These Highlights Do Not Include All The Information Needed To Use Toujeo U-300 Safely And Effectively. See Full Prescribing Information For Toujeo®

Limitations of Use:

TOUJEO is not recommended for the treatment of diabetic ketoacidosis.

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)]. Mild episodes of hypoglycemia can be treated with oral glucose. Lowering the insulin dosage, and adjustments in meal patterns, or physical activity level may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with glucagon for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

Insulin glargine is a long-acting human insulin analog produced by recombinant DNA technology utilizing a nonpathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines remain at the C-terminus of the B-chain. Insulin glargine has a molecular weight of 6063 Da.

TOUJEO (insulin glargine) injection is a sterile, clear and colorless solution for subcutaneous injection. Each mL of TOUJEO contains 300 units of insulin glargine dissolved in a clear aqueous fluid.

The 1.5 mL TOUJEO SoloStar prefilled pen presentation contains the following inactive ingredients per mL: glycerin (20 mg), metacresol (2.7 mg), zinc (90 mcg), and Water for Injection, USP.

The 3 mL TOUJEO Max SoloStar prefilled pen presentation contains the following inactive ingredients per mL: glycerin (20 mg), metacresol (2.7 mg), zinc (90 mcg), and Water for Injection, USP.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. TOUJEO has a pH of approximately 4.

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).

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.

The safety and effectiveness of TOUJEO to improve glycemic control in pediatric patients 6 years of age and older with diabetes mellitus have been established.

The use of TOUJEO for this indication is supported by evidence from an adequate and well-controlled study in 463 pediatric patients 6 to 17 years of age with type 1 diabetes mellitus [see Clinical Studies (14.2)] and from studies in adults with diabetes mellitus [see Clinical Pharmacology (12.3), Clinical Studies (14.3)].

The safety and effectiveness of TOUJEO have not been established in pediatric patients less than 6 years of age.

In controlled clinical studies, 30 of 304 (9.8%) TOUJEO-treated patients with type 1 diabetes and 327 of 1242 (26.3%) TOUJEO-treated patients with type 2 diabetes were ≥65 years of age, among them 2.0% of the patients with type 1 and 3.0% of the patients with type 2 diabetes were ≥75 years of age. No overall differences in safety or effectiveness of TOUJEO have been observed between patients 65 years of age and older and younger adult patients.

Nevertheless, caution should be exercised when TOUJEO is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia [see Warnings and Precautions (5.3), Adverse Reactions (6), and Clinical Studies (14)].

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.

TOUJEO is contraindicated:

• During episodes of hypoglycemia [see Warnings and Precautions (5.3)].
• In patients with hypersensitivity to insulin glargine or any excipients in TOUJEO [see Warnings and Precautions (5.5)].

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)]

Table 3 includes clinically significant drug interactions with TOUJEO.

The effect of kidney impairment on the pharmacokinetics of TOUJEO has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with kidney failure. Frequent glucose monitoring and dose adjustment may be necessary for TOUJEO in patients with kidney impairment [see Warnings and Precautions (5.3)].

TOUJEO^® U-300 SoloStar^® (Too-Jay-o)

(insulin glargine)

injection, for subcutaneous use

1.5 mL single-patient-use prefilled pen

Read this first

Do not share your TOUJEO SoloStar pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

TOUJEO contains 300 units/mL of insulin glargine

• Do not re-use needles. If you do, you might not get your dose (underdosing) or get too much (overdosing) as the needle could block.
• Do not use a syringe to remove insulin from your pen. If you do, you will get too much insulin. The scale on most syringes is made for U-100 (non-concentrated) insulin only.
• The dose selector of your TOUJEO SoloStar pen dials by 1 unit.

People who are blind or have vision problems should not use the TOUJEO SoloStar pen without help from a person trained to use the TOUJEO SoloStar pen.

Important information

• Do not use your pen if it is damaged or if you are not sure that it is working properly.
• Always perform a safety test (see Step 3 ).
• Always carry a spare pen and spare needles in case they are lost or stop working.
• Change (rotate) your injection sites within the area you choose for each dose (see "Places to inject").

Learn to inject

• Talk with your healthcare provider about how to inject, before using your pen.
• Read all of these instructions before using your pen. If you do not follow all of these instructions, you may get too much or too little insulin.

Need help?

If you have any questions about your pen or about diabetes, ask your healthcare provider, go to www.Toujeo.com or call sanofi-aventis at 1-800-633-1610.

Extra items you will need:

• a new sterile needle (not included with the pen) (see Step 2 ).
• an alcohol swab.
• a puncture-resistant container for used needles and pens (see "Throwing your pen away").

