TOUJEO
Generic: INSULIN GLARGINE
Basic Information
Manufacturer
A-S Medication Solutions
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
257ca17b-6ff7-4f2e-9037-4c185bac5768
Indications & Usage
1 INDICATIONS AND USAGE TOUJEO is indicated to improve glycemic control in adults and pediatric patients 6 years of age and older with diabetes mellitus.
TOUJEO is a long-acting human insulin analog indicated to improve glycemic control in adults and pediatric patients 6 years and older with diabetes mellitus.
( 1 ) Limitations of Use : Not recommended for the treatment of diabetic ketoacidosis.
( 1 ) Limitations of Use: TOUJEO is not recommended for the treatment of diabetic ketoacidosis.
TOUJEO is a long-acting human insulin analog indicated to improve glycemic control in adults and pediatric patients 6 years and older with diabetes mellitus.
( 1 ) Limitations of Use : Not recommended for the treatment of diabetic ketoacidosis.
( 1 ) Limitations of Use: TOUJEO is not recommended for the treatment of diabetic ketoacidosis.
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 commonly associated with TOUJEO (≥5%) are: Hypoglycemia, allergic reactions, injection site reaction, lipodystrophy, pruritus, rash, edema, and weight gain.
( 6.1 , 6.2 ) 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 actually observed in clinical practice.
The data in Table 1 reflect the exposure of 304 patients with type 1 diabetes to TOUJEO with mean exposure duration of 23 weeks.
The type 1 diabetes population had the following characteristics: Mean age was 46 years and mean duration of diabetes was 21 years.
Fifty-five percent were male, 86% were Caucasian, 5% were Black or African American, and 5% were Hispanic.
At baseline, the mean eGFR was 82 mL/min/1.73 m 2 and 35% of patients had eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 28 kg/m 2 .
HbA1c at baseline was greater than or equal to 8% in 58% of patients.
The data in Table 2 reflect the exposure of 1242 patients with type 2 diabetes to TOUJEO with mean exposure duration of 25 weeks.
The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 13 years.
Fifty-three percent were male, 88% were Caucasian, 7% were Black or African American, and 17% were Hispanic.
At baseline, mean eGFR was 79 mL/min/1.73 m 2 and 27% of patients had an eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 35 kg/m 2 .
HbA1c at baseline was greater than or equal to 8% in 66% of patients.
TOUJEO was studied in 233 pediatric patients (6–17 years of age) with type 1 diabetes for a mean duration of 26 weeks [see Clinical Studies (14.1) ] .
Common adverse reactions (occurring ≥5%) in TOUJEO-treated subjects during clinical trials in adult patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively.
Common adverse reactions for TOUJEO-treated pediatric subjects with type 1 diabetes mellitus were similar to the adverse reactions listed in Table 1.
Hypoglycemia is discussed in a dedicated subsection below.
Table 1: Adverse Reactions Occurring ≥5% in Two Pooled Clinical Trials of 26 Weeks and 16 Weeks Duration in Adults with Type 1 Diabetes TOUJEO + Mealtime Insulin "mealtime insulin" refers to insulin glulisine, insulin lispro, or insulin aspart.
, % (n=304) Nasopharyngitis 12.8 Upper respiratory tract infection 9.5 Table 2: Adverse Reactions Occurring ≥5% in Three Pooled Clinical Trials of 26 Weeks Duration in Adults with Type 2 Diabetes TOUJEO one of the trials in type 2 diabetes included mealtime insulin.
, % (n=1242) Nasopharyngitis 7.1 Upper respiratory tract infection 5.7 Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients treated with TOUJEO.
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 TOUJEO 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 TOUJEO adult program, severe hypoglycemia was defined as an event requiring assistance of another person to administer a resuscitative action.
In the pediatric program, severe hypoglycemia was defined as an event with semiconsciousness, unconsciousness, coma and/or convulsions in a patient who had altered mental status and could not assist in his own care, and who may have required glucagon or intravenous glucose.
