Lantus (Insulin glargine): Uses, Dosage, Side Effects & Warnings

Uses

1 INDICATIONS AND USAGE LANTUS is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. LANTUS is a long-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. ( 1 ) Limitations of Use Not recommended for the treatment of diabetic ketoacidosis. ( 1 ) Limitations of Use LANTUS is not recommended for the treatment of diabetic ketoacidosis.

Dosage and administration

Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, and prior insulin use. ( 2.2 ) Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time of day, but at the same time every day. ( 2.1 ) Do not dilute or mix with any other insulin or solution. ( 2.1 ) Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 ) See Full Prescribing Information for the recommended starting dosage in patients with type 2 diabetes ( 2.3 ) and how to change to LANTUS from other insulins ( 2.4 ) Closely monitor glucose when switching to LANTUS and during initial weeks thereafter. ( 2.4 ) 2.1 Important Administration Instructions Always check insulin labels before administration [see Warnings and Precautions (5.4) ] . Visually inspect LANTUS vials and SoloStar prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles. Administer LANTUS subcutaneously into the abdominal area, thigh, or deltoid, and rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) and Adverse Reactions (6) ] . During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2) ] . Do not administer intravenously or via an insulin pump. Do not dilute or mix LANTUS with any other insulin or solution. The LANTUS SoloStar prefilled pen dials in 1-unit increments. Use LANTUS SoloStar prefilled pen with caution in patients with visual impairment who may rely on audible clicks to dial their dose. 2.2 General Dosing Instructions Administer LANTUS subcutaneously once daily at any time of day but at the same time every day. Individualize and adjust the dosage of LANTUS based on the patient's metabolic needs, blood glucose monitoring results and glycemic control goal. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring [see Warnings and Precautions (5.2) ] . In patients with type 1 diabetes, LANTUS must be used concomitantly with short-acting insulin. 2.3 Initiation of LANTUS Therapy Recommended Starting Dosage in Patients with Type 1 Diabetes The recommended starting dosage of LANTUS in patients with type 1 diabetes is approximately one-third of the total daily insulin requirements. Use short-acting, premeal insulin to satisfy the remainder of the daily insulin requirements. Recommended Starting Dosage in Patients with Type 2 Diabetes The recommended starting dosage of LANTUS 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. 2.4 Switching to LANTUS from Other Insulin Therapies Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to LANTUS from other insulin therapies [see Warnings and Precautions (5.3) ]. When switching from: Once-daily TOUJEO (insulin glargine 300 units/mL) to once-daily LANTUS (100 units/mL), the recommended starting LANTUS dosage is 80% of the TOUJEO dosage that is being discontinued. Once-daily NPH insulin to once-daily LANTUS, the recommended starting LANTUS dosage is the same as the dosage of NPH that is being discontinued. Twice-daily NPH insulin to once-daily LANTUS, the recommended starting LANTUS dosage is 80% of the total NPH dosage that is being discontinued.

Dosage forms and strengths

Injection: 100 units/mL (U-100) a clear and colorless solution available as: 10 mL multiple-dose vial 3 mL single-patient-use LANTUS SoloStar prefilled pen Injection: 100 units/mL (U-100) available as: 10 mL multiple-dose vial ( 3 ) 3 mL single-patient-use SoloStar prefilled pen ( 3 )

Contraindications

4 CONTRAINDICATIONS LANTUS is contraindicated: During episodes of hypoglycemia [see Warnings and Precautions (5.3) ] In patients with hypersensitivity to insulin glargine or any of the excipients in LANTUS [see Warnings and Precautions (5.5) ] During episodes of hypoglycemia ( 4 ) Hypersensitivity to insulin glargine or any of the excipients in LANTUS ( 4 )

