insulin degludec and insulin aspart

Insulin degludec/insulin aspart is a combination of two types of insulins used to improve glycemic control in adults and children above 12 months of age who have diabetes mellitus type I or II. Insulin used to treat diabetes is a biological product, manufactured in the lab using recombinant DNA technology, and is structurally similar to human insulin, a natural hormone produced by the pancreas. Insulin degludec is long-acting insulin and insulin aspart is a rapid-acting insulin, both of which help maintain glycemic control.

Insulin is released by the pancreas after a meal to regulate the metabolism of carbohydrates, fats and proteins absorbed from food. Diabetes is a metabolic disorder with high blood glucose levels (hyperglycemia), caused by insulin dysfunction which impairs the ability of cells to absorb glucose for energy. Diabetes affects the entire body and can damage all organs, particularly, nerves, kidneys and eyes.

Type I diabetes is a genetic autoimmune condition in which the immune cells destroy the insulin-producing cells in the pancreas, resulting in little or complete absence of insulin secretion. Type I diabetes develops typically in adolescence. Type II diabetes is more common and is mostly related to lifestyle, and develops later in life because the pancreas produces less insulin or the body becomes resistant to insulin.

Insulin degludec and insulin aspart provide the insulin the body requires for regulating glucose metabolism in the body and for maintaining optimal glucose levels. Insulin reduces blood glucose by stimulating the uptake of glucose from blood into the organs and tissues, particularly skeletal muscle, fat cells and the liver. Insulin inhibits glucose production in the liver, inhibits breakdown of fats and proteins, and enhances protein synthesis.

Insulin degludec/insulin aspart is a solution containing 70% insulin degludec and 30% insulin aspart, and is injected once daily into the tissue under the skin (subcutaneous) with a prefilled pen. Insulin aspart is a rapid-acting insulin with onset of effect within 15 minutes, peak effect in 30-90 minutes and duration of 3-7 hours. Insulin degludec takes effect in 30 to 90 minutes and is slowly released, and its sugar-lowering (hypoglycemic) effects last for 24 hours.

• Do not administer insulin degludec/insulin aspart to patients:
  • With hypersensitivity to any component of insulin degludec/insulin aspart
  • During episodes of hypoglycemia
• Train patients to self-administer insulin degludec/insulin aspart appropriately with the prefilled pens and advise them to never share the delivery devices, to prevent the risk of bloodborne infections.
• Changes in insulin type, manufacturer or mode of administration can affect glycemic control and cause hyperglycemia or hypoglycemia. Insulin regimen changes should be made under close medical supervision with the recommended dosage and increased frequency of blood glucose monitoring. Type II patients may require concomitant oral anti-diabetic treatment.
• Hypoglycemia is the most common adverse effect with all insulin treatments.
  • Hypoglycemia can happen suddenly and symptoms differ in patients and may change over time in the same patient.
  • Prolonged or severe hypoglycemia can cause convulsions, unconsciousness, temporary or permanent brain damage, or even death. 
  • Hypoglycemia risk increases in patients with impaired liver or kidney function.
  • Patients with long-standing diabetes, diabetic nerve disease (neuropathy), recurrent hypoglycemia, or patients taking beta-blockers may have reduced awareness of hypoglycemic symptoms.
  • Blood glucose monitoring should be performed more frequently in patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia.
  • Patients and caregivers must be educated to self-monitor glucose levels, recognize and manage hypoglycemia.
• Insulin degludec/insulin aspart can cause severe, life-threatening, generalized allergic reactions including anaphylaxis. If a patient develops hypersensitivity reactions, discontinue insulin degludec/insulin aspart and monitor the patient until symptoms resolve. Do not use in patients who have had hypersensitivity reactions to any component of insulin degludec/insulin aspart.
• Insulin causes shift of potassium into the cells and can lead to low blood potassium (hypokalemia), which, if untreated, can cause respiratory paralysis and life-threatening irregular ventricular rhythm (ventricular arrhythmia) and death. Monitor potassium levels in patients at risk for hypokalemia, including patients taking potassium-lowering medications or medications sensitive to potassium concentrations.
• Concurrent use with thiazolidinediones, a class of oral antidiabetic drugs known as peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention and increase the risk for heart failure. Closely monitor such patients for symptoms and if the patient develops heart failure, treat appropriately and consider discontinuation or dose reduction of PPAR-gamma agonist.
• Repeated insulin injections into the same areas can cause skin thickening or depression (lipodystrophy). Injecting in these areas can reduce insulin absorption and result in hyperglycemia. A sudden change in the injection site (to an unaffected area) may result in hypoglycemia.

