Ryzodeg FlexTouch Pen

Ryzodeg FlexTouch Pen is indicated to improve glycemic control in adults with diabetes mellitus.

Limitations of Use

Ryzodeg FlexTouch Pen is not recommended for the treatment of diabetic ketoacidosis

Insulin Aspart (Ryzodeg FlexTouch Pen) is a fast-acting type of insulin. Insulin Degludec (Ryzodeg FlexTouch Pen) is a long-acting type of insulin that works slowly, over about 24 hours. Insulin is one of many hormones that help the body turn the food we eat into energy. This is done by using the glucose (sugar) in the blood as quick energy. Also, insulin helps us store energy that we can use later. When you have diabetes mellitus, your body cannot make enough insulin or does not use insulin properly. This causes you to have too much sugar in your blood. Like other types of insulin, Ryzodeg FlexTouch Pen combination is used to keep your blood sugar level close to normal.

Ryzodeg FlexTouch Pen is available only with your doctor's prescription.

Important Administration Instructions

• Always check insulin label before administration.
• Inspect visually for particulate matter and discoloration. Only use Ryzodeg FlexTouch Pen if the solution appears clear and colorless.
• Train patients on proper use and injection technique before initiating Ryzodeg FlexTouch Pen. Training reduces the risk of administration errors such as needle sticks and incomplete dosing.
• Inject Ryzodeg FlexTouch Pen subcutaneously into the thigh, upper arm, or abdomen.
• Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy.
• DO NOT administer Ryzodeg FlexTouch Pen intravenously, intramuscularly, or in an insulin infusion pump.
• DO NOT dilute or mix Ryzodeg FlexTouch Pen with any other insulin products or solutions.

General Dosing Instructions

• Inject Ryzodeg FlexTouch Pen subcutaneously once or twice daily with any main meal.
• Administer a rapid- or a short-acting insulin at other meals if needed.
• Patients with type 1 diabetes, will generally require a rapid- or short-acting insulin at meals when Ryzodeg FlexTouch Pen is not administered for optimal glucose control.
• Individualize and titrate the dose of Ryzodeg FlexTouch Pen based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
• Adjust the Ryzodeg FlexTouch Pen dose according to blood glucose measurements before breakfast (fasting).
• The recommended time between dose increases is 3 to 4 days.
• Dose 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.
• If a dose of Ryzodeg FlexTouch Pen is missed, the next dose should be taken with the next main meal of that day and thereafter resume the usual dosing schedule. Patients should not take an extra dose to make up for a missed dose.

Starting Dose In Insulin-Naive Patients

Type 1 Diabetes Mellitus

The recommended starting dose of Ryzodeg FlexTouch Pen 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 administered as a short- or rapid-acting insulin 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.

Type 2 Diabetes Mellitus

The recommended starting dose of Ryzodeg FlexTouch Pen in insulin-naive patients with type 2 diabetes mellitus is 10 units once daily.

Starting Dose In Patients With Type 1 Or Type 2 Diabetes On A Once Or Twice Daily Premix Or Self-mix Insulin Alone Or As Part of A Regimen Of Multiple Daily Injections

• Start Ryzodeg FlexTouch Pen at the same unit dose and injection schedule as the premix or self-mix insulin. In patients also using short- or rapid-acting insulin at mealtimes continue the short- or rapid-acting insulin at the same dose for meals NOT covered by Ryzodeg FlexTouch Pen.

Starting Dose In Patients With Type 1 Or Type 2 Diabetes On A Once Or Twice Daily Basal Insulin Alone Or As Part Of A Regimen Of Multiple Daily Injections

• In patient with type 2 diabetes switching from a regimen that includes only a once- or twice-daily basal insulin, start Ryzodeg FlexTouch Pen at the same unit dose and injection schedule. For patients switching from once-daily basal insulin to once-daily Ryzodeg FlexTouch Pen, monitor blood glucose after starting therapy due to the rapid-acting insulin component.
• In patients switching from a multiple daily injections regimen that includes a basal and short- or rapid-acting insulin at mealtimes, start Ryzodeg FlexTouch Pen once daily with the main meal at the same unit dose as the basal insulin. Continue the short- or rapid-acting insulin at the same dose for meals NOT covered by Ryzodeg FlexTouch Pen.

How supplied

Dosage Forms And Strengths

Ryzodeg FlexTouch Pen is available as a clear and colorless solution for injection in:

• 100 units/mL (U-100): 3 mL FlexTouch disposable prefilled pen

Storage And Handling

Ryzodeg FlexTouch Pen is as a clear, and colorless solution available as a 3mL FlexTouch disposable prefilled pen.

Table 11 : Presentations of Ryzodeg FlexTouch Pen

Recommended Storage

Unused Ryzodeg FlexTouch Pen should be stored between 36° to 46°F (2° and 8°C). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze. Do not use Ryzodeg FlexTouch Pen if it has been frozen.

