3 ML insulin glargine 100 UNT/ML Pen Injector [Lantus]

INDICATIONS AND USAGE Insulin glargine is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Insulin glargine is a long-acting human insulin analog indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use Not recommended for treating diabetic ketoacidosis. ( 1 ) Limitations of Use Insulin glargine is not recommended for the treatment of diabetic ketoacidosis.

DOSAGE AND ADMINISTRATION Individualize dose based on type of diabetes, metabolic needs, blood glucose monitoring results and glycemic control goal. ( 2.2 ) Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time during the day, at the same time every day. ( 2.1 ) Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 ) Do not dilute or mix with any other insulin or solution. ( 2.1 ) See Full Prescribing Information for the recommended starting dosage in patients with type 2 diabetes ( 2.3 ) and how to switch to Insulin Glargine, U-300 from other insulins ( 2.4 ) Closely monitor glucose when switching to Insulin Glargine, U-300 and during initial weeks thereafter. ( 2.4 ) 2.1 Important Administration Instructions Always check insulin labels before administration. This product is TOUJEO (insulin glargine). [see Warnings and Precautions (5.4) ] . Visually inspect the Insulin Glargine, U-300 solution for particulate matter and discoloration prior to administration and only use if the solution is clear and colorless with no visible particles. Inject Insulin Glargine, U-300 subcutaneously into the abdominal area, thigh, or deltoid. Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) , Adverse Reactions (6) ] . Use Insulin Glargine, U-300 with caution in patients with visual impairment who may rely on audible clicks to dial their dose. Do not administer Insulin Glargine, U-300 intravenously or in an insulin pump. Do not dilute or mix Insulin Glargine, U-300 with any other insulin products or solutions. Never transfer Insulin Glargine, U-300 from the cartridges of the Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar prefilled pen into a syringe for administration [see Warnings and Precautions (5.4) ] . 2.2 General Dosing Instructions Insulin Glargine, U-300 is available in 2 single-patient-use prefilled pens: The Insulin Glargine, U-300 SoloStar prefilled pen contains 450 units of insulin glargine. It delivers doses in 1-unit increments and can deliver up to 80 units in a single injection. The Insulin Glargine, U-300 Max SoloStar prefilled pen contains 900 units of insulin glargine. It delivers doses in 2-unit increments and can deliver up to 160 units in a single injection. It is recommended for patients requiring at least 20 units per day. When changing between Insulin Glargine, U-300 SoloStar and Insulin Glargine, U-300 Max SoloStar, if the patient's previous dose was an odd number, the dose should be increased or decreased by 1 unit to match the dose increments dialable on each prefilled pen. The dose counter of the Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar prefilled pen shows the number of units of Insulin Glargine, U-300 to be injected and no conversion is required. Inject Insulin Glargine, U-300 subcutaneously once a day at the same time of day. During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2) ] . Individualize and titrate the dosage of Insulin Glargine, U-300 based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal. Titrate the dose of Insulin Glargine, U-300 no more frequently than every 3 to 4 days. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness to minimize the risk of hypoglycemia or hyperglycemia [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6 , 8.7) ] . 2.3 Starting Dose in Insulin-Naive Pediatric and Adult Patients Recommended Starting Dosage in Patients with Type 1 Diabetes The recommended starting dose of Insulin Glargine, U-300 in insulin-naive patients with type 1 diabetes is approximately one-third to one-half of the total daily insulin dose. The remainder of the total daily insulin dose should be given as a short-acting insulin and divided between each daily meal. As a general rule, 0.2 to 0.4 units of insulin per kilogram of body weight can be used to calculate the initial total daily insulin dose in insulin-naive patients with type 1 diabetes. The maximum glucose lowering effect of a dose of Insulin Glargine, U-300 may take five days to fully manifest and the first dose may be insufficient to cover metabolic needs in the first 24 hours of use [see Clinical Pharmacology (12.2) ] . When initiating Insulin Glargine, U-300, monitor glucose daily. Recommended Starting Dosage in Patients with Type 2 Diabetes The recommended starting dose of Insulin Glargine, U-300 in insulin-naive patients with type 2 diabetes is 0.2 units per kilogram of body weight once daily. 2.4 Starting Dose in Pediatric and Adult Patients with Either Type 1 or Type 2 Diabetes Already on Insulin Therapy Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to Insulin Glargine, U-300 from another insulin therapy [see Warnings and Precautions (5.3) ]. For patients currently on once-daily long or intermediate-acting insulin, start Insulin Glargine, U-300 at the same unit dose as the once-daily long-acting insulin dose. For patients controlled on LANTUS (insulin glargine, 100 units/mL), expect that a higher daily dose of Insulin Glargine, U-300 will be needed to maintain the same level of glycemic control [see Clinical Pharmacology (12.2) and Clinical Studies (14.1) ] . For patients currently on twice-daily long or intermediate-acting insulin, start Insulin Glargine, U-300 at 80% of the total daily NPH or insulin detemir twice-daily dosage. When switching patients to Insulin Glargine, U-300, monitor glucose frequently in the first weeks of therapy [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ] .