Places to inject

• Inject your insulin exactly as your healthcare provider has shown you.
• Inject your insulin under the skin (subcutaneously) of your upper legs (thighs), upper arms, or stomach area (abdomen).
• Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting pits or thickening of the skin (lipodystrophy) and lumps in the skin (localized cutaneous amyloidosis) at the injection sites.
• Do not inject where the skin has pits, is thickened, or has lumps.
  • Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.

Get to know your pen

Step 1: Check your pen

Take a new pen out of the refrigerator at least 1 hour before you inject. Cold insulin is more painful to inject.

• 1A
  Check the name and expiration date on the label of your pen.
  • Make sure you have the correct insulin.
    
    

  • Do not use your pen after the expiration date printed on the label.
    
    

• 1B
  Pull off the pen cap.
  
  

• 1C
  Check that the insulin is clear.
  • Do not use the pen if the insulin looks cloudy, colored or contains particles.
    
    

• 1D
  Wipe the rubber seal with an alcohol swab.
  
  

If you have other injector pens

• Making sure you have the correct medicine is especially important if you have other injector pens.

Step 2: Attach a new needle

• Do not re-use needles. Always use a new sterile needle for each injection. This helps stop blocked needles, contamination and infection.
• Always use needles
  Other brands listed are the registered trademarks of their respective owners and are not trademarks of sanofi-aventis U.S. LLC.
  from BD (such as BD Ultra-Fine^®), Ypsomed (such as Clickfine^®), or Owen Mumford (such as Unifine^® Pentips^®).

• 2A
  Take a new needle and peel off the protective seal.
  
  

• 2B
  Keep the needle straight and screw it onto the pen until fixed. Do not over-tighten.
  
  

• 2C
  Pull off the outer needle cap. Keep this for later.
  
  

• 2D
  Pull off the inner needle cap and throw away.
  
  

Handling needles

• Be careful when you are handling needles to help prevent accidental needle-stick injury. You may give other people a serious infection, or get a serious infection from them.

Step 3: Do a safety test

Always do a safety test before each injection to:

• check your pen and the needle to make sure they are working properly.
• make sure that you get the correct insulin dose.

If the pen is new, you must perform safety tests before you use the pen for the first time until you see insulin coming out of the needle tip. If you see insulin coming out of the needle tip, the pen is ready to use. If you do not see insulin coming out before taking your dose, you could get an underdose or no insulin at all. This could cause high blood sugar.

• 3A
  Select 3 units by turning the dose selector until the dose pointer is at the mark between 2 and 4.
  
  

• 3B
  Press the injection button all the way in.
  • When insulin comes out of the needle tip, your pen is working correctly.
    
    

If no insulin appears:

• You may need to repeat this step up to 3 times before seeing insulin.
• If no insulin comes out after the third time, the needle may be blocked. If this happens:
  • -
    change the needle (see Step 6 and Step 2 ),
  • -
    then repeat the safety test (see Step 3 ).
• Do not use your pen if there is still no insulin coming out of the needle tip. Use a new pen.
• Do not use a syringe to remove insulin from your pen.

If you see air bubbles

• You may see air bubbles in the insulin. This is normal, they will not harm you.

Step 4: Select the dose

• Do not select a dose or press the injection button without a needle attached. This may damage your pen.
• TOUJEO SoloStar is made to deliver the number of insulin units that your healthcare provider prescribed. You do not need to do any dose calculations.
• The dose selector of your TOUJEO SoloStar pen dials by 1 unit.

• 4A
  Make sure a needle is attached and the dose is set to "0."
  
  

• 4B
  Turn the dose selector until the dose pointer lines up with your dose.
  • Set the dose by turning the dose selector to a line in the dose window. Each line equals 1 unit.
  • The dose selector clicks as you turn it.
  • Always check the number in the dose window to make sure you dialed the correct dose.
  • Do not dial your dose by counting the clicks. You may dial the wrong dose. This may lead to you getting too much insulin or not enough insulin.
  • If you turn past your dose, you can turn back down.
  • If there are not enough units left in your pen for your dose, the dose selector will stop at the number of units left.
  • If you cannot select your full prescribed dose, split the dose into 2 injections or use a new pen. If you use a new pen, perform a safety test (see Step 3 ).

How to read the dose window

The dose selector dials by 1 unit.

Even numbers are shown in line with the dose pointer:

Odd numbers are shown as a line between even numbers:

Units of insulin in your pen

• Your pen contains a total of 450 units of insulin. You can select doses from 1 to 80 units. Each pen contains more than 1 dose.
• You can see roughly how many units of insulin are left by looking at where the plunger is on the insulin scale.

Step 5: Inject your dose

If you find it hard to press the injection button in, do not force it as this may break your pen. See the section below for help.

• 5A
  Choose a place to inject as shown in the picture labeled "Places to inject."
  • The site you choose for the injection should be clean and dry.
  • If your skin is dirty, clean it as instructed by your healthcare provider.
• 5B
  Push the needle into your skin as shown by your healthcare provider.
  • Do not touch the injection button yet.
    
