BASAGLAR KwikPen

1 INDICATIONS AND USAGE BASAGLAR ® is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. BASAGLAR ® 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 BASAGLAR 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. ( 2.2 , 2.3 , 2.4 ) Administer subcutaneously once daily at any time of day, but at the same time every day. ( 2.2 ) Rotate injection sites into the abdominal area, thigh, or deltoid to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 ) Closely monitor glucose when converting to BASAGLAR and during initial weeks thereafter. ( 2.2 ) Do not dilute or mix with any other insulin or solution. ( 2.1 ) 2.1 Important Administration Instructions Always check insulin labels before administration [see Warnings and Precautions ( 5.4 )] . Visually inspect BASAGLAR prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles. Administer BASAGLAR subcutaneously into the abdominal area, thigh, or deltoid, and rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6 )] . During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ( 5.2 )] . Use BASAGLAR with caution in patients with visual impairment that may rely on audible clicks to dial their dose. Do not dilute or mix BASAGLAR with any other insulin or solution. Do not administer intravenously or via an insulin pump. 2.2 General Dosing Instructions In patients with type 1 diabetes, BASAGLAR must be used concomitantly with short-acting insulin. Inject BASAGLAR subcutaneously once daily at any time of day but at the same time every day. Individualize and adjust the dosage of BASAGLAR based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring [see Warnings and Precautions ( 5.2 )] . The BASAGLAR prefilled pens each dials in 1 unit increments and delivers a maximum dose of 80 units per injection. 2.3 Initiation of BASAGLAR Therapy The recommended starting dose of BASAGLAR in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Short- or rapid-acting, pre-meal insulin should be used to satisfy the remainder of the daily insulin requirements. The recommended starting dose of BASAGLAR in patients with type 2 diabetes is 0.2 units/kg or up to 10 units once daily. 2.4 Changing to BASAGLAR from Other Insulin Therapies If changing patients from another insulin glargine product, 100 units/mL, to BASAGLAR, the dose of BASAGLAR should be the same as the other insulin glargine product, 100 units/mL. If changing patients from a once-daily insulin glargine product, 300 units/mL, to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the insulin glargine product, 300 units/mL [see Warnings and Precautions ( 5.2 )] . If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with BASAGLAR, a change in the dose of the basal insulin may be required. If changing patients from twice-daily NPH insulin to once-daily BASAGLAR, the recommended initial BASAGLAR dosage is 80% of the total daily NPH dosage [see Warnings and Precautions ( 5.2 )] .

5 WARNINGS AND PRECAUTIONS Never share a BASAGLAR prefilled pen between patients, even if the needle is changed. ( 5.1 ) Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. ( 5.2 ) Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with renal or hepatic impairment and hypoglycemia unawareness. ( 5.3 , 6.1 ) Hypoglycemia due to medication errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. ( 5.4 ) Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue BASAGLAR, monitor and treat if indicated. ( 5.5 , 6.1 ) Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. ( 5.6 ) Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. ( 5.7 ) 5.1 Never Share a BASAGLAR Prefilled Pen Between Patients BASAGLAR prefilled pens must never be shared between patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens. 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 an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ( 6 )] . Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulins, including BASAGLAR [see Adverse Reactions ( 6.1 )] . Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). BASAGLAR, or any insulin, should not be used during episodes of hypoglycemia [see Contraindications ( 4 )] . Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ( 7 )] , or in patients who experience recurrent hypoglycemia. 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 BASAGLAR may vary in different individuals or at different times in the same individual and depends on many conditions, inclu…

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

7 DRUG INTERACTIONS Table 6 includes clinically significant drug interactions with BASAGLAR Table 6: Clinically Significant Drug Interactions with BASAGLAR 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), and sulfonamide antibiotics. Intervention: Dose reductions and increased frequency of glucose monitoring may be required when BASAGLAR is co-administered with these drugs. Drugs That May Decrease the Blood Glucose Lowering Effect of BASAGLAR 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: Dose increases and increased frequency of glucose monitoring may be required when BASAGLAR is co-administered with these drugs. Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of BASAGLAR Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when BASAGLAR is co-administered 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 BASAGLAR is co-administered with these drugs. Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics ( 7 ). Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, 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 ( 7 ). Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine ( 7 ). Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine ( 7 ).

