MERILOG
Generic: INSULIN ASPART-SZJJ
Basic Information
Manufacturer
Sanofi-Aventis U.S. LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
eee07a52-1102-4d48-9782-26061db175ad
Indications & Usage
1 INDICATIONS AND USAGE MERILOG is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.
MERILOG is rapid acting human insulin analog indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus ( 1 ).
MERILOG is rapid acting human insulin analog indicated to improve glycemic control in adults 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) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Hypokalemia [see Warnings and Precautions (5.6) ] Adverse reactions observed with insulin aspart products include: hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus ( 6 ).
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 designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
The safety of insulin aspart was evaluated in two treat-to-target trials of 6 months duration, conducted in patients with type 1 diabetes or type 2 diabetes [see Clinical Studies (14) ] .
The data in Table 1 reflect the exposure of 596 patients with type 1 diabetes to insulin aspart in one clinical trial with a mean exposure duration to insulin aspart of 24 weeks.
The mean age was 39 years.
Fifty-one percent were male, 94% were Caucasian, 2% were Black and 4% were other races.
The mean body mass index (BMI) was 25.6 kg/m 2 .
The mean duration of diabetes was 15.7 years and the mean HbA 1c at baseline was 7.9%.
The data in Table 2 reflect the exposure of 91 patients with type 2 diabetes to insulin aspart in one clinical trial with a mean exposure duration to insulin aspart of 24 weeks.
The mean age was 57 years.
Sixty-three percent were male, 76% were Caucasian, 9% were Black and 15% were other races.
The mean BMI was 29.7 kg/m 2 .
The mean duration of diabetes was 12.7 years and the mean HbA 1c at baseline was 8.1%.
Common adverse reactions were defined as events that occurred in ≥5%, excluding hypoglycemia, of the population studied.
Common adverse events that occurred at the same rate or greater for insulin aspart-treated patients than in comparator-treated patients during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2, respectively.
Table 1: Adverse reactions that occurred in ≥5% of Type 1 Diabetes Mellitus Adult Patients treated with insulin aspart and at the same rate or greater on insulin aspart than on comparator Insulin aspart + NPH (%) (n= 596) Regular Human Insulin + NPH (%) (n= 286) Headache 12 10 Injury accidental 11 10 Nausea 7 5 Diarrhea 5 3 Table 2: Adverse reactions that occurred in ≥5% of Type 2 Diabetes Mellitus Adult Patients treated with insulin aspart and at the same rate or greater on insulin aspart than on comparator Insulin aspart + NPH (%) (n= 91) Human Regular Insulin + NPH (%) (n= 91) Hyporeflexia 11 7 Onychomycosis 10 5 Sensory disturbance 9 7 Urinary tract infection 8 7 Chest pain 5 3 Headache 5 3 Skin disorder 5 2 Abdominal pain 5 1 Sinusitis 5 1 Severe Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including insulin aspart products [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 insulin aspart 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.
Severe hypoglycemia was defined as hypoglycemia associated with central nervous system symptoms and requiring the intervention of another person or hospitalization.
The incidence of severe hypoglycemia in: Adult and pediatric patients with type 1 diabetes mellitus who received subcutaneous insulin aspart was 17% at 24 weeks and 6% at 24 weeks, respectively [see Clinical Studies (14) ] .
Adult patients with type 2 diabetes mellitus who received subcutaneous insulin aspart was 10% at 24 weeks.
Allergic Reactions Some patients taking insulin, including insulin aspart products have 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.
Adverse Reactions Associated with Insulin Initiation and Glucose Control Intensification 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 Administration of insulin, including insulin aspart products subcutaneously, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients [see Dosage and Administration (2.2) ] .
Peripheral Edema Insulins, including insulin aspart products, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Weight Gain Weight gain has occurred with insulins, including insulin aspart products, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
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 medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other insulin aspart products may be misleading.
In a 6-month study with a 6-month extension in adult subjects with type 1 diabetes, 99.8% of patients who received insulin aspart were positive for anti-insulin antibodies (AIA) at least once during the study, including 97.2% that were positive at baseline.
A total of 92.1% of patients who received insulin aspart were positive for anti-drug antibodies (ADA) at least once during the study, including 64.6% that were positive at baseline.
In a phase 3 type 1 diabetes clinical trial of insulin aspart, initial increase in titers of antibodies to insulin, followed by a decrease to baseline values, was observed in regular human insulin and insulin aspart treatment groups with similar incidences.