    

• 5C
  Place your thumb on the injection button. Then press all the way in and hold.
  • Do not press at an angle. Your thumb could block the dose selector from turning.
    
    

• 5D
  Keep the injection button held in and when you see "0" in the dose window, slowly count to 5.
  • This will make sure you get your full dose.
    
    

• 5E
  After holding and slowly counting to 5, release the injection button. Then remove the needle from your skin.

If you find it hard to press the injection button in:

• Change the needle (see Step 6 and Step 2) then do a safety test (see Step 3).
• If you still find it hard to press in, get a new pen.
• Do not use a syringe to remove insulin from your pen.

Step 6: Remove the needle

• Take care when handling needles to prevent needle injury and cross-infection.
• Do not put the inner needle cap back on.

• 6A
  Grip the widest part of the outer needle cap. Keep the needle straight and guide it into the outer needle cap.
  
  Then push firmly on.
  • The needle can puncture the cap if it is recapped at an angle.
    
    

• 6B
  Grip and squeeze the widest part of the outer needle cap. Turn your pen several times with your other hand to remove the needle.
  • Try again if the needle does not come off the first time.
    
    

• 6C
  Throw away the used needle in a puncture-resistant container (see "Throwing your pen away" at the end of this Instructions for Use).
  
  

• 6D
  Put the pen cap back on.
  • Do not put the pen back in the refrigerator.
    
    

Use by

• Only use your pen for up to 56 days after its first use.

How to store your pen

Before first use

• Keep new pens in the refrigerator between 36°F and 46°F (2°C and 8°C).
• Do not freeze. Throw away your pen if it has been frozen (See " Throwing your pen away ").

After first use

• Keep your pen at room temperature up to 86°F (30°C).
• Protect your pen from direct heat and light.
• Do not put your pen back in the refrigerator.
• Do not store your pen with the needle attached.
• Store your pen with the pen cap on.
• Keep TOUJEO SoloStar pens and needles out of the reach of children.

How to care for your pen

Handle your pen with care

• Do not drop your pen or knock it against hard surfaces.
• If you think that your pen may be damaged, do not try to fix it. Use a new one.

Protect your pen from dust and dirt

• You can clean the outside of your pen by wiping it with a damp cloth (water only). Do not soak, wash or lubricate your pen. This may damage it.

Throwing your pen away

• The used TOUJEO SoloStar pen may be thrown away in your household trash after you have removed the needle.
• Put the used needle in a FDA-cleared sharps disposal container right away after use.
  
  Do not throw away (dispose of) needles in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • –
    made of a heavy-duty plastic,
  • –
    can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • –
    upright and stable during use,
  • –
    leak-resistant, and
  • –
    properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Manufactured by:

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

U.S. License No. 1752

©2022 sanofi-aventis U.S. LLC

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: August 2022

The effect of hepatic impairment on the pharmacokinetics of TOUJEO has not been studied. Frequent glucose monitoring and dose adjustment may be necessary for TOUJEO in patients with hepatic impairment [see Warnings and Precautions (5.3)].

TOUJEO is indicated to improve glycemic control in adults and pediatric patients 6 years of age and older with diabetes mellitus.

The primary activity of insulin, including insulin glargine, 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.

• 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)

• Individualize dose based on type of diabetes, metabolic needs, blood glucose monitoring results and glycemic control goal. (2.1, 2.2, 2.3)
• 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 and how to switch to TOUJEO from other insulins (2.3, 2.4)
• Closely monitor glucose when changing switching to TOUJEO and during initial weeks thereafter. (2.4)

Injection: 300 units/mL (U-300) of insulin glargine available as a clear, colorless, solution in:

• 1.5 mL TOUJEO SoloStar single-patient-use prefilled pen (450 units per 1.5 mL pen)
• 3 mL TOUJEO Max SoloStar single-patient-use prefilled pen (900 units per 3 mL pen)

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.

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.

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 m² and 35% of patients had eGFR ≥90 mL/min/1.73 m². The mean BMI was 28 kg/m². 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 m² and 27% of patients had an eGFR ≥90 mL/min/1.73 m². The mean BMI was 35 kg/m². 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.

• TOUJEO is available in 2 single-patient-use prefilled pens:
  • TOUJEO SoloStar contains 450 units of TOUJEO U-300. It delivers doses in 1-unit increments and can deliver up to 80 units in a single injection.
  • TOUJEO Max SoloStar contains 900 units of TOUJEO U-300. 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 TOUJEO SoloStar and TOUJEO 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 TOUJEO SoloStar or TOUJEO Max SoloStar prefilled pen shows the number of units of TOUJEO to be injected and no conversion is required.
• Inject TOUJEO 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 TOUJEO based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
• Titrate the dose of TOUJEO 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)].

