Ryzodeg (Insulin Aspart_Insulin Degludec)

Ryzodeg (Insulin Aspart_Insulin Degludec) Uses, Dosage, Side Effects, Food Interaction and all others data.

The primary activity of Insulin Aspart is the regulation of glucose metabolism. Insulin Aspart bind to the insulin receptors on muscle and fat cells and lower blood glucose by facilitating the cellular uptake of glucose and simultaneously inhibiting the output of glucose from the liver.

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours.

The primary activity of insulin, including Insulin Degludec, is regulation of glucose metabolism. Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis. Insulin Degludec forms multihexamers when injected into the subcutaneous tissue resulting in a subcutaneous insulin degludec depot. The protracted time action profile of Insulin Degludec is predominantly due to delayed absorption of insulin degludec from the subcutaneous tissue to the systemic circulation and to a lesser extent due to binding of insulin degludec to circulating albumin.

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, the pancreas produces a continuous supply of low levels of basal insulin along with spikes of insulin following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by the liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin detemir is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. The onset of action of insulin detemir is 1 to 2 hours and its duration of action is up to 24 hours. Interestingly, it has a lower affinity (30%) for the insulin receptor than human insulin.

Ryzodeg (Insulin Aspart_Insulin Degludec)
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Ryzodeg (Insulin Aspart_Insulin Degludec)
Generic	Insulin aspart + insulin degludec
Type
Therapeutic Class
Manufacturer
Available Country	Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom, USA
Last Updated:	September 19, 2023 at 7:00 am

Ryzodeg (Insulin Aspart_Insulin Degludec)

Uses

Insulin Aspart is a rapid acting human insulin analog used to improve glycemic control in adults and children with diabetes mellitus.

Insulin Degludec is used for once-daily treatment of adults with diabetes mellitus to improve glycemic control. Insulin Degludec is not recommended for the treatment of diabetic ketoacidosis.

Ryzodeg (Insulin Aspart_Insulin Degludec) is also used to associated treatment for these conditions: Diabetes Mellitus, Diabetic Ketoacidosis, Gestational Diabetes Mellitus (GDM), Hyperglycemia during critical illnessDiabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus

How Ryzodeg (Insulin Aspart_Insulin Degludec) works

Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action.

Insulin detemir binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signalling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism.

Dosage

Ryzodeg (Insulin Aspart_Insulin Degludec) dosage

Usual range: 0.5-1 units/kg/day. When used in a meal-related SC inj treatment regimen, insulin aspart may provide 50-70% of total insulin requirement with the remainder provided by an intermediate-acting or long-acting insulinThe dosage of insulin aspart must be individualized

Subcutaneous injection: insulin aspart should generally be given immediately (within 5-10 minutes) prior to the start of a meal

Use in pumps: Change the insulin aspart in the reservoir at least every 6 days, change the infusion set, and the infusion set insertion site at least every 3 daysinsulin aspart should not be mixed with other insulins or with a diluent when it is used in the pump

Intravenous use: Insulin aspart should be used at concentrations from 0.05 U/mL to 1.0 U/mL insulin aspart in infusion systems using polypropylene infusion bags. insulin aspart has been shown to be stable in infusion fluids such as 0.9% sodium chloride

Insulin Degludec is ultra long-acting basal insulin for once-daily at any time of the day, preferably at the same time every day.

Patients with type 2 diabetes mellitus: The recommended daily starting dose is 10 units followed by individual dosage adjustments.

Patients with type 1 diabetes mellitus: Insulin Degludec is to be used once-daily with meal-time insulin and requires subsequent individual dosage adjustments.

In patients with type 2 diabetes mellitus,Insulin Degludec can be administered alone or in any combination with oral anti-diabetic medicinal products, GLP-1 receptor agonists and bolus insulin. In type 1 diabetes mellitus, Insulin Degludec must be combined with short-/rapid-acting insulin to cover mealtime insulin requirements. On occasions when administration at the same time of the day is not possible, Insulin Degludec allows for flexibility in the timing of insulin administration. A minimum of 8 hours between injections should always be ensured. Patients who forget a dose, are advised to take it upon discovery and then resume their usual once-daily dosing schedule.

