Basaglar

Limitations of Use

BASAGLAR is not recommended for the treatment of diabetic ketoacidosis.

BAS-0006-PPI-20231129

PACKAGE CARTON – BASAGLAR KwikPen 80 UNIT PEN

Dispense in this sealed carton.

NDC 0002-7715-59

Basaglar^®

KwikPen^®

(insulin glargine)

injection

For Single Patient Use Only

100 units per mL (U-100)

For subcutaneous use only

Can inject from 1 to 80 units in a single injection

5 x 3 mL prefilled pens

prefilled insulin delivery device

Rx only

Read Basaglar^® KwikPen^® Instructions for Use.

NEEDLES NOT INCLUDED

This device is recommended for use with Becton, Dickinson & Company's insulin pen needles.

Lilly

Excess insulin administration relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)]. Mild episodes of hypoglycemia can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or physical activity level may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

Insulin glargine is a long-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, insulin glargine is 21^A-Gly-30^B-a-L-Arg-30^Bb-L-Arg-human insulin and has the empirical formula C₂₆₇H₄₀₄N₇₂O₇₈S₆ and a molecular weight of 6.063 kDa. Insulin glargine has the following structural formula:

BASAGLAR (insulin glargine) injection is a sterile clear and colorless aqueous solution for subcutaneous use. Each mL contains 100 units of insulin glargine (3.6378 mg).

The 3 mL BASAGLAR prefilled pen presentations contain the following inactive ingredients per mL: glycerin (17 mg), metacresol (2.7 mg), zinc oxide (content adjusted to provide 30 mcg zinc ion), and Water for Injection, USP.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid 10% and/or sodium hydroxide 10%. BASAGLAR has a pH of approximately 4.

All insulins, including BASAGLAR, 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 BASAGLAR [see Adverse Reactions (6.1)]. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). BASAGLAR, or any insulin, should not be used during episodes of hypoglycemia [see Contraindications (4)].

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7)], or in patients who experience recurrent hypoglycemia.

BASAGLAR (insulin glargine) injection is a clear, colorless solution, 100  units/mL (U-100), available as:

The BASAGLAR KwikPen and Tempo Pen dial in 1 unit increments.

Needles are not included.

This device is recommended for use with Becton, Dickinson & Company's insulin pen needles which are sold separately.

The safety and effectiveness of BASAGLAR have been established in pediatric patients (age 6 to 15 years) with type 1 diabetes based on an adequate and well-controlled trial of another insulin glargine product, 100 units/mL, in pediatric patients (age 6 to 15 years) with type 1 diabetes and additional data in adults with type 1 diabetes [see Clinical Studies (14.2)]. The safety and effectiveness of BASAGLAR in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes has not been established.

In the pediatric clinical trial, pediatric patients (age 6 to 15 years) with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in trials with type 1 diabetes [see Adverse Reactions (6.1)].

Of the total number of subjects in clinical studies of patients with type 2 diabetes who were treated with BASAGLAR or another insulin glargine product, 100 units/mL, each in combination with oral agents in a controlled clinical trial environment, 28.3% were 65 and over, while 4.5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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

As with all therapeutic proteins, there is potential for immunogenicity.

In a 52-week study of type 1 diabetes patients, 42% of patients who received BASAGLAR once daily were positive for anti-drug antibodies (ADA) at least once during the study, including 17% that were positive at baseline and 25% of patients who developed ADA during the study. Sixty-five percent of the ADA positive patients on BASAGLAR with antibody testing at week 52 remained ADA positive at week 52.

In a 24-week study of type 2 diabetes patients, 17% of patients who received BASAGLAR once daily were positive for ADA at least once during the study. Among the subjects who were positive, 5% had ADA at baseline and 12% developed antibodies during the study. The percent binding of patients positive at baseline on BASAGLAR did not increase significantly during the study. Fifty-one percent of the ADA positive patients on BASAGLAR with antibody testing at week 24 remained ADA positive at week 24. There was no evidence that these antibodies had an impact on efficacy and safety outcomes.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to BASAGLAR with the incidence of antibodies in other studies or to other products may be misleading.

BASAGLAR 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 BASAGLAR [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 6 includes clinically significant drug interactions with BASAGLAR

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

The pharmacodynamic profile for BASAGLAR was determined after subcutaneous administration of a single 0.5 U/kg dose in a euglycemic clamp study conducted in 91 healthy subjects. The median time to maximum effect of BASAGLAR (measured by the peak rate of glucose infusion) was approximately 12.0 hours. The pharmacodynamic profile of BASAGLAR following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) and maximum glucose infusion rate were 1670 mg/kg and 2.12 mg/kg/min, respectively.

A euglycemic clamp study in 20 patients with type 1 diabetes showed a similar pharmacodynamic profile with a sustained glucose lowering activity over 24 hours following a single 0.3 U/kg subcutaneous dose of BASAGLAR.

After subcutaneous injection of 0.3 units/kg of another insulin glargine product, 100 units/mL, in patients with type 1 diabetes, the duration of action after abdominal, deltoid, or thigh subcutaneous administration was similar.

The time course of action of insulins, including insulin glargine, may vary between individuals and within the same individual.

The effect of hepatic impairment on the pharmacokinetics of BASAGLAR has not been studied. However, as with all insulin products, more frequent glucose monitoring and dose adjustment may be necessary for BASAGLAR in patients with hepatic impairment [see Warnings and Precautions (5.3)].

BASAGLAR^® is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.

The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analog 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.

Dispense in the original sealed carton with the enclosed Instructions for Use.

Protect BASAGLAR from heat and light. Do not freeze BASAGLAR.

In-use BASAGLAR prefilled pens must be used within 28 days or be discarded, even if they still contain BASAGLAR.

Storage conditions are summarized in the following table:

• Never share a BASAGLAR prefilled pen between patients, even if the needle is changed. (5.1)
• Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. (5.2)
• Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, 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)
• Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue BASAGLAR, monitor and treat if indicated. (5.5, 6.1)
• Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. (5.6)
• Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. (5.7)

• Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, prior insulin use. (2.2, 2.3, 2.4)
• Administer subcutaneously once daily at any time of day, but at the same time every day. (2.2)
• Rotate injection sites into the abdominal area, thigh, or deltoid to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. (2.1)
• Closely monitor glucose when converting to BASAGLAR and during initial weeks thereafter. (2.2)
• Do not dilute or mix with any other insulin or solution. (2.1)

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

• 3 mL single-patient-use BASAGLAR KwikPen
• 3 mL single-patient-use BASAGLAR Tempo Pen

The following adverse reactions have been identified during post-approval use of insulin glargine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported in which other insulin products, particularly rapid-acting 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.

