Lansulin70/30 Cartridge

Indications And Usage

70/30 is a fixed ratio insulin formulation indicated to improve glycemic control in adult patients with diabetes mellitus.

Administration

Inspect 70/30 visually before use. It should not contain particulate matter and should appear uniformly cloudy after mixing. Do not use 70/30 if particulate matter is seen. Do not mix 70/30 with any other insulins or diluents. Use 70/30 Pen with caution in patients with visual impairment that may rely on audible clicks to dial their dose. Route of Administration: 70/30 should only be administered subcutaneously. Administer in the subcutaneous tissue of 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. During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring . The 70/30 Pen dials in 1 unit increments. Do not administer 70/30 intravenously or intramuscularly and do not use 70/30 in an insulin infusion pump.

Contraindications

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

Precautions

Never Share a HUMULIN 70/30 Pen or Syringe Between Patients70/30 Pens must never be shared between patients, even if the needle is changed. Patients using 70/30 vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant antidiabetic products may be needed. Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulins, including HUMULIN 70/30. Severe hypoglycemia can cause seizures, 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) Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions], or in patients who experience recurrent hypoglycemia. Risk Factors for Hypoglycemia: 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 70/30 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 [see Clinical Pharmacology]. 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. Risk Mitigation Strategies for Hypoglycemia: Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including HUMULIN 70/30. If hypersensitivity reactions occur, discontinue HUMULIN 70/30; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6)]. HUMULIN 70/30 is contraindicated in patients who have had hypersensitivity reactions to HUMULIN 70/30 or any of its excipients [see Contraindications (4)]. Hypokalemia: All insulin products, including HUMULIN 70/30, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations). Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: 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 70/30, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

Adverse Reactions

The following additional adverse reactions have been identified during post-approval use of 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. 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 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 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 some insulin therapies including 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 insulin, including 70/30.

Pregnancy and lactation

Lactation:

Available data from published literature suggests that exogenous human insulin products, including HUMULIN 70/30, are transferred into human milk. There are no adverse reactions reported in breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including HUMULIN 70/30 on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for HUMULIN 70/30 and any potential adverse effects on the breastfed child from HUMULIN 70/30 or from the underlying maternal condition.

Pregnancy:

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. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy. 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.

Renal and liver Impairment

Renal Impairment

The effect of renal impairment on the pharmacokinetics and pharmacodynamics of 70/30 has not been studied. Patients with renal impairment are at increased risk of hypoglycemia and may require more frequent 70/30 dose adjustment and more frequent blood glucose monitoring.

Laboratory Tests