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Find Lowest Prices on HUMULIN®R (regular insulin human) Injection, USP (rDNA Origin) 100 Units per ML (U-100) DESCRIPTION Humulin® R U-100 is a polypeptide hormone structurally identical to human insulin synthesized through rDNA technology in a special non-disease-producing laboratory strain of Escherichia coli bacteria. Humulin R (insulin human recombinant) U-100 has the empirical formula C257H383N65O77S6 and a molecular weight of 5808. Humulin R (insulin human recombinant) U-100 is a sterile, clear, aqueous, and colorless solution that contains human insulin (rDNA origin) 100 units/mL, glycerin 16 mg/mL and metacresol 2.5 mg/mL, endogenous zinc (approximately 0.015 mg/100 units) and water for injection. The pH is 7.0 to 7.8. Sodiumhydroxide and/or hydrochloric acid may be added during manufacture to adjust the pH. Adequate insulin dosage permits patients with diabetes to effectively utilize carbohydrates, proteins and fats. Regardless of dose strength, insulin enables carbohydrate metabolism to occur and thus to prevent the production of ketone bodies by the liver. Some patients develop severe insulin resistance such that daily doses of several hundred units of insulin or more are required.

INDICATIONS Humulin R (insulin (human recombinant)) U-100 is indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 1 and type 2 diabetes mellitus. Humulin R (insulin (human recombinant)) U-100 may be administered intravenously under proper medical supervision in a clinical setting for glycemic control (see DOSAGE AND ADMINISTRATION and Storage). DOSAGE AND ADMINISTRATION Humulin R (insulin (human recombinant)) U-100, when used subcutaneously, is usually given three or more times daily before meals. The dosage and timing of Humulin R (insulin (human recombinant)) U-100 should be individualized and determined, based on the physician's advice, in accordance with the needs of the patient. Humulin R (insulin (human recombinant)) U-100 may also be used in combination with oral antihyperglycemic agents or longer-acting insulin products to suit the needs of the individual patients with diabetes. The injection of Humulin R (insulin (human recombinant)) U-100 should be followed by a meal within approximately 30 minutes of administration. The average range of total daily insulin requirement for maintenance therapy in insulin-treated patients without severe insulin resistance lies between 0.5 and 1 unit/kg/day. However, in prepubertal children it usually varies from 0.7 to 1 unit/kg/day, but can be much lower during the period of partial remission. In situations of insulin resistance, e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher. Initial dosages for patients with diabetes are often lower, e.g., 0.2 to 0.4 units/kg/day. Humulin R (insulin (human recombinant)) U-100 may be administered by subcutaneous injection in the abdominal wall, the thigh, the gluteal region or in the upper arm. Subcutaneous injection into the abdominal wall ensures a faster absorption than from other injection sites. Injection into a lifted skin fold minimizes the risk of intramuscular injection. Injection sites should be rotated within the sameregion. As with all insulin, the duration of action will vary according to the dose, injection site, blood flow, temperature, and level of physical activity. Intravenous administration of Humulin R (insulin (human recombinant)) U-100 is possible under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia. For intravenous use, Humulin R (insulin (human recombinant)) U-100 should be used at concentrations from 0.1 unit/mL to 1 unit/mL in infusion systems with the infusion fluids 0.9% sodium chloride using polyvinyl chloride infusion bags. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Never use Humulin R (insulin (human recombinant)) U-100 if it has become viscous (thickened) or cloudy; use it only if it is clear and colorless. Humulin R (insulin (human recombinant)) U-100 should not be used after the printed expiration date. Mixing of Insulins Humulin R (insulin (human recombinant)) U-100 should only be mixed as directed by the physician Humulin R (insulin (human recombinant)) U-100 is short-acting and is often used in combination with intermediate- or long-acting insulins. The order of mixing and brand or model of syringe should be specified by the physician. A U-100 insulin syringe should always be used. Failure to use the correct syringe can lead to dosage errors. In general, when an intermediate-acting insulin (e.g., NPH insulin isophane suspension) is mixed with short-acting soluble insulin (e.g., regular), the short-acting insulin should be drawn into the syringe first. Storage Not in-use (unopened): Humulin R (insulin (human recombinant)) U-100 vials not in-use should be stored in a refrigerator (2° to 8°C [36° to 46°F]), but not in the freezer. In-use (opened): The Humulin R (insulin (human recombinant)) U-100 vial currently in-use can be kept unrefrigerated as long as it is kept as cool as possible [below 30°C (86°F)] away from heat and light. In-use vials must be used within 31 days or be discarded, even if they still contain Humulin R (insulin (human recombinant)) U-100. Admixture: Infusion bags prepared with Humulin R (insulin (human recombinant)) U-100 as indicated under DOSAGE AND ADMINISTRATION are stable when stored in a refrigerator (2° to 8°C [36° to 46°F]) for 48 hours and then may be used at room temperature for up to an additional 48 hours. Do not use Humulin R (insulin (human recombinant)) U-100 after the expiration date stamped on the label or if it has been frozen. HOW SUPPLIED Humulin R (insulin (human recombinant)) U-100, Regular, insulin human injection, USP (rDNA origin), 100 units/mL, is supplied as follows: 10 mL vials NDC 0002-8215-01 (HI-210) 3 mL vials NDC 0002-8215-17 (HI-213) Literature issued March, 2011. Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

