Insulin glargine U-300 Max

insulin glargine · Injection, Solution · Subcutaneous

Uses

Insulin Glargine, U-300 is indicated to improve glycemic control in adults and pediatric patients 6 years of age and older with diabetes mellitus. Insulin Glargine, U-300 is a long-acting human insulin analog indicated to improve glycemic control in adults and pediatric patients 6 years and older with diabetes mellitus. ( 1 ) Limitations of Use : Not recommended for the treatment of diabetic ketoacidosis. ( 1 ) Limitations of Use: Insulin Glargine, U-300 is not recommended for the treatment of diabetic ketoacidosis.

Dosage and administration

Individualize dose based on type of diabetes, metabolic needs, blood glucose monitoring results and glycemic control goal. ( 2.2 ) Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time during the day, at the same time every day. ( 2.1 ) Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 ) Do not dilute or mix with any other insulin or solution. ( 2.1 ) See Full Prescribing Information for the recommended starting dosage in patients with type 2 diabetes ( 2.3 ) and how to switch to Insulin Glargine, U-300 from other insulins ( 2.4 ) Closely monitor glucose when switching to Insulin Glargine, U-300 and during initial weeks thereafter. ( 2.4 ) 2.1 Important Administration Instructions Always check insulin labels before administration. This product is TOUJEO (insulin glargine). [see Warnings and Precautions (5.4) ] . Visually inspect the Insulin Glargine, U-300 solution for particulate matter and discoloration prior to administration and only use if the solution is clear and colorless with no visible particles. Inject Insulin Glargine, U-300 subcutaneously into the abdominal area, thigh, or deltoid. 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) , Adverse Reactions (6) ] . Use Insulin Glargine, U-300 with caution in patients with visual impairment who may rely on audible clicks to dial their dose. Do not administer Insulin Glargine, U-300 intravenously or in an insulin pump. Do not dilute or mix Insulin Glargine, U-300 with any other insulin products or solutions. Never transfer Insulin Glargine, U-300 from the cartridges of the Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar prefilled pen into a syringe for administration [see Warnings and Precautions (5.4) ] . 2.2 General Dosing Instructions Insulin Glargine, U-300 is available in 2 single-patient-use prefilled pens: The Insulin Glargine, U-300 SoloStar prefilled pen contains 450 units of insulin glargine. It delivers doses in 1-unit increments and can deliver up to 80 units in a single injection. The Insulin Glargine, U-300 Max SoloStar prefilled pen contains 900 units of insulin glargine. It delivers doses in 2-unit increments and can deliver up to 160 units in a single injection. It is recommended for patients requiring at least 20 units per day. When changing between Insulin Glargine, U-300 SoloStar and Insulin Glargine, U-300 Max SoloStar, if the patient's previous dose was an odd number, the dose should be increased or decreased by 1 unit to match the dose increments dialable on each prefilled pen. The dose counter of the Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar prefilled pen shows the number of units of Insulin Glargine, U-300 to be injected and no conversion is required. Inject Insulin Glargine, U-300 subcutaneously once a day at the same time of day. During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2) ] . Individualize and titrate the dosage of Insulin Glargine, U-300 based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal. Titrate the dose of Insulin Glargine, U-300 no more frequently than every 3 to 4 days. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness to minimize the risk of hypoglycemia or hyperglycemia [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6 , 8.7) ] . 2.3 Starting Dose in Insulin-Naive Pediatric and Adult Patients Recommended Starting Dosage in Patients with Type 1 Diabetes The recommended starting dose of Insulin Glargine, U-300 in insulin-naive patients with type 1 diabetes is approximately one-third to one-half of the total daily insulin dose. The remainder of the total daily insulin dose should be given as a short-acting insulin and divided between each daily meal. As a general rule, 0.2 to 0.4 units of insulin per kilogram of body weight can be used to calculate the initial total daily insulin dose in insulin-naive patients with type 1 diabetes. The maximum glucose lowering effect of a dose of Insulin Glargine, U-300 may take five days to fully manifest and the first dose may be insufficient to cover metabolic needs in the first 24 hours of use [see Clinical Pharmacology (12.2) ] . When initiating Insulin Glargine, U-300, monitor glucose daily. Recommended Starting Dosage in Patients with Type 2 Diabetes The recommended starting dose of Insulin Glargine, U-300 in insulin-naive patients with type 2 diabetes is 0.2 units per kilogram of body weight once daily. 2.4 Starting Dose in Pediatric and Adult Patients with Either Type 1 or Type 2 Diabetes Already on Insulin Therapy Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to Insulin Glargine, U-300 from another insulin therapy [see Warnings and Precautions (5.3) ]. For patients currently on once-daily long or intermediate-acting insulin, start Insulin Glargine, U-300 at the same unit dose as the once-daily long-acting insulin dose. For patients controlled on LANTUS (insulin glargine, 100 units/mL), expect that a higher daily dose of Insulin Glargine, U-300 will be needed to maintain the same level of glycemic control [see Clinical Pharmacology (12.2) and Clinical Studies (14.1) ] . For patients currently on twice-daily long or intermediate-acting insulin, start Insulin Glargine, U-300 at 80% of the total daily NPH or insulin detemir twice-daily dosage.

