Dopamine HCl

Micafungin sodium

Nafcillin sodium

Nesiritide

Norepinephrine bitartrate

Ranitidine HCl

Variable

Digoxin

Levofloxacin

Actions

  • Supplements deficient levels of endogenous insulin and temporarily restores the ability of the body to properly utilize carbohydrates, fats, and proteins.e Facilitates cellular uptake of glucose in muscle and fat cells.d e

  • Inhibits output of glucose from the liver.d e In the liver, insulin facilitates phosphorylation of glucose to glucose-6-phosphate which is converted to glycogen or further metabolized.e

  • Stimulates lipogenesis and inhibits lipolysis and release of free fatty acids from adipose cells.e Insulin also stimulates protein synthesis.e

  • Promotes an intracellular shift of potassium and magnesium and thereby appears to temporarily decrease elevated blood concentrations of these ions.e

  • When used in patients following an AMI, insulin in combination with dextrose (d-glucose) and potassium (referred to as glucose-insulin-potassium [GIK] therapy) decreases both circulating concentrations of free fatty acids (FFAs) and myocardial uptake of FFAs. Rationale for G1K therapy: Stimulation of myocardial potassium uptake by insulin via Na+-K+-ATPase and provision of glucose (substrate) for glycolic ATP production. Aids in critical membrane functions such as calcium and sodium homeostasis.

  • Insulin human has essentially identical pharmacologic effects compared with purified pork insulin.12 13 17 18 19 20 21 22 23 38 39 40

Advice to Patients

  • Importance of strict adherence to manufacturer’s instructions regarding assembly, administration, and care of specialized delivery systems, such as insulin pens or pumps.n

  • Provide instructions regarding insulin storage and injection technique.d n

  • Provide instructions regarding the use of intensive insulin therapy with multiple injections.d Advise patients of the risks of such therapy (e.g., hypoglycemia).

  • Provide instructions regarding self-monitoring of blood glucose concentrations.c n Particular importance of frequent self-monitoring of blood glucose concentrations in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes.

  • Provide instructions regarding adherence to meal planning, regular physical exercise, periodic hemoglobin A1c (HbA1c) monitoring, and management of hypoglycemia or hyperglycemia.d n

  • Importance of changing insulin dosage with caution and only under medical supervision.d Discuss potential for alterations in insulin requirements in special situations (e.g., illness, concomitant agents that alter glycemic control, travel, emotional disturbances or other stresses).c d Discuss potential for alterations in insulin requirements as a result of changes in physical activity, missed doses, or inadvertent administration of incorrect doses.c d

  • Importance of not changing the order of mixing insulins or the model or brand of syringe or needle without medical supervision.c e When mixing with other insulin preparations, importance of drawing regular insulin into the syringe first.e n

  • Importance of informing clinicians of the development of skin reactions (erythema, pruritus, edema, lipodystrophy) at injection site.c

  • Importance of informing clinicians of the development of generalized hypersensitivity reactions (shortness of breath, hypotension, wheezing, whole body rash, tachycardia, diaphoresis).c

  • Importance of patient wearing a medical identification bracelet or pendant, carrying ample insulin supply and syringes on trips, having carbohydrates (sugar or candy) on hand for emergencies, and of noting time-zone changes for dose schedule when traveling.c n

  • Inform patient that use of marijuana may increase insulin requirements.n

  • Importance of patient not smoking within 30 minutes after insulin injection due to potential for decreased absorption of insulin.n

  • Instruct patient on the appropriate measures for safe disposal of needles.n

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

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.c

  • Importance of informing patients of other important precautionary information.c (See Cautions.)