The safety and effectiveness of TOUJEO given once daily was compared to that of once-daily LANTUS in 26-week, open-label, randomized, active-control, parallel studies of 546 adult patients and 463 pediatric patients with type 1 diabetes mellitus and 2,474 patients with type 2 diabetes mellitus (Tables 4 and 5). At trial end, the reduction in glycated hemoglobin (HbA1c) and fasting plasma glucose with TOUJEO titrated to goal was similar to that with LANTUS titrated to goal. At the end of the trial, depending on the patient population and concomitant therapy, patients were receiving a higher dose of TOUJEO than LANTUS.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). There are separate Instructions for Use for TOUJEO SoloStar and TOUJEO Max SoloStar.

Product: 50090-2193

NDC: 50090-2193-0 1.5 mL in a SYRINGE / 3 in a CARTON

• Always check insulin labels before administration [see Warnings and Precautions (5.4)].
• Visually inspect the TOUJEO solution for particulate matter and discoloration prior to administration and only use if the solution is clear and colorless with no visible particles.
• Inject TOUJEO 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 TOUJEO with caution in patients with visual impairment who may rely on audible clicks to dial their dose.
• Do not administer TOUJEO intravenously or in an insulin pump.
• Do not dilute or mix TOUJEO with any other insulin products or solutions.
• Never transfer TOUJEO from the cartridges of the TOUJEO SoloStar or TOUJEO Max SoloStar prefilled pen into a syringe for administration [see Warnings and Precautions (5.4)].

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)].

In mice and rats, standard two-year carcinogenicity studies with insulin glargine were performed at doses up to 0.455 mg/kg, which was for the rat approximately 65 times the recommended human subcutaneous starting dosage of 0.2 Units/kg/day (0.007 mg/kg/day). The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats (statistically significant) and male mice (not statistically significant) in acid vehicle containing groups. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown.

Insulin glargine was not mutagenic in tests for detection of gene mutations in bacteria and mammalian cells (Ames and HGPRT test) and in tests for detection of chromosomal aberrations (cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters).

In a combined fertility and prenatal and postnatal study in male and female rats at subcutaneous doses up to 0.36 mg/kg/day, which was approximately 50 times the recommended human subcutaneous starting dose of 0.2 Units/kg/day (0.007 mg/kg/day), maternal toxicity due to dose-dependent hypoglycemia, including some deaths, was observed. Consequently, a reduction of the rearing rate occurred in the high-dose group only. Similar effects were observed with NPH insulin.

In a 26-week open-label, controlled study (Study C, n=804), adults with type 2 diabetes were randomized to once-daily treatment in the evening with either TOUJEO or LANTUS. Short-acting mealtime insulin analogues with or without metformin were also administered. The average age was 60 years. The majority of patients were White (92%) and 53% were male; 20% of patients had GFR >90 mL/min/1.73 m². The mean BMI was approximately 36.6 kg/m². At week 26, treatment with TOUJEO provided a mean reduction in HbA1c that met the prespecified noninferiority margin of 0.4% compared to LANTUS (Table 6). Patients treated with TOUJEO used 11% more basal insulin than patients treated with LANTUS. There were no clinically important differences in body weight between treatment groups.

In two open-label, controlled studies (n=1670), adults with type 2 diabetes mellitus were randomized to either TOUJEO or LANTUS once daily for 26 weeks as part of a regimen of combination therapy with noninsulin antidiabetic drugs. At the time of randomization, 808 patients were treated with basal insulin for more than 6 months (Study D) and 862 patients were insulin-naive (Study E).

In Study D, the average age was 58.2 years. The majority of patients were White (94%) and 46% were male; 33% of patients had GFR >90 mL/min/1.73 m². The mean BMI was approximately 34.8 kg/m². At week 26, treatment with TOUJEO provided a mean reduction in HbA1c that met the prespecified noninferiority margin of 0.4% compared to LANTUS (Table 6). Patients treated with TOUJEO used 12% more basal insulin than patients treated with LANTUS. There were no clinically important differences in body weight between treatment groups.

In Study E, the average age was 58 years. The majority of patients were White (78%) and 58% were male; 29% of patients had GFR >90 mL/min/1.73 m². The mean BMI was approximately 33 kg/m². At week 26, treatment with TOUJEO provided a mean reduction in HbA1c that met the prespecified noninferiority margin compared to LANTUS (Table 6). Patients treated with TOUJEO used 15% more basal insulin than patients treated with LANTUS. There were no clinically important differences in body weight between treatment groups.

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.

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 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.

Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to TOUJEO from another insulin therapy [see Warnings and Precautions (5.3)].

• For patients currently on once-daily long or intermediate-acting insulin, start TOUJEO 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 TOUJEO 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 TOUJEO at 80% of the total daily NPH or insulin detemir twice-daily dosage.
• When switching patients to TOUJEO, monitor glucose frequently in the first weeks of therapy [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].

