Toujeo

Toujeo is part of the drug class:

• Insulins and analogues for injection, long acting

Tell your doctor if you are pregnant or plan to become pregnant.

There are no clinical studies of theuse of Toujeo in pregnant women. Toujeo should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Never share insulin pens or cartridges with others under any circumstances. It is not safe for one pen to be used for more than one person. Sharing needles or pens can result in transmission of hepatitis viruses, HIV, or other bloodborne illnesses.

Your doctor will want to check your progress at regular visits, especially during the first few weeks you take this medicine. Blood tests may be needed to check for unwanted effects.

It is very important to follow carefully any instructions from your health care team about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team.
• Other medicines—Do not take other medicines during the time you are using insulin glargine unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.
• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy is needed because of the problems that can occur in patients with diabetes during pregnancy.
• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.

In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to:

• Wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.
• Keep an extra supply of insulin glargine and syringes with needles or injection devices on hand in case high blood sugar occurs.
• Keep some kind of quick-acting sugar handy to treat low blood sugar.
• Have a glucagon kit and a syringe and needle available in case severe low blood sugar occurs. Check and replace any expired kits regularly.

Too much insulin glargine can cause hypoglycemia (low blood sugar). Low blood sugar also can occur if you use insulin glargine with another antidiabetic medicine, delay or miss a meal or snack, exercise more than usual, or drink alcohol. Symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). Different people may feel different symptoms of low blood sugar. It is important that you learn which symptoms of low blood sugar you usually have so that you can treat it quickly.

Symptoms of low blood sugar include anxiety, behavior change similar to being drunk, blurred vision, cold sweats, confusion, difficulty in thinking, dizziness or lightheadedness, drowsiness, excessive hunger, fast heartbeat, headache, irritability or abnormal behavior, nervousness, nightmares, restless sleep, shakiness, slurred speech, and tingling in the hands, feet, lips, or tongue.

If symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes, or drink fruit juice, non diet soft drink, or sugar dissolved in water to relieve the symptoms. Also, check your blood for low blood sugar. Get to a doctor or a hospital right away if the symptoms do not improve. Someone should call for emergency help immediately if severe symptoms such as convulsions (seizures) or unconsciousness occur. Have a glucagon kit available, along with a syringe and needle, and know how to use it. Members of your household also should know how to use it.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your antidiabetic medicine, overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual.

Symptoms of high blood sugar include blurred vision, drowsiness, dry mouth, flushed, dry skin, fruit-like breath odor, increased urination, ketones in the urine, loss of appetite, stomachache, nausea, or vomiting, tiredness, troubled breathing (rapid and deep), unconsciousness, and unusual thirst.

If symptoms of high blood sugar occur, check your blood sugar level and then call your doctor for instructions.

This medicine may make you dizzy or drowsy. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

This medicine may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

This medicine may cause low levels of potassium in your blood. Do not use medicines, supplements, or salt substitutes that contain potassium unless you have discussed this with your doctor.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Anxiety
• behavior change similar to being drunk
• blurred vision
• chills
• cold sweats
• confusion
• convulsions (seizures)
• cool, pale skin
• difficulty with thinking
• dizziness or lightheadedness
• drowsiness
• excessive hunger
• fast heartbeat
• headache
• nausea
• nervousness
• nightmares
• restless sleep
• shakiness
• slurred speech
• tingling in the hands, feet, lips, or tongue
• unusual tiredness or weakness

• Fast pulse
• skin rash or itching over the entire body
• sweating
• trouble breathing

• Bloating or swelling of the face, hands, lower legs, or feet
• cough
• decreased urine
• difficulty with swallowing
• dry mouth
• hives
• increased thirst
• irregular heartbeat
• muscle pain or cramps
• numbness or tingling in the hands, feet, or lips
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Fever
• sore throat
• stuffy or runny nose

• Depression of the skin at the injection site
• itching, pain, redness, or swelling at the injection site
• thickening of the skin at injection site

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Toujeo is indicated to improve glycemic control in adults with diabetes mellitus.

Limitations of Use

Toujeo is not recommended for the treatment of diabetic ketoacidosis.

Injection: 300 units per mL of insulin glargine available as a clear, colorless, solution in a 1.5 mL Toujeo SoloStar disposable prefilled pen (450 Units/1.5 mL).

Never Share a Toujeo SoloStar pen Between Patients

Toujeo SoloStar disposable 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.

Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3)] or hyperglycemia. These changes should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage adjustments of concomitant oral anti-diabetic products may be needed.

On a unit to unit basis, Toujeo has a lower glucose lowering effect than LANTUS [See Clinical Pharmacology (12.2)]. In clinical trials, patients who changed to Toujeo 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. To minimize the risk of hyperglycemia when initiating Toujeo monitor glucose daily, titrate Toujeo according to labeling instructions, and adjust co-administered glucose lowering therapies per standard of care [See Dosage and Administration (2.2, 2.3)]. Higher doses of Toujeo 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 Toujeo develops over 6 hours following an injection. In type 1 diabetes patients treated with IV insulin, consider the longer onset of action of Toujeo 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)].

Hypoglycemia

Hypoglycemia is the most common adverse reaction associated with insulin, including Toujeo. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving, or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [See Drug Interactions (7)], or in patients who experience recurrent hypoglycemia.

