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

Limitations of Use

LANTUS 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 2022

INSTRUCTIONS FOR USE

LANTUS^® (LAN-tus)

(insulin glargine)

injection, for subcutaneous use

VIAL: 100 Units/mL (U-100)

These Instructions for Use contain information on how to inject LANTUS using the vial. Read these Instructions for Use before you start taking LANTUS and each time you get a new LANTUS 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 LANTUS 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:

• a LANTUS 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 LANTUS:

• Wash your hands with soap and water or clean your hands with alcohol.
• Check the LANTUS 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 LANTUS in the vial to make sure it is clear and colorless. Do not use LANTUS if it is colored or cloudy, or if you see particles in the solution.
• Do not use LANTUS 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 LANTUS.
• 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 LANTUS 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 LANTUS before use.

Step 3:

Draw air into the syringe equal to your LANTUS 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 LANTUS 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 LANTUS

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

Step 7:

Choose your injection site:

• LANTUS 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 LANTUS.
• 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 LANTUS?

Unopened (not in-use) LANTUS vials

• Store unused LANTUS vials in the refrigerator from 36°F to 46°F (2°C to 8°C).
• Do not freeze LANTUS.
• Keep LANTUS 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 LANTUS vials have been opened (in-use)

• Store in-use (opened) LANTUS 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 LANTUS. If a vial has been frozen, throw it away.
• Keep LANTUS out of direct heat and light.
• The LANTUS 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

A SANOFI COMPANY

U.S. License No. 1752

©2022 sanofi-aventis U.S. LLC.

Revised: June 2022

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.

LANTUS (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 (LANTUS Solostar).

Prefilled Pen (LANTUS 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. LANTUS has a pH of approximately 4.

All insulins, including LANTUS, 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 LANTUS. 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 LANTUS may delay recovery from hypoglycemia.

The safety and effectiveness of LANTUS to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of LANTUS for this indication is supported by evidence from an adequate and well-controlled study (Study D) in 174 LANTUS-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of LANTUS 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 LANTUS, 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 LANTUS have been observed between patients 65 years of age and older and younger adult patients.

Nevertheless, caution should be exercised when LANTUS 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 LANTUS, increases in titers of antibodies to insulin were observed in NPH insulin and LANTUS treatment groups with similar incidences.

LANTUS 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 LANTUS [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 8 includes clinically significant drug interactions with LANTUS.

The effect of kidney impairment on the pharmacokinetics of LANTUS 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 LANTUS in patients with kidney impairment [see Warnings and Precautions (5.3)].

In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous LANTUS 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 LANTUS 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 LANTUS.

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

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

LANTUS 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 a LANTUS 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, 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, 6.3)
• Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue LANTUS. 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 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. (2.1, 2.2, 2.3, 2.4)
• 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 and how to change to LANTUS from other insulins (2.3, 2.4)
• Closely monitor glucose when switching to LANTUS 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 LANTUS SoloStar prefilled pen

The following adverse reactions have been identified during postapproval use of LANTUS. 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 LANTUS

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 LANTUS [see Adverse Reactions (6.1)]. If hypersensitivity reactions occur, discontinue LANTUS; treat per standard of care and monitor until symptoms and signs resolve. LANTUS 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 LANTUS or NPH in Studies A, B, C, and D [see Clinical Studies (14.2)]. The type 1 diabetes population had the following characteristics: Mean age was 39 years. Fifty-four percent were male, 97% were Caucasian, 22% were Black or African American and 33% were Hispanic. The mean BMI was 25.1 kg/m².

The data in Table 2 reflect the exposure of 1,563 patients with type 2 diabetes to LANTUS or NPH in Studies E, F, and G [see Clinical Studies (14.3)]. The type 2 diabetes population had the following characteristics: Mean age was 59 years. Fifty-eight percent were male, 87% were Caucasian, 8% were Black or African American and 9% were Hispanic. The mean BMI was 29.2 kg/m².

The frequencies of adverse reactions during LANTUS 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 LANTUS subcutaneously once daily at any time of day but at the same time every day.
• Individualize and adjust the dosage of LANTUS 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, LANTUS must be used concomitantly with short-acting insulin.

The safety and effectiveness of LANTUS 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 LANTUS 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 LANTUS SoloStar Pen.

Product: 50090-0876

NDC: 50090-0876-0 10 mL in a VIAL, GLASS

• Always check insulin labels before administration [see Warnings and Precautions (5.4)]
• Visually inspect LANTUS 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 LANTUS 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 LANTUS with any other insulin or solution.
• The LANTUS SoloStar prefilled pen dials in 1-unit increments.

Use LANTUS 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 LANTUS 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, LANTUS 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. LANTUS 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 LANTUS 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 LANTUS 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. LANTUS 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 LANTUS or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dosage of LANTUS 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 LANTUS 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 LANTUS and NPH insulin dosages to a target fasting plasma glucose ≤100 mg/dL. After the LANTUS 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 LANTUS 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 LANTUS group (Table 11). The incidences of severe symptomatic hypoglycemia were similar between groups [see Adverse Reactions (6.1)].

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

When switching from:

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

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 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.

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 LANTUS, 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.

