insulin (regular)
Humulin-R, Novolin R, Novolin R PenFill, Regular (Concentrated) Iletin II, Regular Insulin, Regular Purified Pork Insulin, Velosulin BR, Velosulin Human ◆

insulin (lispro)
Humalog

isophane insulin suspension (NPH)
Humulin N, NPH-N, Novolin N, Novolin N PenFill, NPH Iletin II

insulin zinc suspension (lente)
Humulin L, Lente Iletin II, Lente L, Novolin L

extended zinc insulin suspension (ultralente)
Humulin U Ultralente, Ultralente ◆

isophane insulin suspension and insulin injection (70% isophane insulin and 30% insulin injection)
Humulin 70/30, Novolin 70/30, Novolin 70/30 PenFill

isophane insulin suspension and insulin injection (50% isophane insulin and 50% insulin injection)
Humulin 50/50

Available forms
Available by prescription only
insulin (lispro)
Cartridge (human): 100 units/ml in 3-ml cartridges
Injection (human): 100 units/ml
regular (concentrated) Iletin II insulin
Injection (human): 500 units/ml Available without a prescription
insulin (regular)
Injection (human): 100 units/ml
Injection (pork): 100 units/ml
isophane insulin suspension (NPH)
Injection (human): 100 units/ml
Injection (pork): 100 units/ml
insulin zinc suspension (lente)
Injection (human): 100 units/ml
Injection (pork): 100 units/ml
extended zinc insulin suspension (ultralente)
Injection (human): 100 units/ml

Indications and dosages
 Diabetic ketoacidosis.
Regular insulin. Adults: Administer loading dose of 0.15 units/kg I.V. followed by 0.1 units/kg/hour as a continuous infusion. Decrease insulin infusion when plasma glucose level reaches 300 mg/dl. Start infusion of D₅W separately from the insulin infusion when plasma glucose reaches 250 mg/dl. Thirty minutes before discontinuing insulin infusion, administer a dose of insulin S.C.; intermediate-acting insulin is recommended.
 Alternative dosage schedule is 50 to 100 units I.V. and 50 to 100 units S.C. immediately; base subsequent doses on therapeutic response and glucose, acetone, or ketone levels monitored at 1- to 2-hour intervals, or 2.4 to 7.2 units I.V. loading dose followed by 2.4 to 7.2 units/hour.
Children: 0.5 to 1 unit/kg in two divided doses, one given I.V. and the other S.C., followed by 0.5 to 1 unit/kg I.V. q 1 to 2 hours; or 0.1 unit/kg I.V. bolus, then 0.1 unit/kg/hour continuous I.V. infusion until serum glucose decreases to 250 mg/dl; then start S.C. insulin.
 Ketosis-prone diabetes, type 1 diabetes mellitus, diabetes melltius inadequately controlled by diet and oral antidiabetics. Adults and children: Individualized dosage adjusted based on patient’s serum and urine glucose levels.
 Hyperkalemia. Adults: 5 to 10 units of regular insulin with 50 ml of D⁵W over 5 minutes. Alternatively, 25 units of regular insulin given S.C. and an infusion of 1,000 ml D¹⁰W with 90 mEq sodium bicarbonate; infuse 330 ml over 30 minutes and the remainder over 3 hours.
 Provocative test for growth hormone secretion. Adults: Rapid I.V. injection of regular insulin 0.05 to 0.15 units/kg.
 Control of hyperglycemia with longer-acting insulin in patients with type 1 diabetes mellitus and with sulfonylureas in patients with type 2 diabetes mellitus.
Lispro. Adults and children older than age 3: Dosage varies among patients and must be determined by a health care professional familiar with patient’s metabolic needs, eating habits, and other lifestyle variables. Inject S.C. within 15 minutes before or immediately after a meal.

Pharmacodynamics
Antidiabetic action: Insulin is used as a replacement for the physiologic production of endogenous insulin in patients with insulin-dependent diabetes mellitus (type 1) and diabetes mellitus inadequately controlled by diet and oral hypoglycemic agents (type 2). Insulin increases glucose transport across muscle and fat-cell membranes to reduce blood glucose levels. It also promotes conversion of glucose to its storage form, glycogen; triggers amino acid uptake and conversion to protein in muscle cells and inhibits protein degradation; stimulates triglyceride formation and inhibits release of free fatty acids from adipose tissue; and stimulates lipoprotein lipase activity, which converts circulating lipoproteins to fatty acids. Insulin is available in various forms and these differ mainly in onset, peak, and duration of action.

Pharmacokinetics
Absorption: Insulin must be given parenterally because it’s destroyed in the GI tract.
Distribution: Distributed widely throughout the body.
Metabolism: Some insulin is bound and inactivated by peripheral tissues, but the majority appears to be degraded in the liver and kidneys.
Excretion: Filtered by the renal glomeruli and undergoes some tubular reabsorption. Plasma half-life is about 9 minutes after I.V. administration.

Contraindications and precautions
No known contraindications.

Interactions
Drug-drug. Anabolic steroids, beta blockers, clofibrate, fenfluramine, MAO inhibitors, salicylates, tetracycline: Prolongs hypoglycemic effect. Monitor blood glucose levels carefully.
Corticosteroids, dextrothyroxine sodium, epinephrine, thiazide diuretics: Diminishes insulin response. Monitor patient for hyperglycemia.
Rosiglitazone: May increase the risk of heart failure and other CV effects in patients. Monitor patient closely and check liver function test values periodically.
Drug-herb. Basil, bay, bee pollen, burdock, ginseng, glucomannan, horehound, marshmallow, myrrh, sage: May affect glycemic control. Monitor blood glucose level carefully and discourage use together.
Drug-lifestyle. Alcohol use: May cause a prolonged hypoglycemic effect. Discourage alcohol use.
Marijuana use: May increase insulin requirements. Inform patient of this interaction.
Smoking: Decreases absorption of insulin administered S.C. Advise patient to avoid smoking within 30 minutes of insulin injection.

