NOVOLOG
Generic: INSULIN ASPART
Basic Information
Manufacturer
A-S Medication Solutions
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
e172b4f8-9b25-4019-8e09-afc10b2f30c9
Indications & Usage
1 INDICATIONS AND USAGE NOVOLOG is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.
NOVOLOG is rapid acting human insulin analog indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus ( 1 ).
NOVOLOG 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 NOVOLOG include: hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus ( 6 ).
To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc.
at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial 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 NOVOLOG 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 NOVOLOG in one clinical trial with a mean exposure duration to NOVOLOG 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 NOVOLOG in one clinical trial with a mean exposure duration to NOVOLOG 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 NOVOLOG-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 NOVOLOG and at the same rate or greater on NOVOLOG than on comparator NOVOLOG + 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 NOVOLOG and at the same rate or greater on NOVOLOG than on comparator NOVOLOG + 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 NOVOLOG .
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 NOVOLOG 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 NOVOLOG 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 NOVOLOG was 10% at 24 weeks.
• Adult and pediatric patients with type 1 diabetes mellitus, who received NOVOLOG via continuous subcutaneous insulin infusion by external pump was 2% at 16 weeks and 10% at 16 weeks respectively.
No severe hypoglycemic episodes were reported in adult patients with type 2 diabetes mellitus receiving NOVOLOG via continuous subcutaneous insulin infusion by external pump at 16 weeks.
Allergic Reactions Some patients taking insulin, including NOVOLOG 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 NOVOLOG, subcutaneously and via subcutaneous insulin infusion by external pump, 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 NOVOLOG, 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 NOVOLOG, 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 to NOVOLOG in the studies described below with the incidence of antibodies in other studies or to other 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 NOVOLOG 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 NOVOLOG 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 NOVOLOG, 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 Post Marketing Experience The following adverse reactions have been identified during post-approval use of NOVOLOG.
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 NOVOLOG.
Localized cutaneous amyloidosis at the injection site has occurred with insulin aspart.
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 Novo Nordisk Inc.
at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial 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 NOVOLOG 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 NOVOLOG in one clinical trial with a mean exposure duration to NOVOLOG 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 NOVOLOG in one clinical trial with a mean exposure duration to NOVOLOG 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 NOVOLOG-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 NOVOLOG and at the same rate or greater on NOVOLOG than on comparator NOVOLOG + 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 NOVOLOG and at the same rate or greater on NOVOLOG than on comparator NOVOLOG + 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 NOVOLOG .
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 NOVOLOG 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 NOVOLOG 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 NOVOLOG was 10% at 24 weeks.
• Adult and pediatric patients with type 1 diabetes mellitus, who received NOVOLOG via continuous subcutaneous insulin infusion by external pump was 2% at 16 weeks and 10% at 16 weeks respectively.
No severe hypoglycemic episodes were reported in adult patients with type 2 diabetes mellitus receiving NOVOLOG via continuous subcutaneous insulin infusion by external pump at 16 weeks.
Allergic Reactions Some patients taking insulin, including NOVOLOG 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 NOVOLOG, subcutaneously and via subcutaneous insulin infusion by external pump, 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 NOVOLOG, 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 NOVOLOG, 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 to NOVOLOG in the studies described below with the incidence of antibodies in other studies or to other 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 NOVOLOG 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 NOVOLOG 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 NOVOLOG, 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 Post Marketing Experience The following adverse reactions have been identified during post-approval use of NOVOLOG.
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 NOVOLOG.
Localized cutaneous amyloidosis at the injection site has occurred with insulin aspart.
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.