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

Two clinical trials with BASAGLAR were conducted: one in type 1 diabetes and one in type 2 diabetes.

The type 1 diabetes population had the following characteristics: Mean age was 41 years and mean duration of diabetes was 16 years. 58% were male. 75% were Caucasian, 2% Black or African American and 4% American Indian or Alaskan native. 4% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 73.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 26 kg/m². HbA_1c at baseline was 7.8%. The data in Table 1 reflect exposure of 268 patients to BASAGLAR with a mean exposure duration of 49 weeks.

The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 11 years. 50% were male. 78% were Caucasian, 8% Black or African American and 5% American Indian or Alaskan native. 28% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 67.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 32 kg/m². HbA_1c at baseline was 8.3%. The data in Table 2 reflect exposure of 376 patients to BASAGLAR with a mean exposure duration of 22 weeks.

Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Common adverse reactions during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2, respectively.

The frequencies of adverse reactions during a clinical trial of 5 years duration with another insulin glargine product, 100 units/mL, in patients with type 2 diabetes mellitus are listed in Table 3.

The frequencies of adverse reactions during clinical trials with another insulin glargine product, 100 units/mL, in children and adolescents with type 1 diabetes mellitus are listed in Table 4.

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including BASAGLAR. If hypersensitivity reactions occur, discontinue BASAGLAR; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6.1)]. BASAGLAR is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or one of the excipients [see Contraindications (4)].

• In patients with type 1 diabetes, BASAGLAR must be used concomitantly with short-acting insulin.
• Inject BASAGLAR subcutaneously once daily at any time of day but at the same time every day.
• Individualize and adjust the dosage of BASAGLAR based on the individual'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)].
• The BASAGLAR prefilled pens each dials in 1 unit increments and delivers a maximum dose of 80 units per injection.

The safety and effectiveness of another insulin glargine product, 100 units/mL, 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 adults and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 8, 9, 11, and 12). In general, the reduction in glycated hemoglobin (HbA_1c) with this other insulin glargine product was similar to that with NPH insulin.

See FDA-approved patient labeling (Patient Information and Instructions for Use).

• The recommended starting dose of BASAGLAR in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Short- or rapid-acting, pre-meal insulin should be used to satisfy the remainder of the daily insulin requirements.
• The recommended starting dose of BASAGLAR in patients with type 2 diabetes is 0.2 units/kg or up to 10 units once daily.

Instructions for Use

BASAGLAR^® KwikPen^®

(insulin glargine)

injection, for subcutaneous use

100 units/mL, 3 mL single-patient-use pen

Read the Instructions for Use before you start using BASAGLAR and each time you get another BASAGLAR^® KwikPen^®. 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 BASAGLAR KwikPen 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.

BASAGLAR KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units (3mL) of BASAGLAR. One pen contains multiple doses of medicine.

• Your healthcare provider will tell you how many units to give as your dose and how to inject your prescribed dose of medicine.
• You can give a dose of 1 to 80 units in a single injection.
• If your prescribed dose is more than 80 units, you will need to give yourself more than 1 injection.
• The plunger only moves a little with each injection, and you may not notice that it moves. When the plunger reaches the end of the cartridge, you have used all 300 units in the Pen.

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

How to recognize your BASAGLAR KwikPen

• Pen color: Light grey
• Dose Knob: Light grey with green ring on the end
• Labels: Light grey with green color bars

Supplies needed to give your injection

• BASAGLAR KwikPen
• KwikPen compatible Needle (Becton, Dickinson and Company Pen Needles recommended)
• Alcohol swab

Preparing your Pen

• Wash your hands with soap and water.
• Check the Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Do not use your Pen past the expiration date printed on the Label or for more than 28 days after you first start using the Pen.
• Always use a new needle for each injection to help prevent infections and blocked needles. Do not reuse or share your needles with other people. You may give other people a serious infection or get a serious infection from them.

Priming your Pen

Prime before each injection.

• Priming means removing the air from the Needle and Cartridge that may collect during normal use. It is important to prime your Pen before each injection so that it will work correctly.
• If you do not prime before each injection, you may get too much or too little insulin.

Selecting your dose

• If your dose is more than 80 units, you will need to give more than 1 injection.
  • -
    Talk to your healthcare provider about how to give your dose.
  • -
    Use a new Needle for each injection and repeat the priming step.

The Pen will not let you dial more than the number of units left in the Pen.

• If you need to inject more than the number of units left in the Pen, you may either:
  • -
    inject the amount left in your Pen and then use a new Pen to give the rest of your dose, or
  • -
    get a new Pen and inject the full dose.
• It is normal to see a small amount of insulin left in the Pen that you can not inject.

Giving your injection

• Inject your insulin as your healthcare provider has shown you.
• 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.
• Do not try to change your dose while injecting.

After your injection

Disposing of Pens and Needles

• Put your used needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose 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.
• The used Pen may be discarded in your household trash after you have removed the needle.

Storing your BASAGLAR KwikPen

Unused Pens

• Store unused Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze BASAGLAR. Do not use if it has been frozen.
• Unused Pens may be used until the expiration date printed on the Label, if the Pen has been kept in the refrigerator.

In-use Pen

• Store the Pen you are currently using at room temperature [up to 86°F (30°C)] and away from heat and light.
• Throw away the Pen you are using after 28 days, even if it still has insulin left in it.

General information about the safe and effective use of your Pen

• Keep your Pen and needles out of the sight and reach of children.
• Always use a new needle for each injection.
• Do not share your Pen or needles with other people. You may give other people a serious infection or get a serious infection from them.
• Do not use your Pen if any part looks broken or damaged.
• Always carry an extra Pen in case yours is lost or damaged.

