These Highlights Do Not Include All The Information Needed To Use Insulin Glargine Safely And Effectively. See Full Prescribing Information For Insulin Glargine.

Limitations of Use

Insulin Glargine is not recommended for the treatment of diabetic ketoacidosis.

This Patient Information has been approved by the U.S. Food and Drug Administration

Revised: June 2023

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)].

Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. Lowering the insulin dosage, and adjustments in meal patterns or exercise 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. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia.

Hypokalemia must be corrected appropriately.

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

Insulin Glargine injection is a sterile, clear and colorless solution for subcutaneous use in a 10 mL multiple-dose vial or a 3 mL single-patient use prefilled pen (Insulin Glargine Solostar).

Prefilled Pen (Insulin Glargine Solostar) and Vial: Each mL contains 100 units of insulin glargine and the inactive ingredients: glycerol 85% (20 mg), m-cresol (2.7 mg), zinc (30 mcg), and Water for Injection, USP. The vial also contains polysorbate 20 (20 mcg). The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. Insulin Glargine has a pH of approximately 4.

All insulins, including Insulin Glargine, 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 insulins, including Insulin Glargine. 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, 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 Insulin Glargine may delay recovery from hypoglycemia.

The safety and effectiveness of Insulin Glargine to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of Insulin Glargine for this indication is supported by evidence from an adequate and well-controlled study (Study D) in 174 Insulin Glargine-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of Insulin Glargine in adults with diabetes mellitus [see Clinical Pharmacology (12.3), Clinical Studies (14.2)].

In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in studies with type 1 diabetes [see Adverse Reactions (6.1)].

Of the total number of subjects in controlled clinical studies of patients with type 1 and type 2 diabetes who were treated with Insulin Glargine, 15% (n=316) were ≥65 years of age and 2% (n=42) were ≥75 years of age. No overall differences in safety or effectiveness of Insulin Glargine have been observed between patients 65 years of age and older and younger adult patients.

Nevertheless, caution should be exercised when Insulin Glargine is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dosage increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in geriatric patients.

As with all therapeutic proteins, there is potential for immunogenicity. All insulin products can elicit the formation of insulin antibodies. The presence of such insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In clinical studies of Insulin Glargine, increases in titers of antibodies to insulin were observed in NPH insulin and Insulin Glargine treatment groups with similar incidences.

Insulin Glargine is contraindicated:

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

The following adverse reactions are discussed elsewhere:

• Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen [see Warnings and Precautions (5.2)]
• 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 8 includes clinically significant drug interactions with Insulin Glargine.

Read these Instructions for Use before you start taking the Insulin Glargine SoloStar pen and each time you get a new Insulin Glargine SoloStar pen. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Do not share your Insulin Glargine 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.

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

Insulin Glargine SoloStar is a disposable prefilled pen used to inject Insulin Glargine. Each Insulin Glargine SoloStar pen has 300 units of insulin which can be used for multiple injections. You can select doses from 1 to 80 units in steps of 1 unit. The pen plunger moves with each dose. The plunger will only move to the end of the cartridge when 300 units of Insulin Glargine have been given.

Important Information You Need to Know Before Injecting Insulin Glargine

• Do not use your pen if it is damaged or if you are not sure that it is working properly.
• Do not use a syringe to remove Insulin Glargine from your pen.
• Do not reuse needles. If you do, you might get the wrong dose of Insulin Glargine and/or increase the chance of getting an infection.
• Always perform a safety test (see Step 3 ).
• Always carry a spare pen and spare needles in case they got 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.
• Ask for help if you have problems handling the pen, for example if you have problems with your sight.
• Read all these instructions before using your pen. If you do not follow all 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, or go to www.winthropus.com or call sanofi-aventis at 1-800-633-1610.

Extra Items You Will Need

• a new sterile needle (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 lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) 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.

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 reuse needles. Always use a new sterile needle for each injection. This helps stop blocked needles, contamination, and infection.

Only use needles

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

• Take care when handling needles to prevent needle-stick injury and cross-infection.

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 Glargine dose.

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

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 (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.

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.

• 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, use a new pen or inject the remaining units and use a new pen to complete your dose.

How to read the dose window

Even numbers are shown in line with dose pointer.

Odd numbers are shown as a line between even numbers.

Units of Insulin Glargine in your pen:

• Your pen contains a total of 300 units of Insulin Glargine. You can select doses from 1 to 80 units in steps of 1 unit. 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: Injecting Your Insulin Glargine 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 above.

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 10.

• This will make sure you get your full dose.

5E After holding and slowly counting to 10, release the injection button. Then remove the needle from your skin.

If you find it hard to press the 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-stick 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 your pen cap back on.

