Ryzodeg contains a combination of insulin aspart and insulin degludec. Insulin is a hormone that works by lowering levels of glucose (sugar) in the blood. Insulin aspart is a fast-acting insulin. Insulin degludec is a long-acting insulin. This combination insulin starts to work within 10 to 20 minutes after injection, peaks in about 1 hour, and keeps working for 24 hours or longer.

Ryzodeg is used to improve blood sugar control in adults with diabetes mellitus.

Ryzodeg may be used for type 1 or type 2 diabetes.

You should not use Ryzodeg if you are having an episode of hypoglycemia (low blood sugar).

Never share a Ryzodeg injection pen with another person, even if the needle has been changed.

Before taking this medicine

You should not use Ryzodeg if you are allergic to insulin aspart or insulin degludec, or if you are having an episode of hypoglycemia (low blood sugar).

Ryzodeg is not approved for use by anyone younger than 18 years old.

To make sure Ryzodeg is safe for you, tell your doctor if you have:

• liver or kidney disease;

• low levels of potassium in your blood (hypokalemia); or

• diabetic ketoacidosis (call your doctor for treatment).

Tell your doctor if you also take pioglitazone or rosiglitazone (sometimes contained in combinations with glimepiride or metformin). Taking certain oral diabetes medicines while you are using Ryzodeg may increase your risk of serious heart problems.

Follow your doctor's instructions about using Ryzodeg if you are pregnant. Blood sugar control is very important during pregnancy, and your dose needs may be different during each trimester of pregnancy.

Ask your doctor about using Ryzodeg if you are breast-feeding a baby. Your dose needs may be different while you are nursing.

Use Ryzodeg exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Ryzodeg is injected under the skin. You will be shown how to use injections at home. Do not give yourself Ryzodeg if you do not understand how to use the injection and properly dispose of used needles and syringes.

Ryzodeg must not be given with an insulin pump, or mixed with other insulins.

Ryzodeg 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.

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

Never share an injection pen with another person, even if the needle has been changed. Sharing these devices can allow infections or disease to pass from one person to another.

Use a disposable needle only once. 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.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your insulin dose or schedule.

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

Keep this medicine in its original container protected from heat and light. Do not freeze Ryzodeg or store it near the cooling element in a refrigerator. Throw away any Ryzodeg that has been frozen.

Storing unopened (not in use) Ryzodeg:

• Refrigerate and use until expiration date.

Storing opened (in use) Ryzodeg:

• Store the injection pen at room temperature (do not refrigerate) and use within 28 days. Do not store the injection pen with a needle attached.

Do not use the medicine if it has changed colors or looks cloudy. Call your pharmacist for new medicine.

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

Usual Adult Dose of Ryzodeg for Diabetes Type 1:

Dose should be individualized based on clinical response; Generally used in regimens with additional short or rapid acting insulin at meals not covered by this insulin mix.

Insulin-naive patients:
Initial dose: One-third to one-half the total daily insulin requirement subcutaneously once a day.
-The initial total daily insulin requirement in insulin naive patients is generally 0.2 to 0.4 units of insulin per kilogram of body weight.

Switching from Once or Twice Daily Premix Insulin:
-Initiate at the same unit dose and injection schedule as the current premix or self-mix insulin.
-Short or rapid-acting insulin should be used for meals not covered by this insulin mix.

Switching from Once or Twice Daily Basal Insulin:
-Initiate at the same unit dose as the basal insulin once a day with the main meal of the day.
-Short or rapid-acting insulin should be used for meals not covered by this insulin mix.

Comments:
-Adjust dosage according to metabolic needs, blood glucose measurements, and glycemic goals.
-Dose increases should occur no sooner than every 3 to 4 days; dose adjustment should be made based on morning fasting blood glucose measurement (before breakfast).
-When changing treatment regimens, the dose and frequency of short or rapid-acting insulin may need to be adjusted.
-To minimize hypoglycemia, closely monitor blood glucose, especially with changing regimens.

Use: To improve glycemic control in patients with diabetes mellitus.

Usual Adult Dose of Ryzodeg for Diabetes Type 2:

Initial dose: 10 units subcutaneously once a day

Switching from Once or Twice Daily Premix Insulin:
-Initiate subcutaneously at the same unit dose and injection schedule as the current premix or self-mix insulin.
-Short or rapid-acting insulin may be used for meals not covered by this insulin mix.

Switching from Once or Twice Daily Basal Insulin:
-Initiate at the same unit dose as the basal insulin once a day with the main meal of the day.
-For patients switching from once-daily basal insulin to this insulin mix, monitor blood glucose after starting therapy due to the rapid-acting insulin component.
-Short or rapid-acting insulin may be used for meals not covered by this insulin mix.

Comments:
-Adjust dosage according to metabolic needs, blood glucose measurements, and glycemic goals; dose increases should occur no sooner than every 3 to 4 days.
-When changing treatment regimens, the dose and frequency of short or rapid-acting insulin or other anti-diabetic medications may need to be adjusted.
-To minimize hypoglycemia, closely monitor blood glucose, especially with changing regimens.

Use: To improve glycemic control in patients with diabetes mellitus.

You should not use Ryzodeg if you are allergic to insulin aspart or insulin degludec, or if you are having an episode of hypoglycemia (low blood sugar).

Ryzodeg is not approved for use by anyone younger than 18 years old.

To make sure Ryzodeg is safe for you, tell your doctor if you have:

• liver or kidney disease;

• low levels of potassium in your blood (hypokalemia); or

• diabetic ketoacidosis (call your doctor for treatment).

Tell your doctor if you also take pioglitazone or rosiglitazone (sometimes contained in combinations with glimepiride or metformin). Taking certain oral diabetes medicines while you are using Ryzodeg may increase your risk of serious heart problems.

Follow your doctor's instructions about using Ryzodeg if you are pregnant. Blood sugar control is very important during pregnancy, and your dose needs may be different during each trimester of pregnancy.

Ask your doctor about using Ryzodeg if you are breast-feeding a baby. Your dose needs may be different while you are nursing.

Skip the missed dose and use the medicine at your next main meal on the same day. Then continue your regular dosing schedule. Do not use extra insulin to make up the missed dose.

Keep Ryzodeg on hand at all times. Get your prescription refilled before you run out of medicine completely.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Insulin overdose can cause life-threatening hypoglycemia. Symptoms include drowsiness, confusion, blurred vision, numbness or tingling in your mouth, trouble speaking, muscle weakness, clumsy or jerky movements, seizure (convulsions), or loss of consciousness.

Avoid medication errors by always checking the medicine label before injecting your insulin.

Avoid drinking alcohol. It can cause low blood sugar and may interfere with your diabetes treatment.

Get emergency medical help if you have signs of an allergic reaction to Ryzodeg: hives, itching, skin rash; wheezing, tiredness, trouble breathing; feeling like you might pass out; nausea, diarrhea; swelling of your face, lips, tongue, or throat.

Call your doctor if you have:

• fluid retention - weight gain, swelling in your hands or feet, feeling short of breath; or

• low potassium - leg cramps, constipation, irregular heartbeats, fluttering in your chest, extreme thirst, increased urination, numbness or tingling, muscle weakness or limp feeling.

Common Ryzodeg side effects may include:

• low blood sugar;

• itching, mild skin rash; or

• thickening or hollowing of the skin where you injected the medicine.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Many other medicines can affect your blood sugar, and some medicines can increase or decrease the effects of insulin. Some drugs can also cause you to have fewer symptoms of hypoglycemia, making it harder to tell when your blood sugar is low. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. This includes prescription and over-the-counter medicines, vitamins, and herbal products.