Troubleshooting

• If you can not remove the Pen Cap, gently twist the cap back and forth, and then pull the cap straight off.
• If the Dose Knob is hard to push:
  • -
    Pushing the Dose Knob more slowly will make it easier to inject.
  • -
    Your Needle may be blocked. Put on a new Needle and prime the Pen.
  • -
    You may have dust, food, or liquid inside the Pen. Throw the Pen away and get a new Pen.

If you have any questions or problems with your BASAGLAR KwikPen, contact Lilly at 1-800-LillyRx (1-800- 545-5979) or call your healthcare provider for help. For more information on BASAGLAR KwikPen and insulin, go to www.basaglar.com.

Scan this code to launch www.basaglar.com

This Instructions for Use have been approved by the U.S. Food and Drug Administration. BASAGLAR^® and BASAGLAR^® KwikPen^® are trademarks of Eli Lilly and Company.

Instructions for Use revised: November 2022

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 2015, 2022, Eli Lilly and Company. All rights reserved.

BASKP-0009-IFU-20221115

Instructions for Use

BASAGLAR^® Tempo Pen™ (insulin glargine) injection, for subcutaneous use

100 units/mL, 3 mL pen, single-patient-use

Read the Instructions for Use before you start using BASAGLAR and each time you get another BASAGLAR Tempo 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 BASAGLAR Tempo 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.

BASAGLAR Tempo Pen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units (3mL) of BASAGLAR. One pen contains multiple doses of medicine.

• Your healthcare provider will tell you how many units to give as your dose and how to inject your prescribed dose of medicine.
• You can give a dose of 1 to 80 units in a single injection.
• If your prescribed dose is more than 80 units, you will need to give yourself more than 1 injection.
• The Plunger only moves a little with each injection, and you may not notice that it moves. When the Plunger reaches the end of the cartridge, you have used all 300 units in the Pen.

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

This BASAGLAR Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter.

How to recognize your BASAGLAR Tempo Pen

• Pen color: Light grey
• Dose Knob: Light grey
• Labels: Light grey with green color bars

Supplies needed to give your injection

• BASAGLAR Tempo Pen
• Tempo Pen compatible Needle (Becton, Dickinson and Company Pen Needles recommended)
• Alcohol swab

Preparing your Pen

• Wash your hands with soap and water.
• Check the Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Do not use your Pen past the expiration date printed on the Label or for more than 28 days after you first start using the Pen.
• Always use a new needle for each injection to help prevent infections and blocked needles. Do not reuse or share your needles with other people. You may give other people a serious infection or get a serious infection from them.

Priming your Pen

Prime before each injection.

• Priming means removing the air from the Needle and Cartridge that may collect during normal use. It is important to prime your Pen before each injection so that it will work correctly.
• If you do not prime before each injection, you may get too much or too little insulin.

Selecting your dose

• You can give a dose of 1 to 80 units in a single injection.
• If your dose is more than 80 units, you will need to give more than 1 injection.
  • -
    Talk to your healthcare provider about how to give your dose.
  • -
    Use a new Needle for each injection and repeat the priming step.

• The Pen will not let you dial more than the number of units left in the Pen.
• If you need to inject more than the number of units left in the Pen, you may either:
  • -
    inject the amount left in your Pen and then use a new Pen to give the rest of your dose, or
  • -
    get a new Pen and inject the full dose.
• It is normal to see a small amount of insulin left in the Pen that you cannot inject.

Giving your injection

• Inject your insulin as your healthcare provider has shown you.
• 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 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.
• Do not try to change your dose while injecting.

After your injection

Disposing of Pens and Needles

• Put your used needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose 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.
• The used Pen may be thrown away (discarded) in your household trash after you have removed the needle.

Storing your BASAGLAR Tempo Pen

Unopened Pens

• Store unopened Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze BASAGLAR. Do not use if it has been frozen.
• Unopened Pens may be used until the expiration date printed on the Label, if the Pen has been kept in the refrigerator.

In-use Pen

• Store the Pen you are currently using at room temperature [up to 86°F (30°C)] and away from heat and light.
• Throw away the Pen you are using after 28 days, even if it still has insulin left in it.

General information about the safe and effective use of your Pen

• Keep your Pen and needles out of the sight and reach of children.
• Always use a new needle for each injection.
• Do not share your Pen or needles with other people. You may give other people a serious infection or get a serious infection from them.
• Do not use your Pen if any part looks broken or damaged.
• Always carry an extra Pen in case yours is lost or damaged.

Troubleshooting

• If you cannot remove the Pen Cap, gently twist the cap back and forth, and then pull the cap straight off.
• If the Dose Knob is hard to push:
  • -
    Pushing the Dose Knob more slowly will make it easier to inject.
  • -
    Your Needle may be blocked. Put on a new Needle and prime the Pen.
  • -
    You may have dust, food, or liquid inside the Pen. Throw the Pen away and get a new Pen.

If you have any questions or problems with your BASAGLAR Tempo Pen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on BASAGLAR Tempo Pen and insulin, go to www.basaglar.com.

Scan this code to launch

www.basaglar.com

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

BASAGLAR^® is a registered trademark and Tempo Pen^TM is a trademark of Eli Lilly and Company.

Instructions for Use revised: November 2022

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 2021, 2022, Eli Lilly and Company. All rights reserved.

BASTP-0004-IFU-20221115

• Always check insulin labels before administration [see Warnings and Precautions (5.4)].
• Visually inspect BASAGLAR prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles.
• Administer BASAGLAR 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)].
• Use BASAGLAR with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
• Do not dilute or mix BASAGLAR with any other insulin or solution.
• Do not administer intravenously or via an insulin pump.

Accidental mix-ups between insulin products have been reported. To avoid medication errors between BASAGLAR and other insulins, instruct patients to always check the insulin label before each injection.