Warnings and precautions

Never share a LANTUS SoloStar prefilled pen, insulin syringe, or needle between patients, even if the needle is changed. ( 5.1 ) Hyperglycemia or hypoglycemia with changes in insulin regimen : Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. ( 5.2 ) Hypoglycemia : May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, concomitant drugs, meal pattern, physical activity; and in patients with renal or hepatic impairment and hypoglycemia unawareness. ( 5.3 ) Hypoglycemia due to medication errors : Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. ( 5.4 ) Hypersensitivity reactions : Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue LANTUS. Monitor and treat if indicated. ( 5.5 ) Hypokalemia : May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. ( 5.6 ) Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs) : Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation of TZD if heart failure occurs. ( 5.7 ) 5.1 Never Share a LANTUS SoloStar Prefilled Pen, Insulin Syringe, or Needle Between Patients LANTUS SoloStar prefilled pens must never be shared between patients, even if the needle is changed. Patients using LANTUS vials must never re-use or share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3) ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6) ] . Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant oral and antidiabetic products may be needed. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulins, including LANTUS. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly, and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7) ] , or who experience recurrent hypoglycemia. The long-acting effect of LANTUS may delay recovery from hypoglycemia. 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 insulins, the glucose lowering effect time course of LANTUS may vary in different patients or at different times in the same patient and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology (12.2) ] . 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 concomitant drugs [see Drug Interactions (7) ] . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6 , 8.7) ] . 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. 5.4 Hypoglycemia Due to Medication Errors Accidental mix-ups among insulin products have been reported. To avoid medication errors between LANTUS and other insulins, instruct patients to always check the insulin label before each injection [see Adverse Reactions (6.3) ] . 5.5 Hypersensitivity Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including LANTUS [see Adverse Reactions (6.1) ] . If hypersensitivity reactions occur, discontinue LANTUS; treat per standard of care and monitor until symptoms and signs resolve. LANTUS is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or one of the excipients. 5.6 Hypokalemia All insulins, including LANTUS, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death.

Side effects

The following adverse reactions are discussed elsewhere: Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen [see Warnings and Precautions (5.2) ] Hypoglycemia [see Warnings and Precautions (5.3) ] Hypoglycemia Due to Medication Errors [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Hypokalemia [see Warnings and Precautions (5.6) ] Adverse reactions commonly associated with LANTUS 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 Trials 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 2,327 patients with type 1 diabetes to LANTUS or NPH in Studies A, B, C, and D [see Clinical Studies (14.2) ] . The type 1 diabetes population had the following characteristics: the mean age was 39 years, 54% were male, and mean body mass index (BMI) was 25.1 kg/m 2 . Ninety-seven percent were White, 2% were Black or African American and less than 1% were Asian. Approximately 3% of the patients in studies B and C were Hispanic. The data in Table 2 reflect the exposure of 1,563 patients with type 2 diabetes to LANTUS or NPH in Studies