Lantus Solostar

Lantus Solostar uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Lantus Solostar reviews

1. INDICATIONS AND USAGE

Lantus Solostar is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.

Lantus Solostar is a long-acting human insulin analog indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. (1)

Limitations of Use:

• Not recommended for treating diabetic ketoacidosis. (1)

Limitations of Use

Lantus Solostar is not recommended for the treatment of diabetic ketoacidosis.

2. DOSAGE AND ADMINISTRATION

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

2.1 Important Administration Instructions

• Administer Lantus Solostar subcutaneously once daily at any time of day but at the same time every day.
• Prior to initiation of Lantus Solostar, train patients on proper use and injection technique.
• Patient should follow the Instructions for Use to correctly administer Lantus Solostar.
• Administer Lantus Solostar 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 .
• Visually inspect Lantus Solostar vials and SoloStar prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles.
• Refrigerate unused (unopened) Lantus Solostar vials and SoloStar^® prefilled pens.
• Do not administer intravenously or via an insulin pump.
• Do not dilute or mix Lantus Solostar with any other insulin or solution.
• The SoloStar prefilled pen is for single patient use only .

2.2 General Dosing Instructions

• Individualize and adjust the dosage of Lantus Solostar 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, during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring .

2.3 Initiation of Lantus Solostar Therapy

Type 1 Diabetes:

• In patients with type 1 diabetes, Lantus Solostar must be used concomitantly with short-acting insulin. The recommended starting dose of Lantus Solostar 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.

Type 2 Diabetes:

• The recommended starting dose of Lantus Solostar in patients with type 2 diabetes who are not currently treated with insulin is 0.2 units/kg or up to 10 units once daily. One may need to adjust the amount and timing of short- or rapid-acting insulins and dosages of any oral anti-diabetic drugs.

2.4 Changing to Lantus Solostar from Other Insulin Therapies

• If changing patients from once daily TOUJEO (insulin glargine) 300 Units/mL to once daily Lantus Solostar, the recommended initial Lantus Solostar dose is 80% of the TOUJEO dose that is being discontinued. This dose reduction will lower the likelihood of hypoglycemia .
• If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with Lantus Solostar, a change in the dose of the basal insulin may be required and the amount and timing of the shorter-acting insulins and doses of any oral anti-diabetic drugs may be needed to be adjusted.
• If changing patients from once-daily NPH insulin to once-daily Lantus Solostar, the recommended initial Lantus Solostar dose is the same as the dose of NPH that is being discontinued.
• If changing patients from twice-daily NPH insulin to once-daily Lantus Solostar, the recommended initial Lantus Solostar dosage is 80% of the total NPH dose that is being discontinued. This dosage reduction will lower the likelihood of hypoglycemia .

3. DOSAGE FORMS AND STRENGTHS

Injection: 100 units per mL of Lantus Solostar. Lantus Solostar is available as:

• 10 mL vial
• 3 mL SoloStar prefilled pen

Injection: 100 units/mL Lantus Solostar is available as:

• 10 mL vials (3)
• 3 mL SoloStar prefilled pen (3)

4. CONTRAINDICATIONS

Lantus Solostar is contraindicated

• During episodes of hypoglycemia .
• In patients with hypersensitivity to Lantus Solostar or one of its excipients .

• During episodes of hypoglycemia (4)
• Hypersensitivity to Lantus Solostar or one of its excipients (4)

5. WARNINGS AND PRECAUTIONS

• Never share a Lantus Solostar SoloStar prefilled pen between patients, even if the needle is changed
• Hyper- or hypoglycemia with changes in insulin regimen: Carry out under close medical supervision (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)
• Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. (5.4, 6.3)
• Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Lantus Solostar. Monitor and treat if indicated (5.5, 6.1)
• Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. (5.6)
• Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation of TZD if heart failure occurs (5.7)

5.1 Never Share a Lantus Solostar SoloStar Prefilled Pen, Syringe, or Needle between Patients

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

5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage adjustments of concomitant oral and anti-diabetic products may be needed.

