LYUMJEV (insulin lispro-aabc) injection

Gafacom March 18, 2023

LYUMJEV (insulin lispro-aabc) injection

Insulin lispro-aabc is a rapid-acting human insulin analog used to lower blood glucose. Insulin lispro-aabc is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli. Insulin lispro-aabc differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin analog and has the empirical formula C257H383N65O77S6 and a molecular weight of 5808 daltons, both identical to that of human insulin.

LYUMJEV (insulin lispro-aabc) injection is a sterile, aqueous, clear, and colorless solution for subcutaneous or intravenous administration. Each mL of LYUMJEV U-100 contains 100 units of insulin lispro-aabc and the inactive ingredients: glycerol (12.1 mg), magnesium chloride hexahydrate (1.02 mg), metacresol (3.15 mg), sodium citrate dihydrate (4.41 mg), treprostinil sodium (1.06 mcg), zinc oxide (content adjusted to provide 39 mcg zinc ion), and Water for Injection, USP.

LYUMJEV (insulin lispro-aabc) injection


Each mL of LYUMJEV U-200 contains 200 units of insulin lispro-aabc and the inactive ingredients: glycerol (12.1 mg), magnesium chloride hexahydrate (1.02 mg), metacresol (3.15 mg), sodium citrate dihydrate (4.41 mg), treprostinil sodium (1.06 mcg), zinc oxide (content adjusted to provide 52 mcg zinc ion), and Water for Injection, USP. Hydrochloric acid and/or sodium hydroxide may be added to adjust the pH. LYUMJEV has a pH of 7.0 to 7.8.

INDICATIONS AND USAGE

LYUMJEV® is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

Mechanism of Action

The primary activity of LYUMJEV is the regulation of glucose metabolism. Insulins, including insulin lispro-aabc, exert their specific action through binding to insulin receptors. Receptor-bound insulin lowers glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis, and enhance protein synthesis.

DOSAGE AND ADMINISTRATION

  • Always check insulin labels before administration.
  • Inspect LYUMJEV visually before use. It should appear clear and colorless. Do not use LYUMJEV if particulate matter and discoloration is seen.
  • Use LYUMJEV prefilled pens with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • Do not perform dose conversion when using any LYUMJEV U-100 or U-200 prefilled pens. The dose window of LYUMJEV prefilled pens shows the number of units of LYUMJEV to be delivered and no conversion is needed.
  • Do not transfer LYUMJEV U-200 from the prefilled pen to a syringe for administration.
  • Do not mix LYUMJEV with any other insulin products.
  • Do not administer LYUMJEV U-200 using continuous subcutaneous infusion insulin pump.
  • Do not administer LYUMJEV U-200 intravenously.

Route of Administration Instructions

Subcutaneous Injection for LYUMJEV U-100 or U-200

  • Administer LYUMJEV at the start of a meal or within 20 minutes after starting a meal subcutaneously into the abdomen, upper arm, thigh, 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.
  • LYUMJEV given by subcutaneous injection should generally be used in regimens with intermediate or long-acting insulin.
  • The LYUMJEV U-100 KwikPen, LYUMJEV U-100 Tempo Pen, and LYUMJEV U-200 KwikPen each dial in 1 unit increments and deliver a maximum dose of 60 units per injection.
  • The LYUMJEV U-100 Junior KwikPen dials in 0.5 unit increments and delivers a maximum dose of 30 units per injection.

Continuous Subcutaneous Insulin Infusion (Insulin Pump) for LYUMJEV U-100 Only

  • Do not administer LYUMJEV U-200 using an insulin pump.
  • Refer to the continuous subcutaneous insulin infusion pump user manual to see if LYUMJEV can be used with the insulin pump. Use LYUMJEV in accordance with the insulin pump system’s instructions for use.
  • Train patients using continuous subcutaneous insulin infusion (CSII) therapy to administer insulin by injection and have alternate insulin therapy available in case of insulin pump failure.
  • Change LYUMJEV U-100 in the pump reservoir at least every 9 days or according to the pump user manual, whichever is shorter.
  • Change the infusion sets and the infusion set insertion site according to the manufacturer’s user manual.
  • Do not dilute or mix LYUMJEV U-100 when administering by CSII.
  • Do not expose LYUMJEV in the pump reservoir to temperatures greater than 98.6°F (37°C).

