Lantus

LANTUS is a recombinant human insulin analog for once daily subcutaneous administration with potency that is approximately the same as the potency of human insulin. LANTUS exhibits a relatively constant glucose-lowering profile over 24 hours that permits once-daily dosing.

LANTUS may be administered at any time during the day. LANTUS should be administered subcutaneously once a day at the same time every day. The dose of LANTUS must be individualized based on clinical response. Blood glucose monitoring is essential in all patients receiving insulin therapy.

Patients adjusting the amount or timing of dosing with LANTUS, should only do so under medical supervision with appropriate glucose monitoring .] [see Warnings and Precautions (5.1)

In patients with type 1 diabetes, LANTUS must be used in regimens with short-acting insulin.

The intended duration of activity of LANTUS is dependent on injection into subcutaneous tissue . LANTUS should not be administered intravenously or via an insulin pump. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia . [see ] Clinical pharmacology (12.2) [see ] Warnings and Precautions (5.3)

As with all insulins, injection sites should be rotated within the same region (abdomen, thigh, or deltoid) from one injection to the next to reduce the risk of lipodystrophy [See ]. Adverse Reactions (6.1)

In clinical studies, there was no clinically relevant difference in insulin glargine absorption after abdominal, deltoid, or thigh subcutaneous administration. As for all insulins, the rate of absorption, and consequently the onset and duration of action, may be affected by exercise and other variables, such as stress, intercurrent illness, or changes in co-administered drugs or meal patterns .

The recommended starting dose of LANTUS in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Short-acting, premeal insulin should be used to satisfy the remainder of the daily insulin requirements.

The recommended starting dose of LANTUS in patients with type 2 diabetes who are not currently treated with insulin is 10 units (or 0.2 Units/kg) once daily, which should subsequently be adjusted to the patient's needs.

The dose of LANTUS should be adjusted according to blood glucose measurements. The dosage of LANTUS should be individualized under the supervision of a healthcare provider in accordance with the needs of the patient.

If changing from a treatment regimen with an intermediate-or long-acting insulin to a regimen with LANTUS, the amount and timing of shorter-acting insulins and doses of any oral anti-diabetic drugs may need to be adjusted.

• If transferring patients from once-daily NPH insulin to once-daily LANTUS, the recommended initial LANTUS dose is the same as the dose of NPH that is being discontinued.
• If transferring patients from twice-daily NPH insulin to once-daily LANTUS, the recommended initial LANTUS dose is 80% of the total NPH dose that is being discontinued. This dose reduction will lower the likelihood of hypoglycemia [ see ]. Warnings and Precautions (5.3)

Glucose monitoring is essential for all patients receiving insulin therapy. Changes to an insulin regimen should be made cautiously and only under medical supervision.

Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral anti-diabetic treatment.

As with all insulin preparations, the time course of action for LANTUS may vary in different individuals or at different times in the same individual and is dependent on many conditions, including the local blood supply, local temperature, and physical activity.

Do not administer LANTUS intravenously or via an insulin pump. The intended duration of activity of LANTUS is dependent on injection into subcutaneous tissue

Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia . [see ] Warnings and Precautions (5.3)

Do not dilute or mix LANTUS with any other insulin or solution. If LANTUS is diluted or mixed, the solution may become cloudy, and the pharmacokinetic or pharmacodynamic profile (e.g., onset of action, time to peak effect) of LANTUS and the mixed insulin may be altered in an unpredictable manner. When LANTUS and regular human insulin were mixed immediately before injection in dogs, a delayed onset of action and a delayed time to maximum effect for regular human insulin was observed. The total bioavailability of the mixture was also slightly decreased compared to separate injections of LANTUS and regular human insulin. The relevance of these observations in dogs to humans is unknown.

Do not share disposable or reusable insulin devices or needles between patients, because doing so carries a risk for transmission of blood-borne pathogens.

Hypoglycemia is the most common adverse reaction of insulin, including LANTUS. The risk of hypoglycemia increases with intensive glycemic control. Patients must be educated to recognize and manage hypoglycemia. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with LANTUS.

The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulations. Other factors such as changes in food intake (e.g., amount of food or timing of meals), exercise, and concomitant medications may also alter the risk of hypoglycemia [ ]. See Drug Interactions (7)

The prolonged effect of subcutaneous LANTUS may delay recovery from hypoglycemia. Patients being switched from twice daily NPH insulin to once-daily LANTUS should have their initial LANTUS dose reduced by 20% from the previous total daily NPH dose to reduce the risk of hypoglycemia [see ]. Dosage and Administration (2.3)

As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g., the pediatric population and patients who fast or have erratic food intake). The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.

Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic neuropathy, use of medications such as beta-blockers, or intensified glycemic control. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient's awareness of hypoglycemia.

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including LANTUS.

Due to its long duration of action, Lantus is not recommended during periods of rapidly declining renal function because of the risk for prolonged hypoglycemia.

Although studies have not been performed in patients with diabetes and renal impairment, a reduction in the LANTUS dose may be required in patients with renal impairment because of reduced insulin metabolism, similar to observations found with other insulins. [See ]. Clinical Pharmacology (12.3)

Due to its long duration of action, Lantus is not recommended during periods of rapidly declining hepatic function because of the risk for prolonged hypoglycemia.

Although studies have not been performed in patients with diabetes and hepatic impairment, a reduction in the LANTUS dose may be required in patients with hepatic impairment because of reduced capacity for gluconeogenesis and reduced insulin metabolism, similar to observations found with other insulins. [See ]. Clinical Pharmacology (12.3)

Some medications may alter insulin requirements and subsequently increase the risk for hypoglycemia or hyperglycemia [See ]. Drug Interactions (7)

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 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.

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

The frequencies of treatment-emergent adverse events during LANTUS clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

The following adverse reactions have been identified during post-approval use of LANTUS.

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 insulins, particularly short-acting insulins, have been accidentally administered instead of LANTUS ]. To avoid medication errors between LANTUS and other insulins, patients should be instructed to always verify the insulin label before each injection. [See Patient Counseling Information (17)

It is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when LANTUS is administered to a nursing woman. Use of LANTUS is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.

The safety and effectiveness of subcutaneous injections of LANTUS have been established in pediatric patients (age 6 to 15 years) with type 1 diabetes . LANTUS has not been studied in pediatric patients younger than 6 years of age with type 1 diabetes. LANTUS has not been studied in pediatric patients with type 2 diabetes. [see ] Clinical Studies (14)

Based on the results of a study in pediatric patients, the dose recommendation when switching to LANTUS is the same as that described for adults and As in adults, the dosage of LANTUS must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose. [see Dosage and Administration (2.3) ]. Clinical Studies (14)

In controlled clinical studies comparing LANTUS to NPH insulin, 593 of 3890 patients (15%) with type 1 and type 2 diabetes were ≥65 years of age and 80 (2%) patients were ≥75 years of age. The only difference in safety or effectiveness in the subpopulation of patients ≥65 years of age compared to the entire study population was a higher incidence of cardiovascular events typically seen in an older population in both LANTUS and NPH insulin-treated patients.

Nevertheless, caution should be exercised when LANTUS 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 [See ]. Warnings and Precautions (5.3)

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.

Insulin glargine is a human insulin analog that has been designed to have low aqueous solubility at neutral pH. At pH 4, as in the LANTUS injection solution, insulin glargine is completely soluble. After injection into the subcutaneous tissue, the acidic solution is neutralized, leading to formation of microprecipitates from which small amounts of insulin glargine are slowly released, resulting in a relatively constant concentration/time profile over 24 hours with no pronounced peak. This profile allows once-daily dosing as a basal insulin.

In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous insulin glargine is approximately the same as that for human insulin. In euglycemic clamp studies in healthy subjects or in patients with type 1 diabetes, the onset of action of subcutaneous insulin glargine was slower than NPH insulin. The effect profile of insulin glargine was relatively constant with no pronounced peak and the duration of its effect was prolonged compared to NPH insulin. shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after the injection. The median time between 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 >24.0 hours) (24 hours was the end of the observation period) for insulin glargine. Figure 1

Figure 1. Activity Profile in Patients with Type 1 Diabetes

Figure

* Determined as amount of glucose infused to maintain constant plasma glucose levels (hourly mean values); indicative of insulin activity.

The longer duration of action (up to 24 hours) of LANTUS is directly related to its slower rate of absorption and supports once-daily subcutaneous administration. The time course of action of insulins, including LANTUS, may vary between individuals and within the same individual.

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 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/m . 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. ²

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 7 times the recommended human subcutaneous starting dose of 10 Units/day (0.008 mg/kg/day), based on mg/m , 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. ²

(see ). Type 1 Diabetes–Adult Table 11

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 LANTUS or NPH insulin. Regular human insulin was administered before each meal. LANTUS was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily.

In another clinical study (Study C), patients with type 1 diabetes (n=619) were randomized to 16 weeks of basal-bolus treatment with LANTUS or NPH insulin. Insulin lispro was used before each meal. LANTUS was administered once daily at bedtime and NPH insulin was administered once or twice daily.