5.3 Hypoglycemia

Hypoglycemia is the most common adverse reaction associated with insulin, including Lantus Solostar. 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).

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) , or in patients who experience recurrent hypoglycemia.

Risk Factors for Hypoglycemia

The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin preparations, the glucose lowering effect time course of Lantus Solostar may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature . Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia .

Risk Mitigation Strategies for Hypoglycemia

Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.

The long-acting effect of Lantus Solostar may delay recovery from hypoglycemia.

5.4 Medication Errors

Accidental mix-ups among insulin products, particularly between long-acting insulins and rapid-acting insulins, have been reported. To avoid medication errors between Lantus Solostar and other insulins, instruct patients to always check the insulin label before each injection .

5.5 Hypersensitivity and Allergic Reactions

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

5.6 Hypokalemia

All insulin products, including Lantus Solostar, 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.

5.7 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists

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 Solostar, 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.

6. ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere:

• Hypoglycemia
• Hypersensitivity and allergic reactions
• Hypokalemia .

Adverse reactions commonly associated with Lantus Solostar include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema and weight gain. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact sanofi- aventis at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trial Experience

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

The data in Table 1 reflect the exposure of 2327 patients with type 1 diabetes to Lantus Solostar or NPH. The type 1 diabetes population had the following characteristics: Mean age was 38.5 years. Fifty four percent were male, 96.9% were Caucasian, 1.8 % were Black or African American and 2.7 % were Hispanic. The mean BMI was 25.1 kg/m².

The data in Table 2 reflect the exposure of 1563 patients with type 2 diabetes to Lantus Solostar or NPH. The type 2 diabetes population had the following characteristics: Mean age was 59.3 years. Fifty eight percent were male, 86.7% were Caucasian, 7.8 % were Black or African American and 9 % were Hispanic. The mean BMI was 29.2 kg/m².

The frequencies of adverse events during Lantus Solostar clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

Severe Hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Lantus Solostar . Tables 5, and 6 and 7 summarize the incidence of severe hypoglycemia in the Lantus Solostar individual clinical trials. Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dL (≤56 mg/dL in the 5-year trial and ≤36 mg/dL in the ORIGIN trial) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.

Percentages of LANTUS-treated adult patients experiencing severe symptomatic hypoglycemia in the Lantus Solostar clinical trials were comparable to percentages of NPH-treated patients for all treatment regimens. In the pediatric phase 3 clinical trial, children and adolescents with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to the adult trials with type 1 diabetes.

Table 7 displays the proportion of patients experiencing severe symptomatic hypoglycemia in the Lantus Solostar and Standard Care groups in the ORIGIN Trial .

Peripheral Edema

Some patients taking Lantus Solostar have experienced sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Lipodystrophy

Administration of insulin subcutaneously, including Lantus Solostar, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients .

Insulin initiation and intensification of glucose control

Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Weight gain

Weight gain has occurred with some insulin therapies including Lantus Solostar and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Allergic Reactions

Local Allergy

As with any insulin therapy, patients taking Lantus Solostar may experience injection site reactions, including redness, pain, itching, urticaria, edema, and inflammation. In clinical studies in adult patients, there was a higher incidence of treatment-emergent injection site pain in LANTUS-treated patients (2.7%) compared to NPH insulin-treated patients (0.7%). The reports of pain at the injection site did not result in discontinuation of therapy.

Systemic Allergy

Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including Lantus Solostar and may be life threatening.

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. All insulin products can elicit the formation of insulin antibodies. The presence of such insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In phase 3 clinical trials of Lantus Solostar, increases in titers of antibodies to insulin were observed in NPH insulin and Lantus Solostar treatment groups with similar incidences.

6.3 Postmarketing Experience

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

Medication errors have been reported in which other insulins, particularly rapid-acting insulins, have been accidentally administered instead of Lantus Solostar . To avoid medication errors between Lantus Solostar and other insulins, patients should be instructed to always verify the insulin label before each injection.

