Humulin 70 30 Drug Information

70/30 is a fixed ratio insulin formulation indicated to improve glycemic control in adults with diabetes mellitus. HUMULIN ® 70/30 is a mixture of insulin isophane human, an intermediate-acting human insulin, and insulin human, a short-acting insulin human, indicated to improve glycemic control in adults with diabetes mellitus.

Important

Administration Instructions Inspect HUMULIN 70/30 visually before use. It should not contain particulate matter and should appear uniformly cloudy after mixing. Do not use HUMULIN 70/30 if particulate matter is seen.

Administer HUMULIN 70/30 subcutaneously into the abdominal wall, thigh, upper arm, or buttocks. 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 . The HUMULIN 70/30 KwikPen dials in 1 unit increments.

Use HUMULIN 70/30 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose. Do not administer HUMULIN 70/30 intravenously and do not use in an insulin infusion pump. Do not mix HUMULIN 70/30 with any other insulins or diluents.

Dosage Information Inject

HUMULIN 70/30 subcutaneously approximately 30-45 minutes before a meal. The proportion of rapid acting and long acting insulin is fixed in a premixed insulin such as HUMULIN 70/30. Independent adjustment of the basal or prandial dose is not possible when using a premixed insulin. Individualize and adjust the dosage of HUMULIN 70/30 based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.

Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness . During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring . HUMULIN 70/30 dose requirements may change with changes in level of physical activity, meal patterns (i.e., macronutrient content or timing of food intake), during major illness, or with some coadministered drugs .

The following adverse reactions are discussed elsewhere in the labeling: Hypoglycemia . Hypoglycemia Due to Medication Errors . Hypersensitivity Reactions . Hypokalemia . The following additional adverse reactions have been identified during post-approval use of HUMULIN 70/30. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Adverse reactions observed with insulin therapy include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, weight gain, and edema. To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Allergic Reactions Some patients taking HUMULIN 70/30 have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy (anaphylaxis) have been reported . Peripheral Edema Some patients taking HUMULIN 70/30 have experienced sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Lipodystrophy Administration of insulin subcutaneously, including HUMULIN 70/30, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients. Localized Cutaneous Amyloidosis Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

Weight gain Weight gain has occurred with insulins, including HUMULIN 70/30, and has been attributed to the anabolic effects of insulin and the decrease in glycosuria. Immunogenicity Development of antibodies that react with human insulin have been observed with all insulins, including HUMULIN 70/30.

• Table 1: Clinically Significant Drug Interactions with HUMULIN 70/30 Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN 70/30 is co-administered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of HUMULIN 70/30 Drugs: 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.
• Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN 70/30 is co-administered with these drugs. Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of HUMULIN 70/30 Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
• Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN 70/30 is co-administered with these drugs.
• Drugs that May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine Intervention: Increased frequency of glucose monitoring may be required when HUMULIN 70/30 is co-administered with these drugs.
• Drugs that Affect Glucose Metabolism: Adjustment of insulin dosage may be needed. Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent.

Pregnancy Risk Summary 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 ( see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations). Animal reproduction studies were not performed. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7% and has been reported to be as high as 20-25% in women with a HbA1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data While available studies cannot definitively establish the absence of risk, published data from retrospective studies, open-label, randomized, parallel studies and meta-analyses over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes.

All available studies have methodological limitations, including lack of blinding, unclear methods or randomization, and small sample size.

Pediatric Use The safety and effectiveness of HUMULIN 70/30 in pediatric patients have not been established.

70/30 is contraindicated: During episodes of hypoglycemia, and In patients who have had hypersensitivity reactions to HUMULIN 70/30 or any of its excipients . During episodes of hypoglycemia. In patients with hypersensitivity to HUMULIN 70/30 or any of its excipients.

Excess insulin administration may cause hypoglycemia and hypokalemia . Mild episodes of hypoglycemia can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or physical activity level may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use 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.