Adverse reactions
Skin: urticaria, pruritus, swelling, redness, stinging, warmth at injection site.
Metabolic: hypoglycemia, hyperglycemia (rebound, or Somogyi, effect).
Other: lipoatrophy, lipohypertrophy,hypersensitivity reactions (anaphylaxis, rash).

Effects on lab test results
• May increase or decrease glucose levels.

Overdose and treatment
Insulin overdose may produce signs and symptoms of hypoglycemia (tachycardia, palpitations, anxiety, hunger, nausea, diaphoresis, tremors, pallor, restlessness, headache, and speech and motor dysfunction).
 Treatment is directed toward treating hypoglycemia and is based on patient’s symptoms. If patient is responsive, give 10 to 15 g of a fast-acting oral carbohydrate. If patient’s signs and symptoms persist after 15 minutes, give an additional 10 g carbohydrate. If patient is unresponsive, an I.V. bolus of D₅₀W solution should immediately increase blood glucose. Some prefer to use D₂₅W because it’s less irritating should extravasation occur. A common infusion rate is based on glucose content: 10 to 20 mg/kg/minute. Parenteral glucagon or epinephrine S.C. also may be given; both drugs elevate blood glucose levels in a few minutes by stimulating glycogenolysis. Fluid and electrolyte imbalance may require I.V. fluids and electrolyte (such as potassium) replacement.

Special considerations
• Human insulin may help non-insulin-dependent patients requiring intermittent or short-term therapy (such as pregnancy, surgery, infection, or total parenteral nutrition therapy), patients with insulin resistance, or those with lipoatrophy.
 ALERT To avoid a possible 10-fold overdose, always spell out the word "units" when prescribing insulin. Never use the abbreviation "U."
• Lente and ultralente insulins may be mixed in any proportion.
• Regular insulin may be mixed with NPH or lente insulins in any proportion. However, in vitro binding occurs over time until an equilibrium is reached. Administer these mixtures either immediately after preparation or after stability occurs (15 minutes for NPH regular, 24 hours for lente regular) in order to minimize variability in patient response. Switching from separate injections to a prepared mixture also may alter the patient’s response. When mixing two insulins, always draw regular insulin into the syringe first.
• Lispro insulin may be mixed with Humulin N or Humulin U and given within 15 minutes before a meal to prevent a hypoglycemic reaction.
• Store insulin in cool area. Refrigeration is desirable but not essential, except with regular insulin concentrated.
• Administration route is S.C. because it allows slower absorption and causes less pain than I.M. injections. Ketosis-prone, type 1, severely ill, and newly diagnosed diabetics with very high blood glucose levels may require hospitalization and I.V. treatment with regular fast-acting insulin. Ketosis-resistant diabetics may be treated as outpatients with intermediate-acting insulin after they have received instructions on how to alter dosage according to self-performed urine or blood glucose determinations. Some patients, especially pregnant or brittle diabetics, may use a dextrometer to perform fingerstick blood glucose tests at home.
• Injection sites should be rotated; however, unstable diabetics may achieve better control if injection site is rotated within same anatomic region.
• In pregnant diabetic women, insulin requirements increase, sometimes drastically, then decline immediately postpartum.
• Human insulin may be used in patients allergic to pork forms. Humulin is synthesized by a genetically altered strain of Escherichia coli. Novolin brands are derived by enzymatic alteration of pork insulin.
• Some patients may develop insulin resistance and require large insulin doses to control symptoms of diabetes. Iletin II, Regular Purified Pork, 500 units/ml may be used for these patients.
• Patient should notify pharmacist several days before prescription refill is needed in case U-500 is not in stock. Give hospital pharmacy sufficient notice before refill of in-house prescription.
• Never store U-500 insulin in same area with other insulin preparations because of danger of severe overdose if given accidentally to other patients. U-500 insulin must be administered with a U-100 syringe because no syringes are made for this drug.
 ALERT Don’t confuse Lente with Lantus.
• With regular insulin concentrated, monitor patient for a secondary hypoglycemic reaction that may occur 18 to 24 hours after injection. This may be caused by a repository effect of drug and the high concentration of insulin in the preparation (500 units/ml).
Pregnant patients
• Monitor insulin use during pregnancy.
Breast-feeding patients
• Monitor drug use closely in breast-feeding women.
Geriatric patients
• These patients have an increased risk of CVA, MI, and hypoglycemia.

Patient education
• Instruct patient to strictly adhere to manufacturer’s instructions regarding assembly, administration, and care of specialized delivery systems, such as insulin pumps.
• Emphasize importance of regular meal times and that meals must not be skipped.
• Tell patient that insulin can be injected immediately after a meal.
• Teach patient that blood glucose monitoring is an essential guide to correct dosage and to therapeutic success.
• Emphasize importance of recognizing hypoglycemic symptoms because insulin-induced hypoglycemia is hazardous and may cause brain damage if prolonged.
• Advise patient to always wear a medical identification bracelet or pendant, to carry ample insulin supply and syringes on trips, to have carbohydrates (sugar or candy) on hand for emergency, and to note time-zone changes for dose schedule when traveling.
• Instruct patient not to change the order of mixing insulins or change the model or brand of syringe or needle. Make sure he knows that when mixing two insulins, always to draw regular insulin into the syringe first.
• Inform patient that marijuana use may increase insulin requirements.
• Inform patient that cigarette smoking decreases absorption of insulin administered S.C. Advise him not to smoke within 30 minutes after insulin injection.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use