8.1 Pregnancy Risk Summary Published studies with use of insulin glargine products during pregnancy have not reported a clear association with insulin glargine products and adverse developmental outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). In animal reproduction studies, another insulin glargine product was administered to rats before, during and throughout pregnancy at doses up to 7 times the clinical dose of 10 units/day and to rabbits during organogenesis at doses approximately 2 times the clinical dose of 10 units/day. The effects of this other insulin glargine product did not generally differ from those observed with regular human insulin in rats or rabbits (see Data). The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, 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 products and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin glargine products are used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations including small sample size and some with no comparative group. Animal Data Subcutaneous reproduction and teratology studies have been performed with another insulin glargine product and with regular human insulin in rats and Himalayan rabbits. This other insulin glargine product was given to female rats before mating, during mating, and throughout pregnancy at dose 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/m 2 . 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/m 2 , were administered during organogenesis. The effects of this other insulin glargine product did not generally differ from those observed with regular human insulin in rats and 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.

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere: Hypoglycemia [see Warnings and Precautions ( 5.3 )] . Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )] . Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] . Hypokalemia [see Warnings and Precautions ( 5.6 )] . Adverse reactions commonly (≥5%) associated with insulin glargine products are: Hypoglycemia, allergic reactions, injection site reaction, lipodystrophy, pruritus, rash, edema, and weight gain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) 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 the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Two clinical trials with BASAGLAR were conducted: one in type 1 diabetes and one in type 2 diabetes. The type 1 diabetes population had the following characteristics: Mean age was 41 years and mean duration of diabetes was 16 years. 58% were male. 75% were Caucasian, 2% Black or African American and 4% American Indian or Alaskan native. 4% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m 2 . 73.5 percent of patients had eGFR>90 mL/min/1.73m 2 . The mean BMI was approximately 26 kg/m 2 . HbA 1c at baseline was 7.8%. The data in Table 1 reflect exposure of 268 patients to BASAGLAR with a mean exposure duration of 49 weeks. The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 11 years. 50% were male. 78% were Caucasian, 8% Black or African American and 5% American Indian or Alaskan native. 28% were Hispanic. At baseline, mean eGFR was 109 mL/min/1.73m 2 . 67.5 percent of patients had eGFR>90 mL/min/1.73m 2 . The mean BMI was approximately 32 kg/m 2 . HbA 1c at baseline was 8.3%. The data in Table 2 reflect exposure of 376 patients to BASAGLAR with a mean exposure duration of 22 weeks. Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Common adverse reactions during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2 , respectively. Table 1: Adverse reactions occurring in ≥5% of adult patients with type 1 diabetes treated with BASAGLAR in a 52-week trial a Infections other than nasopharyngitis or upper respiratory tract infection. BASAGLAR + Insulin Lispro, % (n=268) Infection a 24 Nasopharyngitis 16 Upper respiratory tract infection 8 Table 2: Adverse reactions occurring in ≥5% of adult patients with type 2 diabetes treated with BASAGLAR in a 24-week trial a Infections other than nasopharyngitis or upper respiratory tract infection. BASAGLAR + Oral Antidiabetic Medication, % (n=376) Infection a 17 Nasopharyngitis 6 Upper respiratory tract infection 5 The frequencies of adverse reactions during a clinical trial of 5 years duration with another insulin glargine product, 100 units/mL, in patients with type 2 diabetes mellitus are listed in Table 3 . Table 3: Common adverse reactions in 5-year trial of adult patients with type 2 diabetes (adverse reactions with incidence ≥10% and higher with another insulin glargine product, 100 units/mL, than comparator) Another Insulin Glargine Product, % (n=514) NPH, % (n=503) Hypertension 20 19 Sinusitis 19 18 Cataract 18 16 Bronchitis 15 14 Back pain 13 12 Cough 12 7 Urinary tract infection 11 10 Diarrhea 11 10 Depression 11 10 Headache 10 9 The frequencies of adverse reactions during clinical trials with another insulin glargine product, 100 units/mL, in children and adolescents with type 1 diabetes mellitus are listed in Table 4 . Table 4: Adverse reactions in a 28-week clinical trial of pediatric patients with type 1…