E, F, and G [see Clinical Studies (14.3) ] . The type 2 diabetes population had the following characteristics: the mean age was 59 years, 58% were male, and mean BMI was 29.2 kg/m 2 . Eighty-seven percent were White, 8% were Black or African American and 3% were Asian. Approximately 9% of patients in Study F were Hispanic. The frequencies of adverse reactions during LANTUS clinical studies in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below (Tables 1, 2, 3, and 4). Table 1: Adverse Reactions Occurring ≥5% in Pooled Clinical Studies up to 28 Weeks Duration in Adults with Type 1 Diabetes LANTUS, % (n=1,257) NPH, % (n=1,070) Upper respiratory tract infection 22.4 23.1 Infection Body system not specified 9.4 10.3 Accidental injury 5.7 6.4 Headache 5.5 4.7 Table 2: Adverse Reactions Occurring ≥5% in Pooled Clinical Studies up to 1 Year Duration in Adults with Type 2 Diabetes LANTUS, % (n=849) NPH, % (n=714) Upper respiratory tract infection 11.4 13.3 Infection Body system not specified 10.4 11.6 Retinal vascular disorder 5.8 7.4 Table 3: Adverse Reactions Occurring ≥10% in a 5-Year Study of Adults with Type 2 Diabetes LANTUS, % (n=514) NPH, % (n=503) Upper respiratory tract infection 29.0 33.6 Edema peripheral 20.0 22.7 Hypertension 19.6 18.9 Influenza 18.7 19.5 Sinusitis 18.5 17.9 Cataract 18.1 15.9 Bronchitis 15.2 14.1 Arthralgia 14.2 16.1 Pain in extremity 13.0 13.1 Back pain 12.8 12.3 Cough 12.1 7.4 Urinary tract infection 10.7 10.1 Diarrhea 10.7 10.3 Depression 10.5 9.7 Headache 10.3 9.3 Table 4: Adverse Reactions Occurring ≥5% in a 28-Week Clinical Study in Pediatric Patients with Type 1 Diabetes LANTUS, % (n=174) NPH, % (n=175) Infection Body system not specified 13.8 17.7 Upper respiratory tract infection 13.8 16.0 Pharyngitis 7.5 8.6 Rhinitis 5.2 5.1 Severe Hypoglycemia Hypoglycemia was the most commonly observed adverse reaction in patients treated with LANTUS. Tables 5, 6, and 7 summarize the incidence of severe hypoglycemia in the LANTUS clinical studies. 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 study and ≤36 mg/dL in the ORIGIN study) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration. Percentages of LANTUS-treated adult patients who experienced severe symptomatic hypoglycemia in the LANTUS clinical studies [see Clinical Studies (14) ] were comparable to percentages of NPH-treated patients for all treatment regimens (see Tables 5 and 6 ). In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to the adult studies with type 1 diabetes. Table 5: Severe Symptomatic Hypoglycemia in Patients with Type 1 Diabetes Study A Type 1 Diabetes Adults 28 weeks In combination with regular insulin Study B Type 1 Diabetes Adults 28 weeks In combination with regular insulin Study C Type 1 Diabetes Adults 16 weeks In combination with insulin lispro Study D Type 1 Diabetes Pediatrics 26 weeks In combination with regular insulin LANTUS N=292 NPH N=293 LANTUS N=264 NPH N=270 LANTUS N=310 NPH N=309 LANTUS N=174 NPH N=175 Percent of patients 10.6 15.0 8.7 10.4 6.5 5.2 23.0 28.6 Table 6: Severe Symptomatic Hypoglycemia in Patients with Type 2 Diabetes Study E Type 2 Diabetes Adults 52 weeks In combination with oral agents Study F Type 2 Diabetes Adults 28 weeks In combination with regular insulin Study G Type 2 Diabetes Adults 5 years In combination with regular insulin LANTUS N=289 NPH N=281 LANTUS N=259 NPH N=259 LANTUS N=513 NPH N=504 Percent of patients 1.7 1.1 0.4 2.3 7.8 11.9 Table 7 displays the proportion of patients who experienced severe symptomatic hypoglycemia in the LANTUS and Standard Care groups in the ORIGIN study [see Clinical Studies (14) ] . Table 7: Severe Symptomatic Hypoglycemia in the ORIGIN Study ORIGIN Study Median duration of follow-up: 6.2 years LANTUS N=6231 Standard Care N=6273 Percent of patients 5.6 1.8 Peripheral Edema Some patients taking LANTUS have experienced sodium retention and edema, particularly if previously poor metabolic control was improved by intensified insulin therapy.