The incidence of severe hypoglycemia in adult patients with type 1 diabetes receiving TOUJEO as part of a multiple daily injection regimen was 6.6% at 26 weeks.
The incidence of hypoglycemia with a glucose level less than 54 mg/dL with or without symptoms was 77.7% at 26 weeks.
The incidence of severe hypoglycemia in pediatric patients with type 1 diabetes receiving TOUJEO as part of a multiple daily injection regimen was 6% at 26 weeks and the incidence of hypoglycemia accompanied by a self-monitored or plasma glucose value less than 54 mg/dL regardless of symptoms was 80.3%.
The incidence of severe hypoglycemia in adult patients with type 2 diabetes was 5% at 26 weeks in patients receiving TOUJEO as part of a multiple daily injection regimen, and 1.0% and 0.9% respectively at 26 weeks in the two studies where patients received TOUJEO as part of a basal-insulin only regimen.
The incidence of hypoglycemia accompanied by a self-monitored or plasma glucose value less than 54 mg/dL regardless of symptoms in patients with type 2 diabetes receiving TOUJEO ranged from 9% to 44.6% at 26 weeks and the highest risk was again seen in patients receiving TOUJEO as part of a multiple daily injection regimen.
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.
Peripheral Edema Insulin, including TOUJEO, may cause sodium retention and edema, particularly if previously poor metabolic control was improved by intensified insulin therapy.
Lipodystrophy Long-term use of insulin, including TOUJEO, can cause lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients and may affect insulin absorption [see Dosage and Administration (2.1) ] .
Weight Gain Weight gain has occurred with insulins including TOUJEO and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Hypersensitivity Reactions Patients taking TOUJEO 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.
6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
In a 6-month study of type 1 diabetes patients, 79% of patients who received TOUJEO once daily were positive for anti-insulin antibodies (AIA) at least once during the study, including 62% that were positive at baseline and 44% of patients who developed antidrug antibody (i.e., anti-insulin glargine antibody [ADA]) during the study.
Eighty percent of the AIA-positive patients on TOUJEO with antibody test at baseline remained AIA positive at month 6.
In two 6-month studies in type 2 diabetes patients, 25% of patients who received TOUJEO once daily were positive for AIA at least once during the study, including 42% who were positive at baseline and 20% of patients who developed ADA during the study.
Ninety percent of the AIA-positive patients on TOUJEO with antibody test at baseline, remained AIA positive at month 6.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease.
For these reasons, comparison of the incidence of antibodies to TOUJEO with the incidence of antibodies in other studies or to other products may be misleading.
6.3 Postmarketing Experience The following additional adverse reactions have been identified during postapproval use of TOUJEO.
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.
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 , 6.2 ) 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 actually observed in clinical practice.
The data in Table 1 reflect the exposure of 304 patients with type 1 diabetes to TOUJEO with mean exposure duration of 23 weeks.
The type 1 diabetes population had the following characteristics: Mean age was 46 years and mean duration of diabetes was 21 years.
Fifty-five percent were male, 86% were Caucasian, 5% were Black or African American, and 5% were Hispanic.
At baseline, the mean eGFR was 82 mL/min/1.73 m 2 and 35% of patients had eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 28 kg/m 2 .
HbA1c at baseline was greater than or equal to 8% in 58% of patients.
The data in Table 2 reflect the exposure of 1242 patients with type 2 diabetes to TOUJEO with mean exposure duration of 25 weeks.
The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 13 years.
Fifty-three percent were male, 88% were Caucasian, 7% were Black or African American, and 17% were Hispanic.
At baseline, mean eGFR was 79 mL/min/1.73 m 2 and 27% of patients had an eGFR ≥90 mL/min/1.73 m 2 .
The mean BMI was 35 kg/m 2 .
HbA1c at baseline was greater than or equal to 8% in 66% of patients.
TOUJEO was studied in 233 pediatric patients (6–17 years of age) with type 1 diabetes for a mean duration of 26 weeks [see Clinical Studies (14.1) ] .
Common adverse reactions (occurring ≥5%) in TOUJEO-treated subjects during clinical trials in adult patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively.
