LYUMJEV
Generic: INSULIN LISPRO-AABC
Basic Information
Manufacturer
Eli Lilly and Company
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
c5a056e2-b568-4ca6-9ed8-79c010942d00
Indications & Usage
1 INDICATIONS AND USAGE LYUMJEV ® is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
LYUMJEV ® is a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
( 1 )
LYUMJEV ® is a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere: Hypoglycemia [see Warnings and Precautions ( 5.3 )] .
Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )] Hypokalemia [see Warnings and Precautions ( 5.5 )] .
Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] .
Adverse reactions observed with LYUMJEV include hypoglycemia, injection/infusion site reactions, allergic reactions, rash, pruritus, lipodystrophy, and weight gain.
( 6.1 ) 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.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates actually observed in clinical practice.
Adverse Reaction Database – Adult Patients with Type 1 and Type 2 Diabetes The data in Table 1 reflect the exposure of 780 adult patients with type 1 diabetes to LYUMJEV with a mean exposure duration of 26 weeks [see Clinical Studies ( 14.2 )] .
The mean age was 44 years, the mean duration of diabetes was 19 years, 55% were male, 77% were White, 2% were Black or African American, and 9% were Hispanic.
The mean BMI was 26.6 kg/m 2 and the mean HbA 1c at baseline was 7.3%.
The data in Table 2 reflect the exposure of 336 adult patients with type 2 diabetes to LYUMJEV with a mean exposure duration of 26 weeks [see Clinical Studies ( 14.3 )] .
The mean age was 60 years, the mean duration of diabetes was 16 years, 55% were male, 69% were White, 4% were Black or African American, and 24% were Hispanic.
The mean BMI was 32.1 kg/m 2 and the mean HbA 1c at baseline was 7.3%.
The data in Table 3 reflect the exposure of 215 adult patients with type 1 diabetes to LYUMJEV via CSII administration with a mean exposure duration of 16 weeks [see Clinical Studies ( 14.4 )] .
The mean age was 48 years, the mean duration of diabetes was 26 years, 44% were male, 94% were White, 3% were Black or African American, and 8% were Hispanic.
The mean BMI was 27.0 kg/m 2 and the mean HbA 1c at baseline was 7.6%.
Common adverse reactions, excluding hypoglycemia, were defined as events that occurred in ≥5% and at the same rate or greater for LYUMJEV-treated patients than HUMALOG-treated patients.
Table 1.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Adult Patients with Type 1 Diabetes Mealtime LYUMJEV + basal insulin (N=451) % Postmeal LYUMJEV + basal insulin (N=329) % Nasopharyngitis 14.2 14.6 Table 2.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Adult Patients with Type 2 Diabetes Mealtime LYUMJEV + basal insulin (N=336) % Nasopharyngitis 12.5 Upper Respiratory Tract Infection 7.4 Table 3.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Adult Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion CSII LYUMJEV administration (N=215) % Infusion site reaction 19.1 Infusion site pain 15.8 Nasopharyngitis 6.0 Adverse Reaction Database – Pediatric Patients with Type 1 Diabetes The data in Table 4 reflect the exposure of 418 pediatric patients with type 1 diabetes to LYUMJEV with a mean exposure duration of 26 weeks [see Clinical Studies ( 14.5 )] .
The mean age was 12 years; 50% were male, 91% were White, 1% were Black or African American; and 24% of the US subpopulation in this trial were Hispanic.
The mean BMI was 20.5 kg/m 2 , the mean duration of diabetes was 5 years, and the mean HbA 1c at baseline was 7.8%.
Common adverse reactions, excluding hypoglycemia, were defined as events that occurred in ≥5% and at the same rate or greater for LYUMJEV-treated patients than HUMALOG-treated patients.
Table 4.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Pediatric Patients with Type 1 Diabetes Mealtime LYUMJEV + basal insulin (N=280) % Postmeal LYUMJEV + basal insulin (N=138) % Nasopharyngitis 8.2 5.1 Upper Respiratory Tract Infection 5.4 1.4 Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including LYUMJEV.