Common side effects of insulin degludec and insulin aspart include:

• Hypoglycemia
• Nose and throat inflammation (nasopharyngitis)
• Headache
• Upper respiratory tract infection
• Influenza
• Allergic/hypersensitivity reactions including:
  • Generalized skin reactions
  • Drop in blood pressure (hypotension)
  • Bronchospasm
  • Swelling in subcutaneous and mucous tissue (angioedema)
  • Shock
  • Anaphylaxis
  • Swelling of tongue and lips
  • Nausea
  • Diarrhea
  • Tiredness
  • Hives (urticaria)
  • Itching (pruritus)
• Injection site reactions such as:
  • Hematoma
  • Hemorrhage
  • Redness (erythema)
  • Pain
  • Nodules
  • Swelling
  • Discoloration
  • Itching (pruritus)
  • Warmth
  • Mass
  • Wasting of skin tissue (lipoatrophy)
  • Thickening of skin tissue (lipohypertrophy)
• Weight gain
• Swelling of extremities (peripheral edema)
• Development of anti-insulin antibodies

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

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

Prefilled pen

• Insulin degludec 70 units/insulin aspart 30 units per mL (i.e., 100 units/mL for combination)

Adult:

Diabetes Mellitus Types 1 and 2

• Indicated to improve glycemic control in adults with diabetes mellitus

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 remainder 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 subcutaneously (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 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 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 of 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

Dosing Considerations

• Not recommended for treatment of diabetic ketoacidosis

Pediatric:

Diabetes Mellitus Types 1 and 2

Starting dose in insulin naïve patients

• Children below 1 year: Not studied
• Children 1 year and above:
  • Type 1 diabetes mellitus: One-third to one-half of the total daily insulin dose; as a general rule; the remainder 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

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

• Children below 1 year: Not studied
• Children 1 year and above
  • Start insulin degludec/insulin aspart 70/30 80% of total daily mixed insulin dose in order to minimize risk of hypoglycemia and administer once daily with main meal of the day
  • In patients also using short- or rapid-acting insulin at mealtimes continue the short- or rapid-acting insulin at same dose for meals NOT covered by insulin 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 of multiple daily injections

• Children below 1 year: Not studied
• Children 1 year and above:
  • Start insulin degludec/insulin aspart 70/30 at 80% of long- or intermediate-acting insulin component of daily regimen in order to minimize risk of hypoglycemia and administer once-daily with the main meal of the day
  • In patients also using short- or rapid-acting insulin at meantime continue the short- or rapid-acting insulin at the same dose for meals NOT covered by insulin degludec/insulin aspart 70/30

Overdose

• Overdose of insulin degludec/insulin aspart can cause severe hypoglycemia and hypokalemia.
• Mild hypoglycemia can be treated with oral glucose and appropriate adjustments in drug dosage, meal patterns and exercise, as appropriate.
• Severe hypoglycemic episodes with coma, seizure or neurologic impairment may be treated with concentrated intravenous glucose or intramuscular or subcutaneous injection of glucagon. After recovery, additional carbohydrate intake and continued observation of the patient may be required to prevent recurrence of hypoglycemia.
• Hypokalemia should be corrected with appropriate supplemental potassium.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Insulin degludec/insulin aspart has no listed severe interactions with other drugs.
• Serious interactions of insulin degludec/insulin aspart include:
  • ethanol
• Insulin degludec/insulin aspart has moderate interactions with at least 172 different drugs.
• Mild interactions of insulin degludec/insulin aspart include:
  • stevia

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There is inadequate information on the use of insulin degludec/insulin aspart in pregnant women to determine an insulin-related risk for major birth defect or miscarriage.
• Good glycemic control before conception and throughout pregnancy in patients with diabetes or history of gestational diabetes is essential for maternal and fetal health.
• Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications, and fetal risks for birth defects and abnormally large growth (macrosomia).
• Natural insulin is present in breastmilk, however, there is no information on the presence of insulin degludec/insulin aspart is in breastmilk, or its effects on milk production or the breastfed infant.
• Decision to breastfeed during treatment with insulin degludec/insulin aspart should be based on the mother’s clinical need for the drug, the developmental and health benefits of breastfeeding and potential risks to the breastfed infant from exposure to the drug or mother’s underlying condition.

• Never share your pen, needles, or syringes with others, or use those used by others.
• Always check labels before every injection to avoid errors of mix-up with other insulin products.
• Do not transfer insulin degludec/insulin aspart from the pen into a syringe, the syringe markings will not be a correct measure and can result in overdose and hypoglycemia.
• Administer your insulin degludec/insulin aspart injections exactly as prescribed, any regimen change must be done only under your physician’s supervision.
• Rotate your injection sites and do not inject into areas of skin that have scars, pits, lumps, scales, or are tender or bruised.
• Learn to monitor glucose levels and to recognize symptoms of hypoglycemia. Always carry sweets such as hard candy for immediate use and seek medical help if symptoms don’t resolve.
• Report to your physician immediately if you experience any allergic reaction to insulin degludec/insulin aspart.
• Avoid alcohol, it can have an additive effect and increase the risk for hypoglycemia.
• Hypoglycemia can impair concentration ability and reaction time, be cautious about activities such as driving and operating heavy machinery.
• Store insulin degludec/insulin aspart prefilled pens safely out of reach of children.
• In case of overdose, seek medical help immediately or call Poison Control.