WARNINGS AND PRECAUTIONS Never share a TOUJEO SoloStar or TOUJEO Max SoloStar single-patient-use prefilled pen 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. Increase frequency of glucose monitoring with changes to: insulin dosage, concomitant drugs, meal pattern, physical activity, and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness. ( 5.3 , 6.1 ) 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: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue TOUJEO, monitor and treat if indicated. ( 5.5 , 6.1 ) 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 ) 5.1 Never Share a TOUJEO SoloStar or TOUJEO Max SoloStar Pen Between Patients TOUJEO SoloStar or TOUJEO Max SoloStar single-patient-use prefilled pens must never be shared between patients, even if the needle is changed. Pen sharing poses a risk for transmission of blood-borne pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in Insulin Regimen Including Changes to Administration Site 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 oral antidiabetic products may be needed. Changing to TOUJEO from other Insulin Therapies On a unit-to-unit basis, TOUJEO has a lower glucose lowering effect than LANTUS [see Clinical Pharmacology (12.2) ] . In clinical trials, patients who changed to TOUJEO from other basal insulins experienced higher average fasting plasma glucose levels in the first weeks of therapy compared to patients who were changed to LANTUS. Higher doses of TOUJEO were required to achieve similar levels of glucose control compared to LANTUS in clinical trials [see Clinical Studies (14.1) ] . The onset of action of TOUJEO develops over 6 hours following an injection. In type 1 diabetes patients treated with IV insulin, consider the longer onset of action of TOUJEO before stopping IV insulin. The full glucose lowering effect may not be apparent for at least 5 days [see Dosage and Administration (2.2) and Clinical Pharmacology (12.2) ] . To minimize the risk of hyperglycemia when initiating TOUJEO monitor glucose daily, titrate TOUJEO as described in this prescribing information, and adjust coadministered glucose-lowering therapies per standard of care [see Dosage and Administration (2.2 , 2.3) ] . 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulin, including TOUJEO. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient 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 patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, in patients using drugs that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7) ] , or who experience recurrent hypoglycemia. The long-acting effect of TOUJEO may delay recovery from hypoglycemia compared to shorter-acting insulins. Risk Factors for Hypoglycemia The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulation. As with all insulins, the glucose lowering effect time course of TOUJEO may vary in different patients or at different times in the same patient 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 concomitant drugs [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. To minimize the risk of hypoglycemia, do not administer TOUJEO intravenously, intramuscularly or in an insulin pump, or dilute or mix TOUJEO with any other insulin products or solutions. 5.4 Hypoglycemia Due to Medication Errors Accidental mix-ups between insulin products have been reported. To avoid medication errors between TOUJEO and other insulins, instruct patients to always check the insulin label before each injection. To avoid dosing errors and potential overdose, never use a syringe to remove TOUJEO from the TOUJEO SoloStar or TOUJEO Max SoloStar prefilled pen into a syringe [see Dosage and Administration (2.4) and Warnings and Precautions (5.3) ] . 5.5 Hypersensitivity Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including TOUJEO. If hypersensitivity reactions occur, discontinue TOUJEO; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6) ] . TOUJEO is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or any of the excipients in TOUJEO. 5.6 Hypokalemia All insulins, including TOUJEO, 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, when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including TOUJEO, and a

CONTRAINDICATIONS Insulin Glargine-yfgn is contraindicated: • During episodes of hypoglycemia [see Warnings and Precautions (5.3) ] • In patients with hypersensitivity to insulin glargine products or any of the excipients in Insulin Glargine-yfgn [see Warnings and Precautions (5.5) ] • During episodes of hypoglycemia ( 4 ) • Hypersensitivity to insulin glargine products or any excipient in Insulin Glargine-yfgn ( 4 )

Mechanism of Action The primary activity of insulin, including insulin glargine products, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.