Dosage forms and strengths

Injection: 300 units/mL (U-300) of insulin glargine in a clear, colorless, solution available as: 1.5 mL SoloStar single-patient-use prefilled pen (450 units per 1.5 mL pen) 3 mL Max SoloStar single-patient-use prefilled pen (900 units per 3 mL pen) Injection: 300 units/mL (U-300) insulin glargine in: 1.5 mL SoloStar single-patient-use prefilled pen ( 3 ) 3 mL Max SoloStar single-patient-use prefilled pen ( 3 )

Contraindications

Insulin Glargine, U-300 is contraindicated: During episodes of hypoglycemia [see Warnings and Precautions (5.3) ] . In patients with hypersensitivity to insulin glargine or any excipients in Insulin Glargine, U-300 [see Warnings and Precautions (5.5) ] . During episodes of hypoglycemia ( 4 ) Hypersensitivity to insulin glargine or any excipients in Insulin Glargine, U-300 ( 4 )

Warnings and precautions

Never share an Insulin Glargine, U-300 SoloStar or Max SoloStar single-patient-use 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, concomitant drugs, meal pattern, physical activity, and in patients with renal impairment or hepatic impairment or 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 Insulin Glargine, U-300, 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 an Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar Pen Between Patients Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar single-patient-use prefilled pens must never be shared between patients, even if the needle is changed. Pen sharing poses a risk for transmission of blood-borne pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in Insulin Regimen Including Changes to Administration Site 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 antidiabetic products may be needed. Changing to Insulin Glargine, U-300 from other Insulin Therapies On a unit-to-unit basis, Insulin Glargine, U-300 has a lower glucose lowering effect than LANTUS [see Clinical Pharmacology (12.2) ] . In clinical trials, patients who changed to Insulin Glargine, U-300 from other basal insulins experienced higher average fasting plasma glucose levels in the first weeks of therapy compared to patients who were changed to LANTUS. Higher doses of Insulin Glargine, U-300 were required to achieve similar levels of glucose control compared to LANTUS in clinical trials [see Clinical Studies (14.1) ] . The onset of action of Insulin Glargine, U-300 develops over 6 hours following an injection. In type 1 diabetes patients treated with IV insulin, consider the longer onset of action of Insulin Glargine, U-300 before stopping IV insulin. The full glucose lowering effect may not be apparent for at least 5 days [see Dosage and Administration (2.2) and Clinical Pharmacology (12.2) ] . To minimize the risk of hyperglycemia when initiating Insulin Glargine, U-300 monitor glucose daily, titrate Insulin Glargine, U-300 as described in this prescribing information, and adjust coadministered glucose-lowering therapies per standard of care [see Dosage and Administration (2.2 , 2.3) ] . 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulin, including Insulin Glargine, U-300. 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, in patients 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 an Insulin Glargine, U-300 may delay recovery from hypoglycemia compared to shorter-acting insulins. Risk Factors for Hypoglycemia The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulation. As with all insulins, the glucose lowering effect time course of Insulin Glargine, U-300 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) ] .