The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors.
For these reasons, comparing rates of hypoglycemia in clinical trials for LYUMJEV with the incidence of hypoglycemia for other products may be misleading and also may not be representative of hypoglycemia rates that occur in clinical practice.
Incidence rates for severe hypoglycemia in adults with type 1 and type 2 diabetes mellitus and pediatric patients with type 1 diabetes mellitus treated with LYUMJEV in clinical trials are shown in Table 5 [see Clinical Studies ( 14 )] .
Table 5.
Proportion of Patients with Type 1 Diabetes and Type 2 Diabetes Who Experienced at Least One Episode of Severe Hypoglycemia in Adult and Pediatric Clinical Trials a Severe hypoglycemia: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions PRONTO-T1D (Adult Type 1) PRONTO-T2D (Adult Type 2) PRONTO-Pump-2 (Adult Type 1 CSII) PRONTO-Peds (Pediatric Type 1) Mealtime LYUMJEV + basal insulin (N=451) % Postmeal LYUMJEV + basal insulin (N=329) % Mealtime LYUMJEV + basal insulin (N=336) % LYUMJEV (N=215) % Mealtime LYUMJEV + basal insulin (N=280) % Postmeal LYUMJEV + basal insulin (N=298) % Severe hypoglycemia a 5.5 4.6 0.9 1.4 1.1 0 Allergic Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including LYUMJEV, and may be life threatening.
Generalized hypersensitivity reactions such as skin rashes and hypersensitivity were reported in adult patients treated with LYUMJEV: eczema (0.4%), rash (0.4%), dermatitis (0.3%), hypersensitivity (0.2%), and pruritus (0.2%).
Generalized hypersensitivity reactions reported in more than 1 pediatric patient treated with LYUMJEV included: rhinitis (0.7%), dermatitis (0.7%), rash (0.5%), and hypersensitivity (0.5%).
Lipodystrophy Administration of insulin, including LYUMJEV, has resulted in lipohypertrophy (enlargement or thickening of tissue) and lipoatrophy (depression in the skin).
Lipodystrophy was reported in 0.2% of adult and pediatric patients treated with LYUMJEV [see Dosage and Administration ( 2.2 )] .
Injection/Infusion Site Reactions Injection or infusion site reactions can occur with insulin therapy.
With LYUMJEV, adult and pediatric patients have experienced rash, redness, inflammation, pain, bruising, or itching at the site of LYUMJEV injection or infusion.
LYUMJEV contains treprostinil sodium and sodium citrate dihydrate as inactive ingredients [see Description ( 11 )] which have been associated with infusion and injection site reactions with other non-insulin products.
Subcutaneous Injection Site-Related Reactions : In studies PRONTO-T1D and PRONTO-T2D, injection site-related reactions occurred in 2.7% of adult patients treated with LYUMJEV (mild in 2.2% and moderate in 0.5%).
with <0.1% of patients discontinuing from treatment due to injection site-related reactions.
In Study PRONTO-Peds, injection site-related reactions occurred in 6.2% of pediatric patients treated with LYUMJEV (mild in 5.7% and moderate in 0.5%), with <0.5% of patients discontinuing from treatment due to injection site-related reactions.
Continuous Subcutaneous Insulin Infusion (CSII) Site-Related Reactions: In Study PRONTO-Pump-2, infusion site-related reactions were reported in 37.7% of adult patients treated with LYUMJEV (mild in 27.9%, moderate in 7.9%, and severe in 1.9%), with 3.3% of patients discontinuing from treatment due to infusion site-related reactions.
See Table 4 .
Weight Gain Weight gain can occur with insulin therapy, including LYUMJEV, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Adult patients with type 1 diabetes treated with LYUMJEV gained an average of 0.6 kg and patients with type 2 diabetes treated with LYUMJEV gained an average of 1.5 kg.
Peripheral Edema Insulin, including LYUMJEV, may cause sodium retention and edema, particularly if previous poor metabolic control is improved by intensified insulin therapy.