• Do not put the pen back in the refrigerator.

Storing the Insulin Glargine Solostar Pen

Before first use

• Keep new pens in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze. Do not use Insulin Glargine if it has been frozen.

After first use

• Keep your pen at room temperature below 86°F (30°C).
• Keep your pen away from heat or light.
• Store your pen with the pen cap on.
• Do not put your pen back in the refrigerator.
• Do not store your pen with the needle attached.
• Keep out of the reach of children.
• Only use your pen for up to 28 days after its first use. Throw away the Insulin Glargine SoloStar pen you are using after 28 days, even if it still has insulin left in it.

Caring for Your Insulin Glargine SoloStar 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 Insulin Glargine SoloStar pen may be thrown away in your household trash after you have removed the needle.
• Put the used needle in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the used 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.

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

Manufactured by:

sanofi-aventis U.S. LLC

U.S. License No. 1752

Manufactured for:

Winthrop U.S.,

a business of sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

©2023 sanofi-aventis U.S. LLC

LANTUS is a registered trademark of sanofi-aventis U.S. LLC.

Revised: June 2023

The effect of kidney impairment on the pharmacokinetics of Insulin Glargine 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 dosage adjustment may be necessary for Insulin Glargine in patients with kidney impairment [see Warnings and Precautions (5.3)].

These Instructions for Use contain information on how to inject Insulin Glargine using the vial. Read these Instructions for Use before you start taking Insulin Glargine and each time you get a new Insulin Glargine vial. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Do not share your Insulin Glargine syringes 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.

Supplies Needed to Give Your Injection:

• an Insulin Glargine 10 mL vial
• a U-100 insulin syringe and needle
• 2 alcohol swabs
• 1 sharps container for throwing away used needles and syringes. See "Disposing of used needles and syringes" at the end of these instructions.

Preparing to inject Insulin Glargine:

• Wash your hands with soap and water or clean your hands with alcohol.
• Check the Insulin Glargine label to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Check the Insulin Glargine in the vial to make sure it is clear and colorless. Do not use Insulin Glargine if it is colored or cloudy, or if you see particles in the solution.
• Do not use Insulin Glargine after the expiration date stamped on the label or 28 days after you first use it.
• Always use a syringe that is marked for U-100 insulin. If you use a syringe other than a U-100 insulin syringe, you may get the wrong dose of Insulin Glargine.
• Always use a new syringe and a new needle for each injection to help prevent infections and prevent blocked needles.

Step 1:

If you are using a new Insulin Glargine vial, remove the protective cap. Do not remove the stopper.

Step 2:

Wipe the top of the vial with an alcohol swab. You do not have to shake the vial of Insulin Glargine before use.

Step 3:

Draw air into the syringe equal to your Insulin Glargine dose. Put the needle through the rubber top of the vial and push the plunger to inject the air into the vial.

Step 4:

Leave the syringe in the vial and turn both upside down. Hold the syringe and vial firmly in one hand. Make sure the tip of the needle is in the Insulin Glargine solution. With your free hand, pull the plunger to withdraw the correct dose into the syringe.

Step 5:

Before you take the needle out of the vial, check the syringe for air bubbles. If bubbles are in the syringe, hold the syringe straight up and tap the side of the syringe until the bubbles float to the top. Push the bubbles out with the plunger and draw insulin back in until you have the correct dose.

Step 6:

Remove the needle from the vial. Do not let the needle touch anything. You are now ready to inject.

Injecting Insulin Glargine:

• Inject your Insulin Glargine (with a syringe) exactly as your healthcare provider has shown you.
• Insulin Glargine is injected once daily at any time of the day but at the same time every day.

Step 7:

Choose your injection site:

• Insulin Glargine is injected under the skin (subcutaneously) of your upper arms, thighs, or stomach area (abdomen).
• Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting lipodystrophy (pits in the skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) 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.
  
  

• Wipe the skin with an alcohol swab to clean the injection site. Let the injection site dry before you inject your dose.
  
  

Step 8:

• Pinch the skin.
• Insert the needle under the skin in the way your healthcare provider showed you.
• Release the skin.
• Slowly push in the plunger of the syringe all the way, making sure you have injected all the Insulin Glargine.
• Leave the needle in the skin for about 10 seconds.

Step 9:

• Pull the needle straight out of your skin.
• Gently press the injection site for several seconds. Do not rub the area.
• Do not recap the used needle. Recapping the needle can lead to a needle-stick injury.

Disposing of Used Needles and Syringes

• Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have a FDA-cleared sharps 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.

Storing and Disposing Insulin Glargine?