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 Insulin Glargine, U-300 (≥5%) are: Hypoglycemia, allergic reactions, injection site reaction, lipodystrophy, pruritus, rash, edema, and weight gain. ( 6.1 , 6.2 ) 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 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 actually observed in clinical practice. The data in Table 1 reflect the exposure of 304 patients with type 1 diabetes to Insulin Glargine, U-300 with mean exposure duration of 23 weeks. The type 1 diabetes population had the following characteristics: Mean age was 46 years and mean duration of diabetes was 21 years. Fifty-five percent were male, 86% were White, 5% were Black or African American, and 5% were Hispanic or Latino. At baseline, the mean eGFR was 82 mL/min/1.73 m 2 and 35% of patients had eGFR ≥90 mL/min/1.73 m 2 . The mean body mass index (BMI) was 28 kg/m 2 . HbA1c at baseline was greater than or equal to 8% in 58% of patients. The data in Table 2 reflect the exposure of 1242 patients with type 2 diabetes to Insulin Glargine, U-300 with mean exposure duration of 25 weeks. The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 13 years. Fifty-three percent were male, 88% were White, 7% were Black or African American, and 17% were Hispanic or Latino. At baseline, mean eGFR was 79 mL/min/1.73 m 2 and 27% of patients had an eGFR ≥90 mL/min/1.73 m 2 . The mean BMI was 35 kg/m 2 . HbA1c at baseline was greater than or equal to 8% in 66% of patients. Insulin Glargine, U-300 was studied in 233 pediatric patients (6–17 years of age) with type 1 diabetes for a mean duration of 26 weeks [see Clinical Studies (14.1) ] . Common adverse reactions (occurring ≥5%) in Insulin Glargine, U-300-treated subjects during clinical trials in adult patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively. Common adverse reactions for Insulin Glargine, U-300-treated pediatric subjects with type 1 diabetes mellitus were similar to the adverse reactions listed in Table 1. Hypoglycemia is discussed in a dedicated subsection below. Table 1: Adverse Reactions Occurring ≥5% in Two Pooled Clinical Trials of 26 Weeks and 16 Weeks Duration in Adults with Type 1 Diabetes Insulin Glargine, U-300 + Mealtime Insulin "mealtime insulin" refers to insulin glulisine, insulin lispro, or insulin aspart. , % (n=304) Nasopharyngitis 12.8 Upper respiratory tract infection 9.5 Table 2: Adverse Reactions Occurring ≥5% in Three Pooled Clinical Trials of 26 Weeks Duration in Adults with Type 2 Diabetes Insulin Glargine, U-300 one of the trials in type 2 diabetes included mealtime insulin. , % (n=1242) Nasopharyngitis 7.1 Upper respiratory tract infection 5.7 Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients treated with Insulin Glargine, U-300. The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for Insulin Glargine, U-300 with the incidence of hypoglycemia for other products may be misleading and also may not be representative of hypoglycemia rates that will occur in clinical practice. In the Insulin Glargine, U-300 adult program, severe hypoglycemia was defined as an event requiring assistance of another person to administer a resuscitative action. In the pediatric program, severe hypoglycemia was defined as an event with semiconsciousness, unconsciousness, coma and/or convulsions in a patient who had altered mental status and could not assist in his own care, and who may have required glucagon or intravenous glucose. The incidence of severe hypoglycemia in adult patients with type 1 diabetes receiving Insulin Glargine, U-300 as part of a multiple daily injection regimen was 6.6% at 26 weeks. The incidence of hypoglycemia with a glucose level less than 54 mg/dL with or without symptoms was 77.7% at 26 weeks. The incidence of severe hypoglycemia in pediatric patients with type 1 diabetes receiving Insulin Glargine, U-300 as part of a multiple daily injection regimen was 6% at 26 weeks and the incidence of hypoglycemia accompanied by a self-monitored or plasma glucose value less than 54 mg/dL regardless of symptoms was 80.3%. The incidence of severe hypoglycemia in adult patients with type 2 diabetes was 5% at 26 weeks in patients receiving Insulin Glargine, U-300 as part of a multiple daily injection regimen, and 1.0% and 0.9% respectively at 26 weeks in the two studies where patients received Insulin Glargine, U-300 as part of a basal-insulin only regimen. The incidence of hypoglycemia accompanied by a self-monitored or plasma glucose value less than 54 mg/dL regardless of symptoms in patients with type 2 diabetes receiving Insulin Glargine, U-300 ranged from 9% to 44.6% at 26 weeks and the highest risk was again seen in patients receiving Insulin Glargine, U-300 as part of a multiple daily injection regimen.