Patients with type 2 diabetes participated in a double-blind, active-controlled study to evaluate the glucose lowering effect of once-daily BASAGLAR plus oral antidiabetic medication (OAM) compared to that of another insulin glargine product, 100 units/mL, or a non-U.S.-licensed insulin glargine, 100 units/mL (comparator insulin glargine products, 100 units/mL) administered once-daily along with OAMs. Patients were either insulin naïve (approximately 60%) and had failed to achieve adequate glycemic control on at least 2 OAMs, or were already on another insulin glargine product, 100 units/mL, or a non-U.S.-licensed insulin glargine, 100 units/mL, along with at least 2 OAMs with adequate or inadequate glycemic control (approximately 40%). A total of 759 patients were randomized. Three patients randomized to BASAGLAR did not receive study drug and were not included in efficacy analysis. The average age was approximately 59 years. The majority of patients were White (78%) and 50% of the patients were male. Sixty-eight percent of patients had GFR>90 mL/min/1.73m². The mean BMI was approximately 32 kg/m². At week 24, treatment with BASAGLAR provided a mean reduction in HbA_1c that was non-inferior to that achieved with comparator insulin glargine products, 100 units/mL (see Table 10).

In a randomized, controlled clinical study (Study E) (n=570), another insulin glargine product, 100 units/mL, was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combination of these drugs). The average age was 59.5 years. The majority of patients were Caucasian (92.8%) and 53.7% were male. The mean BMI was approximately 29.1 kg/m². The mean duration of diabetes was 10.3 years. This other insulin glargine product administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA_1c and fasting glucose (see Table 11). The rate of hypoglycemia was similar in this other insulin glargine product and NPH insulin treated patients [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study F), in patients with type 2 diabetes not using oral anti-diabetic medications (n=518), a basal-bolus regimen of another insulin glargine product, 100 units/mL, 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 59.3 years. The majority of patients were Caucasian (80.7%) and 60% were male. The mean BMI was approximately 30.5 kg/m². The mean duration of diabetes was 13.7 years. This other insulin glargine product had similar effectiveness as either once- or twice daily NPH insulin in reducing HbA_1c and fasting glucose (see Table 11) with a similar incidence of hypoglycemia [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study G), patients with type 2 diabetes were randomized to 5 years of treatment with another insulin glargine product, 100 units/mL, once-daily or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dose of this other insulin glargine product 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 this other insulin glargine product at a dose that was 80% of the total previous NPH insulin dose. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the ETDRS scale. HbA_1c 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 this other insulin glargine product and NPH insulin doses to a target fasting plasma glucose ≤100 mg/dL. After this other insulin glargine product or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added. The average age was 55.1 years. The majority of patients were Caucasian (85.3%) and 53.9% were male. The mean BMI was approximately 34.3 kg/m². The mean duration of diabetes was 10.8 years. This other insulin glargine product group had a smaller mean reduction from baseline in HbA_1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in this other insulin glargine product group (see Table 11). Both treatment groups had a similar incidence of reported symptomatic hypoglycemia. The incidence of severe symptomatic hypoglycemia in the ORIGIN Trial is given in Table 5 [see Adverse Reactions (6.1)].

• If changing patients from another insulin glargine product, 100 units/mL, to BASAGLAR, the dose of BASAGLAR should be the same as the other insulin glargine product, 100 units/mL.
• If changing patients from a once-daily insulin glargine product, 300 units/mL, to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the insulin glargine product, 300 units/mL [see Warnings and Precautions (5.2)].
• If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with BASAGLAR, a change in the dose of the basal insulin may be required.
• If changing patients from twice-daily NPH insulin to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the total daily NPH dosage [see Warnings and Precautions (5.2)].

In mice and rats, standard two-year carcinogenicity studies with another insulin glargine product were performed at doses up to 0.455 mg/kg, which was for the rat approximately 10 times and for the mouse approximately 5 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m². The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats (statistically significant) and male mice (not statistically significant) in acid vehicle containing groups. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown.

Another insulin glargine product 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 of another insulin glargine product in male and female rats at subcutaneous doses up to 0.36 mg/kg/day, which was approximately 7 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m², 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.

BASAGLAR prefilled pens must never be shared between patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.

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 an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6)].

Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

Patients with inadequately controlled type 1 diabetes participated in a 24-week open-label, active-controlled study with a 28 week extension to evaluate the glucose lowering effect of once-daily BASAGLAR compared to that of once-daily administration of another insulin glargine product, 100 units/mL, or a non-U.S.-licensed insulin glargine, 100 units/mL, (comparator insulin glargine products, 100 units/mL) both in combination with mealtime insulin lispro. Randomized were 535 adults with type 1 diabetes. Mean age was 41.2 years and mean duration of diabetes was 16.39 years. 57.9% were male. 74.5% were Caucasian, 2.1% Black or African American and 4.3% American Indian or Alaskan native. 3.9% were Hispanic. 73.5 percent of patients had GFR>90 mL/min/1.73m². The mean BMI was approximately 25.54 kg/m². At week 24, treatment with BASAGLAR provided a mean reduction in HbA_1c that was non-inferior to that achieved with comparator insulin glargine products, 100 units/mL (see Table 7).

In two clinical studies (Studies A and B), patients with type 1 diabetes (Study A; n=585, Study B; n=534) were randomized to 28 weeks of basal-bolus treatment with another insulin glargine product, 100 units/mL, or NPH insulin. Regular human insulin was administered before each meal. This other insulin glargine product was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily. In Study A, the average age was 39.2 years. The majority of patients were Caucasian (99%) and 55.7% were male. The mean BMI was approximately 24.9 kg/m². The mean duration of diabetes was 15.5 years. In Study B, the average age was 38.5 years. The majority of patients were Caucasian (95.3%) and 50.6% were male. The mean BMI was approximately 25.8 kg/m². The mean duration of diabetes was 17.4 years.

In another clinical study (Study C), patients with type 1 diabetes (n=619) were randomized to 16 weeks of basal-bolus treatment with another insulin glargine product, 100 units/mL, or NPH insulin. Insulin lispro was used before each meal. This other insulin glargine product was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was 39.2 years. The majority of patients were Caucasian (96.9%) and 50.6% were male. The mean BMI was approximately 25.6 kg/m². The mean duration of diabetes was 18.5 years.

In these 3 studies, another insulin glargine product, 100 units/mL, and NPH insulin had similar effects on HbA_1c (see Table 8) with a similar overall rate of hypoglycemia [see Adverse Reactions (6.1)].

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including BASAGLAR, 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.

Limitations of Use

BASAGLAR is not recommended for the treatment of diabetic ketoacidosis.