Administer 5-10 min before meal

Side Effects

Hypoglycaemia; oedema; pruritus; rash; hypersensitivity reactions; lipoatrophy or lipohypertrophy with SC Inj (rotate Inj site).

Nasopharyngitis, Severe hypoglycemic episode, Upper respiratory tract infection, Headache, Diarrhea, Sinusitis, Gastroenteritis, Injection site reactions, Peripheral edema

Toxicity

Inappropriately high dosages relative to food intake and/or energy expenditure may result in severe and sometimes prolonged and life-threatening hypoglycemia. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia.

Observe for signs and symptoms of hypoglycemia, hypokalemia, and fluid retention and heart failure with concomitant use of Thiazolidinediones. Pregnancy Category C

Precaution

Renal or hepatic impairment; pregnancy; lactation. Transferring from other insulin. Monitor serum glucose, potassium, electrolytes, HbA1c and lipid profile. Concomitant illness esp infections; hypokalaemia.

Insulin Degludecs must not be injected into a vein (intravenously) or a muscle (intramuscularly) and must not be used in infusion pumps.

There is no experience with Insulin Degludec in children and adolescents under 18 years of age.

Interaction

Effects may be increased by: oral antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, propoxyphene, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics. Effects may be decreased by: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents, isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, oral contraceptives, lithium. Signs of hypoglycaemia may be masked by β-blockers, clonidine.

Decreased hypoglycaemic effect with corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somatropin, sympathomimetic agents, thyroid hormones, oestrogens, progestins (e.g. in oral contraceptives), protease inhibitors and atypical antipsychotic (e.g. olanzapine and clozapine). Increased hypoglycaemic effect with oral antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics. Decreased insulin resistance with octreotide and lanreotide. Increased risk of wt gain and peripheral oedema with pioglitazone, rosiglitazone. Decreased effect of sermorelin.

Elimination Route

In studies of healthy volunteers and patients with type 1 diabetes, the median time to maximum concentration of insulin aspart in these trials was 40 to 50 minutes versus 80 to 120 minutes, for regular human insulin respectively. Compared to human insulin, insulin aspart has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. It takes 40 - 50 minutes to reach maximum concentration. When a dose of 0.15 U/kg body weight was injected in type 1 diabetes patients, the mean maximum concentration (Cmax) was 82 mU/L. The site of injection has no impact on extent or speed of absorption.

In patients with type 1 diabetes, after 8 days of once daily subcutaneous dosing with 0.4 U/kg, maximum degludec concentrations of 4472 pmol/L were attained at a median of 9 hours (tmax). After the first dose of, median onset of appearance was around one hour. The glucose lowering effect lasted at least 42 hours after the last of 8 once-daily injections. Insulin degludec concentration reach steady state levels after 3-4 days.

Half Life

Elimination half-life was found to be 81 minutes (following subcutaneous administration in healthy subjects).

The half-life after subcutaneous administration is determined primarily by the rate of absorption from the subcutaneous tissue. On average, the half-life at steady state is approximately 25 hours independent of dose.

Clearance

1.2 L/h/kg

The mean apparent clearance of insulin degludec is 0.03 L/kg (2.1 L/h in 70 kg individual) after single subcutaneous dose of 0.4 units/kg.

Pregnancy & Breastfeeding use

Pregnancy Category B. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physician if they intend to become, or if they become pregnant while taking insulin aspart.

Pregnant Women: There is no clinical experience from well-controlled studies with Insulin degludec in pregnant women. Animal reproduction studies have not revealed any differences between insulin degludec and human insulin regarding embryotoxicity and teratogenicity. Animal reproduction studies are not always predictive of human response; therefore, Insulin degludec should not be used during pregnancy unless the potential benefits to the mother justify the potential risks to the fetus

Nursing Women: There is no clinical experience from well controlled studies with Insulin degludec during breast-feeding. It is unknown whether insulin degludec is excreted in human milk. In rats, insulin degludec was secreted in milk; the concentration in milk was lower than in plasma.