Drug interactions

Table 3 includes clinically significant drug interactions with Insulin Glargine, U-300. Table 3: Clinically Significant Drug Interactions with Insulin Glargine, U-300 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, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when Insulin Glargine, U-300 is coadministered with these drugs. Drugs That May Decrease the Blood Glucose Lowering Effect of Insulin Glargine, U-300 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 Insulin Glargine, U-300 is coadministered with these drugs. Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Insulin Glargine, U-300 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 Insulin Glargine, U-300 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 Insulin Glargine, U-300 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. ( 5.3 , 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 dose of 0.2 unit/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). 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 (0.007 mg/kg/day), 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 Insulin Glargine, U-300, and any potential adverse effects on the breastfed child from Insulin Glargine, U-300 or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of Insulin Glargine, U-300 to improve glycemic control in pediatric patients 6 years of age and older with diabetes mellitus have been established. The use of Insulin Glargine, U-300 for this indication is supported by evidence from an adequate and well-controlled study in 463 pediatric patients 6 to 17 years of age with type 1 diabetes mellitus [see Clinical Studies (14.2) ] and from studies in adults with diabetes mellitus [see Clinical Pharmacology (12.3) , Clinical Studies (14.3) ] . The safety and effectiveness of Insulin Glargine, U-300 have not been established in pediatric patients less than 6 years of age. 8.5 Geriatric Use In controlled clinical studies, 30 of 304 (9.8%) Insulin Glargine, U-300-treated patients with type 1 diabetes and 327 of 1242 (26.3%) Insulin Glargine, U-300-treated patients with type 2 diabetes were ≥65 years of age, among them 2.0% of the patients with type 1 and 3.0% of the patients with type 2 diabetes were ≥75 years of age. No overall differences in safety or effectiveness of Insulin Glargine, U-300 have been observed between patients 65 years of age and older and younger adult patients. Nevertheless, caution should be exercised when Insulin Glargine, U-300 is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia [see Warnings and Precautions (5.3) , Adverse Reactions (6) , and Clinical Studies (14) ] . 8.6 Renal Impairment The effect of kidney impairment on the pharmacokinetics of Insulin Glargine, U-300 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 dose adjustment may be necessary for Insulin Glargine, U-300 in patients with kidney impairment [see Warnings and Precautions (5.3) ] . 8.7 Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of Insulin Glargine, U-300 has not been studied. Frequent glucose monitoring and dose adjustment may be necessary for Insulin Glargine, U-300 in patients with hepatic impairment [see Warnings and Precautions (5.3) ] .

Pregnancy

Pediatric use

8.4 Pediatric Use The safety and effectiveness of Insulin Glargine, U-300 to improve glycemic control in pediatric patients 6 years of age and older with diabetes mellitus have been established. The use of Insulin Glargine, U-300 for this indication is supported by evidence from an adequate and well-controlled study in 463 pediatric patients 6 to 17 years of age with type 1 diabetes mellitus [see Clinical Studies (14.2) ] and from studies in adults with diabetes mellitus [see Clinical Pharmacology (12.3) , Clinical Studies (14.3) ] . The safety and effectiveness of Insulin Glargine, U-300 have not been established in pediatric patients less than 6 years of age.

Geriatric use

8.5 Geriatric Use In controlled clinical studies, 30 of 304 (9.8%) Insulin Glargine, U-300-treated patients with type 1 diabetes and 327 of 1242 (26.3%) Insulin Glargine, U-300-treated patients with type 2 diabetes were ≥65 years of age, among them 2.0% of the patients with type 1 and 3.0% of the patients with type 2 diabetes were ≥75 years of age. No overall differences in safety or effectiveness of Insulin Glargine, U-300 have been observed between patients 65 years of age and older and younger adult patients. Nevertheless, caution should be exercised when Insulin Glargine, U-300 is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia [see Warnings and Precautions (5.3) , Adverse Reactions (6) , and Clinical Studies (14) ] .

Overdosage

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3 , 5.6) ] . Mild episodes of hypoglycemia can be treated with oral glucose. Lowering the insulin dosage, and adjustments in meal patterns, or physical activity level 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. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

Description

Insulin glargine is a long-acting human insulin analog produced by recombinant DNA technology utilizing a nonpathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines remain at the C-terminus of the B-chain. Insulin glargine has a molecular weight of 6063 Da. Insulin Glargine, U-300 injection is a sterile, clear and colorless solution for subcutaneous injection. Each mL of Insulin Glargine, U-300 contains 300 units of insulin glargine dissolved in a clear aqueous fluid. The 1.5 mL Insulin Glargine, U-300 SoloStar prefilled pen presentation contains the following inactive ingredients per mL: glycerin (20 mg), metacresol (2.7 mg), zinc (90 mcg), and Water for Injection, USP. The 3 mL Insulin Glargine, U-300 Max SoloStar prefilled pen presentation contains the following inactive ingredients per mL: glycerin (20 mg), metacresol (2.7 mg), zinc (90 mcg), and Water for Injection, USP. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. Insulin Glargine, U-300 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 Insulin Glargine injection, 300 units/mL (U-300), is a clear and colorless solution and is available as: Insulin Glargine, U-300 Total volume Total units available in presentation Max dose per injection Dose increment NDC number Package size SoloStar single-patient-use prefilled pen 1.5 mL 450 units 80 units 1 unit 0955-3900-01 0955-3900-03 3 pens/pack Max SoloStar single-patient-use prefilled pen 3 mL 900 units 160 units 2 units 0955-2900-01 0955-2900-02 2 pens/pack Needles are not included in the packs of Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar single-patient-use prefilled pen. BD (such as BD Ultra-Fine ® ), Ypsomed (such as Clickfine ® ) or Owen Mumford (such as Unifine ® Pentips ® ) needles can be used in conjunction with Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar single-patient-use prefilled pen and are sold separately. A new sterile needle must be attached before each injection. Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar single-patient-use prefilled pens must never be shared between patients, even if the needle is changed. 16.2 Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar prefilled pen should not be stored in the freezer and should not be allowed to freeze. Discard Insulin Glargine, U-300 prefilled pen if it has been frozen. Protect Insulin Glargine, U-300 SoloStar/ Insulin Glargine, U-300 Max SoloStar from direct heat and light. Storage conditions are summarized in the following table: Insulin Glargine, U-300 Not in-use (unopened) Refrigerated 36°F–46°F (2°C–8°C) In-use (opened) To prevent degradation, always store the prefilled pens with the cap on during in-use period. Room temperature only (Do not refrigerate) up to 86°F (30°C) 1.5 mL SoloStar single-patient-use prefilled pen Until expiration date 56 days 3 mL Max SoloStar single-patient-use prefilled pen Until expiration date 56 days

