Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 01 April 2018

Indication(s)

1 INDICATIONS AND USAGE TOUJEO is indicated to improve glycemic control in adults with diabetes mellitus. TOUJEO is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. (1) Limitations of Use: Not recommended for treating diabetic ketoacidosis. (1) Limitations of Use: TOUJEO is not recommended for the treatment of diabetic ketoacidosis.

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Advisory information

contraindications
4 CONTRAINDICATIONS TOUJEO is contraindicated: During episodes of hypoglycemia [see Warnings and Precautions (5.3)]. In patients with hypersensitivity to insulin glargine or one of its excipients [see Warnings and Precautions (5.5)]. During episodes of hypoglycemia (4) Hypersensitivity to TOUJEO or one of its excipients (4)
Adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere: Hypoglycemia [see Warnings and Precautions (5.3)] Medication Errors [see Warnings and Precautions (5.4)] Hypersensitivity and allergic reactions [see Warnings and Precautions (5.5)] Hypokalemia [see Warnings and Precautions (5.6)] Adverse reactions commonly associated with TOUJEO (≥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 TOUJEO 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 Caucasian, 5% were Black or African American, and 5% were Hispanic. At baseline, the mean eGFR was 82 mL/min/1.73 m2 and 35% of patients had eGFR ≥90 mL/min/1.73 m2. The mean BMI was 28 kg/m2. HbA1c at baseline was greater or equal to 8% in 58% of patients. The data in Table 2 reflect the exposure of 1242 patients with type 2 diabetes to TOUJEO 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 Caucasian, 7% were Black or African American, and 17% were Hispanic. At baseline, mean eGFR was 79 mL/min/1.73 m2 and 27% of patients had an eGFR ≥90 mL/min/1.73 m2. The mean BMI was 35 kg/m2. HbA1c at baseline was greater or equal to 8% in 66% of patients. Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Common adverse reactions occurring for TOUJEO-treated subjects during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively. Hypoglycemia is discussed in a dedicated subsection below. Table 1: Adverse Reactions in Two Pooled Clinical Trials of 26 Weeks and 16 Weeks Duration in Adults with Type 1 Diabetes (with incidence ≥5%) TOUJEO + 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 in Three Pooled Clinical Trials of 26 Weeks Duration in Adults with Type 2 Diabetes (with incidence ≥5%) TOUJEOone 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 using insulin, including TOUJEO [see Warnings and Precautions (5.3)]. In the TOUJEO program, severe hypoglycemia was defined as an event requiring assistance of another person to administer a resuscitative action and documented symptomatic hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by a self-monitored or plasma glucose value equal to or less than 54 mg/dL. The incidence of severe hypoglycemia in patients with type 1 diabetes receiving TOUJEO as part of a multiple daily injection regimen was 6.6% at 26 weeks. The incidence of documented symptomatic hypoglycemia was 69% at 26 weeks. There were no clinically important differences in hypoglycemia between TOUJEO and LANTUS among type 1 diabetes patients. The incidence of severe hypoglycemia in patients with type 2 diabetes was 5% at 26 weeks in patients receiving TOUJEO 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 TOUJEO as part of a basal-insulin only regimen. The incidence of documented symptomatic hypoglycemia in patients with type 2 diabetes receiving TOUJEO ranged from 8% to 37% at 26 weeks and the highest risk was again seen in patients receiving TOUJEO as part of a multiple daily injection regimen. 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. Peripheral Edema Insulin, including TOUJEO, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Lipodystrophy Long-term use of insulin, including TOUJEO, can cause lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients and may affect insulin absorption [see Dosage and Administration (2.1)]. Weight Gain Weight gain has occurred with some insulin therapies including TOUJEO and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. Allergic Reactions Some patients taking insulin therapy, including TOUJEO have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy (anaphylaxis) have been reported [see Warnings and Precautions (5.5)]. Cardiovascular Safety No clinical studies to establish the cardiovascular safety of TOUJEO have been conducted. A cardiovascular outcomes trial, ORIGIN, has been conducted with LANTUS. It is unknown whether the results of ORIGIN can be applied to TOUJEO. The Outcome Reduction with Initial Glargine Intervention trial (i.e., ORIGIN) was an open-label, randomized, 12,537 patient study that compared LANTUS to standard care on the time to first occurrence of a major adverse cardiovascular event (MACE). MACE was defined as the composite of CV death, nonfatal myocardial infarction and nonfatal stroke. The incidence of MACE was similar between LANTUS and standard care in ORIGIN (Hazard Ratio [95% CI] for MACE; 1.02 [0.94, 1.11]). In the ORIGIN trial, the overall incidence of cancer (all types combined) (Hazard Ratio [95% CI]; 0.99 [0.88, 1.11]) or death from cancer (Hazard Ratio [95% CI]; 0.94 [0.77, 1.15]) was also similar between treatment groups. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. In a 6-month study of type 1 diabetes patients, 79% of patients who received TOUJEO once daily were positive for anti-insulin antibodies (AIA) at least once during the study, including 62% that were positive at baseline and 44% of patients who developed antidrug antibody (i.e., anti-insulin glargine antibody [ADA]) during the study. Eighty percent of the AIA-positive patients on TOUJEO with antibody test at baseline remained AIA positive at month 6. In two 6-month studies in type 2 diabetes patients, 25% of patients who received TOUJEO once daily were positive for AIA at least once during the study, including 42% who were positive at baseline and 20% of patients who developed ADA during the study. Ninety percent of the AIA-positive patients on TOUJEO with antibody test at baseline, remained AIA positive at month 6. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to TOUJEO with the incidence of antibodies in other studies or to other products may be misleading.