In these 3 studies, LANTUS and NPH insulin had similar effects on HbA1c (Table 11) with a similar overall rate of hypoglycemia . [See ] Adverse Reactions (6.1)

Type 1 Diabetes–Pediatric (see ). Table 12

In a randomized, controlled clinical study (Study D), pediatric patients (age range 6 to 15 years) with type 1 diabetes (n=349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. LANTUS was administered once daily at bedtime and NPH insulin was administered once or twice daily. Similar effects on HbA1c (Table 12) and the incidence of hypoglycemia were observed in both treatment groups . [See ] Adverse Reactions (6.1)

Type 2 Diabetes–Adult (see ). Table 13

In a randomized, controlled clinical study (Study E) (n=570), LANTUS was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs). LANTUS administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 13). The rate of hypoglycemia was similar in LANTUS 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 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. LANTUS had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 13) 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 once-daily LANTUS or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dose 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 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 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 doses to a target fasting plasma glucose ≤100 mg/dL. After the LANTUS or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added. 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 13). Both treatment groups had a similar incidence of reported symptomatic hypoglycemia. The incidences of severe symptomatic hypoglycemia are given in Table 6 . [See ] Adverse Reactions (6.1)

LANTUS Timing of Daily Dosing (see ). Table 14

The safety and efficacy of LANTUS administered pre-breakfast, pre-dinner, or at bedtime were evaluated in a randomized, controlled clinical study in patients with type 1 diabetes (study H, n=378). Patients were also treated with insulin lispro at mealtime. LANTUS administered at different times of the day resulted in similar reductions in HbA1c compared to that with bedtime administration (see ). In these patients, data are available from 8-point home glucose monitoring. The maximum mean blood glucose was observed just prior to injection of LANTUS regardless of time of administration. Table 14

In this study, 5% of patients in the LANTUS-breakfast arm discontinued treatment because of lack of efficacy. No patients in the other two arms discontinued for this reason. The safety and efficacy of LANTUS administered pre-breakfast or at bedtime were also evaluated in a randomized, active-controlled clinical study (Study I, n=697) in patients with type 2 diabetes not adequately controlled on oral anti-diabetic therapy. All patients in this study also received glimepiride 3 mg daily. LANTUS given before breakfast was at least as effective in lowering HbA1c as LANTUS given at bedtime or NPH insulin given at bedtime (see ). Table 14

LANTUS solution for injection 100 units per mL (U-100) is available as:

Needles are not included in the packs.

BD Ultra-Fine™ needles to be used in conjunction with SoloStar are sold separately and are manufactured by BD. ⁹

LANTUS should not be stored in the freezer and should not be allowed to freeze. Discard LANTUS if it has been frozen.

Parenteral drug products should be inspected visually prior to administration whenever the solution and the container permit. LANTUS must only be used if the solution is clear and colorless with no particles visible.

Mixing and diluting: LANTUS must NOT be diluted or mixed with any other insulin or solution [S . ee ] Warnings and Precautions (5.2)

The syringes must not contain any other medicinal product or residue. Vial:

: If SoloStar disposable insulin device, malfunctions, LANTUS may be drawn from the cartridge system or from SoloStar into a U-100 syringe and injected. SoloStar

Patients should be informed that changes to insulin regimens must be made cautiously and only under medical supervision.

Patients should be informed about the potential side effects of insulin therapy, including lipodystrophy (and the need to rotate injection sites within the same body region), weight gain, allergic reactions, and hypoglycemia. Patients should be informed that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia should be advised to use caution when driving or operating machinery.

Accidental mix-ups between LANTUS and other insulins, particularly short-acting insulins, have been reported. To avoid medication errors between LANTUS and other insulins, patients should be instructed to always check the insulin label before each injection.

LANTUS must only be used if the solution is clear and colorless with no particles visible Patients must be advised that LANTUS must NOT be diluted or mixed with any other insulin or solution . .

Patients should be advised not to share disposable or reusable insulin devices or needles with other patients, because doing so carries a risk for transmission of blood-borne pathogens.

Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals.

Patients with diabetes should be advised to inform their health care professional if they are pregnant or are contemplating pregnancy.

Refer patients to the LANTUS "Patient Information" for additional information.

See attached document at end of Full Prescribing Information.

