Generic: INSULIN LISPRO
Insulin Analog [EPC]
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 )
5 WARNINGS AND PRECAUTIONS Never share an ADMELOG SoloStar disposable prefilled pen or syringe between patients, even if the needle is changed. ( 5.1 ) Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. ( 5.2 ) Hypoglycemia: May be life-threatening. Monitor blood glucose and increase monitoring frequency with changes to insulin dosage, use of glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. ( 5.3 , 6 , 7 , 8.6 , 8.7 ) Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. ( 5.4 ) Hypersensitivity Reactions: May be life-threatening. Discontinue ADMELOG, monitor and treat if indicated. ( 5.5 ) Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. ( 5.6 ) Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. ( 5.7 ) Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Monitor glucose and administer ADMELOG by subcutaneous injection if pump malfunction occurs. ( 5.8 ) 5.1 Never Share an ADMELOG SoloStar Pen or Syringe Between Patients ADMELOG SoloStar prefilled pen must never be shared between patients, even if the needle is changed. Patients using ADMELOG vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3) ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6) ] . Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulins, including ADMELOG. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly, and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7) ] , or in patients who experience recurrent hypoglycemia. Risk Factors for Hypoglycemia The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of ADMELOG may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology (12.2) ] . Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication [see Drug Interactions (7) ] . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6 , 8.7) ] . Risk Mitigation Strategies for Hypoglycemia Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. 5.4 Hypoglycemia Due to Medication Errors Accidental mix-ups between insulin products have been reported. To avoid medication errors between ADMELOG and other insulins, instruct patients to always check the insulin label before each injection. 5.5 Hypersensitivity Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including ADMELOG. If hypersensitivity reactions occur, discontinue ADMELOG; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6.1) ] . ADMELOG is contraindicated in patients who have had hypersensitivity reactions to insulin lispro or any of the excipients in ADMELOG [see Contraindications (4) ] . 5.6 Hypokalemia All insulins, including ADMELOG, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations). 5.7 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including ADMELOG, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered. 5.8 Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with ADMELOG may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see How Supplied/Storage and Handling (16.2) and Patient Counseling Information (17) ] .
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 โฅ90 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 โฅ90 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 โฅ5% 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 โฅ5% of ADMELOG-treated patients (n=253) were observed. Table 1: Adverse Reactions that Occurred in โฅ5% 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 โฅ300 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.
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.