Peripheral edema occurred in 0.2% of adult patients treated with LYUMJEV.
6.2 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of insulin lispro.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Localized cutaneous amyloidosis at the injection site has occurred with insulin use.
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.
Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )] Hypokalemia [see Warnings and Precautions ( 5.5 )] .
Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] .
Adverse reactions observed with LYUMJEV include hypoglycemia, injection/infusion site reactions, allergic reactions, rash, pruritus, lipodystrophy, and weight gain.
( 6.1 ) 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.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates actually observed in clinical practice.
Adverse Reaction Database – Adult Patients with Type 1 and Type 2 Diabetes The data in Table 1 reflect the exposure of 780 adult patients with type 1 diabetes to LYUMJEV with a mean exposure duration of 26 weeks [see Clinical Studies ( 14.2 )] .
The mean age was 44 years, the mean duration of diabetes was 19 years, 55% were male, 77% were White, 2% were Black or African American, and 9% were Hispanic.
The mean BMI was 26.6 kg/m 2 and the mean HbA 1c at baseline was 7.3%.
The data in Table 2 reflect the exposure of 336 adult patients with type 2 diabetes to LYUMJEV with a mean exposure duration of 26 weeks [see Clinical Studies ( 14.3 )] .
The mean age was 60 years, the mean duration of diabetes was 16 years, 55% were male, 69% were White, 4% were Black or African American, and 24% were Hispanic.
The mean BMI was 32.1 kg/m 2 and the mean HbA 1c at baseline was 7.3%.
The data in Table 3 reflect the exposure of 215 adult patients with type 1 diabetes to LYUMJEV via CSII administration with a mean exposure duration of 16 weeks [see Clinical Studies ( 14.4 )] .
The mean age was 48 years, the mean duration of diabetes was 26 years, 44% were male, 94% were White, 3% were Black or African American, and 8% were Hispanic.
The mean BMI was 27.0 kg/m 2 and the mean HbA 1c at baseline was 7.6%.
Common adverse reactions, excluding hypoglycemia, were defined as events that occurred in ≥5% and at the same rate or greater for LYUMJEV-treated patients than HUMALOG-treated patients.
Table 1.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Adult Patients with Type 1 Diabetes Mealtime LYUMJEV + basal insulin (N=451) % Postmeal LYUMJEV + basal insulin (N=329) % Nasopharyngitis 14.2 14.6 Table 2.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Adult Patients with Type 2 Diabetes Mealtime LYUMJEV + basal insulin (N=336) % Nasopharyngitis 12.5 Upper Respiratory Tract Infection 7.4 Table 3.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Adult Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion CSII LYUMJEV administration (N=215) % Infusion site reaction 19.1 Infusion site pain 15.8 Nasopharyngitis 6.0 Adverse Reaction Database – Pediatric Patients with Type 1 Diabetes The data in Table 4 reflect the exposure of 418 pediatric patients with type 1 diabetes to LYUMJEV with a mean exposure duration of 26 weeks [see Clinical Studies ( 14.5 )] .
The mean age was 12 years; 50% were male, 91% were White, 1% were Black or African American; and 24% of the US subpopulation in this trial were Hispanic.
The mean BMI was 20.5 kg/m 2 , the mean duration of diabetes was 5 years, and the mean HbA 1c at baseline was 7.8%.
Common adverse reactions, excluding hypoglycemia, were defined as events that occurred in ≥5% and at the same rate or greater for LYUMJEV-treated patients than HUMALOG-treated patients.
Table 4.
Adverse Reactions That Occurred in ≥5% of LYUMJEV-Treated Pediatric Patients with Type 1 Diabetes Mealtime LYUMJEV + basal insulin (N=280) % Postmeal LYUMJEV + basal insulin (N=138) % Nasopharyngitis 8.2 5.1 Upper Respiratory Tract Infection 5.4 1.4 Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including LYUMJEV.
The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors.
For these reasons, comparing rates of hypoglycemia in clinical trials for LYUMJEV with the incidence of hypoglycemia for other products may be misleading and also may not be representative of hypoglycemia rates that occur in clinical practice.