BAS-0006-PPI-20231129

PACKAGE CARTON – BASAGLAR KwikPen 80 UNIT PEN

Dispense in this sealed carton.

NDC 0002-7715-59

Basaglar^®

KwikPen^®

(insulin glargine)

injection

For Single Patient Use Only

100 units per mL (U-100)

For subcutaneous use only

Can inject from 1 to 80 units in a single injection

5 x 3 mL prefilled pens

prefilled insulin delivery device

Rx only

Read Basaglar^® KwikPen^® Instructions for Use.

NEEDLES NOT INCLUDED

This device is recommended for use with Becton, Dickinson & Company's insulin pen needles.

Lilly

Excess insulin administration relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)]. Mild episodes of hypoglycemia can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or physical activity level may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

Insulin glargine is a long-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, insulin glargine is 21^A-Gly-30^B-a-L-Arg-30^Bb-L-Arg-human insulin and has the empirical formula C₂₆₇H₄₀₄N₇₂O₇₈S₆ and a molecular weight of 6.063 kDa. Insulin glargine has the following structural formula:

BASAGLAR (insulin glargine) injection is a sterile clear and colorless aqueous solution for subcutaneous use. Each mL contains 100 units of insulin glargine (3.6378 mg).

The 3 mL BASAGLAR prefilled pen presentations contain the following inactive ingredients per mL: glycerin (17 mg), metacresol (2.7 mg), zinc oxide (content adjusted to provide 30 mcg zinc ion), and Water for Injection, USP.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid 10% and/or sodium hydroxide 10%. BASAGLAR has a pH of approximately 4.

All insulins, including BASAGLAR, 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 BASAGLAR [see Adverse Reactions (6.1)]. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). BASAGLAR, or any insulin, should not be used during episodes of hypoglycemia [see Contraindications (4)].

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7)], or in patients who experience recurrent hypoglycemia.

BASAGLAR (insulin glargine) injection is a clear, colorless solution, 100  units/mL (U-100), available as:

The BASAGLAR KwikPen and Tempo Pen dial in 1 unit increments.

Needles are not included.

This device is recommended for use with Becton, Dickinson & Company's insulin pen needles which are sold separately.

The safety and effectiveness of BASAGLAR have been established in pediatric patients (age 6 to 15 years) with type 1 diabetes based on an adequate and well-controlled trial of another insulin glargine product, 100 units/mL, in pediatric patients (age 6 to 15 years) with type 1 diabetes and additional data in adults with type 1 diabetes [see Clinical Studies (14.2)]. The safety and effectiveness of BASAGLAR in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes has not been established.

In the pediatric clinical trial, pediatric patients (age 6 to 15 years) with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in trials with type 1 diabetes [see Adverse Reactions (6.1)].

Of the total number of subjects in clinical studies of patients with type 2 diabetes who were treated with BASAGLAR or another insulin glargine product, 100 units/mL, each in combination with oral agents in a controlled clinical trial environment, 28.3% were 65 and over, while 4.5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

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

As with all therapeutic proteins, there is potential for immunogenicity.

In a 52-week study of type 1 diabetes patients, 42% of patients who received BASAGLAR once daily were positive for anti-drug antibodies (ADA) at least once during the study, including 17% that were positive at baseline and 25% of patients who developed ADA during the study. Sixty-five percent of the ADA positive patients on BASAGLAR with antibody testing at week 52 remained ADA positive at week 52.

In a 24-week study of type 2 diabetes patients, 17% of patients who received BASAGLAR once daily were positive for ADA at least once during the study. Among the subjects who were positive, 5% had ADA at baseline and 12% developed antibodies during the study. The percent binding of patients positive at baseline on BASAGLAR did not increase significantly during the study. Fifty-one percent of the ADA positive patients on BASAGLAR with antibody testing at week 24 remained ADA positive at week 24. There was no evidence that these antibodies had an impact on efficacy and safety outcomes.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to BASAGLAR with the incidence of antibodies in other studies or to other products may be misleading.

BASAGLAR 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 BASAGLAR [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 6 includes clinically significant drug interactions with BASAGLAR

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

The pharmacodynamic profile for BASAGLAR was determined after subcutaneous administration of a single 0.5 U/kg dose in a euglycemic clamp study conducted in 91 healthy subjects. The median time to maximum effect of BASAGLAR (measured by the peak rate of glucose infusion) was approximately 12.0 hours. The pharmacodynamic profile of BASAGLAR following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) and maximum glucose infusion rate were 1670 mg/kg and 2.12 mg/kg/min, respectively.

A euglycemic clamp study in 20 patients with type 1 diabetes showed a similar pharmacodynamic profile with a sustained glucose lowering activity over 24 hours following a single 0.3 U/kg subcutaneous dose of BASAGLAR.

After subcutaneous injection of 0.3 units/kg of another insulin glargine product, 100 units/mL, in patients with type 1 diabetes, the duration of action after abdominal, deltoid, or thigh subcutaneous administration was similar.

The time course of action of insulins, including insulin glargine, may vary between individuals and within the same individual.

The effect of hepatic impairment on the pharmacokinetics of BASAGLAR has not been studied. However, as with all insulin products, more frequent glucose monitoring and dose adjustment may be necessary for BASAGLAR in patients with hepatic impairment [see Warnings and Precautions (5.3)].

BASAGLAR^® is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.

The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analog 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.

Dispense in the original sealed carton with the enclosed Instructions for Use.

Protect BASAGLAR from heat and light. Do not freeze BASAGLAR.

In-use BASAGLAR prefilled pens must be used within 28 days or be discarded, even if they still contain BASAGLAR.

Storage conditions are summarized in the following table:

• Never share a BASAGLAR prefilled pen between patients, even if the needle is changed. (5.1)
• Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. (5.2)
• Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, 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)
• Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue BASAGLAR, monitor and treat if indicated. (5.5, 6.1)
• Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. (5.6)
• Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. (5.7)

• Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, prior insulin use. (2.2, 2.3, 2.4)
• Administer subcutaneously once daily at any time of day, but at the same time every day. (2.2)
• Rotate injection sites into the abdominal area, thigh, or deltoid to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. (2.1)
• Closely monitor glucose when converting to BASAGLAR and during initial weeks thereafter. (2.2)
• Do not dilute or mix with any other insulin or solution. (2.1)

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

• 3 mL single-patient-use BASAGLAR KwikPen
• 3 mL single-patient-use BASAGLAR Tempo Pen

The following adverse reactions have been identified during post-approval use of insulin glargine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported in which other insulin products, particularly rapid-acting 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.