Risk Factors for Hypoglycemia

The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulation.

As with all insulin preparations, the glucose lowering effect time course of Toujeo may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [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 co-administered medication [see Drug Interactions (7)]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.5, 8.6)].

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. To minimize the risk of hypoglycemia do not administer Toujeo intravenously, intramuscularly or in an insulin pump or dilute or mix Toujeo with any other insulin products or solutions.

Medication Errors

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

Hypersensitivity and Allergic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including Toujeo. If hypersensitivity reactions occur, discontinue Toujeo; treat per standard of care and monitor until symptoms and signs resolve [See Adverse Reactions (6)]. Toujeo is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or other of the excipients [See Contraindications (4)].

Hypokalemia

All insulin products, including Toujeo, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).

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

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including Toujeo, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

Drugs That May Increase the Risk of Hypoglycemia

The risk of hypoglycemia associated with Toujeo use may be increased with 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. Dose adjustment and increased frequency of glucose monitoring may be required when Toujeo is co-administered with these drugs.

Drugs That May Decrease the Blood Glucose Lowering Effect of Toujeo

The glucose lowering effect of Toujeo may be decreased when co-administered with atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isonazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline) and thyroid hormones. Dose adjustment and increased frequency of glucose monitoring may be required when Toujeo is co-administered with these drugs.

Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Toujeo

The glucose lowering effect of Toujeo may be increased or decreased when co-administered with alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Dose adjustment and increased frequency of glucose monitoring may be required when Toujeo is co-administered with these drugs.

Drugs That May Affect Signs and Symptoms of Hypoglycemia

The signs and symptoms of hypoglycemia [see Warnings and Precautions (5.3)] may be blunted when beta-blockers, clonidine, guanethidine, and reserpine are co-administered with Toujeo.

Toujeo (insulin glargine injection) is a long-acting insulin supplied as a sterile solution for subcutaneous injection containing 300 Units/mL of insulin glargine.

Insulin glargine is a human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic 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. Chemically, insulin glargine is 21A-Gly-31B-32B-Di-Arg -human insulin and has the empirical formula C267H404N72O78S6 and a molecular weight of 6063. Insulin glargine has the following structural formula:

Each milliliter of Toujeo contains 300 Units (10.91 mg) insulin glargine dissolved in a clear aqueous fluid.

The 1.5 mL SoloStar disposable prefilled pen presentation contains the following inactive ingredients per mL: 90 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, and water for injection.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. Toujeo has a pH of approximately 4. At pH 4, insulin glargine is completely soluble. After injection into the subcutaneous tissue, the acidic solution is neutralized, leading to formation of a precipitate from which small amounts of insulin glargine are slowly released.

See FDA-approved patient labeling (Instruction Leaflet)

General Counseling InformationPrior to treatment, patients should fully understand the risks and benefits of Toujeo. Ensure that all patients receive the Instruction Leaflet prior to initiating Toujeo therapy.

Never Share a Toujeo SoloStar Pen Between Patients

[see Warnings and Precautions (5.1)]

Advise patients that they must never share Toujeo SoloStar pen with another person even if the needle is changed. Pen sharing poses a risk for transmission of blood-borne pathogens.

Hyperglycemia or Hypoglycemia

[see Warnings and Precautions (5.2), (5.3)]

Inform patients that hypoglycemia is the most common adverse reaction with insulin. Inform patients of the symptoms of hypoglycemia. Inform patients that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.

Advise patients that changes in insulin regimen can predispose to hyper- or hypoglycemia. Advise patients that changes in insulin regimen should be made under close medical supervision.

Inform patients that if they change to Toujeo 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 Toujeo.

Medication Errors

[see Warnings and Precautions (5.4)]

Instruct patients to always check the insulin label before each injection. The "300 Units/mL (U-300)" is highlighted in honey gold on the label of Toujeo SoloStar disposable prefilled pen.

Inform patients that Toujeo (insulin glargine 300 U/mL) contains 3 times as much insulin in 1 mL as standard insulin (100 U/mL).

Inform patients that the dose counter of Toujeo SoloStar disposable prefilled pen shows the number of units of Toujeo to be injected. No dose re-calculation is required.

Instruct patients to not re-use needles. A new needle must be attached before each injection. Re-use of needles increases the risk of blocked needles which may cause under-dosing or overdosing. In the event of blocked needle, the patients must follow the instructions described in Step 3 of the Instructions for Use.

Instruct Patients to never use a syringe to remove Toujeo from the SoloStar disposable insulin prefilled pen.

Administration

Toujeo must only be used if the solution is clear and colorless with no particles visible. Patients must be advised that Toujeo must NOT be diluted or mixed with any other insulin or solution.

Management of Hypoglycemia and Handling of Special Situations

Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals.

Pregnancy

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

Refer patients to the Toujeo "Patient Information" for additional information about the potential side effects of insulin therapy, including lipodystrophy (and the need to rotate injection sites within the same body region), weight gain, allergic reactions, and hypoglycemia.

FDA Approved Patient Labeling

See attached document at end of Full Prescribing Information.

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LANTUS, Toujeo and SoloStar are registered trademarks of sanofi-aventis U.S. LLC.