Product Information
Registration Status: ActiveRYZODEG FLEXTOUCH SOLUTION FOR INJECTION IN PRE-FILLED PEN 100 U/ML is approved to be sold in Singapore with effective from 2019-05-31. It is marketed by NOVO NORDISK PHARMA (SINGAPORE) PTE LTD, with the registration number of SIN15706P.
This product contains Insulin Aspart 180nmol/ml, and Insulin Degludec 420nmol/ml in the form of INJECTION, SOLUTION. It is approved for Not Available use.
This product is manufactured by Novo Nordisk A/S (Bagsvaerd) (Bulk production and Primary Packager) in DENMARK.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Insulin aspart is a recombinant, biosynthetic, fast-acting insulin analogue. It has a single amino acid substitution at position B28 where proline is replaced with aspartic acid. This substitution decreases its propensity to form hexamers and gives it a higher rate of absorption following subcutaneous administration compared to native insulin. Insulin aspart is produced in a genetically modified strain of _Saccharomyces cerevisiae_ and harvested from a bioreactor.
Indication
For the treatment of Type 1 or 2 diabetes mellitus. Should normally be used in conjunction with an intermediate or long-acting insulin.
Mechanism of Action
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.
Pharmacokinetics
- Absorption
- Rapidly absorbed following subcutaneous administration (more so than regular human insulin). Furthermore, 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.
- Distribution
- Metabolism
- Elimination
Clearance
* 1.2 L/h/kg [healthy Caucasian male], excreted in the urine
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.
Active Ingredient/Synonyms
Aspart | Aspart Insulin | B28-Aspart-Insulin | Insulin aspart protamine | Insulin aspart protamine recombinant | Insulin aspart recombinant | Insulin X14 | Insulin, aspart protamine, human | Insulin, aspart, human | Insulin,aspart protamine | Insulin Aspart |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Insulin Degludec is an ultra-long-acting insulin analogue used for glycemic control in Diabetes Mellitus. Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake and by preventing hepatic glucose production. Compared to endogenous insulin, this product has an added hexadecanedioic acid to lysine at the B29 position which allows for the formation of multi-hexamers. When injected subcutaneously, these multi-hexamers form a drug depot store from which monomers are slowly and continuously absorbed into the circulation. As a result, Insulin Degludec has a protracted time action profile due to the delayed absorption from subcutaneous tissue depots into the systemic circulation. Compared to available long-acting analogues such as insulin glargine and insulin detemir, which have a duration of action of 20-24 hours, insulin degludec provides a consistent level of basal insulin over 42 hours with a low peak:trough ratio. Limitations of shorter acting analogues include more frequent dosing and less stable pharmacokinetics, which may negatively impact patient adherence and glucose control, particularly nocturnal control. Insulin Degludec was approved by the FDA in September 2015 as the product Tresiba, for use in providing glycemic control to adults with diabetes mellitus.
Indication
Insulin degludec is indicated to improve glycemic control in adults with diabetes mellitus.
Mechanism of Action
Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake and by preventing hepatic glucose production. Compared to endogenous insulin, Insulin Degludec has an added hexadecanedioic acid to lysine at the B29 position which allows for the formation of multi-hexamers in subcutaneous tissues. When injected subcutaneously, these multi-hexamers form a drug depot store that slowly release. As a result, Insulin Degludec has a protracted time action profile due to the delayed absorption from subcutaneous tissue depots into the systemic circulation
Pharmacokinetics
- 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.
- Distribution
- Metabolism
- All insulin degludec metabolites are inactive.
- Elimination
Clearance
0.03 L/kg
Toxicity
Observe for signs and symptoms of hypoglycemia, hypokalemia, and fluid retention and heart failure with concomitant use of Thiazolidinediones. Pregnancy Category C
Active Ingredient/Synonyms
Insulin Degludec | Insulin Degludec |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.