Patient Information LANTUS SOLOSTAR 3 mL disposable insulin delivery device (300 units per device) 100 units per mL (U-100) (insulin glargine [recombinant DNA origin] injection)
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• What is the most important information I should know about LANTUS?
• What is LANTUS?
• Who should NOT take LANTUS?
• How should I use LANTUS?
• Mixing with LANTUS
• Instructions for Use
• What can affect how much insulin I need?
• What are the possible side effects of LANTUS and other insulins?
• How should I store LANTUS?
• General Information about LANTUS

Read this "Patient Information" that comes with LANTUS (LAN-tus) before you start using it and each time you get a refill because there may be new information. This leaflet does not take the place of talking with your healthcare provider about your condition or treatment. If you have questions about LANTUS or about diabetes, talk with your healthcare provider.

What is the most important information I should know about LANTUS?

• Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (for example: Regular, NPH, analogs), species (beef, pork, beef-pork, human) or method of manufacture (recombinant DNA versus animal-source insulin) may need a change in the dose. This dose change may be needed right away or later on during the first several weeks or months on the new insulin. Doses of oral anti-diabetic medicines may also need to change, if your insulin is changed. Do not change the insulin you are using without talking to your healthcare provider.
• Your healthcare provider will tell you how often you should test your blood sugar level, and what to do if it is high or low. You must test your blood sugar levels while using an insulin, such as LANTUS.
• It will not work and you may lose blood sugar control, which could be serious. Do NOT dilute or mix LANTUS with any other insulin or solution.
• comes as U-100 insulin and contains 100 units of LANTUS per milliliter (mL). One milliliter of U-100 insulin contains 100 units of insulin. (1 mL = 1 cc). LANTUS

What is Diabetes?

• Your body needs insulin to turn sugar (glucose) into energy. If your body does not make enough insulin, you need to take more insulin so you will not have too much sugar in your blood.
• Insulin injections are important in keeping your diabetes under control. But the way you live, your diet, careful checking of your blood sugar levels, exercise, and planned physical activity, all work with your insulin to help you control your diabetes.

What is LANTUS?

• LANTUS (insulin glargine [recombinant DNA origin]) is a long-acting insulin. Because Lantus is made by recombinant DNA technology (rDNA) and is chemically different from the insulin made by the human body, it is called an insulin analog. LANTUS is used to treat patients with diabetes for the control of high blood sugar. It is used once a day to lower blood glucose.
• LANTUS is a clear, colorless, sterile solution for injection under the skin (subcutaneously).
• The active ingredient in LANTUS is insulin glargine. The concentration of insulin glargine is 100 units per milliliter (mL), or U-100. LANTUS also contains zinc, metacresol, glycerol, and water for injection as inactive ingredients. Hydrochloric acid and/or sodium hydroxide may be added to adjust the pH.
• You need a prescription to get LANTUS. Always be sure you receive the right insulin from the pharmacy.

Who should NOT take LANTUS?

or any of the inactive ingredients in LANTUS. Check with your healthcare provider if you are not sure. Do not take LANTUS if you are allergic to insulin glargine

• Before starting LANTUS, tell your healthcare provider about all your medical conditions including if you:
  • Your dose may need to be adjusted. have liver or kidney problems.
  • It is not known if LANTUS may harm your unborn baby. It is very important to maintain control of your blood sugar levels during pregnancy. Your healthcare provider will decide which insulin is best for you during your pregnancy. are pregnant or plan to become pregnant.
  • It is not known whether LANTUS passes into your milk. Many medicines, including insulin, pass into human milk, and could affect your baby. Talk to your healthcare provider about the best way to feed your baby. are breast-feeding or plan to breast-feed.
  • prescription and non-prescription medicines, vitamins and herbal supplements. are taking any other medicines including
  • , especially ones commonly called TZDs (thiazolidinediones). if you take any other medicines
  • . If you have heart failure, it may get worse while you take TZDs with Lantus. if you have heart failure or other heart problems

How should I use LANTUS?

See the " Instructions for SoloStar Use" section for additional information.

• Follow the instructions given by your healthcare provider about the type or types of insulin you are using. Do not make any changes with your insulin unless you have talked to your healthcare provider. Your insulin needs may change because of illness, stress, other medicines, or changes in diet or activity level. Talk to your healthcare provider about how to adjust your insulin dose.
• You may take LANTUS at any time during the day but you must take it at the same time every day.
• Only use LANTUS that is clear and colorless. If your LANTUS is cloudy or slightly colored, return it to your pharmacy for a replacement.
• Follow your healthcare provider's instructions for testing your blood sugar.
• Inject LANTUS under your skin (subcutaneously) in your upper arm, abdomen (stomach area), or thigh (upper leg). Never inject it into a vein or muscle.
• Change (rotate) injection sites within the same body area.
  
  
• NEEDLES AND SOLOSTAR MUST NOT BE SHARED.
  