Limitations of Use:

TOUJEO is not recommended for the treatment of diabetic ketoacidosis.

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)]. Mild episodes of hypoglycemia can be treated with oral glucose. Lowering the insulin dosage, and adjustments in meal patterns, or physical activity level may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with glucagon for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

Insulin glargine is a long-acting human insulin analog produced by recombinant DNA technology utilizing a nonpathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines remain at the C-terminus of the B-chain. Insulin glargine has a molecular weight of 6063 Da.

TOUJEO (insulin glargine) injection is a sterile, clear and colorless solution for subcutaneous injection. Each mL of TOUJEO contains 300 units of insulin glargine dissolved in a clear aqueous fluid.

The 1.5 mL TOUJEO SoloStar prefilled pen presentation contains the following inactive ingredients per mL: glycerin (20 mg), metacresol (2.7 mg), zinc (90 mcg), and Water for Injection, USP.

The 3 mL TOUJEO Max SoloStar prefilled pen presentation contains the following inactive ingredients per mL: glycerin (20 mg), metacresol (2.7 mg), zinc (90 mcg), and Water for Injection, USP.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. TOUJEO has a pH of approximately 4.

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).

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.

The safety and effectiveness of TOUJEO to improve glycemic control in pediatric patients 6 years of age and older with diabetes mellitus have been established.

The use of TOUJEO for this indication is supported by evidence from an adequate and well-controlled study in 463 pediatric patients 6 to 17 years of age with type 1 diabetes mellitus [see Clinical Studies (14.2)] and from studies in adults with diabetes mellitus [see Clinical Pharmacology (12.3), Clinical Studies (14.3)].

The safety and effectiveness of TOUJEO have not been established in pediatric patients less than 6 years of age.

In controlled clinical studies, 30 of 304 (9.8%) TOUJEO-treated patients with type 1 diabetes and 327 of 1242 (26.3%) TOUJEO-treated patients with type 2 diabetes were ≥65 years of age, among them 2.0% of the patients with type 1 and 3.0% of the patients with type 2 diabetes were ≥75 years of age. No overall differences in safety or effectiveness of TOUJEO have been observed between patients 65 years of age and older and younger adult patients.

Nevertheless, caution should be exercised when TOUJEO is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia [see Warnings and Precautions (5.3), Adverse Reactions (6), and Clinical Studies (14)].

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.

TOUJEO is contraindicated:

• During episodes of hypoglycemia [see Warnings and Precautions (5.3)].
• In patients with hypersensitivity to insulin glargine or any excipients in TOUJEO [see Warnings and Precautions (5.5)].

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)]

Table 3 includes clinically significant drug interactions with TOUJEO.

The effect of kidney impairment on the pharmacokinetics of TOUJEO has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with kidney failure. Frequent glucose monitoring and dose adjustment may be necessary for TOUJEO in patients with kidney impairment [see Warnings and Precautions (5.3)].

TOUJEO^® U-300 SoloStar^® (Too-Jay-o)

(insulin glargine)

injection, for subcutaneous use

1.5 mL single-patient-use prefilled pen

Read this first

Do not share your TOUJEO SoloStar pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

TOUJEO contains 300 units/mL of insulin glargine

• Do not re-use needles. If you do, you might not get your dose (underdosing) or get too much (overdosing) as the needle could block.
• Do not use a syringe to remove insulin from your pen. If you do, you will get too much insulin. The scale on most syringes is made for U-100 (non-concentrated) insulin only.
• The dose selector of your TOUJEO SoloStar pen dials by 1 unit.

People who are blind or have vision problems should not use the TOUJEO SoloStar pen without help from a person trained to use the TOUJEO SoloStar pen.

Important information

• Do not use your pen if it is damaged or if you are not sure that it is working properly.
• Always perform a safety test (see Step 3 ).
• Always carry a spare pen and spare needles in case they are lost or stop working.
• Change (rotate) your injection sites within the area you choose for each dose (see "Places to inject").

Learn to inject

• Talk with your healthcare provider about how to inject, before using your pen.
• Read all of these instructions before using your pen. If you do not follow all of these instructions, you may get too much or too little insulin.

Need help?

If you have any questions about your pen or about diabetes, ask your healthcare provider, go to www.Toujeo.com or call sanofi-aventis at 1-800-633-1610.

Extra items you will need:

• a new sterile needle (not included with the pen) (see Step 2 ).
• an alcohol swab.
• a puncture-resistant container for used needles and pens (see "Throwing your pen away").

Places to inject

• Inject your insulin exactly as your healthcare provider has shown you.
• Inject your insulin under the skin (subcutaneously) of your upper legs (thighs), upper arms, or stomach area (abdomen).
• Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting pits or thickening of the skin (lipodystrophy) and lumps in the skin (localized cutaneous amyloidosis) at the injection sites.
• Do not inject where the skin has pits, is thickened, or has lumps.
  • Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.