7. DRUG INTERACTIONS

Table 8 includes clinically significant drug interactions with Lantus Solostar.

• Drugs that affect glucose metabolism: Adjustment of insulin dosage may be needed; closely monitor of blood glucose. (7)
• Anti-Adrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent. (7)

8. USE IN SPECIFIC POPULATIONS

• Use during pregnancy only if the potential benefit justifies the potential risk to the fetus

8.1 Pregnancy

There are no well-controlled clinical studies of the use of Lantus Solostar in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes, insulin requirements may decrease during the first trimester, generally increase during the second trimester, and rapidly decline after delivery. Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking Lantus Solostar.

Subcutaneous reproduction and teratology studies have been performed with Lantus Solostar and regular human insulin in rats and Himalayan rabbits. Lantus Solostar was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 7 times the recommended human subcutaneous starting dose of 10 Units/day (0.008 mg/kg/day), based on mg/m². In rabbits, doses of 0.072 mg/kg/day, which is approximately 2 times the recommended human subcutaneous starting dose of 10 Units/day (0.008 mg/kg/day), based on mg/m², were administered during organogenesis. The effects of Lantus Solostar did not generally differ from those observed with regular human insulin in rats or rabbits. However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal.

8.3 Nursing Mothers

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

8.4 Pediatric Use

The safety and effectiveness of Lantus Solostar have been established in pediatric patients with type 1 diabetes . The safety and effectiveness of Lantus Solostar in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes have not been established.

The dosage recommendation when changing to Lantus Solostar in pediatric patients (age 6 to 15 years) with type 1 diabetes is the same as that described for adults [see Dosage and Administration (2.2, 2.4) and Clinical Studies (14)]. As in adults, the dosage of Lantus Solostar must be individualized in pediatric patients (age 6 to 15 years) with type 1 diabetes based on metabolic needs and frequent monitoring of blood glucose.

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 .

8.5 Geriatric Use

Of the total number of subjects in controlled clinical studies of patients with type 1 and type 2 diabetes, who were treated with Lantus Solostar, 15% were ≥65 years of age and 2% 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 the Lantus Solostar and NPH treatment groups.

Nevertheless, caution should be exercised when Lantus Solostar 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.

8.6 Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of Lantus Solostar has not been studied. Frequent glucose monitoring and dose adjustment may be necessary for Lantus Solostar in patients with hepatic impairment .

8.7 Renal Impairment

The effect of renal impairment on the pharmacokinetics of Lantus Solostar 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 Lantus Solostar in patients with renal impairment .

8.8 Obesity

In controlled clinical trials, subgroup analyses based on BMI did not show differences in safety and efficacy between Lantus Solostar and NPH.

10. OVERDOSAGE

Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. Adjustments in drug dosage, meal patterns, or exercise may be needed.

More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia. Hypokalemia must be corrected appropriately.

11. DESCRIPTION

Lantus Solostar (insulin glargine injection) is a sterile solution of Lantus Solostar for subcutaneous use. Lantus Solostar is a recombinant human insulin analog that is a long-acting, parenteral blood-glucose-lowering agent . Lantus Solostar has low aqueous solubility at neutral pH. At pH 4 Lantus Solostar is completely soluble. After injection into the subcutaneous tissue, the acidic solution is neutralized, leading to formation of microprecipitates from which small amounts of Lantus Solostar 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. Lantus Solostar is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Lantus Solostar 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, Lantus Solostar is 21^A-Gly-30^Ba-L-Arg-30^Bb-L-Arg-human insulin and has the empirical formula C₂₆₇H₄₀₄N₇₂O₇₈S₆ and a molecular weight of 6063. Lantus Solostar has the following structural formula:

Lantus Solostar consists of Lantus Solostar dissolved in a clear aqueous fluid. Each milliliter of Lantus Solostar (insulin glargine injection) contains 100 Units (3.6378 mg) Lantus Solostar.