LANTUS SoloStar prefilled pens must never be shared between patients, even if the needle is changed. Patients using LANTUS 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

LANTUS 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 2022

INSTRUCTIONS FOR USE

LANTUS^® (LAN-tus)

(insulin glargine)

injection, for subcutaneous use

VIAL: 100 Units/mL (U-100)

These Instructions for Use contain information on how to inject LANTUS using the vial. Read these Instructions for Use before you start taking LANTUS and each time you get a new LANTUS 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 LANTUS 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:

• a LANTUS 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 LANTUS:

• Wash your hands with soap and water or clean your hands with alcohol.
• Check the LANTUS 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 LANTUS in the vial to make sure it is clear and colorless. Do not use LANTUS if it is colored or cloudy, or if you see particles in the solution.
• Do not use LANTUS 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 LANTUS.
• 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 LANTUS 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 LANTUS before use.

Step 3:

Draw air into the syringe equal to your LANTUS 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 LANTUS 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 LANTUS

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

Step 7:

Choose your injection site:

• LANTUS 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 LANTUS.
• 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 LANTUS?

Unopened (not in-use) LANTUS vials

• Store unused LANTUS vials in the refrigerator from 36°F to 46°F (2°C to 8°C).
• Do not freeze LANTUS.
• Keep LANTUS 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 LANTUS vials have been opened (in-use)

• Store in-use (opened) LANTUS 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 LANTUS. If a vial has been frozen, throw it away.
• Keep LANTUS out of direct heat and light.
• The LANTUS 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

A SANOFI COMPANY

U.S. License No. 1752

©2022 sanofi-aventis U.S. LLC.

Revised: June 2022

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.

LANTUS (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 (LANTUS Solostar).

Prefilled Pen (LANTUS 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. LANTUS has a pH of approximately 4.

All insulins, including LANTUS, 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 LANTUS. 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 LANTUS may delay recovery from hypoglycemia.

The safety and effectiveness of LANTUS to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of LANTUS for this indication is supported by evidence from an adequate and well-controlled study (Study D) in 174 LANTUS-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of LANTUS 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 LANTUS, 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 LANTUS have been observed between patients 65 years of age and older and younger adult patients.

Nevertheless, caution should be exercised when LANTUS 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 LANTUS, increases in titers of antibodies to insulin were observed in NPH insulin and LANTUS treatment groups with similar incidences.

LANTUS 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 LANTUS [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 8 includes clinically significant drug interactions with LANTUS.

The effect of kidney impairment on the pharmacokinetics of LANTUS 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 LANTUS in patients with kidney impairment [see Warnings and Precautions (5.3)].

In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous LANTUS 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 LANTUS 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 LANTUS.

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

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

LANTUS 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 a LANTUS 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, 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, 6.3)
• Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue LANTUS. 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 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. (2.1, 2.2, 2.3, 2.4)
• 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 and how to change to LANTUS from other insulins (2.3, 2.4)
• Closely monitor glucose when switching to LANTUS 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 LANTUS SoloStar prefilled pen

The following adverse reactions have been identified during postapproval use of LANTUS. 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 LANTUS

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 LANTUS [see Adverse Reactions (6.1)]. If hypersensitivity reactions occur, discontinue LANTUS; treat per standard of care and monitor until symptoms and signs resolve. LANTUS 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 LANTUS or NPH in Studies A, B, C, and D [see Clinical Studies (14.2)]. The type 1 diabetes population had the following characteristics: Mean age was 39 years. Fifty-four percent were male, 97% were Caucasian, 22% were Black or African American and 33% were Hispanic. The mean BMI was 25.1 kg/m².

The data in Table 2 reflect the exposure of 1,563 patients with type 2 diabetes to LANTUS or NPH in Studies E, F, and G [see Clinical Studies (14.3)]. The type 2 diabetes population had the following characteristics: Mean age was 59 years. Fifty-eight percent were male, 87% were Caucasian, 8% were Black or African American and 9% were Hispanic. The mean BMI was 29.2 kg/m².

The frequencies of adverse reactions during LANTUS 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 LANTUS subcutaneously once daily at any time of day but at the same time every day.
• Individualize and adjust the dosage of LANTUS 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, LANTUS must be used concomitantly with short-acting insulin.

The safety and effectiveness of LANTUS 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 LANTUS 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 LANTUS SoloStar Pen.

Product: 50090-0876

NDC: 50090-0876-0 10 mL in a VIAL, GLASS

• Always check insulin labels before administration [see Warnings and Precautions (5.4)]
• Visually inspect LANTUS 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 LANTUS 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 LANTUS with any other insulin or solution.
• The LANTUS SoloStar prefilled pen dials in 1-unit increments.

Use LANTUS 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 LANTUS 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, LANTUS 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. LANTUS 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 LANTUS 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 LANTUS 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. LANTUS 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 LANTUS or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dosage of LANTUS 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 LANTUS 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 LANTUS and NPH insulin dosages to a target fasting plasma glucose ≤100 mg/dL. After the LANTUS 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 LANTUS 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 LANTUS group (Table 11). The incidences of severe symptomatic hypoglycemia were similar between groups [see Adverse Reactions (6.1)].

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

When switching from:

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

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 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.

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 LANTUS, 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.

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