  
• Disposable needles should be used only once. Used needle should be placed in sharps containers (such as red biohazard containers), hard plastic containers (such as detergent bottles), or metal containers (such as an empty coffee can). Such containers should be sealed and disposed of properly.

Mixing with LANTUS

• It will not work as intended and you may lose blood sugar control, which could be serious. Do NOT dilute or mix LANTUS with any other insulin or solution.

Instructions for SoloStar Use

If you have lost your leaflet or have a question, go to www.lantus.com or call 1-800-633-1610. It is important to read, understand, and follow the step-by-step instructions in the "SoloStar Instruction Leaflet" before using SoloStar disposable insulin Pen. Failure to follow the instructions may result in getting too much or too little insulin.

The following general notes should be taken into consideration before injecting Lantus:

• Always wash your hands before handling the SoloStar disposable insulin Pen.
• Always attach a new needle before use. BD Ultra-Fine™ needles are compatible with SoloStar. These are sold separately and are manufactured by BD. ^†
• Always perform the safety test before use.
• Check the insulin solution in the pen to make sure it is clear, colorless, and free of particles. If it is not, throw it away.
• Do NOT mix or dilute LANTUS with any other insulin or solution. LANTUS will not work if it is mixed or diluted and you may lose blood sugar control, which could be serious.
• Decide on an injection area - either upper arm, thigh, or abdomen. Do not use the same injection site as your last injection.
• After injecting LANTUS, leave the needle in the skin for an additional 10 seconds. Then pull the needle straight out. Gently press on the spot where you injected yourself for a few seconds. Do not rub the area.
• Do not drop the SoloStar disposable insulin Pen.

If your blood glucose reading is high or low, tell your healthcare provider so the dose can be adjusted.

What can affect how much insulin I need?

Illness may change how much insulin you need. It is a good idea to think ahead and make a "sick day" plan with your healthcare provider in advance so you will be ready when this happens. Be sure to test your blood sugar more often and call your healthcare provider if you are sick. Illness.

Other medicines, including prescription and non-prescription medicines, vitamins, and herbal supplements, can change the way insulin works. You may need a different dose of insulin when you are taking certain other medicines. including prescription and non-prescription medicines, vitamins and herbal supplements. You may want to keep a list of the medicines you take. You can show this list to your healthcare provider and pharmacists anytime you get a new medicine or refill. Your healthcare provider will tell you if your insulin dose needs to be changed. Medicines. Many medicines can affect your insulin needs. Know all the medicines you take,

The amount of food you eat can affect your insulin needs. If you eat less food, skip meals, or eat more food than usual, you may need a different dose of insulin. Talk to your healthcare provider if you change your diet so that you know how to adjust your LANTUS and other insulin doses. Meals.

Alcohol, including beer and wine, may affect the way LANTUS works and affect your blood sugar levels. Talk to your healthcare provider about drinking alcohol. Alcohol.

Exercise or activity level may change the way your body uses insulin. Check with your healthcare provider before you start an exercise program because your dose may need to be changed. Exercise or Activity level.

If you travel across time zones, talk with your healthcare provider about how to time your injections. When you travel, wear your medical alert identification. Take extra insulin and supplies with you. Travel.

The effects of LANTUS on an unborn child or on a nursing baby are unknown. Therefore, tell your healthcare provider if you are planning to have a baby, are pregnant, or nursing a baby. Good control of diabetes is especially important during pregnancy and nursing. Pregnancy or nursing.

What are the possible side effects of LANTUS and other insulins?

Insulins, including LANTUS, can cause hypoglycemia (low blood sugar), hyperglycemia (high blood sugar), allergy, and skin reactions.

Hypoglycemia (low blood sugar):

Hypoglycemia is often called an "insulin reaction" or "low blood sugar". It may happen when you do not have enough sugar in your blood. Common causes of hypoglycemia are illness, emotional or physical stress, too much insulin, too little food or missed meals, and too much exercise or activity.

Early warning signs of hypoglycemia may be different, less noticeable or not noticeable at all in some people. That is why it is important to check your blood sugar as you have been advised by your healthcare provider.

Hypoglycemia can happen with:

• This can happen when too much insulin is injected. Taking too much insulin.
• This can happen if a meal or snack is missed or delayed. Not enough carbohydrate (sugar or starch) intake.
• that decreases the amount of sugar absorbed by your body. Vomiting or diarrhea
• Intake of alcohol.
• Be sure to discuss all your medicines with your healthcare provider. Medicines that affect insulin. Do not start any new medicines until you know how they may affect your insulin dose.
• These conditions include diseases of the adrenal glands, the pituitary, the thyroid gland, the liver, and the kidney. Medical conditions that can affect your blood sugar levels or insulin.
• This can happen if you exercise too much or have a fever. Too much glucose use by the body.
• Injecting insulin the wrong way or in the wrong injection area.