Incidence rates for severe hypoglycemia in adults with type 1 and type 2 diabetes mellitus and pediatric patients with type 1 diabetes mellitus treated with LYUMJEV in clinical trials are shown in Table 5 [see Clinical Studies ( 14 )] .
Table 5.
Proportion of Patients with Type 1 Diabetes and Type 2 Diabetes Who Experienced at Least One Episode of Severe Hypoglycemia in Adult and Pediatric Clinical Trials a Severe hypoglycemia: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions PRONTO-T1D (Adult Type 1) PRONTO-T2D (Adult Type 2) PRONTO-Pump-2 (Adult Type 1 CSII) PRONTO-Peds (Pediatric Type 1) Mealtime LYUMJEV + basal insulin (N=451) % Postmeal LYUMJEV + basal insulin (N=329) % Mealtime LYUMJEV + basal insulin (N=336) % LYUMJEV (N=215) % Mealtime LYUMJEV + basal insulin (N=280) % Postmeal LYUMJEV + basal insulin (N=298) % Severe hypoglycemia a 5.5 4.6 0.9 1.4 1.1 0 Allergic Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including LYUMJEV, and may be life threatening.
Generalized hypersensitivity reactions such as skin rashes and hypersensitivity were reported in adult patients treated with LYUMJEV: eczema (0.4%), rash (0.4%), dermatitis (0.3%), hypersensitivity (0.2%), and pruritus (0.2%).
Generalized hypersensitivity reactions reported in more than 1 pediatric patient treated with LYUMJEV included: rhinitis (0.7%), dermatitis (0.7%), rash (0.5%), and hypersensitivity (0.5%).
Lipodystrophy Administration of insulin, including LYUMJEV, has resulted in lipohypertrophy (enlargement or thickening of tissue) and lipoatrophy (depression in the skin).
Lipodystrophy was reported in 0.2% of adult and pediatric patients treated with LYUMJEV [see Dosage and Administration ( 2.2 )] .
Injection/Infusion Site Reactions Injection or infusion site reactions can occur with insulin therapy.
With LYUMJEV, adult and pediatric patients have experienced rash, redness, inflammation, pain, bruising, or itching at the site of LYUMJEV injection or infusion.
LYUMJEV contains treprostinil sodium and sodium citrate dihydrate as inactive ingredients [see Description ( 11 )] which have been associated with infusion and injection site reactions with other non-insulin products.
Subcutaneous Injection Site-Related Reactions : In studies PRONTO-T1D and PRONTO-T2D, injection site-related reactions occurred in 2.7% of adult patients treated with LYUMJEV (mild in 2.2% and moderate in 0.5%).
with <0.1% of patients discontinuing from treatment due to injection site-related reactions.
In Study PRONTO-Peds, injection site-related reactions occurred in 6.2% of pediatric patients treated with LYUMJEV (mild in 5.7% and moderate in 0.5%), with <0.5% of patients discontinuing from treatment due to injection site-related reactions.
Continuous Subcutaneous Insulin Infusion (CSII) Site-Related Reactions: In Study PRONTO-Pump-2, infusion site-related reactions were reported in 37.7% of adult patients treated with LYUMJEV (mild in 27.9%, moderate in 7.9%, and severe in 1.9%), with 3.3% of patients discontinuing from treatment due to infusion site-related reactions.
See Table 4 .
Weight Gain Weight gain can occur with insulin therapy, including LYUMJEV, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Adult patients with type 1 diabetes treated with LYUMJEV gained an average of 0.6 kg and patients with type 2 diabetes treated with LYUMJEV gained an average of 1.5 kg.
Peripheral Edema Insulin, including LYUMJEV, may cause sodium retention and edema, particularly if previous poor metabolic control is improved by intensified insulin therapy.
Peripheral edema occurred in 0.2% of adult patients treated with LYUMJEV.
6.2 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of insulin lispro.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Localized cutaneous amyloidosis at the injection site has occurred with insulin use.
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.