Preparations

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

Extended Insulin Human Zinc (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension

100 units/mL

Humulin U Ultralente

Lilly

Insulin Human (Regular) (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

100 units/mL

Humulin R

Lilly

Novolin R

Novo Nordisk

500 units/mL

Humulin R (concentrated U-500)

Lilly

Injection, for use with NovoPen or other compatible device (e.g., NovolinPen) only

100 units/mL (150 units)

Novolin R PenFill

Novo Nordisk

Insulin Human Zinc (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, sterile

100 units/mL

Humulin L

Lilly

Isophane Insulin Human (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, sterile

100 units/mL

Humulin N

Lilly

Humulin N Pen (available as prefilled cartridge preassembled into pen)

Lilly

Novolin N

Novo Nordisk

Suspension, sterile, for use with NovoPen or other compatible device (e.g., NovolinPen) only

100 units/mL (150 units)

Novolin N PenFill

Novo Nordisk

Insulin Human Combinations (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, sterile

Insulin Human (Regular) 30 units/mL with Isophane Insulin Human 70 units/mL

Humulin 70/30

Lilly

Humulin 70/30 Pen (available as cartridge pressambled into pen)

Lilly

Novolin 70/30

Novo Nordisk

Novolin 70/30 Innolet (available as 3 mL disposable syringe)

Novo Nordisk

Insulin Human (Regular) 50 units/mL with Isophane Insulin Human 50 units/mL

Humulin 50/50

Lilly

Suspension, sterile, for use with NovoPen or other compatible device (e.g., NovolinPen) only

Insulin Human (Regular) 30 units/mL with Isophane Insulin Human 70 units/mL (150 units)

Novolin 70/30 PenFill

Novo Nordisk

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

HumuLIN 70/30 70-30% Suspension (LILLY): 10/$73.99 or 30/$205.97

HumuLIN 70/30 Pen 70-30% Suspension (LILLY): 30/$451.98 or 90/$1,319.01

HumuLIN N 100UNIT/ML Suspension (LILLY): 10/$73.99 or 30/$206.00

HumuLIN R 100UNIT/ML Solution (LILLY): 10/$73.99 or 30/$201.97

HumuLIN R U-500 (Concentrated) 500UNIT/ML Solution (LILLY): 20/$443.01 or 60/$1,298.03

NovoLIN 70/30 70-30% Suspension (NOVO NORDISK): 10/$75.99 or 30/$205.97

NovoLIN N 100UNIT/ML Suspension (NOVO NORDISK): 10/$74.99 or 30/$205.97

NovoLIN R 100UNIT/ML Solution (NOVO NORDISK): 10/$75.99 or 30/$203.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 10, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Chance RE, Kroeff EP, Hoffman BH. Chemical, physical and biological properties of biosynthetic human insulin. Diabetes Care. 1981; 4:147-55. [PubMed 7011716]

2. Markussen J, Jorgensen K, Kim L et al. Human monocomponent insulin: chemistry and characteristics of human insulin (Novo). Diabetologia. 1981; 21:302.

3. Markussen J, Damgaard U, Pingel M et al. Human insulin (Novo): chemistry and characteristics. Diabetes Care. 1981; 6(Suppl 1):4-8.

4. Markussen J. The advent of human insulin in diabetes therapy. Medicographia. 1982; 4:39-44.

5. Eli Lilly and Company. Humulin R injection prescribing information. Indianapolis, IN; 1983 Jun.

6. Eli Lilly and Company. Humulin N sterile suspension prescribing information. Indianapolis, IN; 1987 Feb.

7. Squibb-Novo, Inc. Actrapid Human injection (Regular) prescribing information. Princeton, NJ; 1983 Jul.

8. Squibb-Novo, Inc. Monotard Human Zinc suspension (Lente) prescribing information. Princeton, NJ; 1983 Jul.

9. Larner J. Insulin and oral hypoglycemic drugs; glucagon. In: Gilman AG, Goodman L, Gilman A, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 6th ed. New York: Macmillan Publishing Company; 1980:1497-1523.

10. Anon. Squibb-Novo human insulins. Squibb-Novo, Inc, Princeton, NJ. Publication no 393-019; 1983 Jul.

11. Newton DW. Introduction: physicochemical determinants of incompatibility and instability of drugs for injection and infusion. In: Trissel LA. Handbook on injectable drugs. 3rd ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc., Inc; 1983:xi-xxi.