Hypoglycemia can be mild to severe. Its onset may be rapid. Some patients have few or no warning symptoms, including:

• patients with diabetes for a long time
• patients with diabetic neuropathy (nerve problems)
• or patients using certain medicines for high blood pressure or heart problems.

Hypoglycemia may reduce your ability to drive a car or use mechanical equipment and you may risk injury to yourself or others.

Severe hypoglycemia can be dangerous and can cause temporary or permanent harm to your heart or brain. It may cause unconsciousness, seizures, or death.

Symptoms of hypoglycemia may include:

• anxiety, irritability, restlessness, trouble concentrating, personality changes, mood changes, or other abnormal behavior
• tingling in your hands, feet, lips, or tongue
• dizziness, light-headedness, or drowsiness
• nightmares or trouble sleeping
• headache
• blurred vision
• slurred speech
• palpitations (fast heart beat)
• sweating
• tremor (shaking)
• unsteady gait (walking).

If you have hypoglycemia often or it is hard for you to know if you have the symptoms of hypoglycemia, talk to your healthcare provider.

Mild to moderate hypoglycemia is treated by eating or drinking carbohydrates such as fruit juice, raisins, sugar candies, milk or glucose tablets. Talk to your healthcare provider about the amount of carbohydrates you should eat to treat mild to moderate hypoglycemia.

Severe hypoglycemia may require the help of another person or emergency medical people. A person with hypoglycemia who is unable to take foods or liquids with sugar by mouth, or is unconscious needs medical help fast and will need treatment with a glucagon injection or glucose given intravenously (IV). Without medical help right away, serious reactions or even death could happen.

Hyperglycemia (high blood sugar):

Hyperglycemia happens when you have too much sugar in your blood. Usually, it means there is not enough insulin to break down the food you eat into energy your body can use. Hyperglycemia can be caused by a fever, an infection, stress, eating more than you should, taking less insulin than prescribed, or it can mean your diabetes is getting worse.

Hyperglycemia can happen with:

• This can happen from: Insufficient (too little) insulin.
  • - injecting too little or no insulin
  • - incorrect storage (freezing, excessive heat)
  • - use after the expiration date.
• This can happen if you eat larger meals, eat more often, or increase the amount of carbohydrate in your meals. Too much carbohydrate intake.
• Be sure to discuss all your medicines with your healthcare provider. Medicines that affect insulin. Do not start any new medicines until you know how they may affect your insulin dose.
• These medical conditions include fevers, infections, heart attacks, and stress. Medical conditions that affect insulin.
• Injecting insulin the wrong way or in the wrong injection area.

Testing your blood or urine often will let you know if you have hyperglycemia. If your tests are often high, tell your healthcare provider so your dose of insulin can be changed.

Hyperglycemia can be mild or severe. It can progress to diabetic ketoacidosis (DKA) or very high glucose levels (hyperosmolar coma) and result in unconsciousness and death.

Although diabetic ketoacidosis occurs most often in patients with type 1 diabetes,it can also happen in patients with type 2 diabetes who become very sick. Because some patients get few symptoms of hyperglycemia, it is important to check your blood sugar/urine sugar and ketones regularly.

Symptoms of hyperglycemia include:

• confusion or drowsiness
• increased thirst
• decreased appetite, nausea, or vomiting
• rapid heart rate
• increased urination and dehydration (too little fluid in your body).

Symptoms of DKA also include:

• fruity smelling breath
• fast, deep breathing
• stomach area (abdominal) pain.

Severe or continuing hyperglycemia or DKA needs evaluation and treatment right away by your healthcare provider.

Do not use LANTUS to treat diabetic ketoacidosis.

Other possible side effects of LANTUS include:

Serious allergic reactions:

Some times severe, life-threatening allergic reactions can happen with insulin. If you think you are having a severe allergic reaction, get medical help right away. Signs of insulin allergy include:

• rash all over your body
• shortness of breath
• wheezing (trouble breathing)
• fast pulse
• sweating
• low blood pressure.

Reactions at the injection site:

Injecting insulin can cause the following reactions on the skin at the injection site:

• little depression in the skin (lipoatrophy)
• skin thickening (lipohypertrophy)
• red, swelling, itchy skin (injection site reaction).

You can reduce the chance of getting an injection site reaction if you change (rotate) the injection site each time. An injection site reaction should clear up in a few days or a few weeks. If injection site reactions do not go away or keep happening call your healthcare provider.