The 10 mL vial presentation contains the following inactive ingredients per mL: 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, 20 mcg polysorbate 20, and water for injection.

The 3 mL prefilled pen presentation contains the following inactive ingredients per mL: 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, and water for injection.

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

Chemical Structure

12. CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The primary activity of insulin, including Lantus Solostar, 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.

12.2 Pharmacodynamics

In clinical studies, the glucose-lowering effect on a molar basis of intravenous Lantus Solostar is approximately the same as that for human insulin. Figure 1 shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after 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 Lantus Solostar.

The duration of action after abdominal, deltoid, or thigh subcutaneous administration was similar. The time course of action of insulins, including Lantus Solostar, may vary between individuals and within the same individual.

Figure

12.3 Pharmacokinetics

Absorption and Bioavailability

After subcutaneous injection of Lantus Solostar in healthy subjects and in patients with diabetes, the insulin serum concentrations indicated a slower, more prolonged absorption and a relatively constant concentration/time profile over 24 hours with no pronounced peak in comparison to NPH insulin.

Metabolism and Elimination

A metabolism study in humans indicates that Lantus Solostar is partly metabolized at the carboxyl terminus of the B chain in the subcutaneous depot to form two active metabolites with in vitro activity similar to that of human insulin, M1 (21^A-Gly-insulin) and M2 (21^A-Gly-des-30^B-Thr-insulin). Unchanged drug and these degradation products are also present in the circulation.

Special Populations

Age, Race, and Gender. Effect of age, race, and gender on the pharmacokinetics of Lantus Solostar has not been evaluated. However, in controlled clinical trials in adults (n=3890) and a controlled clinical trial in pediatric patients (n=349), subgroup analyses based on age, race, and gender did not show differences in safety and efficacy between Lantus Solostar and NPH insulin .

Obesity. Effect of Body Mass Index (BMI) on the pharmacokinetics of Lantus Solostar has not been evaluated.

13. NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In mice and rats, standard two-year carcinogenicity studies with Lantus Solostar 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.

Lantus Solostar 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/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.

14. Clinical STUDIES

14.1 Overview of Clinical Studies

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

14.2 Clinical Studies in Adult and Pediatric Patients with Type 1 Diabetes

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 Solostar or NPH insulin. Regular human insulin was administered before each meal. Lantus Solostar was administered at bedtime. NPH insulin was administered either as 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 White (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 White (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 Lantus Solostar or NPH insulin. Insulin lispro was used before each meal. Lantus Solostar 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 White (96.9%) and 50.6% were male. The mean BMI was approximately 25.6 kg/m^2. The mean duration of diabetes was 18.5 years.

In these 3 studies, Lantus Solostar and NPH insulin had similar effects on HbA1c (Table 9) with a similar overall rate of severe symptomatic hypoglycemia .

Type 1 Diabetes – Pediatric.

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 Solostar was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was 11.7 years. The majority of patients were White (96.8%) and 51.9% were male. The mean BMI was approximately 18.9 kg/m². The mean duration of diabetes was 4.8 years. Similar effects on HbA1c (Table 10) were observed in both treatment groups .

14.3 Clinical Studies in Adults with Type 2 Diabetes

In a randomized, controlled clinical study (Study E) (n=570), Lantus Solostar was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs). The average age was 59.5 years. The majority of patients were White (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. Lantus Solostar administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 11). The rate of severe symptomatic hypoglycemia was similar in Lantus Solostar and NPH insulin treated patients .

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 Solostar 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 White (80.7%) and 60% were male. The mean BMI was approximately 30.5 kg/m². The mean duration of diabetes was 13.7 years. Lantus Solostar had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 11) with a similar incidence of hypoglycemia .