Drug interactions

Table 8 includes clinically significant drug interactions with LANTUS. Table 8: Clinically Significant Drug Interactions with LANTUS Drugs that May Increase the Risk of Hypoglycemia Drugs : Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), sulfonamide antibiotics. GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Intervention : Dosage reductions and increased frequency of glucose monitoring may be required when LANTUS is coadministered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of LANTUS Drugs : Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention : Dosage increases and increased frequency of glucose monitoring may be required when LANTUS is coadministered with these drugs. Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of LANTUS Drugs : Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention : Dosage adjustment and increased frequency of glucose monitoring may be required when LANTUS is coadministered with these drugs. Drugs that May Blunt Signs and Symptoms of Hypoglycemia Drugs : Beta-blockers, clonidine, guanethidine, and reserpine. Intervention : Increased frequency of glucose monitoring may be required when LANTUS is coadministered with these drugs. Drugs that Affect Glucose Metabolism : Adjustment of insulin dosage may be needed. ( 7 ) Antiadrenergic Drugs ( e.g., beta-blockers, clonidine, guanethidine, and reserpine ): Signs and symptoms of hypoglycemia may be reduced or absent. ( 7 )

Use in specific populations

8.1 Pregnancy Risk Summary Published studies with use of insulin glargine during pregnancy have not reported a clear association with insulin glargine and adverse developmental outcomes (see Data ) . There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . Rats and rabbits were exposed to insulin glargine in animal reproduction studies during organogenesis, respectively 50 times and 10 times the human subcutaneous dosage of 0.2 units/kg/day. Overall, the effects of insulin glargine did not generally differ from those observed with regular human insulin (see Data ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated background risk of major birth defects is 6% to 10% in women with pregestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20% to 25% in women with a peri-conceptional HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal and/or Embryo-fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data Published data do not report a clear association with insulin glargine and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin glargine is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations including small sample size and some lacking comparator groups. Animal Data Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. Insulin glargine was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 50 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day (0.007 mg/kg/day), on a mg/kg basis. In rabbits, doses of 0.072 mg/kg/day, which is approximately 10 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day on a mg/kg basis, were administered during organogenesis. The effects of insulin glargine 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. 8.2 Lactation Risk Summary There are either no or only limited data on the presence of insulin glargine in human milk, the effects on breastfed infant, or the effects on milk production. Endogenous insulin is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LANTUS, and any potential adverse effects on the breastfed child from LANTUS or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of LANTUS to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of LANTUS for this indication is supported by evidence from an adequate and well-controlled study (Study D) in 174 LANTUS-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of LANTUS in adults with diabetes mellitus [see Clinical Pharmacology (12.3) , Clinical Studies (14.2) ]. In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in studies with type 1 diabetes [see Adverse Reactions (6.1) ] . 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, 15% (n=316) were ≥65 years of age and 2% (n=42) were ≥75 years of age. No overall differences in safety or effectiveness of LANTUS have been observed between patients 65 years of age and older and younger adult patients. Nevertheless, caution should be exercised when LANTUS is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dosage increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in geriatric patients. 8.6 Renal Impairment The effect of kidney impairment on the pharmacokinetics of LANTUS has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with kidney failure. Frequent glucose monitoring and dosage adjustment may be necessary for LANTUS in patients with kidney impairment [see Warnings and Precautions (5.3) ]. 8.7 Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of LANTUS has not been studied. Frequent glucose monitoring and dosage adjustment may be necessary for LANTUS in patients with hepatic impairment [see Warnings and Precautions (5.3) ] .

Pregnancy

8.1 Pregnancy Risk Summary Published studies with use of insulin glargine during pregnancy have not reported a clear association with insulin glargine and adverse developmental outcomes (see Data ) . There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . Rats and rabbits were exposed to insulin glargine in animal reproduction studies during organogenesis, respectively 50 times and 10 times the human subcutaneous dosage of 0.2 units/kg/day. Overall, the effects of insulin glargine did not generally differ from those observed with regular human insulin (see Data ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated background risk of major birth defects is 6% to 10% in women with pregestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20% to 25% in women with a peri-conceptional HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal and/or Embryo-fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data Published data do not report a clear association with insulin glargine and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin glargine is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations including small sample size and some lacking comparator groups. Animal Data Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. Insulin glargine was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 50 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day (0.007 mg/kg/day), on a mg/kg basis. In rabbits, doses of 0.072 mg/kg/day, which is approximately 10 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day on a mg/kg basis, were administered during organogenesis. The effects of insulin glargine 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.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of LANTUS to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of LANTUS for this indication is supported by evidence from an adequate and well-controlled study (Study D) in 174 LANTUS-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of LANTUS in adults with diabetes mellitus [see Clinical Pharmacology (12.3) , Clinical Studies (14.2) ]. In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in studies with type 1 diabetes [see Adverse Reactions (6.1) ] .

Geriatric use

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, 15% (n=316) were ≥65 years of age and 2% (n=42) were ≥75 years of age. No overall differences in safety or effectiveness of LANTUS have been observed between patients 65 years of age and older and younger adult patients. Nevertheless, caution should be exercised when LANTUS is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dosage increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in geriatric patients.

Overdosage

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3 , 5.6) ] . Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. Lowering the insulin dosage, and adjustments in meal patterns or exercise may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with glucagon for emergency use or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia. Hypokalemia must be corrected appropriately.

Description

Insulin glargine is a long-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Insulin glargine has a molecular weight of 6063 Da. LANTUS (insulin glargine) injection is a sterile, clear and colorless solution for subcutaneous use in a 10 mL multiple-dose vial or a 3 mL single-patient use prefilled pen (LANTUS Solostar). Prefilled Pen (LANTUS Solostar) and Vial: Each mL contains 100 units of insulin glargine and the inactive ingredients: glycerol 85% (20 mg), m-cresol (2.7 mg), zinc (30 mcg), and Water for Injection, USP. The vial also contains polysorbate 20 (20 mcg). The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. LANTUS has a pH of approximately 4.