Unopened (not in-use) Insulin Glargine vials

• Store unused Insulin Glargine vials in the refrigerator from 36°F to 46°F (2°C to 8°C).
• Do not freeze Insulin Glargine.
• Keep Insulin Glargine away from direct heat and light.
• If a vial has been frozen or overheated, throw it away.
• Unopened vials can be used until the expiration date on the carton and vial label if they have been stored in the refrigerator (they can be stored past 28 days in the refrigerator).
• Unopened vials should be thrown away after 28 days if they are stored at room temperature.

After Insulin Glargine vials have been opened (in-use)

• Store in-use (opened) Insulin Glargine vials in a refrigerator from 36°F to 46°F (2°C to 8°C) or at room temperature below 86°F (30°C) for up to 28 days.
• Do not freeze Insulin Glargine. If a vial has been frozen, throw it away.
• Keep Insulin Glargine out of direct heat and light.
• The Insulin Glargine vial you are using should be thrown away after 28 days or if the expiration date has passed, even if it still has insulin left in it.

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

Manufactured by:

sanofi-aventis U.S. LLC.

Bridgewater, NJ 08807

U.S. License No. 1752

Manufactured for:

Winthrop U.S.,

A business of sanofi-aventis U.S. LLC

A SANOFI COMPANY

©2023 sanofi-aventis U.S. LLC

Revised: June 2023

In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous Insulin Glargine is approximately the same as that for human insulin. Figure 1 shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after subcutaneous injection of Insulin Glargine or NPH insulin. The median time between subcutaneous injection and the end of pharmacological effect was 14.5 hours (range: 9.5 to 19.3 hours) for NPH insulin, and 24 hours (range: 10.8 to >24 hours) (24 hours was the end of the observation period) for Insulin Glargine.

Figure 1: Glucose-Lowering Effect Over 24 Hours in Patients with Type 1 Diabetes

The duration of action after abdominal, deltoid, or thigh subcutaneous administration of Insulin Glargine was similar. The time course of action of insulins, including Insulin Glargine, may vary between patients and within the same patient.

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

Insulin Glargine is indicated to improve glycemic control in adult and pediatric patients 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 an Insulin Glargine SoloStar prefilled pen, insulin syringe, or needle 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 or hepatic impairment and hypoglycemia unawareness. (5.3)
• 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 Insulin Glargine. 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 of TZD if heart failure occurs. (5.7)

• Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, and prior insulin use. (2.2)
• Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time of day, but at the same time every day. (2.1)
• Do not dilute or mix with any other insulin or solution. (2.1)
• Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. (2.1)
• See Full Prescribing Information for the recommended starting dosage in patients with type 2 diabetes (2.3) and how to change to Insulin Glargine from other insulins (2.4)
• Closely monitor glucose when switching to Insulin Glargine and during initial weeks thereafter. (2.4)

Injection: 100 units/mL (U-100) a clear and colorless solution available as:

• 10 mL multiple-dose vial
• 3 mL single-patient-use Insulin Glargine SoloStar prefilled pen

The following adverse reactions have been identified during postapproval use of Insulin Glargine. 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 have been reported in which rapid-acting insulins and other insulins, have been accidentally administered instead of Insulin Glargine.

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 Insulin Glargine [see Adverse Reactions (6.1)]. If hypersensitivity reactions occur, discontinue Insulin Glargine; treat per standard of care and monitor until symptoms and signs resolve. Insulin Glargine is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or one of the excipients.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

The data in Table 1 reflect the exposure of 2,327 patients with type 1 diabetes to Insulin Glargine or NPH in Studies A, B, C, and D [see Clinical Studies (14.2)]. The type 1 diabetes population had the following characteristics: the mean age was 39 years, 54% were male, and mean body mass index (BMI) was 25.1 kg/m². Ninety-seven percent were White, 2% were Black or African American and less than 1% were Asian. Approximately 3% of the patients in studies B and C were Hispanic.

The data in Table 2 reflect the exposure of 1,563 patients with type 2 diabetes to Insulin Glargine or NPH in Studies E, F, and G [see Clinical Studies (14.3)]. The type 2 diabetes population had the following characteristics: the mean age was 59 years, 58% were male, and mean BMI was 29.2 kg/m². Eighty-seven percent were White, 8% were Black or African American and 3% were Asian. Approximately 9 % of patients in Study F were Hispanic.

The frequencies of adverse reactions during Insulin Glargine clinical studies in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below (Tables 1, 2, 3, and 4).

• Administer Insulin Glargine subcutaneously once daily at any time of day but at the same time every day.
• Individualize and adjust the dosage of Insulin Glargine based on the patient's metabolic needs, blood glucose monitoring results and glycemic control goal.
• Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring [see Warnings and Precautions (5.2)].
• In patients with type 1 diabetes, Insulin Glargine must be used concomitantly with short-acting insulin.