Unopened FlexTouch disposable prefilled pen:

Not in-use (unopened) Ryzodeg FlexTouch Pen disposable prefilled pen should be stored in a refrigerator 36° to 46°F (2° and 8°C ). Discard after expiration date.

Open (In-Use) FlexTouch disposable prefilled pen:

The in-use Ryzodeg FlexTouch Pen FlexTouch pen should NOT be refrigerated but should be kept at room temperature, below 30°C (86°F) away from direct heat and light. The opened (in-use) Ryzodeg FlexTouch Pen FlexTouch pen may be used for up to 28 days (4 weeks) after being opened, if it is kept at room temperature.

The storage conditions are summarized in Table 12:

Table 12: Storage Conditions for Ryzodeg FlexTouch Pen FlexTouch

Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark. For information about Ryzodeg FlexTouch Pen contact: Novo Nordisk Inc.800 Scudders Mill Road, Plainsboro, NJ 08536, 1-800-727-6500. www.novonordi sk-us.com. Revised: Sep 2015

See also:
What is the most important information I should know about Ryzodeg FlexTouch Pen?

Ryzodeg FlexTouch Pen is contraindicated

• During episodes of hypoglycemia.
• In patients with hypersensitivity to Ryzodeg FlexTouch Pen or one of its excipients.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Insulin is injected under the skin. You may be shown how to use injections at home. Do not self-inject this medicine if you do not understand how to give the injection and properly dispose of used needles and syringes.

Ryzodeg FlexTouch Pen is usually given once or twice per day, with any main meal. You may need to use a separate fast-acting insulin at your other meals. Follow your doctor's dosing instructions very carefully. Avoid medication errors by always checking the medicine label before injecting your insulin.

Your care provider will show you the best places on your body to inject Ryzodeg FlexTouch Pen. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

Use only the prefilled injection pen this medicine comes in. Attach a new needle before each use. Do not transfer to a syringe or infusion pump. Do not mix or dilute this medicine with any other insulin product. Do not use if the medicine has changed colors or has particles in it. Call your pharmacist for new medicine.

Never share an injection pen with another person. Sharing injection pens or cartridges can allow disease such as hepatitis or HIV to pass from one person to another.

Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, confusion, irritability, dizziness, or feeling shaky. Always keep a source of sugar with you in case you have low blood sugar. Sugar sources include fruit juice, hard candy, crackers, raisins, and non-diet soda. Be sure your family and close friends know how to help you in an emergency.

If you have severe hypoglycemia and cannot eat or drink, use a glucagon injection. Your doctor can prescribe a glucagon emergency injection kit and tell you how to use it.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss.

Check your blood sugar carefully during times of stress, travel, illness, surgery or medical emergency, vigorous exercise, or if you drink alcohol or skip meals. These things can affect your glucose levels and your dose needs may also change. Do not change your medication dose or schedule without your doctor's advice.

This medicine is only part of a treatment program that may also include diet, exercise, weight control, blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Store unused injection pens in the refrigerator, but not near the cooling element. Do not freeze or expose to high heat. Throw away the medicine if it has become frozen.

Storing after your first use: Keep "in-use" injection pens at room temperature away from heat and light, and use within 28 days. Do not refrigerate.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

See also:
What other drugs will affect Ryzodeg FlexTouch Pen?

Table 5 includes clinically significant drug interactions with Ryzodeg FlexTouch Pen.

Table 5: Clinically Significant Drug Interactions with Ryzodeg FlexTouch Pen

See also:
What are the possible side effects of Ryzodeg FlexTouch Pen?

The following adverse reactions are also discussed elsewhere:

• Hypoglycemia
• Hypersensitivity and allergic reactions
• Hypokalemia

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.

The safety of Ryzodeg FlexTouch Pen in subjects with type 1 diabetes or type 2 diabetes was evaluated in five treat-to-target trials of 6-12 month duration.

The data in Table 1 reflect the exposure of 362 patients with type 1 diabetes to Ryzodeg FlexTouch Pen, with a mean exposure duration to Ryzodeg FlexTouch Pen of 43 weeks. The mean age was 41 years and 1% were older than 75 years. Fifty-two percent were male, 91% were White, 3% were Black or African American and 3% were Hispanic. The mean body mass index (BMI) was 26 kg/m². The mean duration of diabetes was 17 years and the mean HbA1c at baseline was 8.3%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported in 19%, 25%, 6% and 4% respectively. The mean eGFR at baseline was 88 mL/min/1.73 m² and 6% of patients had an eGFR less than 60 mL/min/1.73 m².