These antibodies did not cause deterioration in glycemic control or necessitate increases in insulin dose.
6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of insulin aspart products.
Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Medication errors have been reported in which other insulins have been accidentally substituted for insulin aspart products.
Localized cutaneous amyloidosis at the injection site has occurred with insulin aspart products.
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.
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 designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
The safety of insulin aspart was evaluated in two treat-to-target trials of 6 months duration, conducted in patients with type 1 diabetes or type 2 diabetes [see Clinical Studies (14) ] .
The data in Table 1 reflect the exposure of 596 patients with type 1 diabetes to insulin aspart in one clinical trial with a mean exposure duration to insulin aspart of 24 weeks.
The mean age was 39 years.
Fifty-one percent were male, 94% were Caucasian, 2% were Black and 4% were other races.
The mean body mass index (BMI) was 25.6 kg/m 2 .
The mean duration of diabetes was 15.7 years and the mean HbA 1c at baseline was 7.9%.
The data in Table 2 reflect the exposure of 91 patients with type 2 diabetes to insulin aspart in one clinical trial with a mean exposure duration to insulin aspart of 24 weeks.
The mean age was 57 years.
Sixty-three percent were male, 76% were Caucasian, 9% were Black and 15% were other races.
The mean BMI was 29.7 kg/m 2 .
The mean duration of diabetes was 12.7 years and the mean HbA 1c at baseline was 8.1%.
Common adverse reactions were defined as events that occurred in ≥5%, excluding hypoglycemia, of the population studied.
Common adverse events that occurred at the same rate or greater for insulin aspart-treated patients than in comparator-treated patients during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2, respectively.
Table 1: Adverse reactions that occurred in ≥5% of Type 1 Diabetes Mellitus Adult Patients treated with insulin aspart and at the same rate or greater on insulin aspart than on comparator Insulin aspart + NPH (%) (n= 596) Regular Human Insulin + NPH (%) (n= 286) Headache 12 10 Injury accidental 11 10 Nausea 7 5 Diarrhea 5 3 Table 2: Adverse reactions that occurred in ≥5% of Type 2 Diabetes Mellitus Adult Patients treated with insulin aspart and at the same rate or greater on insulin aspart than on comparator Insulin aspart + NPH (%) (n= 91) Human Regular Insulin + NPH (%) (n= 91) Hyporeflexia 11 7 Onychomycosis 10 5 Sensory disturbance 9 7 Urinary tract infection 8 7 Chest pain 5 3 Headache 5 3 Skin disorder 5 2 Abdominal pain 5 1 Sinusitis 5 1 Severe Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including insulin aspart products [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 insulin aspart 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.
Severe hypoglycemia was defined as hypoglycemia associated with central nervous system symptoms and requiring the intervention of another person or hospitalization.
The incidence of severe hypoglycemia in: Adult and pediatric patients with type 1 diabetes mellitus who received subcutaneous insulin aspart was 17% at 24 weeks and 6% at 24 weeks, respectively [see Clinical Studies (14) ] .
Adult patients with type 2 diabetes mellitus who received subcutaneous insulin aspart was 10% at 24 weeks.
Allergic Reactions Some patients taking insulin, including insulin aspart products have 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.
Adverse Reactions Associated with Insulin Initiation and Glucose Control Intensification 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 Administration of insulin, including insulin aspart products subcutaneously, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients [see Dosage and Administration (2.2) ] .
Peripheral Edema Insulins, including insulin aspart products, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Weight Gain Weight gain has occurred with insulins, including insulin aspart products, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
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 medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other insulin aspart products may be misleading.
In a 6-month study with a 6-month extension in adult subjects with type 1 diabetes, 99.8% of patients who received insulin aspart were positive for anti-insulin antibodies (AIA) at least once during the study, including 97.2% that were positive at baseline.
A total of 92.1% of patients who received insulin aspart were positive for anti-drug antibodies (ADA) at least once during the study, including 64.6% that were positive at baseline.
In a phase 3 type 1 diabetes clinical trial of insulin aspart, initial increase in titers of antibodies to insulin, followed by a decrease to baseline values, was observed in regular human insulin and insulin aspart treatment groups with similar incidences.
These antibodies did not cause deterioration in glycemic control or necessitate increases in insulin dose.
6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of insulin aspart products.
Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Medication errors have been reported in which other insulins have been accidentally substituted for insulin aspart products.
Localized cutaneous amyloidosis at the injection site has occurred with insulin aspart products.
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.