Indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

The dosage of HUMULIN R must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose to reduce the risk of hypoglycemia.

HUMULIN R is contraindicated during episodes of hypoglycemia.

Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis.

Accidental mix-ups between HUMULIN R and other insulins have been reported. To avoid medication errors between HUMULIN R and other insulins, instruct patients to always check the insulin label before each injection.

Elderly patients using HUMULIN R may be at increased risk of hypoglycemia due to co-morbid disease.

Hypoglycemia is the most common adverse reaction of all insulins, including HUMULIN R. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).

The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin preparations, the glucose lowering effect time course of HUMULIN R may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia.

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with HUMULIN R.

HUMULIN R can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia.

Weight gain can occur with insulin therapy, including HUMULIN R, and has been attributed to the anabolic effects of insulin.

Administration of insulin subcutaneously, including HUMULIN R, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients.

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including HUMULIN R, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure.

Use with antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, propoxyphene, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics increase the risk of hypoglycemia.

Use with atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones decrease the blood glucose lowering effect of HUMULIN R.

Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN R is used with alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

Increased frequency of glucose monitoring may be required when HUMULIN R is co-administered with beta-blockers, clonidine, guanethidine, and reserpine.

Available data from published studies over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Available data from published literature suggests that exogenous human insulin products, including HUMULIN R, are transferred into human milk.

GoToSource

• Hyperkalemia. GoToSource

• Diabetic ketoacidosis. GoToSource

• Hyperosmolar non-ketoacidotic diabetic coma. GoToSource

Hypoglycemia (low blood sugar). GoToSource

Lipohypertrophy (fatty lumps under the skin). GoToSource

Edema (swelling). GoToSource

QTc prolongation (heart rhythm disorder). GoToSource

Hypersensitivity reactions. GoToSource

Weight gain. GoToSource

No major injury lawsuits reported.