Get to know your pen

Step 1: Check your pen

Take a new pen out of the refrigerator at least 1 hour before you inject. Cold insulin is more painful to inject.

• 1A
  Check the name and expiration date on the label of your pen.
  • Make sure you have the correct insulin.
    
    

  • Do not use your pen after the expiration date printed on the label.
    
    

• 1B
  Pull off the pen cap.
  
  

• 1C
  Check that the insulin is clear.
  • Do not use the pen if the insulin looks cloudy, colored or contains particles.
    
    

• 1D
  Wipe the rubber seal with an alcohol swab.
  
  

If you have other injector pens

• Making sure you have the correct medicine is especially important if you have other injector pens.

Step 2: Attach a new needle

• Do not re-use needles. Always use a new sterile needle for each injection. This helps stop blocked needles, contamination and infection.
• Always use needles
  Other brands listed are the registered trademarks of their respective owners and are not trademarks of sanofi-aventis U.S. LLC.
  from BD (such as BD Ultra-Fine^®), Ypsomed (such as Clickfine^®), or Owen Mumford (such as Unifine^® Pentips^®).

• 2A
  Take a new needle and peel off the protective seal.
  
  

• 2B
  Keep the needle straight and screw it onto the pen until fixed. Do not over-tighten.
  
  

• 2C
  Pull off the outer needle cap. Keep this for later.
  
  

• 2D
  Pull off the inner needle cap and throw away.
  
  

Handling needles

• Be careful when you are handling needles to help prevent accidental needle-stick injury. You may give other people a serious infection, or get a serious infection from them.

Step 3: Do a safety test

Always do a safety test before each injection to:

• check your pen and the needle to make sure they are working properly.
• make sure that you get the correct insulin dose.

If the pen is new, you must perform safety tests before you use the pen for the first time until you see insulin coming out of the needle tip. If you see insulin coming out of the needle tip, the pen is ready to use. If you do not see insulin coming out before taking your dose, you could get an underdose or no insulin at all. This could cause high blood sugar.

• 3A
  Select 3 units by turning the dose selector until the dose pointer is at the mark between 2 and 4.
  
  

• 3B
  Press the injection button all the way in.
  • When insulin comes out of the needle tip, your pen is working correctly.
    
    

If no insulin appears:

• You may need to repeat this step up to 3 times before seeing insulin.
• If no insulin comes out after the third time, the needle may be blocked. If this happens:
  • -
    change the needle (see Step 6 and Step 2 ),
  • -
    then repeat the safety test (see Step 3 ).
• Do not use your pen if there is still no insulin coming out of the needle tip. Use a new pen.
• Do not use a syringe to remove insulin from your pen.

If you see air bubbles

• You may see air bubbles in the insulin. This is normal, they will not harm you.

Step 4: Select the dose

• Do not select a dose or press the injection button without a needle attached. This may damage your pen.
• TOUJEO SoloStar is made to deliver the number of insulin units that your healthcare provider prescribed. You do not need to do any dose calculations.
• The dose selector of your TOUJEO SoloStar pen dials by 1 unit.

• 4A
  Make sure a needle is attached and the dose is set to "0."
  
  

• 4B
  Turn the dose selector until the dose pointer lines up with your dose.
  • Set the dose by turning the dose selector to a line in the dose window. Each line equals 1 unit.
  • The dose selector clicks as you turn it.
  • Always check the number in the dose window to make sure you dialed the correct dose.
  • Do not dial your dose by counting the clicks. You may dial the wrong dose. This may lead to you getting too much insulin or not enough insulin.
  • If you turn past your dose, you can turn back down.
  • If there are not enough units left in your pen for your dose, the dose selector will stop at the number of units left.
  • If you cannot select your full prescribed dose, split the dose into 2 injections or use a new pen. If you use a new pen, perform a safety test (see Step 3 ).

How to read the dose window

The dose selector dials by 1 unit.

Even numbers are shown in line with the dose pointer:

Odd numbers are shown as a line between even numbers:

Units of insulin in your pen

• Your pen contains a total of 450 units of insulin. You can select doses from 1 to 80 units. Each pen contains more than 1 dose.
• You can see roughly how many units of insulin are left by looking at where the plunger is on the insulin scale.

Step 5: Inject your dose

If you find it hard to press the injection button in, do not force it as this may break your pen. See the section below for help.

• 5A
  Choose a place to inject as shown in the picture labeled "Places to inject."
  • The site you choose for the injection should be clean and dry.
  • If your skin is dirty, clean it as instructed by your healthcare provider.
• 5B
  Push the needle into your skin as shown by your healthcare provider.
  • Do not touch the injection button yet.
    