12. Squibb-Novo, Inc. Insulin monograph. Actrapid Human, Monotard Human. Princeton, NJ; 1983 Sep.

13. Adeniyi-Jones ROC, Jones RH, Barnes DG et al. Porcine and human insulin (Novo): a comparison of their metabolism and hypoglycemic activity in normal man. Diabetes Care. 1983; 6(Suppl 1):9-12. [PubMed 6343043]

14. Crea R, Kraszewski A, Hirose T et al. Chemical synthesis of genes for human insulin. Proc Natl Acad Sci USA. 1978; 75:5765-9. [PubMed 282602]

15. Goeddel DV, Kleid DG, Bolivar F et al. Expression in Escherichia coli of chemically synthesized genes for human insulin. Proc Natl Acad Sci USA. 1979; 76:106-10. [PubMed 85300]

16. Morihara K, Oka T, Tsuzuki H. Semi-synthesis of human insulin by trypsin catalyzed replacement of Ala-B30 by Thr in porcine insulin. Nature. 1979; 280:412-3. [PubMed 460416]

17. Ebihara A, Kondo K, Ohashi K et al. Comparative clinical pharmacology of human insulin (Novo) and porcine insulin in normal subjects. Diabetes Care. 1983; 6(Suppl 1):17-22. [PubMed 6343032]

18. Home PD, Shepherd GAA, Noy G et al. Comparison of the activity and pharmacokinetics of porcine insulin and human insulin (Novo) as assessed by the glucose clamp technique in normal and diabetic man. Diabetes Care. 1983; 6(Suppl 1):23-8. [PubMed 6343033]

19. Charles MA, Szekeres A, Staten M et al. Comparison of porcine insulin and human insulin (Novo) using the glucose-controlled insulin infusion system, glucose-insulin dose-response curves, and the outpatient effectiveness of human insulin (Novo) in insulin-dependent diabetes. Diabetes Care. 1983; 6(Suppl 1):29-34. [PubMed 6343034]

20. Mirouze J, Benghernaout O, Pham TC et al. Comparative analysis of soluble porcine and human insulin (Novo) using the artificial pancreas. Diabetes Care. 1983; 6(Suppl 1):40-2. [PubMed 6343037]

21. Sestoft L, Volund A, Gammeltoft S et al. The biological properties of human insulin. Acta Med Scand. 1982; 212:21-8. [IDIS 159641] [PubMed 6751025]

22. Keen H, Glynne A, Pickup JC et al. Human insulin produced by recombinant DNA technology: safety and hypoglycemic potency in healthy men. Lancet. 1980; 2:398-401. [IDIS 125061] [PubMed 6105520]

23. Clark AJL, Knight G, Wiles PG et al. Biosynthetic human insulin in the treatment of diabetes. Lancet. 1982; 2:354-7. [IDIS 155077] [PubMed 6124760]

24. Sonnenberg GE, Kemmer FW, Cuppers HJ et al. Subcutaneous use of regular human insulin (Novo): pharmacokinetics and continuous insulin infusion therapy. Diabetes Care. 1983; 6(Suppl 1):35-9. [PubMed 6343035]

25. Owens DR, Jones MK, Hayes TM et al. Human insulin: study of safety and efficacy in man. BMJ. 1981; 282:1264-6. [IDIS 130687] [PubMed 6784807]

26. Owens ER, Jones MK, Birtwell AJ et al. The clinical pharmacology of human insulin (Novo) in normal subjects. Diabetes Care. 1983; 6(Suppl 1):13-6. [PubMed 6133710]

27. Karam JH. Introduction: evolution of human insulin in the therapy of diabetes mellitus. Diabetes Care. 1983; 6(Suppl 1):1-2. [PubMed 6343030]

28. Botterman P, Gyaram H, Wahl K et al. Pharmacokinetics of biosynthetic human insulin and characteristics of its effects. Diabetes Care. 1981; 4:168-9. [PubMed 7011719]

29. Federlin K, Laube H, Velcovsky HG. Biologic and immunologic in vivo and in vitro studies with biosynthetic human insulin. Diabetes Care. 1981; 4:170-4. [PubMed 7011720]

30. Berger M, Cuppers HJ, Chantelau EA et al. Absorption kinetics of subcutaneously injected insulin preparations. In: Skyler JS, ed. Insulin update: 1982. Princeton: Excerpta Medica; 1982:97-110.