The safety and effectiveness of Insulin Glargine given once-daily at bedtime was compared to that of once-daily and twice-daily NPH insulin in open-label, randomized, active-controlled, parallel studies of 2,327 adult patients and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 9–11). In general, the reduction in glycated hemoglobin (HbA1c) with Insulin Glargine was similar to that with NPH insulin.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). There are separate Instructions for Use for the Vial and Insulin Glargine SoloStar Pen.

Product: 50090-6184

• Always check insulin labels before administration. This product is LANTUS (insulin glargine) [see Warnings and Precautions (5.4)].
• Visually inspect Insulin Glargine vials and SoloStar prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles.
• Administer Insulin Glargine subcutaneously into the abdominal area, thigh, or deltoid, and 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) and Adverse Reactions (6)].
• During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].
• Do not administer intravenously or via an insulin pump.
• Do not dilute or mix Insulin Glargine with any other insulin or solution.
• The Insulin Glargine SoloStar prefilled pen dials in 1-unit increments.
• Use Insulin Glargine SoloStar prefilled pen with caution in patients with visual impairment who may rely on audible clicks to dial their dose.

Accidental mix-ups among insulin products have been reported. To avoid medication errors between Insulin Glargine and other insulins, instruct patients to always check the insulin label before each injection [see Adverse Reactions (6.3)].

In a randomized, controlled clinical study (Study E) in 570 adults with type 2 diabetes, Insulin Glargine was evaluated for 52 weeks in combination with oral antidiabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs). The average age was 60 years old. The majority of patients were White (93%) and 54% were male. The mean BMI was approximately 29.1 kg/m². The mean duration of diabetes was 10 years. Insulin Glargine administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 11). The rate of severe symptomatic hypoglycemia was similar in Insulin Glargine and NPH insulin treated patients [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study F), in adult patients with type 2 diabetes not using oral antidiabetic medications (n=518), a basal-bolus regimen of Insulin Glargine once daily at bedtime or NPH insulin administered once or twice daily was evaluated for 28 weeks. Regular human insulin was used before meals, as needed. The average age was 59 years. The majority of patients were White (81%) and 60% were male. The mean BMI was approximately 30.5 kg/m². The mean duration of diabetes was 14 years. Insulin Glargine had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 11) with a similar incidence of hypoglycemia [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study G), adult patients with type 2 diabetes were randomized to 5 years of treatment with once-daily Insulin Glargine or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dosage of Insulin Glargine or NPH insulin was 10 units daily. Patients who were already treated with NPH insulin either continued on the same total daily NPH insulin dose or started Insulin Glargine at a dosage that was 80% of the total previous NPH insulin dosage. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. HbA1c change from baseline was a secondary endpoint. Similar glycemic control in the 2 treatment groups was desired in order to not confound the interpretation of the retinal data. Patients or study personnel used an algorithm to adjust the Insulin Glargine and NPH insulin dosages to a target fasting plasma glucose ≤100 mg/dL. After the Insulin Glargine or NPH insulin dosage was adjusted, other antidiabetic agents, including premeal insulin were to be adjusted or added. The average age was 55 years. The majority of patients were White (85%) and 54% were male. The mean BMI was approximately 34.3 kg/m². The mean duration of diabetes was 11 years. The Insulin Glargine group had a smaller mean reduction from baseline in HbA1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in the Insulin Glargine group (Table 11). The incidences of severe symptomatic hypoglycemia were similar between groups [see Adverse Reactions (6.1)].

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) on a mg/kg basis. Histiocytomas were found at injection sites in male rats and mice in acid vehicle containing groups and are considered a response to chronic tissue irritation and inflammation in rodents. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle.

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 dosage 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.

Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to Insulin Glargine from other insulin therapies [see Warnings and Precautions (5.3)].

When switching from:

• Once-daily TOUJEO (insulin glargine 300 units/mL) to once-daily Insulin Glargine (100 units/mL), the recommended starting Insulin Glargine dosage is 80% of the TOUJEO dosage that is being discontinued.
• Once-daily NPH insulin to once-daily Insulin Glargine, the recommended starting Insulin Glargine dosage is the same as the dosage of NPH that is being discontinued.
• Twice-daily NPH insulin to once-daily Insulin Glargine, the recommended starting Insulin Glargine dosage is 80% of the total NPH dosage that is being discontinued.

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 and antidiabetic products may be needed.

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 Insulin Glargine, 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.