    

• 5C
  Place your thumb on the injection button. Then press all the way in and hold.
  • Do not press at an angle. Your thumb could block the dose selector from turning.
    
    

• 5D
  Keep the injection button held in and when you see "0" in the dose window, slowly count to 5.
  • This will make sure you get your full dose.
    
    

• 5E
  After holding and slowly counting to 5, release the injection button. Then remove the needle from your skin.

If you find it hard to press the injection button in:

• Change the needle (see Step 6 and Step 2) then do a safety test (see Step 3).
• If you still find it hard to press in, get a new pen.
• Do not use a syringe to remove insulin from your pen.

Step 6: Remove the needle

• Take care when handling needles to prevent needle injury and cross-infection.
• Do not put the inner needle cap back on.

• 6A
  Grip the widest part of the outer needle cap. Keep the needle straight and guide it into the outer needle cap.
  
  Then push firmly on.
  • The needle can puncture the cap if it is recapped at an angle.
    
    

• 6B
  Grip and squeeze the widest part of the outer needle cap. Turn your pen several times with your other hand to remove the needle.
  • Try again if the needle does not come off the first time.
    
    

• 6C
  Throw away the used needle in a puncture-resistant container (see "Throwing your pen away" at the end of this Instructions for Use).
  
  

• 6D
  Put the pen cap back on.
  • Do not put the pen back in the refrigerator.
    
    

Use by

• Only use your pen for up to 56 days after its first use.

How to store your pen

Before first use

• Keep new pens in the refrigerator between 36°F and 46°F (2°C and 8°C).
• Do not freeze. Throw away your pen if it has been frozen (See " Throwing your pen away ").

After first use

• Keep your pen at room temperature up to 86°F (30°C).
• Protect your pen from direct heat and light.
• Do not put your pen back in the refrigerator.
• Do not store your pen with the needle attached.
• Store your pen with the pen cap on.
• Keep TOUJEO SoloStar pens and needles out of the reach of children.

How to care for your pen

Handle your pen with care

• Do not drop your pen or knock it against hard surfaces.
• If you think that your pen may be damaged, do not try to fix it. Use a new one.

Protect your pen from dust and dirt

• You can clean the outside of your pen by wiping it with a damp cloth (water only). Do not soak, wash or lubricate your pen. This may damage it.

Throwing your pen away

• The used TOUJEO SoloStar pen may be thrown away in your household trash after you have removed the needle.
• Put the used needle in a FDA-cleared sharps disposal container right away after use.
  
  Do not throw away (dispose of) needles in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • –
    made of a heavy-duty plastic,
  • –
    can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • –
    upright and stable during use,
  • –
    leak-resistant, and
  • –
    properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Manufactured by:

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

U.S. License No. 1752

©2022 sanofi-aventis U.S. LLC

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: August 2022

The effect of hepatic impairment on the pharmacokinetics of TOUJEO has not been studied. Frequent glucose monitoring and dose adjustment may be necessary for TOUJEO in patients with hepatic impairment [see Warnings and Precautions (5.3)].

TOUJEO is indicated to improve glycemic control in adults and pediatric patients 6 years of age and older with diabetes mellitus.

The primary activity of insulin, including insulin glargine, 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.

• 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)

• Individualize dose based on type of diabetes, metabolic needs, blood glucose monitoring results and glycemic control goal. (2.1, 2.2, 2.3)
• 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 and how to switch to TOUJEO from other insulins (2.3, 2.4)
• Closely monitor glucose when changing switching to TOUJEO and during initial weeks thereafter. (2.4)

Injection: 300 units/mL (U-300) of insulin glargine available as a clear, colorless, solution in:

• 1.5 mL TOUJEO SoloStar single-patient-use prefilled pen (450 units per 1.5 mL pen)
• 3 mL TOUJEO Max SoloStar single-patient-use prefilled pen (900 units per 3 mL pen)

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.

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.

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 m² and 35% of patients had eGFR ≥90 mL/min/1.73 m². The mean BMI was 28 kg/m². 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 m² and 27% of patients had an eGFR ≥90 mL/min/1.73 m². The mean BMI was 35 kg/m². 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.

• TOUJEO is available in 2 single-patient-use prefilled pens:
  • TOUJEO SoloStar contains 450 units of TOUJEO U-300. It delivers doses in 1-unit increments and can deliver up to 80 units in a single injection.
  • TOUJEO Max SoloStar contains 900 units of TOUJEO U-300. 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 TOUJEO SoloStar and TOUJEO 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 TOUJEO SoloStar or TOUJEO Max SoloStar prefilled pen shows the number of units of TOUJEO to be injected and no conversion is required.
• Inject TOUJEO 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 TOUJEO based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
• Titrate the dose of TOUJEO 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)].