In a randomized, controlled clinical study (Study G), patients with type 2 diabetes were randomized to 5 years of treatment with once-daily Lantus Solostar or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dose of Lantus Solostar 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 Solostar 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 Solostar and NPH insulin doses to a target fasting plasma glucose ≤100 mg/dL. After the Lantus Solostar 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 White (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. The Lantus Solostar 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 Solostar group (Table 11). The incidences of severe symptomatic hypoglycemia were similar between groups .

Lantus Solostar Timing of Daily Dosing.

The safety and efficacy of Lantus Solostar 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. The average age was 40.9 years. All patients were White (100%) and 53.7% were male. The mean BMI was approximately 25.3 kg/m². The mean duration of diabetes was 17.3 years. Lantus Solostar administered at different times of the day resulted in similar reductions in HbA1c compared to that with bedtime administration. 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 Solostar regardless of time of administration.

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 Solostar 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. The average age was 60.8 years. The majority of patients were White (96.6%) and 53.7% were male. The mean BMI was approximately 28.7 kg/m². The mean duration of diabetes was 10.1 years. Lantus Solostar given before breakfast was at least as effective in lowering HbA1c as Lantus Solostar given at bedtime or NPH insulin given at bedtime.

Five-year Trial Evaluating the Progression of Retinopathy

Retinopathy was evaluated in the Lantus Solostar clinical studies by analysis of reported retinal adverse events and fundus photography. The numbers of retinal adverse events reported for Lantus Solostar and NPH insulin treatment groups were similar for patients with type 1 and type 2 diabetes.

Lantus Solostar was compared to NPH insulin in a 5-year randomized clinical trial that evaluated the progression of retinopathy as assessed with fundus photography using a grading protocol derived from the Early Treatment Diabetic Retinopathy Scale (ETDRS). Patients had type 2 diabetes (mean age 55 yrs) with no (86%) or mild (14%) retinopathy at baseline. Mean baseline HbA1c was 8.4%. The primary outcome was progression by 3 or more steps on the ETDRS scale at study endpoint. Patients with pre-specified post-baseline eye procedures (pan-retinal photocoagulation for proliferative or severe nonproliferative diabetic retinopathy, local photocoagulation for new vessels, and vitrectomy for diabetic retinopathy) were also considered as 3-step progressors regardless of actual change in ETDRS score from baseline. Retinopathy graders were blinded to treatment group assignment. The results for the primary endpoint are shown in Table 13 for both the per-protocol and Intent-to-Treat populations, and indicate similarity of Lantus Solostar to NPH in the progression of diabetic retinopathy as assessed by this outcome.

The Origin Study

The Outcome Reduction with Initial Glargine Intervention trial (i.e., ORIGIN) was an open-label, randomized, 2-by-2, factorial design study. One intervention in ORIGIN compared the effect of Lantus Solostar to standard care on major adverse cardiovascular outcomes in 12,537 participants ≥ 50 years of age with abnormal glucose levels [i.e., impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)] or early type 2 diabetes mellitus and established cardiovascular (i.e., CV) disease or CV risk factors at baseline.

The objective of the trial was to demonstrate that Lantus Solostar use could significantly lower the risk of major cardiovascular outcomes compared to standard care. Two co-primary composite cardiovascular endpoints were used in ORIGIN. The first co-primary endpoint was the time to first occurrence of a major adverse cardiovascular event defined as the composite of CV death, nonfatal myocardial infarction and nonfatal stroke. The second co-primary endpoint was the time to the first occurrence of CV death or nonfatal myocardial infarction or nonfatal stroke or revascularization procedure or hospitalization for heart failure.

