Insulin Degludec and Insulin Aspart

Insulin Degludec/Insulin Aspart is a prescription medication used to treat Diabetes Mellitus Types 1 and 2. 

• Insulin Degludec/Insulin Aspart is available under the following different brand names: Ryzodeg. 

Adult dosage

Prefilled pen

• Insulin degludec 70 units/Insulin aspart 30 units per mL (ie, 100 units/mL for combination)

Diabetes Mellitus Types 1 and 2

Adult dosage

Starting dose in insulin naïve patients

• Type 1 diabetes mellitus: ~One third to one half of the total daily insulin dose; as a general rule; the remained of the total daily insulin dose should be administered as a short- or rapid-acting insulin divided between each daily meal; 0.2-0.4 units/kg can be used to calculate the initial total daily insulin dose in insulin-naïve patients with type 1 diabetes
• Type 2 diabetes mellitus: 10 units SC once daily
• Starting dose in patients with types 1 or 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 insulin degludec/insulin aspart 70/30 at the same unit dose and injection schedule as the premix or self-mix insulin
• In patient 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 degludec/insulin aspart 70/30
• Starting dose in patients with types 1 or 2 diabetes on a once or twice daily basal insulin alone or as part of a regimen or multiple daily injections
• Patients with Type 2 diabetes mellitus switching from regimen that includes only a once- or twice-daily basal insulin, start insulin degludec/insulin aspart 70/30 at the same unit dose and injection schedule
• For patients switching from once-daily basal insulin to once-daily insulin degludec/insulin aspart 70/30, 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 insulin degludec/insulin aspart 70/30 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 insulin degludec/insulin aspart 70/30

Dosage Considerations – Should be Given as Follows: 

• See "Dosages."

Common side effects of Insulin Degludec/Insulin Aspart include:

• body aches or pain, 
• fever, 
• hoarseness, 
• muscle aches, 
• sneezing, 
• stuffy or runny nose, 
• stuffy or congested feeling in your ears, 
• injection site reaction (redness, swelling, discoloration of the skin, lumps, pain, rash, tenderness), and
• increased body fat

Serious side effects of Insulin Degludec/Insulin Aspart include:

• hives, 
• difficulty breathing, 
• swelling of your face, lips, tongue, or throat, 
• worsening of your skin condition, 
• anxiety, 
• swelling of the arms, hands, lower legs, or feet,
• vision changes, 
• chills, 
• rapid weight gain, 
• cold sweat, 
• tingling or numbness in the hands or feet, 
• confusion, 
• unusual weight gain or loss,
• cool or pale skin, 
• cough, 
• depression, 
• little or no urination, 
• dizziness, 
• lightheadedness, 
• fast or irregular heartbeat, 
• fainting, 
• headache, 
• dry mouth, 
• increased or loss of appetite, 
• itching, 
• reddening of the skin (especially around the ears),
• sweating, 
• pressure in your chest, 
• rash,
• nausea, 
• vomiting,
• increased thirst, 
• nightmares, 
• seizures, 
• shakiness, 
• slurred speech, 
• tiredness, and
• weakness

Rare side effects of Insulin Degludec/Insulin Aspart include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Insulin Degludec/Insulin Aspart has severe interactions with no other drugs.
• Insulin Degludec/Insulin Aspart has serious interactions with the following drugs:
  • ethanol
• Insulin Degludec/Insulin Aspart has moderate interactions with at least 168 other drugs. 
• Insulin Degludec/Insulin Aspart has minor interactions with the following drugs:
  • stevia

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• During episodes of hypoglycemia.
• Documented hypersensitivity

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Insulin Degludec/Insulin Aspart?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Insulin Degludec/Insulin Aspart?”

Cautions

• Do not share, even if the needle is changed; sharing poses a risk for transmission of blood-borne pathogens
• Changes in insulin, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia; these changes should be made cautiously and only under medical supervision, and the frequency of blood glucose monitoring should be increased
• Severe, life-threatening, generalized allergy, including anaphylaxis, can occur
• All insulin products cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia; monitor potassium levels in patients at risk for hypokalemia including patients using potassium-lowering medications or those taking medications sensitive to serum potassium concentrations; treat if indicated
• Thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists can cause dose-related fluid retention, particularly when used in combination with insulin; this may lead to or exacerbate heart failure
• Hyperglycemia or hypoglycemia with changes in insulin regimen
  • Hypoglycemia is the most common adverse effect and can happen suddenly; severe hypoglycemia can cause seizures, may be life-threatening, or cause death
  • Hypoglycemia can impair concentration ability and reaction time and place an individual and others at risk in situations where these abilities are important (eg, driving or operating other machinery)
  • Risk increases with intensity of glycemic control and is related to the duration of action of the insulin
  • Other factors that may increase the risk of hypoglycemia include changes in meal pattern (eg, macronutrient content or timing of meals), changes in level of physical activity, or changes to coadministered medication
  • Renal or hepatic impairment may increase hypoglycemia risk
  • In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended
  • Accidental mix-ups between basal insulin products and other insulins, particularly rapid-insulins, have been reported
  • Do not transfer insulin degludec from the prefilled pen to a syringe; the markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia
  • Changes in insulin, insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia
  • Changes should be made cautiously and only under close medical supervision and frequency of blood glucose monitoring should be increased
  • Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis reported to result in hyperglycemia; a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia
  • 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 injection site to unaffected areas and closely monitor for hypoglycemia
  • For patients with type 2 diabetes, dosage adjustments in concomitant oral antidiabetic treatment may be needed

Pregnancy and Lactation

• There are no available data in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; available information from published randomized controlled trials with insulin aspart use during second trimester of pregnancy have not reported association with insulin aspart and major birth defects or adverse maternal or fetal outcomes
• Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity.
• Lactation: There are no data on presence of drug in human milk, effects on breastfed infant, or effect on milk production; insulin degludec is present in rat milk; one small published study reported that exogenous insulin, including insulin aspart, was present in human milk; however, there is insufficient information to determine effects on the breastfed infant and no available information on effects on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for insulin, potential adverse effects on breastfed child therapy or from underlying maternal condition.