Mechanism of action

12.1 Mechanism of Action 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.

How supplied

16.1 How Supplied LANTUS (insulin glargine) injection is supplied as a clear and colorless solution containing 100 units/mL (U-100) available as follows: LANTUS NDC number Package size 10 mL Multiple-dose vial 0088-2220-33 1 vial per carton 3 mL SoloStar single-patient-use prefilled pen 0088-2219-05 5 pens per carton Additional Information about LANTUS Solostar: The LANTUS SoloStar prefilled pen dials in 1-unit increments. Needles are not included in the packs. Use BD Ultra-Fine ® needles ‡ with the SoloStar prefilled pens (these BD manufactured needles are sold separately). 16.2 Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Store unused LANTUS in a refrigerator between 36°F and 46°F (2°C and 8°C). Do not freeze. Discard LANTUS if it has been frozen. Protect LANTUS from direct heat and light. Storage conditions are summarized in the following table. Not in-use (unopened) Not in-use (unopened) In-use (opened) Refrigerated Room Temperature (36°F–46°F [2°C–8°C]) (up to 86°F [30°C]) (see temperature below) 10 mL multiple-dose vial Until expiration date 28 days 28 days Refrigerated or room temperature 3 mL single-patient-use SoloStar prefilled pen Until expiration date 28 days 28 days Room temperature only (Do not refrigerate)

Storage

16.2 Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Store unused LANTUS in a refrigerator between 36°F and 46°F (2°C and 8°C). Do not freeze. Discard LANTUS if it has been frozen. Protect LANTUS from direct heat and light. Storage conditions are summarized in the following table. Not in-use (unopened) Not in-use (unopened) In-use (opened) Refrigerated Room Temperature (36°F–46°F [2°C–8°C]) (up to 86°F [30°C]) (see temperature below) 10 mL multiple-dose vial Until expiration date 28 days 28 days Refrigerated or room temperature 3 mL single-patient-use SoloStar prefilled pen Until expiration date 28 days 28 days Room temperature only (Do not refrigerate)

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). There are separate Instructions for Use for the Vial and LANTUS SoloStar Pen. Never Share a LANTUS SoloStar Prefilled Pen or Insulin Syringe Between Patients Advise patients that they must never share a LANTUS SoloStar pen with another person, even if the needle is changed. Advise patients using LANTUS vials not to re-use or share needles or insulin syringes with another person. Sharing carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.1) ] . Hyperglycemia or Hypoglycemia Inform patients that hypoglycemia is the most common adverse reaction with insulin. Inform patients of the symptoms of hypoglycemia (e.g., impaired ability to concentrate and react). 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 [see Warnings and Precautions (5.3) ]. Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions (5.2) ] . Hypoglycemia Due to Medications Errors Instruct patients to always check the insulin label before each injection to reduce the risk of a medication error [see Warnings and Precautions (5.4) ] . Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with LANTUS. Inform patients about the symptoms of hypersensitivity reactions [see Warnings and Precautions (5.5) ].

Active ingredients

Insulin Glargine in 2 products

Lantus NDC products (2)

NDC	Strength & form	Labeler	Type
50090-0876	Insulin Glargine 100 [iU]/mL Injection, Solution	A-S Medication Solutions	BLA
0088-2220	Insulin Glargine 100 [iU]/mL Injection, Solution	sanofi-aventis U.S. LLC	BLA

Frequently asked questions

What is Lantus used for?

1 INDICATIONS AND USAGE LANTUS is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. LANTUS is a long-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. ( 1 ) Limitations of Use Not recommended for the treatment of diabetic ketoacidosis. ( 1 ) Limitations of Use LANTUS is not…

What are the side effects of Lantus?

The following adverse reactions are discussed elsewhere: Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen [see Warnings and Precautions (5.2) ] Hypoglycemia [see Warnings and Precautions (5.3) ] Hypoglycemia Due to Medication Errors [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Hypokalemia [see Warnings and Precautions (5.6) ]… See the full label for the complete list.

Who makes Lantus?

Lantus is listed by 2 labelers in the FDA NDC directory, including A-S Medication Solutions, sanofi-aventis U.S. LLC.