The data in Table 2 reflect the exposure of 998 patients with type 2 diabetes to Ryzodeg FlexTouch Pen with a mean exposure duration to Ryzodeg FlexTouch Pen of 24 weeks. The mean age was 58 years and 3% were older than 75 years. Fifty-four percent were male, 44% were White, 4% were Black or African American and 6% were Hispanic. The mean BMI was 29 kg/m². The mean duration of diabetes was 12 years and the mean HbA1c at baseline was 8.5%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported for 15%, 21%, 10% and 1% respectively. At baseline, the mean eGFR was 84 mL/min/1.73 m² and 11% of patients had an eGFR less than 60 mL/min/1.73 m.

Common adverse reactions (excluding hypoglycemia) occurring in Ryzodeg FlexTouch Pen-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. Common adverse reactions were defined as reactions occurring in ≥ 5% of the population studied. Hypoglycemia is not shown in these tables but discussed in a dedicated subsection below.

Table 1: Adverse Reactions Occurring in ≥ 5% of Ryzodeg FlexTouch Pen-Treated Patients with Type 1 Diabetes Mellitus

Table 2: Adverse Reactions Occurring in ≥ 5% of Ryzodeg FlexTouch Pen-Treated Patients with Type 2 Diabetes Mellitus

Hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Ryzodeg FlexTouch Pen. 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 Ryzodeg FlexTouch Pen with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that occur in clinical practice.

Rates of hypoglycemia by trial are shown in Table 3 for type 1 diabetes and Table 4 for type 2 diabetes for patients treated with Ryzodeg FlexTouch Pen. Severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A Novo Nordisk hypoglycemia episode was defined as a severe hypoglycemia episode or an episode where a laboratory or a self-measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms).

Table 3: Percent (%) of Patients with Type 1 Diabetes Experiencing at Least One Episode of Severe Hypoglycemia or Novo Nordisk Hypoglycemia§ on Ryzodeg FlexTouch Pen in Adult Clinical Trials

Table 4: Percent (%) of Patients with Type 2 Diabetes Experiencing at Least One Episode of Severe Hypoglycemia or Novo Nordisk Hypoglycemia§ on Ryzodeg FlexTouch Pen in Adult Clinical Trials

Allergic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including Ryzodeg FlexTouch Pen and may be life threatening. Hypersensitivity (manifested with swelling of tongue and lips, diarrhea, nausea, tiredness and itching) and urticaria were reported in 0.5% of patients treated with Ryzodeg FlexTouch Pen.

Lipodystrophy

Long-term use of insulin, including Ryzodeg FlexTouch Pen, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection sites within the same region to reduce the risk of lipodystrophy. In the clinical program, lipodystrophy was reported in 0.1% of patients treated with Ryzodeg FlexTouch Pen.

Injection Site Reactions

Patients taking Ryzodeg FlexTouch Pen may experience injection site reactions, including injection site hematoma, pain, hemorrhage, erythema, nodules, swelling, discoloration, pruritis, warmth, and injection site mass. In the clinical program, injection site reactions occurred in 2.0% of patients treated with Ryzodeg FlexTouch Pen.

Weight Gain

Weight gain can occur with insulin therapy, including Ryzodeg FlexTouch Pen, and has been attributed to the anabolic effects of insulin. In the clinical program, patients with type 1 diabetes treated with Ryzodeg FlexTouch Pen gained an average of 2.8 kg and patients with type 2 diabetes treated with Ryzodeg FlexTouch Pen gained an average of 1.6 kg.

Peripheral Edema

Insulin, including Ryzodeg FlexTouch Pen, may cause sodium retention and edema. In the clinical program, peripheral edema, occurred in 2.2% of patients with type 1 diabetes mellitus and 1.8% of patients with type 2 diabetes mellitus treated with Ryzodeg FlexTouch Pen.

Immunogenicity

As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form. 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 Ryzodeg FlexTouch Pen with the incidence of antibodies in other studies or to other products, may be misleading.

In studies of type 1 diabetes patients, 95.9% of patients who received Ryzodeg FlexTouch Pen once daily were positive for anti-insulin antibodies (AIA) at least once during the studies, including 89% that were positive at baseline, while 13% of these patients were positive for anti-IAsp antibodies at least once during the studies, including 6.4% who were positive at baseline. In studies of type 2 diabetes patients, 67.5% of patients who received Ryzodeg FlexTouch Pen once daily were positive for AIA at least once during the studies, including 45.4% that were positive at baseline, while 17.1% of these patients were positive for anti-IAsp antibodies at least once during the studies, including 12.3% who were positive at baseline. The antibody incidence rates for type 2 diabetes may be underreported due to potential assay interference by endogenous insulin in samples in these patients. The presence of antibodies that affect clinical efficacy may necessitate dose adjustments to correct for tendencies toward hyper- or hypoglycemia. The incidence of anti-Insulin Degludec (Ryzodeg FlexTouch Pen) antibodies has not been established.