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

Two clinical trials with BASAGLAR were conducted: one in type 1 diabetes and one in type 2 diabetes.

The type 1 diabetes population had the following characteristics: Mean age was 41 years and mean duration of diabetes was 16 years. 58% were male. 75% were Caucasian, 2% Black or African American and 4% American Indian or Alaskan native. 4% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 73.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 26 kg/m². HbA_1c at baseline was 7.8%. The data in Table 1 reflect exposure of 268 patients to BASAGLAR with a mean exposure duration of 49 weeks.

The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 11 years. 50% were male. 78% were Caucasian, 8% Black or African American and 5% American Indian or Alaskan native. 28% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m². 67.5 percent of patients had eGFR>90 mL/min/1.73m². The mean BMI was approximately 32 kg/m². HbA_1c at baseline was 8.3%. The data in Table 2 reflect exposure of 376 patients to BASAGLAR with a mean exposure duration of 22 weeks.

Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Common adverse reactions during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2, respectively.

The frequencies of adverse reactions during a clinical trial of 5 years duration with another insulin glargine product, 100 units/mL, in patients with type 2 diabetes mellitus are listed in Table 3.

The frequencies of adverse reactions during clinical trials with another insulin glargine product, 100 units/mL, in children and adolescents with type 1 diabetes mellitus are listed in Table 4.

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including BASAGLAR. If hypersensitivity reactions occur, discontinue BASAGLAR; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6.1)]. BASAGLAR is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or one of the excipients [see Contraindications (4)].

• In patients with type 1 diabetes, BASAGLAR must be used concomitantly with short-acting insulin.
• Inject BASAGLAR subcutaneously once daily at any time of day but at the same time every day.
• Individualize and adjust the dosage of BASAGLAR based on the individual'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)].
• The BASAGLAR prefilled pens each dials in 1 unit increments and delivers a maximum dose of 80 units per injection.

The safety and effectiveness of another insulin glargine product, 100 units/mL, 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 adults and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 8, 9, 11, and 12). In general, the reduction in glycated hemoglobin (HbA_1c) with this other insulin glargine product was similar to that with NPH insulin.

See FDA-approved patient labeling (Patient Information and Instructions for Use).

• The recommended starting dose of BASAGLAR in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Short- or rapid-acting, pre-meal insulin should be used to satisfy the remainder of the daily insulin requirements.
• The recommended starting dose of BASAGLAR in patients with type 2 diabetes is 0.2 units/kg or up to 10 units once daily.

Instructions for Use

BASAGLAR^® KwikPen^®

(insulin glargine)

injection, for subcutaneous use

100 units/mL, 3 mL single-patient-use pen

Read the Instructions for Use before you start using BASAGLAR and each time you get another BASAGLAR^® KwikPen^®. 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 BASAGLAR KwikPen 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.

BASAGLAR KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units (3mL) of BASAGLAR. One pen contains multiple doses of medicine.

• Your healthcare provider will tell you how many units to give as your dose and how to inject your prescribed dose of medicine.
• You can give a dose of 1 to 80 units in a single injection.
• If your prescribed dose is more than 80 units, you will need to give yourself more than 1 injection.
• The plunger only moves a little with each injection, and you may not notice that it moves. When the plunger reaches the end of the cartridge, you have used all 300 units in the Pen.

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

How to recognize your BASAGLAR KwikPen

• Pen color: Light grey
• Dose Knob: Light grey with green ring on the end
• Labels: Light grey with green color bars

Supplies needed to give your injection

• BASAGLAR KwikPen
• KwikPen compatible Needle (Becton, Dickinson and Company Pen Needles recommended)
• Alcohol swab

Preparing your Pen

• Wash your hands with soap and water.
• Check the Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Do not use your Pen past the expiration date printed on the Label or for more than 28 days after you first start using the Pen.
• Always use a new needle for each injection to help prevent infections and blocked needles. Do not reuse or share your needles with other people. You may give other people a serious infection or get a serious infection from them.

Priming your Pen

Prime before each injection.

• Priming means removing the air from the Needle and Cartridge that may collect during normal use. It is important to prime your Pen before each injection so that it will work correctly.
• If you do not prime before each injection, you may get too much or too little insulin.

Selecting your dose

• If your dose is more than 80 units, you will need to give more than 1 injection.
  • -
    Talk to your healthcare provider about how to give your dose.
  • -
    Use a new Needle for each injection and repeat the priming step.

The Pen will not let you dial more than the number of units left in the Pen.

• If you need to inject more than the number of units left in the Pen, you may either:
  • -
    inject the amount left in your Pen and then use a new Pen to give the rest of your dose, or
  • -
    get a new Pen and inject the full dose.
• It is normal to see a small amount of insulin left in the Pen that you can not inject.

Giving your injection

• Inject your insulin as your healthcare provider has shown you.
• 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.
• Do not try to change your dose while injecting.

After your injection

Disposing of Pens and Needles

• Put your used needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose 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.
• The used Pen may be discarded in your household trash after you have removed the needle.

Storing your BASAGLAR KwikPen

Unused Pens

• Store unused Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze BASAGLAR. Do not use if it has been frozen.
• Unused Pens may be used until the expiration date printed on the Label, if the Pen has been kept in the refrigerator.

In-use Pen

• Store the Pen you are currently using at room temperature [up to 86°F (30°C)] and away from heat and light.
• Throw away the Pen you are using after 28 days, even if it still has insulin left in it.

General information about the safe and effective use of your Pen

• Keep your Pen and needles out of the sight and reach of children.
• Always use a new needle for each injection.
• Do not share your Pen or needles with other people. You may give other people a serious infection or get a serious infection from them.
• Do not use your Pen if any part looks broken or damaged.
• Always carry an extra Pen in case yours is lost or damaged.

