ADMELOG
Generic: INSULIN LISPRO
Basic Information
Manufacturer
Sanofi-Aventis U.S. LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
0691def8-4a7b-4de3-866f-a280989f47f1
Indications & Usage
1 INDICATIONS AND USAGE ADMELOG is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
ADMELOG is a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
( 1 )
ADMELOG 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 discussed elsewhere: Hypoglycemia [see Warnings and Precautions (5.3) ] Hypoglycemia Due to Medication Errors [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Hypokalemia [see Warnings and Precautions (5.6) ] Adverse reactions associated with ADMELOG include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis at 1-800-633-1610 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 observed in practice.
Adverse Reactions with Subcutaneous Injections of ADMELOG Two clinical trials with ADMELOG were conducted: one in patients with type 1 diabetes and one in patients with type 2 diabetes [see Clinical Studies (14) ] .
The data in Table 1 reflect the exposure of 252 patients with type 1 diabetes to ADMELOG with mean exposure duration of 49 weeks.
The type 1 diabetes population had the following characteristics: Mean age was 43 years and mean duration of diabetes was 20 years.
Fifty-nine percent were male, 80% were White, 6% were Black or African American and 7% were Hispanic.
At baseline, the mean eGFR was 90 mL/min/1.73 m 2 and 49% of patients had eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 26 kg/m 2 .
The mean HbA1c at baseline was 8.07%.
Two hundred fifty-three patients with type 2 diabetes were exposed to ADMELOG with mean exposure duration of 25 weeks.
The type 2 diabetes population had the following characteristics: Mean age was 62 years and mean duration of diabetes was 17 years.
Fifty-four percent were male, 90% were White, 6% were Black or African American and 17% were Hispanic.
At baseline, the mean eGFR was 77 mL/min/1.73 m 2 and 27% of patients had eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 32 kg/m 2 .
The mean HbA1c at baseline was 7.99%.
Common adverse reactions were defined as reactions that occurred in ≥5% of the population studied.
Common adverse reactions (other than hypoglycemia) during a clinical trial in patients with type 1 diabetes mellitus are listed in Table 1.
In a 26-week clinical trial in patients with type 2 diabetes mellitus, no adverse reactions (other than hypoglycemia) occurred in ≥5% of ADMELOG-treated patients (n=253) were observed.
Table 1: Adverse Reactions that Occurred in ≥5% of ADMELOG-Treated Patients with Type 1 Diabetes in a 52-Week Trial ADMELOG + Insulin Glargine (100 units/mL), % (n=252) Nasopharyngitis 13% Upper respiratory tract infection 6% Severe Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including ADMELOG [see Warnings and Precautions (5.3) ] .
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 ADMELOG with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.
In the ADMELOG trials, severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
The incidence of severe hypoglycemia in patients receiving ADMELOG with type 1 diabetes mellitus and type 2 diabetes mellitus was 13.5% at 52 weeks and 2.4% at 26 weeks, respectively [see Clinical Studies (14) ] .
Adverse Reactions Associated with Insulin Initiation and Intensification of Glucose Control Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy.
However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.
Lipodystrophy Long-term use of insulin, including ADMELOG, can cause lipodystrophy at the site of repeated insulin injections or infusion.
Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue) and may affect insulin absorption [see Dosage and Administration (2.2) ] .
Weight Gain Weight gain can occur with insulins, including ADMELOG, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Peripheral Edema Insulins, including ADMELOG, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Adverse Reactions with Continuous Subcutaneous Insulin Infusion (CSII) of ADMELOG In a randomized, open-label crossover study in adult patients with type 1 diabetes treated over two 4-week periods, the incidence of infusion set occlusions (defined as failure to correct hyperglycemia [plasma glucose ≥300 mg/dL] by insulin bolus via insulin pump) in ADMELOG-treated patients (n=25) was evaluated.
Infusion set occlusions were reported by 24% of patients.
In a randomized, 16-week, open-label, parallel design study of pediatric patients with type 1 diabetes, adverse reactions related to infusion site-related reactions for another insulin lispro product, 100 units/mL, occurred in 21% of patients.
The most frequently reported infusion site-related reactions were infusion site erythema and infusion site reaction.
Allergic Reactions Local Allergy As with any insulin therapy, patients taking ADMELOG may experience redness, swelling, or itching at the site of the injection.
These minor reactions usually resolve in a few days to a few weeks, but in some occasions may require discontinuation of ADMELOG.
In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.
Systemic Allergy Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including ADMELOG.
Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.
Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in ADMELOG [see Contraindications (4) ] .
6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease.
For these reasons, comparison of the incidence of antibodies to ADMELOG in the studies described below with the incidence of antibodies in other studies or to other insulin products may be misleading.
In a 52-week study of ADMELOG in type 1 diabetes patients, 49.4% were positive at baseline and 22.6% had treatment-emergent ADA (i.e., either new ADA, or increase in titer of at least 4-fold).
In a 26-week study of ADMELOG in type 2 diabetes patients, 26.4% were positive at baseline and 18.8% had treatment-emergent ADA (i.e., either new ADA, or increase in titer of at least 4-fold).