Intravenous Administration for LYUMJEV U-100 Only

  • Do not administer LYUMJEV U-200 intravenously.
  • Administer LYUMJEV U-100 intravenously only under medical supervision with close monitoring of glucose and potassium levels to avoid hypoglycemia and hypokalemia.
  • Dilute LYUMJEV U-100 to a concentration of 1 unit/mL using 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP infusion solutions. Dilutions to concentrations below 1 unit/mL are not recommended.
  • Diluted LYUMJEV may be stored for up to 4 days when refrigerated or up to 12 hours at room temperature.
  • Administer LYUMJEV U-100 by continuous subcutaneous infusion in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not infuse into areas of lipodystrophy or localized cutaneous amyloidosis.

General Dosage Instructions

  • Individualize and adjust the dosage of LYUMJEV based on the patient’s metabolic needs, glucose monitoring results, and glycemic control goal.
  • If converting from another mealtime insulin to LYUMJEV, the change can be done on a unit-to-unit basis.
  • Dosage adjustments may be needed when switching from another insulin, with changes in physical activity, changes in concomitant medications, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness to minimize the risk of hypoglycemia or hyperglycemia.
  • During changes to a patient’s insulin regimen, increase the frequency of glucose monitoring.
  • Instruct patients who forget a mealtime dose to monitor their glucose level to decide if an insulin dose is needed, and to resume their usual dosing schedule at the next meal.

CONTRAINDICATIONS

LYUMJEV is contraindicated:

  • during episodes of hypoglycemia.
  • in patients with hypersensitivity to insulin lispro-aabc or any of the excipients in LYUMJEV.

WARNINGS AND PRECAUTIONS

Never Share a LYUMJEV Prefilled Pen, Cartridge, or Syringe Between Patients: LYUMJEV prefilled pens or cartridges should never be shared between patients, even if the needle is changed. Patients using LYUMJEV 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, 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 anti-diabetic products may be needed.

Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulins, including LYUMJEV. 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). LYUMJEV, or any insulin, should not be used during episodes of hypoglycemia.

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), or in patients who experience recurrent hypoglycemia.

Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products have been reported. To avoid medication errors between LYUMJEV and

other insulins, instruct patients to always check the insulin label before each injection. Do not transfer LYUMJEV U-200 from the LYUMJEV KwikPen to a syringe. The markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia.

Hypokalemia: All insulins, including LYUMJEV, 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).

Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including LYUMJEV. If hypersensitivity reactions occur, discontinue LYUMJEV; treat per standard of care and monitor until symptoms and signs resolve. LYUMJEV is contraindicated in patients who have had hypersensitivity reactions to insulin lispro-aabc or any of its excipients

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 LYUMJEV, 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.

Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Pump or infusion set malfunctions can lead to a rapid onset of hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim therapy with subcutaneous injection of LYUMJEV may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.

DRUG INTERACTIONS

Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. Dose reductions and increased frequency of glucose monitoring may be required when LYUMJEV is co-administered with these 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. Dose increases and increased frequency of glucose monitoring may be required when LYUMJEV is co-administered with these drugs.

Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Dose adjustment and increased frequency of glucose monitoring may be required when LYUMJEV is co-administered with these drugs.

Beta-blockers, clonidine, guanethidine, and reserpine. Increased frequency of glucose monitoring may be required when LYUMJEV is co-administered with these drugs.

USE IN SPECIFIC POPULATIONS

Pregnancy: Published studies with insulin lispro used during pregnancy have not reported an association between insulin lispro and the induction of 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. Pregnant rats and rabbits were exposed to insulin lispro in animal reproduction studies during organogenesis. No adverse effects on embryo/fetal viability or morphology were observed in offspring of rats exposed to insulin lispro at a dose approximately 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day. No adverse effects on embryo/fetal development were observed in offspring of rabbits exposed to insulin lispro at doses up to approximately 0.2 times the human subcutaneous dose of 1 unit/kg/day.

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.

Lactation: Available data from published literature suggests that exogenous human insulin products, including insulin lispro, 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 insulin lispro, on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for insulin, any potential adverse effects on the breastfed child from LYUMJEV or from the underlying maternal condition.

Renal Impairment: Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent LYUMJEV dose adjustment and more frequent glucose monitoring.

Hepatic Impairment: Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent LYUMJEV dose adjustment and more frequent glucose monitoring.

OVERDOSAGE

Excess insulin administration may cause hypoglycemia and hypokalemia. 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 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.

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