Insulin Degludec/ Insulin Aspart

Registered South African indications:

• Diabetes mellitus

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy

Cautions

• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Omission of a meal or unplanned strenuous physical exercise
• Severe hypoglycaemia
• Severe hyperglycaemia
• Children (especially between 2-5 years old)
• Concomitant illness, especially infections and fever
• Concomitant renal, hepatic diseases or diseases affecting the adrenal, pituitary or thyroid gland
• High doses
• Long-standing diabetes
• Inadequate dosing and/or discontinuation of treatment in patients requiring insulin
• Transfer from other insulin agents (See additional prescribing points)
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: pfp, cat

Diabetes mellitus (Additional agent(s) may be required)
 - As a basal add-on to co-medication in those who are inadequately controlled in type 1 diabetes mellitus, used with short-acting soluble insulin for use at meal times when insulin degludec/ insulin aspart is not used

Insulin Degludec/ Insulin Aspart
70/30 (%)

• SC: 60-70% of the total daily insulin requirements, dly followed by individual dosage adjustments at the remaining meals
  See link: General guidance 

---

In type 1 diabetes mellitus: Is combined with short-/rapid-acting insulin at the remaining meals

---

- As a basal add-on to oral antidiabetic medicines in those who are inadequately controlled in type 2 diabetes mellitus 

Insulin Degludec/ Insulin Aspart
70/30 (%)

• SC: Initial: 10U, dly with meal followed by individual dosage adjustments
  See link: General guidance 

---

Insulin degludec/ insulin aspart can be administered once or twice daily with the main meal(s). When needed, time of administration can be changed as long as insulin degludec/ insulin aspart is dosed with a main meal

---

The potency of insulin analogues, including insulin degludec/ insulin aspart, is expressed in units (U). 1 unit (U) insulin degludec/ insulin aspart corresponds to 1 international unit (IU) of human insulin and one unit of all other insulin analogues

---

Insulin degludec/ insulin aspart is to be dosed in accordance with individual patients' needs. Dose adjustments are recommended to be primarily based on pre-breakfast glucose measurements

---

In type 2 diabetes mellitus: Can be combined with oral anti-diabetic agents approved for use with insulin, with or without bolus insulin

---

Dose adjustment may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness

---

Method of administration and directions of use: See additional prescribing points

---

Missed dose: See additional prescribing points

---

Transfer from other insulin medicinal agents: Close glucose monitoring is recommended during transfer and in the following weeks

---

Insulin degludec/ insulin aspart should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit

Paed. forms avail. in SA and covered in this monograph: pfp, cat

Diabetes mellitus

Insulin Degludec/ Insulin Aspart
70/30 (%)

• Younger than 2 years: Not established for use
• 2 years and older: Individualised dosages
  See link: General guidance 

---

When changing from another insulin regimen to insulin degludec/ insulin aspart, dose reduction of total insulin needs to be considered on an individual basis in order to minimise the risk of hypoglycaemia

---

Insulin degludec/ insulin aspart should be used with special caution in children 2-5 years old because data from the clinical trial indicate that there may be a higher risk for severe hypoglycaemia in children in this age group

---

Insulin degludec/ insulin aspart can be administered once or twice daily with the main meal(s). When needed, time of administration can be changed as long as insulin degludec/ insulin aspart is dosed with a main meal

---

The potency of insulin analogues, including insulin degludec/ insulin aspart, is expressed in units (U). 1 unit (U) insulin degludec/ insulin aspart corresponds to 1 international unit (IU) of human insulin and one unit of all other insulin analogues

---

In type 1 diabetes mellitus, insulin degludec/ insulin aspart is combined with short-/rapid-acting insulin at the remaining meals

---

Insulin degludec/ insulin aspart is to be dosed in accordance with individual patients' needs. Dose adjustments are recommended to be primarily based on pre-breakfast glucose measurements

---

Dose adjustment may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness

---

Method of administration and directions of use: See additional prescribing points

---

Missed dose: See additional prescribing points

Pregnancy

• Contraindicated
• Safety has not been established in pregnancy
• Insulin degludec/ insulin aspart should not be recommended for use during pregnancy

Breastfeeding

• Caution; not recommended
• Safety has not been established in breastfeeding
• It is unknown whether insulin degludec is excreted in human milk

Fertility

• No information available

Renal Impairment

• Caution; dose adjustment recommended 
  Insulin degludec/ insulin aspart can be used in renal impairment. Glucose monitoring is to be intensified and the insulin dose adjusted on an individual basis

Hepatic Impairment

• Caution; dose adjustment recommended 
  Insulin degludec/ insulin aspart can be used in hepatic impairment. Glucose monitoring is to be intensified and the insulin dose adjusted on an individual basis