The safety and effectiveness of TOUJEO given once daily was compared to that of once-daily LANTUS in 26-week, open-label, randomized, active-control, parallel studies of 546 adult patients and 463 pediatric patients with type 1 diabetes mellitus and 2,474 patients with type 2 diabetes mellitus (Tables 4 and 5). At trial end, the reduction in glycated hemoglobin (HbA1c) and fasting plasma glucose with TOUJEO titrated to goal was similar to that with LANTUS titrated to goal. At the end of the trial, depending on the patient population and concomitant therapy, patients were receiving a higher dose of TOUJEO than LANTUS.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). There are separate Instructions for Use for TOUJEO SoloStar and TOUJEO Max SoloStar.

Product: 50090-2193

NDC: 50090-2193-0 1.5 mL in a SYRINGE / 3 in a CARTON

• Always check insulin labels before administration [see Warnings and Precautions (5.4)].
• Visually inspect the TOUJEO solution for particulate matter and discoloration prior to administration and only use if the solution is clear and colorless with no visible particles.
• Inject TOUJEO 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 TOUJEO with caution in patients with visual impairment who may rely on audible clicks to dial their dose.
• Do not administer TOUJEO intravenously or in an insulin pump.
• Do not dilute or mix TOUJEO with any other insulin products or solutions.
• Never transfer TOUJEO from the cartridges of the TOUJEO SoloStar or TOUJEO Max SoloStar prefilled pen into a syringe for administration [see Warnings and Precautions (5.4)].

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)].

In mice and rats, standard two-year carcinogenicity studies with insulin glargine were performed at doses up to 0.455 mg/kg, which was for the rat approximately 65 times the recommended human subcutaneous starting dosage of 0.2 Units/kg/day (0.007 mg/kg/day). The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats (statistically significant) and male mice (not statistically significant) in acid vehicle containing groups. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown.

Insulin glargine was not mutagenic in tests for detection of gene mutations in bacteria and mammalian cells (Ames and HGPRT test) and in tests for detection of chromosomal aberrations (cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters).

In a combined fertility and prenatal and postnatal study in male and female rats at subcutaneous doses up to 0.36 mg/kg/day, which was approximately 50 times the recommended human subcutaneous starting dose of 0.2 Units/kg/day (0.007 mg/kg/day), maternal toxicity due to dose-dependent hypoglycemia, including some deaths, was observed. Consequently, a reduction of the rearing rate occurred in the high-dose group only. Similar effects were observed with NPH insulin.

In a 26-week open-label, controlled study (Study C, n=804), adults with type 2 diabetes were randomized to once-daily treatment in the evening with either TOUJEO or LANTUS. Short-acting mealtime insulin analogues with or without metformin were also administered. The average age was 60 years. The majority of patients were White (92%) and 53% were male; 20% of patients had GFR >90 mL/min/1.73 m². The mean BMI was approximately 36.6 kg/m². At week 26, treatment with TOUJEO provided a mean reduction in HbA1c that met the prespecified noninferiority margin of 0.4% compared to LANTUS (Table 6). Patients treated with TOUJEO used 11% more basal insulin than patients treated with LANTUS. There were no clinically important differences in body weight between treatment groups.

In two open-label, controlled studies (n=1670), adults with type 2 diabetes mellitus were randomized to either TOUJEO or LANTUS once daily for 26 weeks as part of a regimen of combination therapy with noninsulin antidiabetic drugs. At the time of randomization, 808 patients were treated with basal insulin for more than 6 months (Study D) and 862 patients were insulin-naive (Study E).

In Study D, the average age was 58.2 years. The majority of patients were White (94%) and 46% were male; 33% of patients had GFR >90 mL/min/1.73 m². The mean BMI was approximately 34.8 kg/m². At week 26, treatment with TOUJEO provided a mean reduction in HbA1c that met the prespecified noninferiority margin of 0.4% compared to LANTUS (Table 6). Patients treated with TOUJEO used 12% more basal insulin than patients treated with LANTUS. There were no clinically important differences in body weight between treatment groups.

In Study E, the average age was 58 years. The majority of patients were White (78%) and 58% were male; 29% of patients had GFR >90 mL/min/1.73 m². The mean BMI was approximately 33 kg/m². At week 26, treatment with TOUJEO provided a mean reduction in HbA1c that met the prespecified noninferiority margin compared to LANTUS (Table 6). Patients treated with TOUJEO used 15% more basal insulin than patients treated with LANTUS. There were no clinically important differences in body weight between treatment groups.

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.

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 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.

Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to TOUJEO from another insulin therapy [see Warnings and Precautions (5.3)].

• For patients currently on once-daily long or intermediate-acting insulin, start TOUJEO 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 TOUJEO 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 TOUJEO at 80% of the total daily NPH or insulin detemir twice-daily dosage.
• When switching patients to TOUJEO, monitor glucose frequently in the first weeks of therapy [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].