Troubleshooting

• If you can not remove the Pen Cap, gently twist the cap back and forth, and then pull the cap straight off.
• If the Dose Knob is hard to push:
  • -
    Pushing the Dose Knob more slowly will make it easier to inject.
  • -
    Your Needle may be blocked. Put on a new Needle and prime the Pen.
  • -
    You may have dust, food, or liquid inside the Pen. Throw the Pen away and get a new Pen.

If you have any questions or problems with your BASAGLAR KwikPen, contact Lilly at 1-800-LillyRx (1-800- 545-5979) or call your healthcare provider for help. For more information on BASAGLAR KwikPen and insulin, go to www.basaglar.com.

Scan this code to launch www.basaglar.com

This Instructions for Use have been approved by the U.S. Food and Drug Administration. BASAGLAR^® and BASAGLAR^® KwikPen^® are trademarks of Eli Lilly and Company.

Instructions for Use revised: November 2022

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 2015, 2022, Eli Lilly and Company. All rights reserved.

BASKP-0009-IFU-20221115

Instructions for Use

BASAGLAR^® Tempo Pen™ (insulin glargine) injection, for subcutaneous use

100 units/mL, 3 mL pen, single-patient-use

Read the Instructions for Use before you start using BASAGLAR and each time you get another BASAGLAR Tempo 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 BASAGLAR Tempo 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.

BASAGLAR Tempo Pen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units (3mL) of BASAGLAR. One pen contains multiple doses of medicine.

• Your healthcare provider will tell you how many units to give as your dose and how to inject your prescribed dose of medicine.
• You can give a dose of 1 to 80 units in a single injection.
• If your prescribed dose is more than 80 units, you will need to give yourself more than 1 injection.
• The Plunger only moves a little with each injection, and you may not notice that it moves. When the Plunger reaches the end of the cartridge, you have used all 300 units in the Pen.

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

This BASAGLAR Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter.

How to recognize your BASAGLAR Tempo Pen

• Pen color: Light grey
• Dose Knob: Light grey
• Labels: Light grey with green color bars

Supplies needed to give your injection

• BASAGLAR Tempo Pen
• Tempo Pen compatible Needle (Becton, Dickinson and Company Pen Needles recommended)
• Alcohol swab

Preparing your Pen

• Wash your hands with soap and water.
• Check the Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Do not use your Pen past the expiration date printed on the Label or for more than 28 days after you first start using the Pen.
• Always use a new needle for each injection to help prevent infections and blocked needles. Do not reuse or share your needles with other people. You may give other people a serious infection or get a serious infection from them.

Priming your Pen

Prime before each injection.

• Priming means removing the air from the Needle and Cartridge that may collect during normal use. It is important to prime your Pen before each injection so that it will work correctly.
• If you do not prime before each injection, you may get too much or too little insulin.

Selecting your dose

• You can give a dose of 1 to 80 units in a single injection.
• If your dose is more than 80 units, you will need to give more than 1 injection.
  • -
    Talk to your healthcare provider about how to give your dose.
  • -
    Use a new Needle for each injection and repeat the priming step.

• The Pen will not let you dial more than the number of units left in the Pen.
• If you need to inject more than the number of units left in the Pen, you may either:
  • -
    inject the amount left in your Pen and then use a new Pen to give the rest of your dose, or
  • -
    get a new Pen and inject the full dose.
• It is normal to see a small amount of insulin left in the Pen that you cannot inject.

Giving your injection

• Inject your insulin as your healthcare provider has shown you.
• 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 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.
• Do not try to change your dose while injecting.

After your injection

Disposing of Pens and Needles

• Put your used needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose 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.
• The used Pen may be thrown away (discarded) in your household trash after you have removed the needle.

Storing your BASAGLAR Tempo Pen

Unopened Pens

• Store unopened Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze BASAGLAR. Do not use if it has been frozen.
• Unopened Pens may be used until the expiration date printed on the Label, if the Pen has been kept in the refrigerator.

In-use Pen

• Store the Pen you are currently using at room temperature [up to 86°F (30°C)] and away from heat and light.
• Throw away the Pen you are using after 28 days, even if it still has insulin left in it.

General information about the safe and effective use of your Pen

• Keep your Pen and needles out of the sight and reach of children.
• Always use a new needle for each injection.
• Do not share your Pen or needles with other people. You may give other people a serious infection or get a serious infection from them.
• Do not use your Pen if any part looks broken or damaged.
• Always carry an extra Pen in case yours is lost or damaged.

Troubleshooting

• If you cannot remove the Pen Cap, gently twist the cap back and forth, and then pull the cap straight off.
• If the Dose Knob is hard to push:
  • -
    Pushing the Dose Knob more slowly will make it easier to inject.
  • -
    Your Needle may be blocked. Put on a new Needle and prime the Pen.
  • -
    You may have dust, food, or liquid inside the Pen. Throw the Pen away and get a new Pen.

If you have any questions or problems with your BASAGLAR Tempo Pen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on BASAGLAR Tempo Pen and insulin, go to www.basaglar.com.

Scan this code to launch

www.basaglar.com

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

BASAGLAR^® is a registered trademark and Tempo Pen^TM is a trademark of Eli Lilly and Company.

Instructions for Use revised: November 2022

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 2021, 2022, Eli Lilly and Company. All rights reserved.

BASTP-0004-IFU-20221115

• Always check insulin labels before administration [see Warnings and Precautions (5.4)].
• Visually inspect BASAGLAR prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles.
• Administer BASAGLAR 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)].
• Use BASAGLAR with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
• Do not dilute or mix BASAGLAR with any other insulin or solution.
• Do not administer intravenously or via an insulin pump.

Accidental mix-ups between insulin products have been reported. To avoid medication errors between BASAGLAR and other insulins, instruct patients to always check the insulin label before each injection.