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Individualize dose based on type of diabetes, metabolic needs, blood glucose monitoring results and glycemic control goal. (2.1, 2.2, 2.3) Administer subcutaneously once daily at any time during the day, at the same time every day. (2.1) Rotate injection sites to reduce the risk of lipodystrophy. (2.1) Do not dilute or mix with any other insulin or solution. (2.1) Closely monitor glucose when changing to TOUJEO and during initial weeks thereafter. (2.3) 2.1 General Dosing Instructions TOUJEO is available in 2 disposable prefilled pens: TOUJEO SoloStar contains 450 units of TOUJEO U-300. It delivers doses in 1 unit increments and can deliver up to 80 units in a single injection. TOUJEO Max SoloStar contains 900 units of TOUJEO U-300. 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. Inject TOUJEO subcutaneously once a day into the abdominal area, thigh, or deltoid at the same time each day. Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy [see Adverse Reactions (6.1)]. Individualize and titrate the dosage of TOUJEO based on the individual's metabolic needs, blood glucose monitoring results, and glycemic control goal. To minimize the risk of hypoglycemia, titrate the dose of TOUJEO 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)]. Use TOUJEO with caution in patients with visual impairment who may rely on audible clicks to dial their dose. 2.2 Starting Dose in Insulin-Naive Patients Type 1 Diabetes The recommended starting dose of TOUJEO 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 TOUJEO may take five days to fully manifest and the first TOUJEO dose may be insufficient to cover metabolic needs in the first 24 hours of use [see Clinical Pharmacology (12.2)]. To minimize risks associated with insufficient insulinization when initiating TOUJEO, monitor glucose daily, titrate TOUJEO per instructions, and adjust coadministered glucose-lowering therapies per standard of care. Type 2 Diabetes The recommended starting dose of TOUJEO in insulin-naive patients with type 2 diabetes is 0.2 units per kilogram of body weight once daily. The dosage of other antidiabetic drugs may need to be adjusted when starting TOUJEO to minimize the risk of hypoglycemia [see Warnings and Precautions (5.3)]. 2.3 Starting Dose in Patients with Either Type 1 or Type 2 Diabetes Already on Insulin Therapy To minimize the risk of hypoglycemia when changing patients from a once-daily long-acting or intermediate-acting insulin product to TOUJEO, the starting dose of TOUJEO can be the same as the once-daily long-acting dose. For patients controlled on LANTUS (insulin glargine, 100 units/mL) expect that a higher daily dose of TOUJEO will be needed to maintain the same level of glycemic control [see Clinical Pharmacology (12.2) and Clinical Studies (14.1)]. To minimize the risk of hypoglycemia when changing patients from twice-daily NPH insulin to once-daily TOUJEO, the recommended starting TOUJEO dose is 80% of the total daily NPH dosage. To minimize the risk of hyperglycemia when changing patients to TOUJEO, monitor glucose frequently in the first weeks of therapy titrate the dose of TOUJEO per instructions and the dose of other glucose-lowering therapies per standard of care [see Warning and Precautions (5.2) and Clinical Pharmacology (12.2)]. 2.4 Important Administration Instructions Always check insulin labels before administration [see Warnings and Precautions (5.4)]. When changing between TOUJEO SoloStar and TOUJEO Max SoloStar, if the patient's previous dose was an odd number, the dose should be increased or decreased by 1 unit. The dose counter of the TOUJEO SoloStar or TOUJEO Max SoloStar disposable prefilled pen shows the number of units of TOUJEO to be injected and no conversion is required. Instruct patients to visually inspect the TOUJEO solution for particulate matter and discoloration prior to administration and only use if the solution is clear and colorless with no visible particles. Do not administer TOUJEO intravenously, intramuscularly, or in an insulin pump. Do not dilute or mix TOUJEO with any other insulin products or solutions. Never transfer TOUJEO from the cartridges of the TOUJEO SoloStar or TOUJEO Max SoloStar prefilled pen into a syringe for administration [see Warnings and Precautions (5.4)].
Use in special populations
8 USE IN SPECIFIC POPULATIONS Pregnancy: Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. (8.1) 8.1 Pregnancy Risk Summary 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 a 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 and third trimesters, 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 TOUJEO. Human data There are no clinical studies of the use of TOUJEO 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. 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 dose 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 dose 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. 8.3 Nursing Mothers Endogenous insulin is present in human milk; it is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when TOUJEO is administered to a nursing woman. Use of TOUJEO 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 TOUJEO have not been established in pediatric patients. 8.5 Geriatric Use In controlled clinical studies, 30 of 304 (9.8%) TOUJEO-treated patients with type 1 diabetes and 327 of 1242 (26.3%) TOUJEO-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 effectiveness and safety were observed in the subgroup analyses across the age groups. Nevertheless, caution should be exercised when TOUJEO is administered to geriatric patients. In elderly 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 Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of TOUJEO has not been studied. Frequent glucose monitoring and dose adjustment may be necessary for TOUJEO in patients with hepatic impairment [see Warnings and Precautions (5.3)]. 8.7 Renal Impairment The effect of renal impairment on the pharmacokinetics of TOUJEO 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 TOUJEO in patients with renal impairment [see Warnings and Precautions (5.3)]. 8.8 Obesity No overall differences in effectiveness and safety were observed in subgroup analyses based on BMI.
Pregnancy and lactation
8.3 Nursing Mothers Endogenous insulin is present in human milk; it is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when TOUJEO is administered to a nursing woman. Use of TOUJEO is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.