Insulin Glargine SoloStar prefilled pens must never be shared between patients, even if the needle is changed. Patients using Insulin Glargine vials must never re-use or share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

Limitations of Use

Insulin Glargine is not recommended for the treatment of diabetic ketoacidosis.

This Patient Information has been approved by the U.S. Food and Drug Administration

Revised: June 2023

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)].

Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. Lowering the insulin dosage, and adjustments in meal patterns or exercise 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. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia.

Hypokalemia must be corrected appropriately.

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

Insulin Glargine injection is a sterile, clear and colorless solution for subcutaneous use in a 10 mL multiple-dose vial or a 3 mL single-patient use prefilled pen (Insulin Glargine Solostar).

Prefilled Pen (Insulin Glargine Solostar) and Vial: Each mL contains 100 units of insulin glargine and the inactive ingredients: glycerol 85% (20 mg), m-cresol (2.7 mg), zinc (30 mcg), and Water for Injection, USP. The vial also contains polysorbate 20 (20 mcg). The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. Insulin Glargine has a pH of approximately 4.

All insulins, including Insulin Glargine, 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 insulins, including Insulin Glargine. 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, 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 Insulin Glargine may delay recovery from hypoglycemia.

The safety and effectiveness of Insulin Glargine to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of Insulin Glargine for this indication is supported by evidence from an adequate and well-controlled study (Study D) in 174 Insulin Glargine-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of Insulin Glargine in adults with diabetes mellitus [see Clinical Pharmacology (12.3), Clinical Studies (14.2)].

In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in studies with type 1 diabetes [see Adverse Reactions (6.1)].

Of the total number of subjects in controlled clinical studies of patients with type 1 and type 2 diabetes who were treated with Insulin Glargine, 15% (n=316) were ≥65 years of age and 2% (n=42) were ≥75 years of age. No overall differences in safety or effectiveness of Insulin Glargine have been observed between patients 65 years of age and older and younger adult patients.

Nevertheless, caution should be exercised when Insulin Glargine is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dosage increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in geriatric patients.

As with all therapeutic proteins, there is potential for immunogenicity. All insulin products can elicit the formation of insulin antibodies. The presence of such insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In clinical studies of Insulin Glargine, increases in titers of antibodies to insulin were observed in NPH insulin and Insulin Glargine treatment groups with similar incidences.

Insulin Glargine is contraindicated:

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

The following adverse reactions are discussed elsewhere:

• Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen [see Warnings and Precautions (5.2)]
• 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 8 includes clinically significant drug interactions with Insulin Glargine.

Read these Instructions for Use before you start taking the Insulin Glargine SoloStar pen and each time you get a new Insulin Glargine SoloStar pen. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Do not share your Insulin Glargine 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.

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

Insulin Glargine SoloStar is a disposable prefilled pen used to inject Insulin Glargine. Each Insulin Glargine SoloStar pen has 300 units of insulin which can be used for multiple injections. You can select doses from 1 to 80 units in steps of 1 unit. The pen plunger moves with each dose. The plunger will only move to the end of the cartridge when 300 units of Insulin Glargine have been given.

Important Information You Need to Know Before Injecting Insulin Glargine

• Do not use your pen if it is damaged or if you are not sure that it is working properly.
• Do not use a syringe to remove Insulin Glargine from your pen.
• Do not reuse needles. If you do, you might get the wrong dose of Insulin Glargine and/or increase the chance of getting an infection.
• Always perform a safety test (see Step 3 ).
• Always carry a spare pen and spare needles in case they got 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.
• Ask for help if you have problems handling the pen, for example if you have problems with your sight.
• Read all these instructions before using your pen. If you do not follow all 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, or go to www.winthropus.com or call sanofi-aventis at 1-800-633-1610.

Extra Items You Will Need

• a new sterile needle (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 lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) 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.

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 reuse needles. Always use a new sterile needle for each injection. This helps stop blocked needles, contamination, and infection.

Only use needles

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

• Take care when handling needles to prevent needle-stick injury and cross-infection.

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 Glargine dose.

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

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 (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.

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.

• 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, use a new pen or inject the remaining units and use a new pen to complete your dose.

How to read the dose window

Even numbers are shown in line with dose pointer.

Odd numbers are shown as a line between even numbers.

Units of Insulin Glargine in your pen:

• Your pen contains a total of 300 units of Insulin Glargine. You can select doses from 1 to 80 units in steps of 1 unit. 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: Injecting Your Insulin Glargine 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 above.

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 10.

• This will make sure you get your full dose.

5E After holding and slowly counting to 10, release the injection button. Then remove the needle from your skin.

If you find it hard to press the 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-stick 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 your pen cap back on.

• Do not put the pen back in the refrigerator.