31. Owens DR, Jones MK, Hayes TM et al. Comparative study of subcutaneous, intramuscular and intravenous administration of human insulin. Lancet. 1981; 2:118-22. [IDIS 134506] [PubMed 6113483]

32. Massi-Benedetti M, Burrin JM, Capaldo B et al. A comparative study of biosynthetic human insulin and pork insulin using the glucose clamp technique in normal subjects. Diabetes Care. 1981; 4:163-7. [PubMed 7011718]

33. Etzwiler DD. International symposium on human insulin: a summary. Diabetes Care. 1983; 6(Suppl 1):66-8.

34. Schernthaner G, Borkenstein M, Fink M et al. Immunogenicity of human insulin (Novo) or pork monocomponent insulin in HLA-DR-typed insulin-dependent diabetic individuals. Diabetes Care. 1983; 6(Suppl 1):43-8. [PubMed 6343038]

35. Falholt K, Hoskom JAM, Karamanos BG et al. Insulin-specific IgE in serum of 67 diabetic patients against human insulin (Novo), porcine insulin, and bovine insulin. Four case reports. Diabetes Care. 1983; 6(Suppl 1):61-5. [PubMed 6343042]

36. Wu W, Nolte M, Hellmann N et al. Superiority of human monocomponent insulin to pork monocomponent insulin in a diabetic with severe immune insulin resistance. Clin Res. 1983; 31:95A.

37. Karam J, Brink S, Clements R et al. Evaluation of efficacy and safety of human insulin (Novo) in the treatment of insulin-dependent diabetes mellitus: a double-blind, multicenter clinical trial. Diabetes Care. 1983; 6(Suppl 1):56-60. [PubMed 6343041]

38. Johnson IS. Authenticity and purity of human insulin (recombinant DNA). Diabetes Care. 1982; 5(Suppl 2):4-12. [PubMed 6765539]

39. Ebihara A, Kondo K, Ohashi K et al. Clinical pharmacology of human insulin of recombinant DNA origin in healthy volunteers. Diabetes Care. 1982; 5(Suppl 2):35-8. [PubMed 6765537]

40. Miroaze J, Monnier L, Richard JL et al. Comparative study of NPH human insulin (recombinant DNA) and pork insulin in diabetic subjects: preliminary report. Diabetes Care. 1982; 5(Suppl 2):60-2. [PubMed 6765543]

41. Galloway JA, Root MA, Bergstrom R et al. Clinical pharmacologic studies with human insulin (recombinant DNA). Diabetes Care. 1982; 5(Suppl 2):13-22. [PubMed 6765524]

42. Kemmer FW, Sonnenberg G, Cuppers HJ et al. Absorption kinetics of semisynthetic human insulin and biosynthetic (recombinant DNA) human insulin. Diabetes Care. 1982; 5(Suppl 2):23-8. [PubMed 6765535]

43. Pickup JC, Bilous RW, Viberti GC et al. Plasma insulin and C-Peptide after subcutaneous and intravenous administration of human insulin (recombinant DNA) and purified porcine insulin in healthy men. Diabetes Care. 1982; 5(Suppl 2):29-34. [PubMed 6765536]

44. Howey DC, Fineberg SE, Nolen PA. The therapeutic efficacy of human insulin (recombinant DNA) in patients with insulin-dependent diabetes mellitus: a comparative study with purified porcine insulin. Diabetes Care. 1982; 5(Suppl 2):73-7. [PubMed 6765546]

45. Schernthaner G. Affinity of IgG-insulin antibodies to human (recombinant DNA) insulin and porcine insulin in insulin-treated diabetic individuals with and without insulin resistance. Diabetes Care. 1982; 5(Suppl 2):114-8. [PubMed 6765520]

46. Fireman P, Fineberg SE, Galloway JA. Development of IgE antibodies to human (recombinant DNA), porcine, and bovine insulin in diabetic subjects. Diabetes Care. 1982; 5(Suppl 2):119-25. [PubMed 6765521]