Interactions

7 DRUG INTERACTIONS Table 3 includes clinically significant drug interactions with TOUJEO. Table 3: Clinically Significant Drug Interactions with TOUJEO 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, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Intervention: Dose reductions and increased frequency of glucose monitoring may be required when TOUJEO is coadministered with these drugs. Drugs That May Decrease the Blood Glucose Lowering Effect of TOUJEO 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 TOUJEO is coadministered with these drugs. Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of TOUJEO 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 TOUJEO 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 TOUJEO is coadministered with these drugs. Drugs that affect glucose metabolism: Adjustment of insulin dosage may be needed; closely monitor blood glucose. (7) Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent. (7)

More information

Category Value
Authorisation number NDA206538
Agency product number 2ZM8CX04RZ
Orphan designation No
Product NDC 0024-5871,0024-5869
Date Last Revised 22-03-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 1604544
Storage and handling 16.2 Storage TOUJEO SoloStar or TOUJEO Max SoloStar disposable prefilled pen should not be stored in the freezer and should not be allowed to freeze. Discard TOUJEO disposable prefilled pen if it has been frozen. Storage conditions are summarized in the following table: 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) below 86°F (30°C) 1.5 mL TOUJEO SoloStar disposable prefilled pen Until expiration date 42 days 3 mL TOUJEO Max SoloStar disposable prefilled pen Until expiration date 42 days
Marketing authorisation holder Sanofi-Aventis U.S. LLC