OVERDOSE Excess insulin may cause hypoglycemia and hypokalemia, particularly after intravenous administration. Hypoglycemia may occur as a result of an excess of insulin relative to food intake, energy expenditure, or both. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately. CONTRAINDICATIONS Humulin R (insulin (human recombinant)) U-100 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Humulin R (insulin (human recombinant)) U-100 or any of its excipients.

WARNINGS Any change in insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (e.g., regular, NPH, analog, etc.), species, or method of administration may result in the need for a change in dosage. PRECAUTIONS Hypoglycemia Hypoglycemia is the most common adverse reaction of all insulin therapies, including Humulin R (insulin (human recombinant)) U-100. Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person and/or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with Humulin R (insulin (human recombinant)) U-100. As with all insulin preparations, the time course of Humulin R (insulin (human recombinant)) U-100 action may vary in different individuals or at different times in the same individual and is dependent on dose, site of injection, blood supply, temperature, and physical activity. Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stresses. Concomitant antihyperglycemic agents may need to be adjusted. The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulations. Other factors such as changes in food intake (e.g., amount of food or timing of meals), injection site, exercise, and concomitant medications may also alter the risk of hypoglycemia (See PRECAUTIONS: DRUG INTERACTIONS). As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g., the pediatric population and patients who fast or have erratic food intake). The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Hyperglycemia, Diabetic Ketoacidosis, and Hyperosmolar Non-Ketotic Syndrome Hyperglycemia, diabetic ketoacidosis, or hyperosmolar coma may develop if the patient takes less Humulin R (insulin (human recombinant)) U-100 than needed to control blood glucose levels. This could be due to increases in insulin demand during illness or infection, neglect of diet, omission or improper administration of prescribed insulin doses or use of drugs that affect glucose metabolism or insulin sensitivity. Early signs of diabetic ketoacidosis include glycosuria and ketonuria. Polydipsia, polyuria, loss of appetite, fatigue, dry skin, abdominal pain, nausea and vomiting and compensatory tachypnea come on gradually, usually over a period of some hours or days, in conjunction with hyperglycemia and ketonemia. Severe sustained hyperglycemia may result in hyperosmolar coma or death. Hypokalemia Insulin stimulates potassium movement into the cells, possibly leading to hypokalemia, that left untreated may cause respiratory paralysis, ventricular arrhythmia, and death. Since intravenously administered insulin has a rapid onset of action, increased attention to hypokalemia is necessary. Therefore, potassium levels must be monitored closely when Humulin R (insulin (human recombinant)) U-100 or any other insulin is administered intravenously. Use caution in patients who may be at risk for hypokalemia (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations). Hypersensitivity and Allergic Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including Humulin R U-100 (see ADVERSE REACTIONS). Localized reactions and generalized myalgias have been reported with the use of metacresol as an injectable excipient. Renal or Hepatic Impairment Frequent glucose monitoring and insulin dose reduction may be required in patients with renal or hepatic impairment. Drug Interactions Some medications may alter insulin requirements and the risk for hypoglycemia and hyperglycemia (see DRUG INTERACTIONS). Use in Pregnancy Pregnancy Category B. All pregnancies have a background risk of birth defects, miscarriage, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and is decreased with good glucose control. It is important for patients to maintain good control of diabetes before conception and during pregnancy. Special attention should be paid to diet, exercise and insulin regimens. Insulin requirements may decrease during the first trimester, usually increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring is essential in these patients. Female patients should be advised to tell their physician if they intend to become, or if they become pregnant. Studies show that endogenous insulin only crosses the placenta in minimal amounts. While there are no adequate and well-controlled studies in pregnant women, an extensive body of published literature demonstrates the maternal and fetal benefits of insulin treatment in patients with diabetes during pregnancy. Humulin R (insulin (human recombinant)) is a recombinant human insulin that is identical to the endogenous hormone; therefore, reproduction and fertility studies were not performed in animals. Labor and Delivery Careful glucose monitoring and management of patients with diabetes during labor and delivery are required. Nursing Mothers Endogenous insulin is present in human milk. Insulin orally ingested is degraded in the gastrointestinal tract. No adverse reactions have been associated with infant exposure to insulin through the consumption of human milk. In a study of eight preterm infants between 26 to 30 weeks gestation, enteral administration of Humulin R (insulin (human recombinant)) did not result in hypoglycemia. Good glucose control supports lactation in patients with diabetes. Patients with diabetes who are lactating may require adjustments in insulin dose and/or diet.