Storing the Insulin Glargine Solostar Pen

Before first use

• Keep new pens in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze. Do not use Insulin Glargine if it has been frozen.

After first use

• Keep your pen at room temperature below 86°F (30°C).
• Keep your pen away from heat or light.
• Store your pen with the pen cap on.
• Do not put your pen back in the refrigerator.
• Do not store your pen with the needle attached.
• Keep out of the reach of children.
• Only use your pen for up to 28 days after its first use. Throw away the Insulin Glargine SoloStar pen you are using after 28 days, even if it still has insulin left in it.

Caring for Your Insulin Glargine SoloStar 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 Insulin Glargine SoloStar pen may be thrown away in your household trash after you have removed the needle.
• Put the used needle in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the used 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.

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

Manufactured by:

sanofi-aventis U.S. LLC

U.S. License No. 1752

Manufactured for:

Winthrop U.S.,

a business of sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

©2023 sanofi-aventis U.S. LLC

LANTUS is a registered trademark of sanofi-aventis U.S. LLC.

Revised: June 2023

The effect of kidney impairment on the pharmacokinetics of Insulin Glargine 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 dosage adjustment may be necessary for Insulin Glargine in patients with kidney impairment [see Warnings and Precautions (5.3)].

These Instructions for Use contain information on how to inject Insulin Glargine using the vial. Read these Instructions for Use before you start taking Insulin Glargine and each time you get a new Insulin Glargine vial. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Do not share your Insulin Glargine syringes 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.

Supplies Needed to Give Your Injection:

• an Insulin Glargine 10 mL vial
• a U-100 insulin syringe and needle
• 2 alcohol swabs
• 1 sharps container for throwing away used needles and syringes. See "Disposing of used needles and syringes" at the end of these instructions.

Preparing to inject Insulin Glargine:

• Wash your hands with soap and water or clean your hands with alcohol.
• Check the Insulin Glargine label to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Check the Insulin Glargine in the vial to make sure it is clear and colorless. Do not use Insulin Glargine if it is colored or cloudy, or if you see particles in the solution.
• Do not use Insulin Glargine after the expiration date stamped on the label or 28 days after you first use it.
• Always use a syringe that is marked for U-100 insulin. If you use a syringe other than a U-100 insulin syringe, you may get the wrong dose of Insulin Glargine.
• Always use a new syringe and a new needle for each injection to help prevent infections and prevent blocked needles.

Step 1:

If you are using a new Insulin Glargine vial, remove the protective cap. Do not remove the stopper.

Step 2:

Wipe the top of the vial with an alcohol swab. You do not have to shake the vial of Insulin Glargine before use.

Step 3:

Draw air into the syringe equal to your Insulin Glargine dose. Put the needle through the rubber top of the vial and push the plunger to inject the air into the vial.

Step 4:

Leave the syringe in the vial and turn both upside down. Hold the syringe and vial firmly in one hand. Make sure the tip of the needle is in the Insulin Glargine solution. With your free hand, pull the plunger to withdraw the correct dose into the syringe.

Step 5:

Before you take the needle out of the vial, check the syringe for air bubbles. If bubbles are in the syringe, hold the syringe straight up and tap the side of the syringe until the bubbles float to the top. Push the bubbles out with the plunger and draw insulin back in until you have the correct dose.

Step 6:

Remove the needle from the vial. Do not let the needle touch anything. You are now ready to inject.

Injecting Insulin Glargine:

• Inject your Insulin Glargine (with a syringe) exactly as your healthcare provider has shown you.
• Insulin Glargine is injected once daily at any time of the day but at the same time every day.

Step 7:

Choose your injection site:

• Insulin Glargine is injected under the skin (subcutaneously) of your upper arms, thighs, or stomach area (abdomen).
• Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting lipodystrophy (pits in the skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) 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.
  
  

• Wipe the skin with an alcohol swab to clean the injection site. Let the injection site dry before you inject your dose.
  
  

Step 8:

• Pinch the skin.
• Insert the needle under the skin in the way your healthcare provider showed you.
• Release the skin.
• Slowly push in the plunger of the syringe all the way, making sure you have injected all the Insulin Glargine.
• Leave the needle in the skin for about 10 seconds.

Step 9:

• Pull the needle straight out of your skin.
• Gently press the injection site for several seconds. Do not rub the area.
• Do not recap the used needle. Recapping the needle can lead to a needle-stick injury.

Disposing of Used Needles and Syringes

• Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have a FDA-cleared sharps 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.

Storing and Disposing Insulin Glargine?