Common adverse reactions for TOUJEO-treated pediatric subjects with type 1 diabetes mellitus were similar to the adverse reactions listed in Table 1.
Hypoglycemia is discussed in a dedicated subsection below.
Table 1: Adverse Reactions Occurring ≥5% in Two Pooled Clinical Trials of 26 Weeks and 16 Weeks Duration in Adults with Type 1 Diabetes TOUJEO + Mealtime Insulin "mealtime insulin" refers to insulin glulisine, insulin lispro, or insulin aspart.
, % (n=304) Nasopharyngitis 12.8 Upper respiratory tract infection 9.5 Table 2: Adverse Reactions Occurring ≥5% in Three Pooled Clinical Trials of 26 Weeks Duration in Adults with Type 2 Diabetes TOUJEO one of the trials in type 2 diabetes included mealtime insulin.
, % (n=1242) Nasopharyngitis 7.1 Upper respiratory tract infection 5.7 Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients treated with TOUJEO.
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 TOUJEO 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 TOUJEO adult program, severe hypoglycemia was defined as an event requiring assistance of another person to administer a resuscitative action.
In the pediatric program, severe hypoglycemia was defined as an event with semiconsciousness, unconsciousness, coma and/or convulsions in a patient who had altered mental status and could not assist in his own care, and who may have required glucagon or intravenous glucose.
The incidence of severe hypoglycemia in adult patients with type 1 diabetes receiving TOUJEO as part of a multiple daily injection regimen was 6.6% at 26 weeks.
The incidence of hypoglycemia with a glucose level less than 54 mg/dL with or without symptoms was 77.7% at 26 weeks.
The incidence of severe hypoglycemia in pediatric patients with type 1 diabetes receiving TOUJEO as part of a multiple daily injection regimen was 6% at 26 weeks and the incidence of hypoglycemia accompanied by a self-monitored or plasma glucose value less than 54 mg/dL regardless of symptoms was 80.3%.
The incidence of severe hypoglycemia in adult patients with type 2 diabetes was 5% at 26 weeks in patients receiving TOUJEO as part of a multiple daily injection regimen, and 1.0% and 0.9% respectively at 26 weeks in the two studies where patients received TOUJEO as part of a basal-insulin only regimen.
The incidence of hypoglycemia accompanied by a self-monitored or plasma glucose value less than 54 mg/dL regardless of symptoms in patients with type 2 diabetes receiving TOUJEO ranged from 9% to 44.6% at 26 weeks and the highest risk was again seen in patients receiving TOUJEO as part of a multiple daily injection regimen.
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.
Peripheral Edema Insulin, including TOUJEO, may cause sodium retention and edema, particularly if previously poor metabolic control was improved by intensified insulin therapy.
Lipodystrophy Long-term use of insulin, including TOUJEO, can cause lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients and may affect insulin absorption [see Dosage and Administration (2.1) ] .
Weight Gain Weight gain has occurred with insulins including TOUJEO and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Hypersensitivity Reactions Patients taking TOUJEO 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.
6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
In a 6-month study of type 1 diabetes patients, 79% of patients who received TOUJEO once daily were positive for anti-insulin antibodies (AIA) at least once during the study, including 62% that were positive at baseline and 44% of patients who developed antidrug antibody (i.e., anti-insulin glargine antibody [ADA]) during the study.
Eighty percent of the AIA-positive patients on TOUJEO with antibody test at baseline remained AIA positive at month 6.
In two 6-month studies in type 2 diabetes patients, 25% of patients who received TOUJEO once daily were positive for AIA at least once during the study, including 42% who were positive at baseline and 20% of patients who developed ADA during the study.
Ninety percent of the AIA-positive patients on TOUJEO with antibody test at baseline, remained AIA positive at month 6.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease.
For these reasons, comparison of the incidence of antibodies to TOUJEO with the incidence of antibodies in other studies or to other products may be misleading.
6.3 Postmarketing Experience The following additional adverse reactions have been identified during postapproval use of TOUJEO.
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.
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.