6.3 Postmarketing Experience The following additional adverse reactions have been identified during post approval use of another insulin lispro product, 100 units/mL.
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.
Medication errors in which other insulins have been accidentally substituted for another insulin lispro product, 100 units/mL, have been identified during post approval use.
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.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis at 1-800-633-1610 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 observed in practice.
Adverse Reactions with Subcutaneous Injections of ADMELOG Two clinical trials with ADMELOG were conducted: one in patients with type 1 diabetes and one in patients with type 2 diabetes [see Clinical Studies (14) ] .
The data in Table 1 reflect the exposure of 252 patients with type 1 diabetes to ADMELOG with mean exposure duration of 49 weeks.
The type 1 diabetes population had the following characteristics: Mean age was 43 years and mean duration of diabetes was 20 years.
Fifty-nine percent were male, 80% were White, 6% were Black or African American and 7% were Hispanic.
At baseline, the mean eGFR was 90 mL/min/1.73 m 2 and 49% of patients had eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 26 kg/m 2 .
The mean HbA1c at baseline was 8.07%.
Two hundred fifty-three patients with type 2 diabetes were exposed to ADMELOG with mean exposure duration of 25 weeks.
The type 2 diabetes population had the following characteristics: Mean age was 62 years and mean duration of diabetes was 17 years.
Fifty-four percent were male, 90% were White, 6% were Black or African American and 17% were Hispanic.
At baseline, the mean eGFR was 77 mL/min/1.73 m 2 and 27% of patients had eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 32 kg/m 2 .
The mean HbA1c at baseline was 7.99%.
Common adverse reactions were defined as reactions that occurred in ≥5% of the population studied.
Common adverse reactions (other than hypoglycemia) during a clinical trial in patients with type 1 diabetes mellitus are listed in Table 1.
In a 26-week clinical trial in patients with type 2 diabetes mellitus, no adverse reactions (other than hypoglycemia) occurred in ≥5% of ADMELOG-treated patients (n=253) were observed.
Table 1: Adverse Reactions that Occurred in ≥5% of ADMELOG-Treated Patients with Type 1 Diabetes in a 52-Week Trial ADMELOG + Insulin Glargine (100 units/mL), % (n=252) Nasopharyngitis 13% Upper respiratory tract infection 6% Severe Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including ADMELOG [see Warnings and Precautions (5.3) ] .
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 ADMELOG with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.
In the ADMELOG trials, severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
The incidence of severe hypoglycemia in patients receiving ADMELOG with type 1 diabetes mellitus and type 2 diabetes mellitus was 13.5% at 52 weeks and 2.4% at 26 weeks, respectively [see Clinical Studies (14) ] .
Adverse Reactions Associated with Insulin Initiation and Intensification of Glucose Control Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy.
However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.
Lipodystrophy Long-term use of insulin, including ADMELOG, can cause lipodystrophy at the site of repeated insulin injections or infusion.
Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue) and may affect insulin absorption [see Dosage and Administration (2.2) ] .
Weight Gain Weight gain can occur with insulins, including ADMELOG, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Peripheral Edema Insulins, including ADMELOG, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Adverse Reactions with Continuous Subcutaneous Insulin Infusion (CSII) of ADMELOG In a randomized, open-label crossover study in adult patients with type 1 diabetes treated over two 4-week periods, the incidence of infusion set occlusions (defined as failure to correct hyperglycemia [plasma glucose ≥300 mg/dL] by insulin bolus via insulin pump) in ADMELOG-treated patients (n=25) was evaluated.
Infusion set occlusions were reported by 24% of patients.
In a randomized, 16-week, open-label, parallel design study of pediatric patients with type 1 diabetes, adverse reactions related to infusion site-related reactions for another insulin lispro product, 100 units/mL, occurred in 21% of patients.
The most frequently reported infusion site-related reactions were infusion site erythema and infusion site reaction.
Allergic Reactions Local Allergy As with any insulin therapy, patients taking ADMELOG may experience redness, swelling, or itching at the site of the injection.
These minor reactions usually resolve in a few days to a few weeks, but in some occasions may require discontinuation of ADMELOG.
In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.
Systemic Allergy Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including ADMELOG.
Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.
Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in ADMELOG [see Contraindications (4) ] .
6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease.
For these reasons, comparison of the incidence of antibodies to ADMELOG in the studies described below with the incidence of antibodies in other studies or to other insulin products may be misleading.
In a 52-week study of ADMELOG in type 1 diabetes patients, 49.4% were positive at baseline and 22.6% had treatment-emergent ADA (i.e., either new ADA, or increase in titer of at least 4-fold).
In a 26-week study of ADMELOG in type 2 diabetes patients, 26.4% were positive at baseline and 18.8% had treatment-emergent ADA (i.e., either new ADA, or increase in titer of at least 4-fold).
6.3 Postmarketing Experience The following additional adverse reactions have been identified during post approval use of another insulin lispro product, 100 units/mL.
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.
Medication errors in which other insulins have been accidentally substituted for another insulin lispro product, 100 units/mL, have been identified during post approval use.
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.