Insulin

Pronunciation: IN-suh-lin
Class: Antidiabetic agent Regular, Insulin Injection

Trade Names

Humulin R
- Injection 100 units/mL human insulin (rDNA)
- Injection 500 units/mL human insulin (rDNA)

Novolin R
- Injection 100 units/mL human insulin (rDNA)

Novolin ge Toronto (Canada)
NPH, Isophane Insulin Suspension

Humulin N
- Injection 100 units/mL human insulin (rDNA)

Novolin N
- Injection 100 units/mL human insulin (rDNA)

Novolin ge 10/90 (Canada)
Novolin ge 20/80 (Canada)
Novolin ge 30/70 (Canada)
Novolin ge 40/60 (Canada)
Novolin ge 50/50 (Canada)
Novolin ge NPH (Canada)
50% NPH, Human Insulin Isophane Suspension and 50% Regular, Human Insulin Injection (rDNA Origin)

Humulin 50/50
- Injection 100 units/mL human insulin (rDNA)

70% NPH, Human Insulin Isophane Suspension and 30% Regular, Human Insulin Injection (rDNA Origin)

Humulin 70/30
- Injection 100 units/mL human insulin (rDNA)

Novolin 70/30
- Injection 100 units/mL human insulin (rDNA)

Pharmacology

Insulin and its analogs lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis, proteolysis, and enhances protein synthesis.

Pharmacokinetics

Absorption

Inhalation insulin is absorbed as quickly as subcutaneously administered rapid-acting insulin analogs and more quickly than subcutaneous regular human insulin.

Onset

0.5 to 1 h (regular). 1 to 1.6 h (NPH).

Peak

4 to 12 h (NPH).

Duration

8 to 12 h (regular). 24 h (NPH).

Special Populations

Passive cigarette smoking

Insulin C max and AUC may be reduced approximately 30% to 20%, respectively.

Indications and Usage

Management of type 1 diabetes mellitus (insulin-dependent) and type 2 diabetes mellitus (non–insulin-dependent) not properly controlled by diet, exercise, and weight reduction. In hyperkalemia, infusions of glucose and insulin lower serum potassium levels. IV or IM regular insulin may be given for rapid effect in severe ketoacidosis or diabetic coma. Highly purified (single component) and human insulins are used for treatment of local insulin allergy, immunologic insulin resistance, lipodystrophy at injection site, temporary insulin administration, and in newly diagnosed diabetic patients.

Contraindications

Hypersensitivity to any ingredient of the product; during episodes of hypoglycemia.

Dosage and Administration

Parenteral Insulins

Insulin preparations are classified into 3 groups based on promptness, duration, and intensity of action following subcutaneous administration. These classifications are rapid- (regular), intermediate- ( NPH ), or long-acting. Maintenance doses are given subcutaneous and must be individualized by monitoring patients closely. Consider following dosage guidelines.

Children and Adults

Subcutaneous 0.5 to 1 units/kg/day. Adjust doses to achieve premeal and bedtime blood glucose levels of 80 to 140 mg/dL (children younger than 5 yr of age, 100 to 200 mg/dL).

Severe Ketoacidosis or Diabetic Coma

Subcutaneous 0.8 to 1.2 units/kg/day. Regular insulin is given IV or IM.

Dose Adjustments

Titrate all insulin products to optimal dosage based on blood glucose monitoring results.

General Advice

  • Parenteral insulins
  • Regular insulin is for subcutaneous, IM, or IV administration only. Not for intradermal, intra-arterial, or oral administration.
  • Long-acting insulins are for subcutaneous administration only. Not for intradermal, IM, IV, intra-arterial, or oral administration.
  • Administer direct subcutaneous injections into abdominal wall, thigh, or deltoid. Rotate injection sites within same region.
  • Do not use regular insulin if cloudy, thickened, discolored, or contains particulate matter.
  • Do not use long-acting insulin if white material (insulin) remains at bottom of bottle after mixing or if there are clumps.
  • If mixing regular insulin with long-acting insulin, draw regular insulin into syringe first.
  • If using insulin pen, mix contents by rolling between the palms 10 times then inverting 180° 10 times, then prime the pen before each dose. Do not administer if white material (insulin) remains visibly separated from the liquid after mixing, if clumps are noted, or if solid white particles stick to walls of cartridge.

Storage/Stability

Parenteral insulins

Store in refrigerator (36° to 46°F). Protect from freezing. Discard insulin that has been frozen. If refrigeration is not possible, store unrefrigerated at temperature below 86°F, away from heat and light for 1 mo. Store unopened pens in refrigerator. Store in-use pens at room temperature away from heat and light Do not refrigerate. Discard in-use pen after 10 days, even if pen still contains insulin.

Drug Interactions

ACE inhibitors, anabolic steroids, clofibrate, disopyramide, fibrates, fluoxetine, guanethidine, MAOIs, oral antidiabetics, propoxyphene, salicylates, sulfinpyrazone, sulfonamide antibiotics, tetracyclines

May increase hypoglycemic effects of insulin.