Swelling of your hands and feet (edema)

Weight gain

Taking certain diabetes pills called thiazolidinediones or "TZDs" with Lantus may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure it may get worse while you take TZDs with Lantus. Your healthcare provider should monitor you closely while you are taking TZDs with Lantus. Tell your healthcare provider if you have any new or worse symptoms of heart failure including: Heart Failure.

• shortness of breath
• swelling of your ankles or feet
• sudden weight gain

During treatment with TZDs and Lantus, the TZD dose may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure.

Tell your healthcare provider if you have any side effects that bother you.

These are not all the side effects of LANTUS. Ask your healthcare provider or pharmacist for more information.

How should I store LANTUS?

• Unopened SoloStar:

  Store new unopened SoloStar disposable insulin pen in a refrigerator (not the freezer) between 36°F to 46°F (2°C to 8°C). Do not freeze LANTUS. Keep LANTUS out of direct heat and light. If a disposable insulin pen has been frozen or overheated, throw it away.

• Open (In-Use) SoloStar:

  Once SoloStar is opened (in-use), SoloStar should be refrigerated but should be kept at room temperature (below 86°F [30°C]) away from direct heat and light. The opened (in-use) SoloStar kept at room temperature must be discarded after 28 days. NOT

These storage conditions are summarized in the following table:

• Do not use SoloStar with LANTUS after the expiration date stamped on the label.
• Do not use LANTUS if it is cloudy, colored, or if you see particles.

General Information about LANTUS

• Use LANTUS only to treat your diabetes. give or share LANTUS with another person, even if they have diabetes also. It may harm them. Do not
• This leaflet summarizes the most important information about LANTUS. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about LANTUS that is written for healthcare professionals. For more information about LANTUS call 1-800-633-1610 or go to website www.lantus.com.

ADDITIONAL INFORMATION

is a national magazine designed especially for patients with diabetes and their families and is available by subscription from the American Diabetes Association (ADA), P.O. Box 363, Mt. Morris, IL 61054-0363, 1-800-DIABETES (1-800-342-2383). You may also visit the ADA website at www.diabetes.org. DIABETES FORECAST

Another publication, , is available from the Juvenile Diabetes Research Foundation International (JDRF), 120 Wall Street, 19th Floor, New York, New York 10005, 1-800-JDF-CURE (1-800-533-2873). You may also visit the JDRF website at www.jdf.org. COUNTDOWN

To get more information about diabetes, check with your healthcare professional or diabetes educator or visit www.DiabetesWatch.com.

Additional information about LANTUS can be obtained by calling 1-800-633-1610 or by visiting www.lantus.com.

Rev. December 2013

sanofi-aventis U.S. LLC Bridgewater, NJ 08807 A SANOFI COMPANY

©2013 sanofi-aventis U.S. LLC

Lantus and SoloStar are a registered trademark of sanofi-aventis U.S. LLC The brands listed are the trademarks of their respective owners and are not trademarks of sanofi-aventis U.S. LLC ^{® ®
†}

LANTUS SOLOSTAR (insulin glargine [rDNA origin] injection) ^{® ®}

Instruction Leaflet

Your healthcare professional has decided that SoloStar is right for you. Talk with your healthcare professional about proper injection technique before using SoloStar. ^®

Read these instructions carefully before using your SoloStar. If you are not able to follow all the instructions completely on your own, use SoloStar only if you have help from a person who is able to follow the instructions.

Follow these instructions completely each time you use SoloStar to ensure that you get an accurate dose. If you do not follow these instructions you may get too much or too little insulin, which may affect your blood glucose.

SoloStar is a disposable pen for the injection of insulin. Each SoloStar contains in total 300 units of insulin. You can set doses from 1 to 80 units in steps of 1 unit. The pen plunger moves with each dose. The plunger will only move to the end of the cartridge when 300 units of insulin have been given.

Keep this leaflet for future reference.

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

Figure

Important information for use of SoloStar:

• Always attach a new needle before each use.

  BD Ultra-Fine needles are compatible with SoloStar. These are sold separately and are manufactured by BD. Contact your healthcare professional for further information. ^{® 10}

• Always perform the safety test before each injection.
• Do not select a dose or press the injection button without a needle attached.
• This pen is only for your use. Do not share it with anyone else.
• If your injection is given by another person, special caution must be taken by this person to avoid accidental needle injury and transmission of infection.
• Never use SoloStar if it is damaged or if you are not sure that it is working properly.
• Always have a spare SoloStar in case your SoloStar is lost or damaged.