Unopened (not in-use) Insulin Glargine vials

• Store unused Insulin Glargine vials in the refrigerator from 36°F to 46°F (2°C to 8°C).
• Do not freeze Insulin Glargine.
• Keep Insulin Glargine away from direct heat and light.
• If a vial has been frozen or overheated, throw it away.
• Unopened vials can be used until the expiration date on the carton and vial label if they have been stored in the refrigerator (they can be stored past 28 days in the refrigerator).
• Unopened vials should be thrown away after 28 days if they are stored at room temperature.

After Insulin Glargine vials have been opened (in-use)

• Store in-use (opened) Insulin Glargine vials in a refrigerator from 36°F to 46°F (2°C to 8°C) or at room temperature below 86°F (30°C) for up to 28 days.
• Do not freeze Insulin Glargine. If a vial has been frozen, throw it away.
• Keep Insulin Glargine out of direct heat and light.
• The Insulin Glargine vial you are using should be thrown away after 28 days or if the expiration date has passed, even if it still has insulin left in it.

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

Manufactured by:

sanofi-aventis U.S. LLC.

Bridgewater, NJ 08807

U.S. License No. 1752

Manufactured for:

Winthrop U.S.,

A business of sanofi-aventis U.S. LLC

A SANOFI COMPANY

©2023 sanofi-aventis U.S. LLC

Revised: June 2023

In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous Insulin Glargine is approximately the same as that for human insulin. Figure 1 shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after subcutaneous injection of Insulin Glargine or NPH insulin. The median time between subcutaneous injection and the end of pharmacological effect was 14.5 hours (range: 9.5 to 19.3 hours) for NPH insulin, and 24 hours (range: 10.8 to >24 hours) (24 hours was the end of the observation period) for Insulin Glargine.

Figure 1: Glucose-Lowering Effect Over 24 Hours in Patients with Type 1 Diabetes

The duration of action after abdominal, deltoid, or thigh subcutaneous administration of Insulin Glargine was similar. The time course of action of insulins, including Insulin Glargine, may vary between patients and within the same patient.

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

Insulin Glargine is indicated to improve glycemic control in adult and pediatric patients 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 an Insulin Glargine SoloStar prefilled pen, insulin syringe, or needle 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 or hepatic impairment and hypoglycemia unawareness. (5.3)
• 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 Insulin Glargine. 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 of TZD if heart failure occurs. (5.7)

• Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, and prior insulin use. (2.2)
• Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time of day, but at the same time every day. (2.1)
• Do not dilute or mix with any other insulin or solution. (2.1)
• Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. (2.1)
• See Full Prescribing Information for the recommended starting dosage in patients with type 2 diabetes (2.3) and how to change to Insulin Glargine from other insulins (2.4)
• Closely monitor glucose when switching to Insulin Glargine and during initial weeks thereafter. (2.4)

Injection: 100 units/mL (U-100) a clear and colorless solution available as:

• 10 mL multiple-dose vial
• 3 mL single-patient-use Insulin Glargine SoloStar prefilled pen

The following adverse reactions have been identified during postapproval use of Insulin Glargine. 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 have been reported in which rapid-acting insulins and other insulins, have been accidentally administered instead of Insulin Glargine.

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 Insulin Glargine [see Adverse Reactions (6.1)]. If hypersensitivity reactions occur, discontinue Insulin Glargine; treat per standard of care and monitor until symptoms and signs resolve. Insulin Glargine is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or one of the excipients.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

The data in Table 1 reflect the exposure of 2,327 patients with type 1 diabetes to Insulin Glargine or NPH in Studies A, B, C, and D [see Clinical Studies (14.2)]. The type 1 diabetes population had the following characteristics: the mean age was 39 years, 54% were male, and mean body mass index (BMI) was 25.1 kg/m². Ninety-seven percent were White, 2% were Black or African American and less than 1% were Asian. Approximately 3% of the patients in studies B and C were Hispanic.

The data in Table 2 reflect the exposure of 1,563 patients with type 2 diabetes to Insulin Glargine or NPH in Studies E, F, and G [see Clinical Studies (14.3)]. The type 2 diabetes population had the following characteristics: the mean age was 59 years, 58% were male, and mean BMI was 29.2 kg/m². Eighty-seven percent were White, 8% were Black or African American and 3% were Asian. Approximately 9 % of patients in Study F were Hispanic.

The frequencies of adverse reactions during Insulin Glargine clinical studies in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below (Tables 1, 2, 3, and 4).

• Administer Insulin Glargine subcutaneously once daily at any time of day but at the same time every day.
• Individualize and adjust the dosage of Insulin Glargine based on the patient's metabolic needs, blood glucose monitoring results and glycemic control goal.
• Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring [see Warnings and Precautions (5.2)].
• In patients with type 1 diabetes, Insulin Glargine must be used concomitantly with short-acting insulin.

