Pharmacy Diabetes

Insulin-Ryzodeg

Insulin degludec (rys) and insulin aspart (rys)

  • RYZODEG 70/30 is a soluble insulin product consisting of insulin degludec (ultra-long-acting basal insulin) and insulin aspart (rapid acting mealtime insulin) administered in one injection.

  • For use in diabetes mellitus in patients aged 6 years and older.

For the latest PBS indications for Ryzodeg please see
https://www.pbs.gov.au/medicine/item/11417X-11426J

  • RYZODEG 70/30 is a soluble insulin product consisting of the ultra-long-acting basal insulin degludec and the rapid acting prandial insulin aspart in a ratio of 70:30.
  • RYZODEG 70/30 can be administered once or twice a day always with the main meals.
  • If Ryzodeg is only being injected once a day the timing of the dose can be changed to suit changes in daily lifestyle BUT the dose should always be administered with the MAIN carbohydrate containing meal of each day.
  • In individuals with type 2 diabetes mellitus, RYZODEG 70/30 can be administered alone, in combination with oral diabetes products approved for use with insulin, and in combination with bolus insulin. The recommended total daily starting dose of RYZODEG 70/30 is 10 units with meal(s). Dosage adjustments should be on an individual basis according to glucose management and co-morbidities.
    Note: Diabetes MedsCheck with referral for blood glucose monitoring, education on injection technique and managing hypoglycaemia.
  • In type 1 diabetes mellitus, RYZODEG 70/30 is to be used once daily at mealtime in combination with short-/rapid acting insulin at the remaining meals. This should then be followed by individual dosage adjustments according to glucose management and co-morbidities.
    Note: MedsCheck with counselling on blood glucose monitoring and referral to healthcare team for education on injection technique and managing hypoglycaemia. Those with type 1 diabetes do not qualify for a Diabetes MedsCheck so information given will need to be paid under a Medscheck rather than a Diabetes MedsCheck.
  • RYZODEG 70/30 combines the ultra-long-acting basal insulin degludec and the rapid acting prandial insulin aspart in one injection.
  • RYZODEG 70/30 is for subcutaneous administration only and must not be injected intravenously, intramuscularly or for use in insulin infusion pumps.
  • RYZODEG 70/30 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 in order to reduce the risk of lipodystrophy and cutaneous amyloidosis.
  • RYZODEG 70/30 FlexTouch® is a pre-filled pen which delivers 1–80 units in increments of 1 unit.
  • RYZODEG 70/30 Penfill® is designed to be used with Novo Nordisk insulin delivery systems. The cartridge must not be refilled.
  • Use in renal impairment: RYZODEG 70/30 can be used in renal impairment. As with all insulins, glucose monitoring should be intensified, and dosage adjustment should occur on an individual basis.
  • Use in liver impairment: RYZODEG 70/30 can be used in hepatic impairment. As with all insulins, glucose monitoring should be intensified, and dosage adjustment should occur on an individual basis.

  • RYZODEG 70/30 can be used in the elderly. As with all insulins, glucose monitoring should be intensified, and dosage adjustment should occur on an individual basis.

  • RYZODEG 70/30 can be used in children and adolescents from the age of 6 years.

  • Hypersensitivity to insulin degludec, insulin aspart or to any of the excipients.

  • Hypoglycaemia: Hypoglycaemia is the most common adverse effect of insulins. As with all insulins, particular caution (including intensified blood glucose monitoring) should be exercised in individuals who are at greater risk of clinically significant sequelae from hypoglycaemic episodes.
    RYZODEG 70/30 must be taken with a carbohydrate containing meal. Omission of a meal or unplanned strenuous physical exercise may lead to hypoglycaemia.
    Dose reductions and increased frequency of glucose monitoring may be required when RYZODEG 70/30 is co-administered with insulin secretagogues or GLP-1 agonists as they may potentiate the risk of hypoglycaemia. In children, extra care should be taken to match insulin doses with food intake and physical activities to minimise the risk of hypoglycaemia.
    Note: Diabetes MedsCheck with counselling on hypoglycaemia, blood glucose monitoring information and side effect profile. Where hypoglycaemia is occurring regularly, consider referral to healthcare team for dose adjustment.
  • Hyperglycaemia: Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Symptoms of hyperglycaemia usually developed gradually, over a period of hours or days. They include nausea, vomiting, drowsiness, flushed dry skin, dry mouth, increased frequency of urination, thirst, and loss of appetite as well as acetone breath. Untreated hyperglycaemic events may be life threatening. Administration of rapid-acting insulin is recommended in situations with severe hyperglycaemia.
    Note: Diabetes MedsCheck with referral to healthcare team for sick day management plan.

  • Injection site and allergic reactions. As with any insulin therapy, lipodystrophy may occur at the injection site and delay insulin absorption. Other injection site reactions with insulin therapy include redness, pain, itching, hives, swelling and inflammation. (Diabetes Medscheck education about side effects and referral to CDE to establish correct injection technique and allied health care professionals)
  • Insulin antibodies. Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose to correct a tendency to hyper- or hypoglycaemia.
    Note: Diabetes MedsCheck with referral to healthcare team for education where suspected.
  • Eye disorder: Intensification of insulin therapy with abrupt improvement in glycaemic management may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemia decreases the risk of progression of diabetic retinopathy.
    Note: Diabetes MedsCheck with referral to health care team for education if suspected.
  • Skin and subcutaneous tissue disorders: Individuals must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and declined glycaemic management following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia.
    Note: Diabetes MedsCheck with referral to healthcare team for correct injection technique and managing hypoglycaemia.

After subcutaneous injection, soluble and stable multi-hexamers of insulin degludec are formed creating a depot in the subcutaneous tissue, while not interfering with the rapid release of insulin aspart monomers into the circulation. Insulin degludec monomers gradually separate from the multi-hexamers resulting in a slow and continuous delivery of insulin degludec into the circulation. Steady-state serum concentrations of the ultra-long-acting component (insulin degludec) is reached after 2-3 days of daily RYZODEG 70/30 administration. The rapid absorption characteristics of the well-established insulin aspart are maintained by RYZODEG 70/30. The pharmacokinetic profile for insulin aspart appears 14 minutes after injection with a peak concentration after 72 minutes.

The affinity of insulin degludec to serum albumin corresponds to a plasma protein binding of >99% in human plasma. Insulin aspart has a low binding to plasma proteins, <10%, like that seen with regular human insulin.

Degradation of insulin degludec and insulin aspart is like that of human insulin.

The half-life after subcutaneous administration of RYZODEG 70/30 is determined by the rate of absorption from the subcutaneous tissue. The half-life of the basal component, insulin degludec, at steady state is approximately 25 hours independent of dose.
For more information on Ryzodeg, please go to
https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-02728-1&d=202105141016933