Insulin degludec + Insulin aspart 70/30 premixed

Insulin degludec + Insulin aspart 70/30 premixed is used for: Treatment of diabetes mellitus in adults.

Subcutaneous Prefilled pen Insulin degludec 70 units/insulin aspart 30 units per mL (ie, 100 units/mL for combination) 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 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 T2DM 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 Dose Adjustment Individualize and titrate the dose based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal Adjust dose according to blood glucose measurements before breakfast (fasting) The recommended days between dose increases is 3-4 days Dose adjustments may be needed with changes in physical activity, changes in meal patterns (ie, macronutrient content or timing of food intake), changes in renal or hepatic function, or during acute illness to minimize the risk of hypoglycemia or hyperglycemia If a dose of insulin degludec/insulin aspart 70/30 is missed, the next dose should be taken 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

Safety and efficacy not established

Renal impairment: Dose adjustments may be needed.

Administer subcutaneously in the upper arm, thigh or abdominal wall. A subcutaneous injection into the abdominal wall results in a faster absorption than from other injection sites. Inject SC once or twice daily with any main meal Administer a rapid- or a short-acting insulin at other meals if needed Patients with type 1 diabetes, will generally require a rapid- or short-acting insulin at meals when insulin degludec/insulin aspart 70/30 is not administered for optimal glucose control

Hypersensitivity to the active substances or to any of the excipients.

Hypoglycaemia Omission of a meal or unplanned strenuous physical exercise may lead to hypoglycaemia. Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. Concomitant illness, especially infections and fever, usually increases the patient's insulin requirement. Concomitant diseases in the kidney, liver or diseases affecting the adrenal, pituitary or thyroid gland may require changes in the insulin dose. Hyperglycaemia Administration of rapid-acting insulin is recommended in situations with severe hyperglycaemia. Inadequate dosing and/or discontinuation of treatment in patients requiring insulin may lead to hyperglycaemia and potentially to diabetic ketoacidosis. Furthermore, concomitant illness, especially infections, may lead to hyperglycaemia and thereby cause an increased insulin requirement. Eye disorder Intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. Avoidance of accidental mix-ups Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between this and other insulin products. Older patients (> 65 years old) Ryzodeg can be used in older patients. Glucose-monitoring is to be intensified and the insulin dose adjusted on an individual basis. Paediatric population This Insulin has been administered to children and adolescents up to 18 years of age for the investigation of pharmacokinetic properties. Safety and efficacy have not been investigated in children and adolescents.

Pregnancy 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

Side effects of Insulin degludec + Insulin aspart 70/30 premixed : >10% Nasopharyngitis (11.1-24.6%), Severe hypoglycemia (0.4-13.3%) 1-10% Headache (5.6-9.7%), URT infection (5.7-9.1%), Influenza (6.9%), Peripheral edema (1.8-2.2%), Injection site reaction (2%) <1% Allergic reaction, Lipodystrophy

Insulin degludec and insulin aspart binds specifically to the human insulin receptor and results 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.