Patients with type 2 diabetes participated in a double-blind, active-controlled study to evaluate the glucose lowering effect of once-daily BASAGLAR plus oral antidiabetic medication (OAM) compared to that of another insulin glargine product, 100 units/mL, or a non-U.S.-licensed insulin glargine, 100 units/mL (comparator insulin glargine products, 100 units/mL) administered once-daily along with OAMs. Patients were either insulin naïve (approximately 60%) and had failed to achieve adequate glycemic control on at least 2 OAMs, or were already on another insulin glargine product, 100 units/mL, or a non-U.S.-licensed insulin glargine, 100 units/mL, along with at least 2 OAMs with adequate or inadequate glycemic control (approximately 40%). A total of 759 patients were randomized. Three patients randomized to BASAGLAR did not receive study drug and were not included in efficacy analysis. The average age was approximately 59 years. The majority of patients were White (78%) and 50% of the patients were male. Sixty-eight percent of patients had GFR>90 mL/min/1.73m². The mean BMI was approximately 32 kg/m². At week 24, treatment with BASAGLAR provided a mean reduction in HbA_1c that was non-inferior to that achieved with comparator insulin glargine products, 100 units/mL (see Table 10).

In a randomized, controlled clinical study (Study E) (n=570), another insulin glargine product, 100 units/mL, was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combination of these drugs). The average age was 59.5 years. The majority of patients were Caucasian (92.8%) and 53.7% were male. The mean BMI was approximately 29.1 kg/m². The mean duration of diabetes was 10.3 years. This other insulin glargine product administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA_1c and fasting glucose (see Table 11). The rate of hypoglycemia was similar in this other insulin glargine product and NPH insulin treated patients [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study F), in patients with type 2 diabetes not using oral anti-diabetic medications (n=518), a basal-bolus regimen of another insulin glargine product, 100 units/mL, 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 59.3 years. The majority of patients were Caucasian (80.7%) and 60% were male. The mean BMI was approximately 30.5 kg/m². The mean duration of diabetes was 13.7 years. This other insulin glargine product had similar effectiveness as either once- or twice daily NPH insulin in reducing HbA_1c and fasting glucose (see Table 11) with a similar incidence of hypoglycemia [see Adverse Reactions (6.1)].

In a randomized, controlled clinical study (Study G), patients with type 2 diabetes were randomized to 5 years of treatment with another insulin glargine product, 100 units/mL, once-daily or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dose of this other insulin glargine product 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 this other insulin glargine product at a dose that was 80% of the total previous NPH insulin dose. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the ETDRS scale. HbA_1c 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 this other insulin glargine product and NPH insulin doses to a target fasting plasma glucose ≤100 mg/dL. After this other insulin glargine product or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added. The average age was 55.1 years. The majority of patients were Caucasian (85.3%) and 53.9% were male. The mean BMI was approximately 34.3 kg/m². The mean duration of diabetes was 10.8 years. This other insulin glargine product group had a smaller mean reduction from baseline in HbA_1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in this other insulin glargine product group (see Table 11). Both treatment groups had a similar incidence of reported symptomatic hypoglycemia. The incidence of severe symptomatic hypoglycemia in the ORIGIN Trial is given in Table 5 [see Adverse Reactions (6.1)].

• If changing patients from another insulin glargine product, 100 units/mL, to BASAGLAR, the dose of BASAGLAR should be the same as the other insulin glargine product, 100 units/mL.
• If changing patients from a once-daily insulin glargine product, 300 units/mL, to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the insulin glargine product, 300 units/mL [see Warnings and Precautions (5.2)].
• If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with BASAGLAR, a change in the dose of the basal insulin may be required.
• If changing patients from twice-daily NPH insulin to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the total daily NPH dosage [see Warnings and Precautions (5.2)].

In mice and rats, standard two-year carcinogenicity studies with another insulin glargine product were performed at doses up to 0.455 mg/kg, which was for the rat approximately 10 times and for the mouse approximately 5 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m². The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats (statistically significant) and male mice (not statistically significant) in acid vehicle containing groups. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown.

Another insulin glargine product 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 of another insulin glargine product in male and female rats at subcutaneous doses up to 0.36 mg/kg/day, which was approximately 7 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m², 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.

BASAGLAR prefilled pens must never be shared between patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.

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 an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6)].

Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

Patients with inadequately controlled type 1 diabetes participated in a 24-week open-label, active-controlled study with a 28 week extension to evaluate the glucose lowering effect of once-daily BASAGLAR compared to that of once-daily administration of another insulin glargine product, 100 units/mL, or a non-U.S.-licensed insulin glargine, 100 units/mL, (comparator insulin glargine products, 100 units/mL) both in combination with mealtime insulin lispro. Randomized were 535 adults with type 1 diabetes. Mean age was 41.2 years and mean duration of diabetes was 16.39 years. 57.9% were male. 74.5% were Caucasian, 2.1% Black or African American and 4.3% American Indian or Alaskan native. 3.9% were Hispanic. 73.5 percent of patients had GFR>90 mL/min/1.73m². The mean BMI was approximately 25.54 kg/m². At week 24, treatment with BASAGLAR provided a mean reduction in HbA_1c that was non-inferior to that achieved with comparator insulin glargine products, 100 units/mL (see Table 7).

In two clinical studies (Studies A and B), patients with type 1 diabetes (Study A; n=585, Study B; n=534) were randomized to 28 weeks of basal-bolus treatment with another insulin glargine product, 100 units/mL, or NPH insulin. Regular human insulin was administered before each meal. This other insulin glargine product was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily. In Study A, the average age was 39.2 years. The majority of patients were Caucasian (99%) and 55.7% were male. The mean BMI was approximately 24.9 kg/m². The mean duration of diabetes was 15.5 years. In Study B, the average age was 38.5 years. The majority of patients were Caucasian (95.3%) and 50.6% were male. The mean BMI was approximately 25.8 kg/m². The mean duration of diabetes was 17.4 years.

In another clinical study (Study C), patients with type 1 diabetes (n=619) were randomized to 16 weeks of basal-bolus treatment with another insulin glargine product, 100 units/mL, or NPH insulin. Insulin lispro was used before each meal. This other insulin glargine product was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was 39.2 years. The majority of patients were Caucasian (96.9%) and 50.6% were male. The mean BMI was approximately 25.6 kg/m². The mean duration of diabetes was 18.5 years.

In these 3 studies, another insulin glargine product, 100 units/mL, and NPH insulin had similar effects on HbA_1c (see Table 8) with a similar overall rate of hypoglycemia [see Adverse Reactions (6.1)].

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including BASAGLAR, 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.