Storage

16.2 Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar prefilled pen should not be stored in the freezer and should not be allowed to freeze. Discard Insulin Glargine, U-300 prefilled pen if it has been frozen. Protect Insulin Glargine, U-300 SoloStar/ Insulin Glargine, U-300 Max SoloStar from direct heat and light. Storage conditions are summarized in the following table: Insulin Glargine, U-300 Not in-use (unopened) Refrigerated 36°F–46°F (2°C–8°C) In-use (opened) To prevent degradation, always store the prefilled pens with the cap on during in-use period. Room temperature only (Do not refrigerate) up to 86°F (30°C) 1.5 mL SoloStar single-patient-use prefilled pen Until expiration date 56 days 3 mL Max SoloStar single-patient-use prefilled pen Until expiration date 56 days

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 Insulin Glargine, U-300 SoloStar and Insulin Glargine, U-300 Max SoloStar. Never Share an Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar Pen Between Patients Advise patients that they must never share Insulin Glargine, U-300 SoloStar or Insulin Glargine, U-300 Max SoloStar pen with another person even if the needle is changed. Pen sharing poses 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 (5.2 , 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) ] . Inform patients that if they change to Insulin Glargine, U-300 from other basal insulins they may experience higher average fasting plasma glucose levels in the first weeks of therapy. Advise patients to monitor glucose daily when initiating Insulin Glargine, U-300 [see Warnings and Precautions (5.2) ] . Hypoglycemia Due to Medication Errors Instruct patients to always check the insulin label before each injection [see Warnings and Precautions (5.4) ] . The "300 units/mL (U-300)" is highlighted in honey gold on the labels of Insulin Glargine, U-300 and Insulin Glargine, U-300 Max SoloStar single-patient-use prefilled pens. Inform patients that Insulin Glargine, U-300 contains 300 units of insulin glargine per mL (U-300) compared to formulations of insulin glargine that contain100 units/mL (U-100). To avoid dosing errors and potential overdose, instruct patients to never use a syringe to remove Insulin Glargine, U-300 from the Insulin Glargine, U-300 SoloStar or Max SoloStar single-patient-use prefilled pen [see Warnings and Precautions (5.4) ] . Inform patients that the dose counter of Insulin Glargine, U-300, SoloStar or Insulin Glargine, U-300 Max SoloStar single-patient-use prefilled pen shows the number of units of Insulin Glargine, U-300 to be injected and no dose recalculation is required [see Dosage and Administration (2.1 , 2.4) ] . Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with Insulin Glargine, U-300. Inform patients on the symptoms of hypersensitivity reactions [see Warnings and Precautions (5.5) ].

Label text from the FDA structured product label by Sanofi-Aventis U.S. LLC (revised May 30, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Insulin Glargine in 1 product

Insulin glargine U-300 Max NDC products (1)

NDC	Strength & form	Labeler	Type
0955-2900	Insulin Glargine 300 [iU]/mL Injection, Solution	Sanofi-Aventis U.S. LLC	BLA

Frequently asked questions

What is Insulin glargine U-300 Max used for?

What are the side effects of Insulin glargine U-300 Max?

Who makes Insulin glargine U-300 Max?

Insulin glargine U-300 Max is listed by 1 labeler in the FDA NDC directory, including Sanofi-Aventis U.S. LLC.