47. Clark AJ, Wiles PG, Leiper JM. A double-blind crossover trial comparing human insulin (recombinant DNA) with animal insulin in the treatment of previously insulin-treated diabetic patients. Diabetes Care. 1982; 5(Suppl 2):129-34. [PubMed 6765523]

48. Galloway JA, Peck FB Jr, Fineberg SE. The U.S. “new patient” and “transfer” studies. Diabetes Care. 1982; 5(Suppl 2):135-9. [PubMed 6765525]

49. Lotz N, Bachmann W, Menhert H. Human insulin (recombinant DNA) in the treatment of patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Diabetes Care. 1982; 5(Suppl 2):149-51. [PubMed 6765527]

50. Maneschi F, Fineberg SE, Kohner EM. Successful treatment of immune-mediated insulin resistance by human insulin (recombinant DNA). Diabetes Care. 1982; 5(Suppl 2):175-9. [PubMed 6765532]

51. Carveth-Johnson AO, Mylvaganam K, Child DF. Generalized allergic reaction with synthetic human insulin. Lancet. 1982; 2:1287. [IDIS 161380] [PubMed 6128592]

52. Blandford RL, Sewell H, Sharp P et al. Generalized allergic reaction with synthetic human insulin. Lancet. 1982; 2:1468.

53. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Suppl 1. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1984:1732.

54. Welles JS (Eli Lilly and Company, Indianapolis): Personal communication; 1984 Mar 14.

55. Mellowes JR (Squibb-Novo, Inc, Princeton, NJ): Personal communication; 1984 Mar 26.

56. Reviewers’ comments (personal observations); 1984 Mar.

57. Grammer LC, Metzger BE, Patterson R. Cutaneous allergy to human (recombinant DNA) insulin. JAMA. 1984; 251:1459-60. [IDIS 182132] [PubMed 6366262]

58. Anon. Humulin human insulin (recombinant DNA origin). The natural evolution of insulin therapy. Eli Lilly and Company, Indianapolis. Publication No. 60-HI-2006-1; 1983 Jul.

59. Fineberg SE, Galloway JA, Fineberg NS et al. Immunogenicity of recombinant DNA human insulin. Diabetologia. 1983; 25:465-9. [PubMed 6198228]

60. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Suppl 2. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1985:1849.

61. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1985:539.

62. Westby R (Eli Lilly and Company, Indianapolis): Personal communication; 1986 Feb 24.

63. Manufacturer’s comments (Novo Nordisk, Princeton, NJ): Personal communication.

64. Anon. Nordisk human insulins (semi-synthetic). Nordisk-USA, Rockville, MD. Publication No. 17066-9/86-10M; 1986 Sep.

65. Novo Nordisk. Novolin 70/30 sterile suspension prescribing information. Princeton, NJ; 1985 May.

66. Eli Lilly and Company. Humulin BR information for the patient. Indianapolis, IN; 1986 Jun.

67. Novo Nordisk, Princeton, NJ: Personal communication.

68. Squibb-Novo, Inc. NovoPen insulin delivery system. Princeton, NJ; 1987 Feb.

69. Novo Information Center. NovoPen fact sheet. New York; (undated).

70. NovoPen prescribing information. In: Huff BB, ed. Physicians’ desk reference. 42nd ed. Oradell, NJ; Medical Economics Company Inc; 1988:2076.

71. Novo Nordisk. Novolin R PenFill patient information. Princeton, NJ; 2000 Feb.

72. Russell MJ (Squibb-Novo, Inc, Princeton, NJ): Personal communication; 1988 Feb 25.

73. Squibb-Novo, Inc. NovoPen insulin delivery device patient information. Princeton, NJ; 1986 Oct.

74. Squibb-Novo, Inc. NovolinPen Dial-A-Dose insulin delivery device prescribing information. In: Huff BB, ed. Physicians’ desk reference. 43rd ed. Oradell, NJ: Medical Economics Company Inc; 1989:2110-3.