Elderly

• Caution; dose adjustment recommended 
  Insulin degludec/ insulin aspart can be used in elderly patients. Glucose monitoring is to be intensified and the insulin dose adjusted on an individual basis

Drugs in Sport

• Prohibited - In and out of competition

Endocrine and Metabolic Disorders

• Hypoglycaemia

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Injection site reactions
• Lipodystrophy

Immune, Blood and Lymphatic System Disorders

• Peripheral oedema
• Hypersensitivity 

• Thiazolidinediones (TZDs)  
• Oral antidiabetic medicinal products  
• Glucagon-like peptide-1 (GLP-1) receptor agonists  
• Monoamine oxidase inhibitors (MAOIs)  
• Beta-blockers
• Angiotensin-converting enzyme (ACE) inhibitors  
• Salicylates
• Anabolic steroids
• Sulphonamides
• Oral contraceptive 
• Thiazides
• Glucocorticoids
• Thyroid hormones
• Sympathomimetics
• Growth hormones
• Danazol
• Octreotide
• Lanreotide

Other interactions

• Alcohol

• Blood glucose

Method of administration

• Insulin degludec/ insulin aspart is for subcutaneous administration only
• Insulin degludec/ insulin aspart must not be administered intravenously as it may result in severe hypoglycaemia
• Insulin degludec/ insulin aspart must not be administered intramuscularly as it may change the absorption
• Insulin degludec/ insulin aspart must not be used in insulin infusion pumps
• Insulin degludec/ insulin aspart is administered subcutaneously by injection in the abdominal wall, the upper arm or the thigh. Injection sites are always to be rotated within the same region to reduce the risk of lipodystrophy
• Do not use if the solution does not appear clear and colourless
• Do not use insulin degludec/ insulin aspart if it has been frozen
• Discard the needle after each injection

Avoidance of accidental mix-ups

• To avoid accidental mix-ups between insulin degludec/ insulin aspart and other insulin products, patients must be instructed to always check the label for the right type of insulin before each injection

Directions for use
Type 1 diabetes

• Doses and timing of concurrent short-/rapid-acting insulin products may need to be adjusted

Type 2 diabetes

• Patients switching from once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily insulin degludec/ insulin aspart at the same total insulin dose as the patient’s previous total daily insulin dose
• Patients switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to twice-daily insulin degludec/ insulin aspart at the same total insulin dose as the patient’s previous total daily insulin dose
• Patients switching from basal/bolus insulin therapy to insulin degludec/ insulin aspart will need to convert their dose based on individual needs. In general, patients are initiated on the same number of basal units
• Doses and timing of concomitant antidiabetic treatment may need to be adjusted

Flexibility (missed dose)

• Insulin degludec/ insulin aspart allows for flexibility in the timing of insulin administration as long as it is dosed with the main meal(s)
• If a dose of insulin degludec/ insulin aspart is missed, the patient can take the next dose 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

Incompatibilities

• Insulin degludec/ insulin aspart must not be added to infusion fluids or mixed with other medicinal products as this may cause degradation of the active substance
• Insulin degludec/ insulin aspart must not be added to infusion fluids
• Insulin degludec/ insulin aspart must not be mixed with other medicinal products

Transfer from other insulin agents

• Transferring a patient to another type, brand, or manufacturer of insulin must be done under medical supervision and may result in the need for change in dosage

Insulin degludec/insulin aspart is a soluble insulin product consisting of insulin degludec (ultra-long-acting basal insulin) and insulin aspart (rapid-acting meal-time insulin), administered in one injection. Insulin degludec and insulin aspart bind specifically to the human insulin receptor and result in the same pharmacological effects as human insulin. The blood glucose-lowering effect of insulin is due to the facilitated uptake of glucose following the binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.

Insulin degludec
Insulin degludec is an ultra-long-acting basal insulin that forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which insulin degludec is continuously and slowly absorbed into the circulation leading to a flat and stable glucose-lowering effect. Insulin degludec differs from human insulin by the omission of the amino acid threonine in position B-30 of the B-chain, and the subsequent addition of a side chain composed of glutamic acid and a C16 fatty acid. Insulin degludec binds specifically to the human insulin receptor and results in the same pharmacological effects as human insulin. The blood-glucose-lowering effect of insulin degludec is due to the facilitated uptake of glucose following the binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.

Insulin aspart
The blood glucose lowering effect of insulin aspart is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. The substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin. Insulin aspart is therefore more rapidly absorbed from the subcutaneous layer compared to soluble human insulin.

COMBINATION PREPARATIONS

70% Insulin Degludec / 30% Insulin Aspart 

Pre-filled pen (per ml) 100u

• Ryzodeg (Novo Nordisk) originator