Lyumjev
(insulin lispro-aabc)Dosage & Administration
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Lyumjev Prescribing Information
LYUMJEV® is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
Important Administration Instructions
- Always check insulin labels before administration [see Warnings and Precautions ].
- 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 [see Warnings and Precautions ].
- 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 [see Adverse Reactions ].
- 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.
- 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 [see Warnings and Precautions and Adverse Reactions ].
- 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 [see Warnings and Precautions ].
- 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 [see Warnings and Precautions ].
- 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 [see HOW SUPPLIED/STORAGE AND HANDLING ].
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 [see Warnings and Precautions , Drug Interactions and Use in Specific Populations ].
- During changes to a patient's insulin regimen, increase the frequency of glucose monitoring [see Warnings and Precautions ].
- 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.
Injection: 100 units/mL (U-100) clear and colorless solution available as:
- 10 mL multiple-dose vial
- 3 mL single-patient-use LYUMJEV KwikPen
- 3 mL single-patient-use LYUMJEV Junior KwikPen
- 3 mL single-patient-use LYUMJEV Tempo Pen
- 3 mL single-patient-use cartridges
Injection: 200 units/mL (U-200) clear and colorless solution available as:
- 3 mL single-patient-use LYUMJEV KwikPen
Pregnancy
Risk Summary
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 (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). 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 (see Data).
The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a HbA1c>7 and has been reported to be as high as 20% to 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% to 4% and 15% to 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
Published data from retrospective studies and meta-analyses do not report an association with insulin lispro and major birth defects, or adverse maternal or fetal outcomes when insulin lispro is used during pregnancy. However, these studies cannot definitely establish or exclude the absence of any risk because of methodological limitations including small sample size, selection bias, confounding by unmeasured factors, and some lacking comparator groups.
Animal Data
Animal reproduction studies have not been performed with LYUMJEV. However, subcutaneous reproduction and teratology studies have been conducted with insulin lispro. In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 1, 5, and 20 units/kg/day (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19. There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter.
In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.2 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation Days 7 through 19. There were no adverse effects on fetal viability, weight, and morphology at any dose.
Lactation
Risk Summary
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.
Pediatric Use
The safety and effectiveness of LYUMJEV to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of LYUMJEV for this indication is supported by evidence from an adequate and well-controlled study in 716 pediatric patients with type 1 diabetes mellitus aged 1 year and older, and from studies in adult and pediatric patients with diabetes mellitus [see Clinical Pharmacology and Clinical Studies ].
LYUMJEV-treated pediatric patients reported a higher incidence of subcutaneous injection site-related reactions compared to LYUMJEV-treated adults [see Adverse Reactions ]. It is expected that LYUMJEV-treated pediatric patients who receive continuous subcutaneous insulin infusion (CSII) are more likely to have infusion site-related adverse reactions than those who receive subcutaneous injections [see Adverse Reactions ]. Monitor injection and infusion sites closely when initiating therapy with LYUMJEV in pediatric patients. If persistent injection or infusion site reactions occur, discontinue LYUMJEV and initiate therapy with an alternative insulin.
Geriatric Use
Of the total number of LYUMJEV-treated patients in clinical studies for type 1 or type 2 diabetes (PRONTO-T1D and PRONTO-T2D, respectively), 17% (187/1,116) were 65 years of age and older, while 2% (18/1,116) were 75 years of age and older [see Clinical Studies ].
No overall differences in safety or effectiveness of LYUMJEV have been observed between patients 65 years of age and older and younger adult patients.
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 [see Warnings and Precautions and Clinical Pharmacology ].
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 [see Warnings and Precautions and Clinical Pharmacology ].
LYUMJEV is contraindicated:
- during episodes of hypoglycemia.
- in patients with hypersensitivity to insulin lispro-aabc or any of the excipients in LYUMJEV.
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 [see Warnings and Precautions ] 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 [see Adverse Reactions ].
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 [see Adverse Reactions ]. 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 [see Contraindications ].
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. The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulation. As with all insulins, the glucose lowering effect time course of LYUMJEV 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 [see Drug Interactions ]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ].
Risk Mitigation Strategies for Hypoglycemia
Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of 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 glucose monitoring is recommended.
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 [see Dosage and Administration and Warnings and Precautions ].
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 [see Adverse Reactions ]. 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 [see Contraindications ].
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.
5.8 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 [see Dosage and Administration , How Supplied/Storage and Handling , and Patient Counseling Information ].