75. Novo Nordisk. Novolin N PenFill patient information. Princeton, NJ; 1991 Apr.

76. Novo Nordisk. Novolin 70/30 PenFill patient information. Princeton, NJ; 1991 Apr.

77. Frohnauer MK (Eli Lilly and Company, Indianapolis, IN): Personal communication; 1988 Dec 22.

78. Siegler DE, Reeves ML, Goldberg RB et al. Pharmacokinetics of ultralente insulin preparation. Diabetes. 1984; 33(Suppl 1):61A.

79. Reeves ML, Seigler DE, Goldberg RB et al. Pharmacokinetics of ultralente (U) insulin preparations. Diabetes. 1986; 35(Suppl 1):63A.

80. Eli Lilly and Company. Humulin U ultralente (human insulin rDNA origin) extended zinc suspension patient information. Indianapolis, IN; 2000 Aug 3.

81. Gossain VV, Rovner DR, Mohan K. Systemic allergy to human (recombinant DNA) insulin. Ann Allergy. 1985; 55:116-8. [IDIS 204433] [PubMed 3896050]

82. Novo Nordisk. Novolin R patient information. Princeton, NJ; 1991 Apr.

83. Novo Nordisk. Novolin L patient information. Princeton, NJ; 1991 Apr.

84. Novo Nordisk. Novolin N patient information. Princeton, NJ; 1991 Apr.

85. Davidson JA, Ramirez LC, Selam JL. Transfer of patients with diabetes from semisynthetic human insulin to human insulin prepared by recombinant DNA technology using baker’s yeast: a double-blind, randomized study. Clin Therap. 1991; 13:557-68.

86. Raskin P, Clements RS Jr. The use of human insulin derived from baker’s yeast by recombinant DNA technology. Clin Therap. 1991; 13:569-78.

87. Novo Nordisk. Velosulin BR fact sheet. Undated.

88. Novo Nordisk. Velosulin BR regular human insulin injection (semi-synthetic) prescribing information (dated 1995 Jan). In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1795-6.

89. Novo Nordisk. Novolin R regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1795.

90. Novo Nordisk. Novolin N Penfill NPH human insulin isophane suspension injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1798.

91. Novo Nordisk. Novolin R Penfill regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1798.

92. Novo Nordisk. Novolin L lente human insulin zinc suspension injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1795.

93. Novo Nordisk. Novolin 70/30 NPH human insulin isophane suspension injection and regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1794- 5.

94. Novo Nordisk. Novolin 70/30 Penfill NPH human insulin isophane suspension injection and regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1797-8.

95. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From website.

96. Diaz R, Paolasso EA, Piegas LS et al for the ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Metabolic modulation of acute myocardial infarction: The ECLA Glucose-Insulin-Potassium Pilot Trial. Circulation. 1998; 98:2227-34. [IDIS 419032] [PubMed 9867443]

97. Apstein CS. Glucose-insulin-potassium for acute myocardial infarction: remarkable results from a new perspective, randomized trial. Circulation. 1998; 98:2223-6. [IDIS 419031] [PubMed 9826307]

98. Fath-Ordoubadi, Beatt KJ. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation. 1997; 96:1152-6. [IDIS 392642] [PubMed 9286943]

99. Apstein CS. Glucose-insulin-potassium in acute myocardial infarction: the time has come for a large, prospective trial. Circulation. 1997; 96:1074-7. [IDIS 392638] [PubMed 9286931]

100. Anon. Insulin systemic. In: United States Pharmacopeia Dispensing Information (USP DI). Vol II. Advice for the patient: drug information in lay language. 19th ed. Englewood, CO: Micromedex; 1999:962-5.

101. American Diabetes Association. Clinical practice recommendations: insulin administration. Diabetes Care. 2000; 23(Suppl. 1):S86-9.

102. Novo Nordisk. Velosulin BR buffered regular human insulin injection (rDNA origin) patient information. Princeton, NJ; 1999 Jul.