Step 1. Check the insulin

• A.Check the label on your SoloStar to make sure you have the correct insulin. The Lantus SoloStar is grey with a purple injection button. ^{® ®}
• B.Take off the pen cap.
• C.Check the appearance of your insulin. Lantus is a clear insulin. Do not use this SoloStar if the insulin is cloudy, colored or has particles.

Step 2. Attach the needle

Always use a new sterile needle for each injection. This helps prevent contamination, and potential needle blocks.

• A.Wipe the Rubber Seal with alcohol.

• B.Remove the protective seal from a new needle.
• C.Line up the needle with the pen, and keep it straight as you attach it (screw or push on, depending on the needle type).

  Figure

• If the needle is not kept straight while you attach it, it can damage the rubber seal and cause leakage, or break the needle.

  Figure

Step 3. Perform a Safety test

Performing the safety test ensures that you get an accurate dose by: perform the safety test before each injection. Always

• ensuring that pen and needle work properly
• removing air bubbles

• A.Select a dose of 2 units by turning the dosage selector.

  Figure

• B.Take off the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and discard it.

  Figure

• C.Hold the pen with the needle pointing upwards.
• D.Tap the insulin reservoir so that any air bubbles rise up towards the needle.
• E.Press the injection button all the way in. Check if insulin comes out of the needle tip.

  Figure

You may have to perform the safety test several times before insulin is seen.

• If no insulin comes out, check for air bubbles and repeat the safety test two more times to remove them.
• If still no insulin comes out, the needle may be blocked. Change the needle and try again.
• If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use this SoloStar.

Step 4. Select the dose

You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you need a dose greater than 80 units, you should give it as two or more injections.

• A.Check that the dose window shows "0" following the safety test.
• B.Select your required dose (in the below, the selected dose is 30 units). If you turn past your dose, you can turn back down. example

  Figure

• Do not push the injection button while turning, as insulin will come out.
• You cannot turn the dosage selector past the number of units left in the pen. Do not force the dosage selector to turn. In this case, either you can inject what is remaining in the pen and complete your dose with a new SoloStar or use a new SoloStar for your full dose.

Step 5. Inject the dose

• A.Use the injection method as instructed by your healthcare professional.
• B.Insert the needle into the skin.

  Figure

• C.Deliver the dose by pressing the injection button in all the way. The number in the dose window will return to "0" as you inject.

  Figure

• D.Keep the injection button pressed all the way in. This ensures that the full dose will be delivered. Slowly count to 10 before you withdraw the needle from the skin.

Step 6. Remove and discard the needle

Always remove the needle after each injection and store SoloStar without a needle attached. This helps prevent:

• Contamination and/or infection
• Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing.

• A.Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never replace the inner needle cap.
  • If your injection is given by another person, special caution must be taken by this person when removing and disposing the needle. Follow recommended safety measures for removal and disposal of needles (e.g. a one handed capping technique) in order to reduce the risk of accidental needle injury and transmission of infectious diseases.
• B.Dispose of the needle safely. Used needles should be placed in sharps containers (such as red biohazard containers), hard plastic containers (such as detergent bottles), or metal containers (such as an empty coffee can). Such containers should be sealed and disposed of properly. If you are giving an injection to a third person, you should remove the needle in an approved manner to avoid needle-stick injuries.
  
• C.Always put the pen cap back on the pen, then store the pen until your next injection.

Storage Instructions

Please check the leaflet for the insulin for complete instructions on how to store SoloStar.

If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up. Cold insulin is more painful to inject.

Keep SoloStar out of the reach and sight of children.

Keep your SoloStar in cool storage (36°F - 46°F [2°C – 8°C]) until first use. Do not allow it to freeze. Do not put it next to the freezer compartment of your refrigerator, or next to a freezer pack.

Once you take your SoloStar out of cool storage, for use or as a spare, you can use it for up to 28 days. During this time it can be safely kept at room temperature up to 86°F (30°C). Do not use it after this time.

Do not use SoloStar after the expiration date printed on the label of the pen or on the carton.

Protect SoloStar from light.

Discard your used SoloStar as required by your local authorities.

Maintenance

Protect your SoloStar from dust and dirt.

You can clean the outside of your SoloStar by wiping it with a damp cloth.

Do not soak, wash or lubricate the pen as this may damage it.

Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid situations where SoloStar might be damaged. If you are concerned that your SoloStar may be damaged, use a new one.

SoloStar in use must not be stored in a refrigerator.

sanofi-aventis U.S. LLC Bridgewater, NJ 08807 A SANOFI COMPANY

November 2013 Date of revision:

©2013 sanofi-aventis U.S. LLC