The safety and effectiveness of Insulin Glargine given once-daily at bedtime was compared to that of once-daily and twice-daily NPH insulin in open-label, randomized, active-controlled, parallel studies of 2,327 adult patients and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 9–11). In general, the reduction in glycated hemoglobin (HbA1c) with Insulin Glargine was similar to that with NPH insulin.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). There are separate Instructions for Use for the Vial and Insulin Glargine SoloStar Pen.

Product: 50090-6184

• Always check insulin labels before administration. This product is LANTUS (insulin glargine) [see Warnings and Precautions (5.4)].
• Visually inspect Insulin Glargine vials and SoloStar prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles.
• Administer Insulin Glargine subcutaneously into the abdominal area, thigh, or deltoid, and 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) and Adverse Reactions (6)].
• During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].
• Do not administer intravenously or via an insulin pump.
• Do not dilute or mix Insulin Glargine with any other insulin or solution.
• The Insulin Glargine SoloStar prefilled pen dials in 1-unit increments.
• Use Insulin Glargine SoloStar prefilled pen with caution in patients with visual impairment who may rely on audible clicks to dial their dose.

Accidental mix-ups among insulin products have been reported. To avoid medication errors between Insulin Glargine and other insulins, instruct patients to always check the insulin label before each injection [see Adverse Reactions (6.3)].

In a randomized, controlled clinical study (Study E) in 570 adults with type 2 diabetes, Insulin Glargine was evaluated for 52 weeks in combination with oral antidiabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs). The average age was 60 years old. The majority of patients were White (93%) and 54% were male. The mean BMI was approximately 29.1 kg/m². The mean duration of diabetes was 10 years. Insulin Glargine administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 11). The rate of severe symptomatic hypoglycemia was similar in Insulin Glargine and NPH insulin treated patients [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study F), in adult patients with type 2 diabetes not using oral antidiabetic medications (n=518), a basal-bolus regimen of Insulin Glargine once daily at bedtime or NPH insulin administered once or twice daily was evaluated for 28 weeks. Regular human insulin was used before meals, as needed. The average age was 59 years. The majority of patients were White (81%) and 60% were male. The mean BMI was approximately 30.5 kg/m². The mean duration of diabetes was 14 years. Insulin Glargine had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 11) with a similar incidence of hypoglycemia [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study G), adult patients with type 2 diabetes were randomized to 5 years of treatment with once-daily Insulin Glargine or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dosage of Insulin Glargine or NPH insulin was 10 units daily. Patients who were already treated with NPH insulin either continued on the same total daily NPH insulin dose or started Insulin Glargine at a dosage that was 80% of the total previous NPH insulin dosage. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. HbA1c change from baseline was a secondary endpoint. Similar glycemic control in the 2 treatment groups was desired in order to not confound the interpretation of the retinal data. Patients or study personnel used an algorithm to adjust the Insulin Glargine and NPH insulin dosages to a target fasting plasma glucose ≤100 mg/dL. After the Insulin Glargine or NPH insulin dosage was adjusted, other antidiabetic agents, including premeal insulin were to be adjusted or added. The average age was 55 years. The majority of patients were White (85%) and 54% were male. The mean BMI was approximately 34.3 kg/m². The mean duration of diabetes was 11 years. The Insulin Glargine group had a smaller mean reduction from baseline in HbA1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in the Insulin Glargine group (Table 11). The incidences of severe symptomatic hypoglycemia were similar between groups [see Adverse Reactions (6.1)].

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) on a mg/kg basis. Histiocytomas were found at injection sites in male rats and mice in acid vehicle containing groups and are considered a response to chronic tissue irritation and inflammation in rodents. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle.

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 dosage 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.

Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to Insulin Glargine from other insulin therapies [see Warnings and Precautions (5.3)].

When switching from:

• Once-daily TOUJEO (insulin glargine 300 units/mL) to once-daily Insulin Glargine (100 units/mL), the recommended starting Insulin Glargine dosage is 80% of the TOUJEO dosage that is being discontinued.
• Once-daily NPH insulin to once-daily Insulin Glargine, the recommended starting Insulin Glargine dosage is the same as the dosage of NPH that is being discontinued.
• Twice-daily NPH insulin to once-daily Insulin Glargine, the recommended starting Insulin Glargine dosage is 80% of the total NPH dosage that is being discontinued.

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 and antidiabetic products may be needed.

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 Insulin Glargine, 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.

Insulin Glargine SoloStar prefilled pens must never be shared between patients, even if the needle is changed. Patients using Insulin Glargine vials must never re-use or share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.