Participants were randomized to either Lantus Solostar (N=6264) titrated to a goal fasting plasma glucose of ≤ 95 mg/dL or to standard care (N=6273). Anthropometric and disease characteristics were balanced at baseline. The mean age was 64 years and 8% of participants were 75 years of age or older. The majority of participants were male (65%). Fifty nine percent were Caucasian, 25% were Latin, 10% were Asian and 3% were Black. The median baseline BMI was 29 kg/m². Approximately 12% of participants had abnormal glucose levels (IGT and/or IFG) at baseline and 88% had type 2 diabetes. For patients with type 2 diabetes, 59% were treated with a single oral antidiabetic drug, 23% had known diabetes but were on no antidiabetic drug and 6% were newly diagnosed during the screening procedure. The mean HbA1c (SD) at baseline was 6.5% (1.0). Fifty nine percent of participants had had a prior cardiovascular event and 39% had documented coronary artery disease or other cardiovascular risk factors.

Vital status was available for 99.9% and 99.8% of participants randomized to Lantus Solostar and standard care respectively at end of trial. The median duration of follow-up was 6.2 years [range: 8 days to 7.9 years]. The mean HbA1c (SD) at the end of the trial was 6.5% (1.1) and 6.8% (1.2) in the Lantus Solostar and standard care group respectively. The median dose of Lantus Solostar at end of trial was 0.45 U/kg. Eighty-one percent of patients randomized to Lantus Solostar were using Lantus Solostar at end of the study. The mean change in body weight from baseline to the last treatment visit was 2.2 kg greater in the Lantus Solostar group than in the standard care group.

Overall, the incidence of major adverse cardiovascular outcomes was similar between groups. All-cause mortality was also similar between groups.

In the ORIGIN trial, the overall incidence of cancer (all types combined) or death from cancer (Table 15) was similar between treatment groups.

16. HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Lantus Solostar is supplied as a solution containing 100 units per mL (U-100) of Lantus Solostar and is available in:

Needles are not included in the packs.

BD Ultra-Fine needlesThe brands listed are the registered trademarks of their respective owners and are not trademarks of sanofi-aventis U.S. LLC to be used in conjunction with SoloStar are sold separately and are manufactured by BD.

16.2 Storage

Lantus Solostar should not be stored in the freezer and should not be allowed to freeze. Discard Lantus Solostar if it has been frozen. Protect Lantus Solostar from direct heat and light.

Storage conditions are summarized in the following table:

17. PATIENT COUNSELING INFORMATION

Advise the patient to read FDA-approved patient labeling (Patient Information and Instructions for Use).

Never Share a Lantus Solostar SoloStar Prefilled Pen or Syringe between Patients

Advise patients that they must never share a Lantus Solostar SoloStar prefilled pen with another person, even if the needle is changed. Advise patients using Lantus Solostar vials not to reuse or share needles or syringes with another person. Sharing carries a risk for transmission of blood-borne pathogens .

Hyperglycemia or Hypoglycemia

Inform patients that hypoglycemia is the most common adverse reaction with insulin. Inform patients of the symptoms of hypoglycemia. Inform patients 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. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery

Advise patients that changes in insulin regimen can predispose to hyper- or hypoglycemia.

Advise patients that changes in insulin regimen should be made under close medical supervision.

Medications Errors

Instruct patients to always check the insulin label before each injection..

Administration

Advise patients that Lantus Solostar must NOT be diluted or mixed with any other insulin or solution and that Lantus Solostar must only be used if the solution is clear and colorless with no particles visible.

Management of Hypoglycemia and handling of Special Situations

Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia.

Instruct patients 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.

Pregnancy

Advise patients to inform their health care professional if they are pregnant or are contemplating pregnancy.

Refer patients to the Lantus Solostar "Patient Information" for additional information 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.

FDA Approved Patient Labeling

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

©2015 sanofi-aventis U.S. LLC

Lantus Solostar, TOUJEO and SoloStar are registered trademarks of sanofi-aventis U.S. LLC.