103. American Diabetes Association. Insulin administration. Diabetes Care. 2002; 25(Suppl 1):S112-5.

104. Cefalu WT, Skyler JS, Kourides IA et al. Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann Intern Med. 2001; 134:203-7. [IDIS 459539] [PubMed 11177333]

105. Skyler JS, Cefalu WT, Kourides IA et al. Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study. Lancet. 2001; 357:331-5. [IDIS 460904] [PubMed 11210993]

106. Gale EAM. Two cheers for inhaled insulin. Lancet. 2001; 357:324-5. [IDIS 460902] [PubMed 11210986]

107. Nathan DM. Inhaled insulin for type 2 diabetes: Solution or distraction? Ann Intern Med. 2001; 134:242-4. Editorial.

108. Laube BL, Benedict GW, Dobs AS. The lung as an alternative route of delivery for insulin in controlling postprandial glucose levels in patients with diabetes. Chest. 1998; 114:1734-9. [IDIS 421006] [PubMed 9872209]

109. Heinemann L, Traut T, Heise T. Time-action profile of inhaled insulin. Diabetic Med. 1997; 14:63-72. [PubMed 9017356]

110. Laube BL, Georgopoulos A, Adams III GK. Preliminary study of the efficacy of insulin aerosol delivered by oral inhalation in diabetic patients. JAMA. 1993; 269:2106-9. [IDIS 313401] [PubMed 8385716]

111. Novo Nordisk Pharmaceuticals, Inc. NovoPen Junior instruction manual. Princeton, NJ; 2002.

112. Van Den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001; 345:1359-67. [IDIS 471874] [PubMed 11794168]

113. American Diabetes Association. Hyperglycemic crises in patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl. 1):S100-8.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:661-7.

b. Eli Lilly and Company. Humalog (insulin lispro) injection prescribing information. Indianapolis, IN; 2002 May 31.

c. Eli Lilly and Company. Humulin R (insulin human) injection prescribing information. Indianapolis, IN; 2000 Aug. 3.

d. Novo Nordisk Pharmaceuticals Inc.; Novolog (insulin aspart [rDNA origin]) injection prescribing information. Princeton, New Jersey; 2002 May 15.

e. AHFS drug information 2004. McEvoy GK, ed. Insulins general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2994-3002.

f. Novo Nordisk. Novolin N PenFill patient information. Princeton, NJ; 2000 Feb.

g. Novo Nordisk. Novolin N patient information. Princeton, NJ; 1999 Feb.

h. Novo Nordisk. Novolin 70/30 sterile suspension patient information. Princeton, NJ; 1999 Feb.

i. Eli Lilly and Company. Humulin N sterile suspension patient information. Indianapolis, IN; 2000 Aug.

j. Novo Nordisk. Novolin R patient information. Princeton, NJ; 1999 Feb.

k. Eli Lilly and Company. Humulin 50/50 (human insulin isophane suspension injection and regular human insulin injection) sterile suspension patient information. Indianapolis, IN; 2000 Aug 3.

l. Eli Lilly and Company. Humulin L sterile suspension patient information. Indianapolis, IN; 2000 Aug 3.

m. Eli Lilly and Company. Humulin N Pen sterile suspension patient information. Indianapolis, IN; 2003 Oct.

n. Schilling McCann JA, Publisher. Pharmacists drug handbook. 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins and American Society of Health-System Pharmacists; 2003.

o. AHFS drug information 2004. McEvoy GK, ed. Insulin human. Bethesda, MD: American Society of Health-System Pharmacists; 2004:3007-10.

p. Eli Lilly and Company. Humulin 70/30 pen (human insulin isophane suspension injection and regular human insulin injection) suspension patient information. Indianapolis, IN; 2003 Oct 8.

q. Novo Nordisk. Novolin 70/30 Innolet(human insulin isophane suspension and regular human injection) suspension patient information. Princeton, NJ; 2002.

r. Eli Lilly and Company. Humulin 70/30 (human insulin isophane suspension injection and regular human insulin injection) suspension patient information. Indianapolis, IN; 2000 Aug 3.

More about insulin human

Consumer resources

Professional resources

Related treatment guides

Hide
(web4)