Alcohol, beta-blockers, clonidine, lithium salts

May increase or decrease the blood glucose-lowering effect of insulin.

Atypical antipsychotics, corticosteroids, danazol, diazoxide, diltiazem, glucagon, isoniazid, oral contraceptives, phenothiazines, protease inhibitors, somatropin, sympathomimetics, thyroid hormone

May decrease hypoglycemic effects of insulin.

Beta-blockers, clonidine, guanethidine, reserpine

Signs and symptoms of hypoglycemia may be reduced or absent.

Pentamidine

May cause hypoglycemia, which may be followed by hyperglycemia.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Dermatologic

Lipodystrophy.

Lab Tests

Hypokalemia.

Metabolic

Hypoglycemia.

Miscellaneous

Hypersensitivity reaction (eg, anaphylaxis, angioedema, fast pulse, hypotension, rash, shortness of breath, sweating); local reactions (eg, itching at injection site, redness, swelling).

Precautions

Monitor

Check blood sugar frequently and observe for signs of hypoglycemia and hyperglycemia. Periodically measure glycosylated hemoglobin (A 1c ) to monitor long-term glycemic control. Check urine for ketones in patient at risk for ketoacidosis and observe for signs and symptoms of ketoacidosis (eg, drowsiness, frequent urination, fruit-like breath, thirst).


Pregnancy

Category B .

Lactation

Not excreted in breast milk.

Renal Function

Dose requirements may be reduced; careful glucose monitoring and dose adjustments of insulin may be necessary.

Hepatic Function

Dose requirements may be reduced; careful glucose monitoring and dose adjustments of insulin may be necessary.

Changing insulin

Changes in purity, strength, brand, type, or species source of insulin may necessitate dosage adjustment.

Diabetic ketoacidosis

May result from stress, illness, or insulin omission and may develop slowly after long period of poor insulin control. Condition is potentially life-threatening and requires prompt diagnosis and treatment.

Hypoglycemia

May result from excessive insulin dose, increased work or exercise without eating, or from illness with vomiting, fever, or diarrhea. May also occur when insulin requirements decline.

Insulin resistance

Occurs rarely. Requirements of more than 200 units/day of insulin for more than 2 days in absence of ketoacidosis or acute infection may occur, especially in obese patients, patients with acanthosis nigricans, patients with insulin receptor defects, or during infection.

Thyroid

Hyperthyroidism may cause an increase in the renal Cl of insulin; hyperthyroidism may delay insulin turnover.

Overdosage

Symptoms

Hypoglycemia.

Patient Information

  • Caution patient or caregiver not to discontinue therapy or change the dose unless advised by health care provider.
  • Educate patient or caregiver regarding diabetes and its management, including target ranges for blood sugar control. Instruct patient that insulin is not a substitute for diet and exercise and that they should continue to follow prescribed regimens.
  • Educate patient or caregiver regarding potential long-term complications of diabetes and need for regular general physical and eye examinations.
  • Ensure that patient or caregiver understands how to use home glucose monitor and has a plan for monitoring and recording blood sugar measurements (eg, log). Advise patient to take log to each visit with health care provider.
  • Educate patient regarding value of periodic A 1c testing to confirm level of glucose control.
  • Advise patient that insulin dosage will usually be adjusted based on the results of home glucose A 1c monitoring.
  • Ensure that patient with type 1 diabetes understands how to monitor for ketones and has a plan of action if ketones are detected.
  • Review symptoms of hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar) as well as action plans to undertake in the event either event occurs.
  • Advise patient to discuss with health care provider a plan for managing each of the following situations: insulin dosing during intercurrent conditions (eg, infection, stress, sick days, trauma, vomiting); accidental administration of too little or too much insulin; missed insulin dose; inadequate food intake or a skipped meal; travel across time zones; change in physical activity.
  • Advise patient with diabetes to carry medical identification (eg, card, bracelet) indicating condition.
  • Instruct patient to notify health care provider if experiencing severe, continuous, or frequent hypoglycemic episodes, hypoglycemic episodes with few or no warning symptoms, continuous or severe hyperglycemia, or injection-site reactions that do no go away after a few days or continue to occur.
  • Advise patient or caregiver to read the patient information leaflet(s) for their particular insulin product(s) before using the first time and to read and check for new information each time medication is refilled.
  • Instruct patient or caregiver using more than 1 injectable insulin to always check bottle label for name and letter designation of insulin before withdrawing and administering dose.
  • Ensure that patient or caregiver understands how to store, prepare, administer the insulin dose(s), and dispose of used equipment and supplies.
  • Advise patient to continuously rotate injection sites (abdomen, thigh, upper arm) to prevent or reduce severity of injection-site reactions (eg, lipodystrophy, pain, inflammation).
  • Caution patient not to inject into skin sites that are reddened, itching, or show signs of lipodystrophy.

Copyright © 2009 Wolters Kluwer Health.

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