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

Approved: July/2015

Instructions for Use

Lantus Solostar^® (LAN-tus)

(insulin glargine injection) for subcutaneous use

10 mL Vial (100 Units/mL, U-100)

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

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

Supplies needed to give your injection:

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

Preparing your Lantus Solostar dose:

• Wash your hands with soap and water or with alcohol.
• Check the Lantus Solostar label to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Check the insulin to make sure it is clear and colorless. Do not use Lantus Solostar if it is colored or cloudy, or if you see particles in the solution.
• Do not use Lantus Solostar after the expiration date stamped on the label or 28 days after you first use it.
• Always use a syringe that is marked for U-100 insulin. If you use a syringe other than a U-100 insulin syringe, you may get the wrong dose of insulin.
• Always use a new syringe or needle for each injection. Do not reuse or share your syringes or needles with other people. You may give other people a serious infection or get a serious infection from them.

Step 1:

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

Step 2:

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

Step 3:

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

Step 4:

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

Step 5:

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

Step 6:

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

Giving your Lantus Solostar injection:

• Inject your insulin exactly as your healthcare provider has shown you.
• Change (rotate) your injection site for each injection.

Step 7:

Choosing your injection site: Lantus Solostar is injected under the skin (subcutaneously) of your upper arm, thigh, or stomach area (abdomen). Wipe the skin with an alcohol swab to clean the injection site. Let the injection site dry before you inject your dose.

Step 8:

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

Step 9:

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

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

How should I store Lantus Solostar?

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

This Instructions for Use have been approved by the U.S. Food and Drug Administration. Revised: July/2015

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

Approved: July/2015

Lantus Solostar^® SOLOSTAR^®

(insulin glargine 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.

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

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.

Important information for use of SoloStar:

• Do not share your Lantus Solostar SoloStar pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.
• Do not reuse needles. Always attach a new needle before each use.
• 
  

  BD Ultra-Fine^® needlesThe brands listed are the registered trademarks of their respective owners and are not trademarks of sanofi-aventis U.S. LLC are compatible with SoloStar. These are sold separately and are manufactured by BD. Contact your healthcare professional for further information.
  

• Always perform the safety test before each injection.
• Do not select a dose or press the injection button without a needle attached.
• 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

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

Step 2. Attach the needle

Do not reuse needles. Always use a new sterile needle for each injection. This helps prevent contamination, and potential needle blocks.

• Wipe the Rubber Seal with alcohol.

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

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

Step 3. Perform a Safety test

Always perform the safety test before each injection.

Performing the safety test ensures that you get an accurate dose by:

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

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

• 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.
  

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

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.

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

• 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

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

• 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.
  

• Keep the injection button pressed all the way in.
  

  Slowly count to 10 before you withdraw the needle from the skin. This ensures that the full dose will be delivered.

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.

• 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.
• 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.

• 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.

SoloStar in use must not be stored in a refrigerator.

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.

sanofi-aventis U.S. LLC

Bridgewater, NJ 08807

A SANOFI COMPANY

Date of revision:

July 2015

©2015 sanofi-aventis U.S. LLC

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Lantus Solostar pharmaceutical active ingredients containing related brand and generic drugs:

• Insulin Glargine

Lantus Solostar available forms, composition, doses:

• Injectable; Injection; Insulin Glargine 100 IU / ml

Lantus Solostar destination | category:

• Human:
• Insulin preparations

Lantus Solostar Anatomical Therapeutic Chemical codes:

• A10AE04 - Insulin Glargine

Lantus Solostar pharmaceutical companies:

• DKSH
• Four Star
• IDS Group
• Sanofi-Aventis
• Zuellig Pharma

References

1. Dailymed."LANTUS (INSULIN GLARGINE) INJECTION, SOLUTION LANTUS SOLOSTAR (INSULIN GLARGINE) INJECTION, SOLUTION [SANOFI-AVENTIS U.S. LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. "Insulin glargine". https://pubchem.ncbi.nlm.nih.gov/su... (accessed August 28, 2018).
3. "Insulin Glargine - DrugBank". http://www.drugbank.ca/drugs/DB0004... (accessed August 28, 2018).

Frequently asked Questions

Depending on the reaction of the Lantus Solostar after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Lantus Solostar not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology