Nonacog Beta Pegol
Nonacog Beta Pegol Uses, Dosage, Side Effects, Food Interaction and all others data.
Nonacog Beta Pegol is a recombinant coagulation factor IX derivative. It is produced without animal-derived materials and with an attached 40kDa polyethylene glycol (PEG) molecule for peptide activation by a site-directed glycoPEGylation. Once activated, the activation molecule with PEG are cleaved to leave the activated factor IX (Factor IXa). Nonacog Beta Pegol was developed by Novo Nordisk, obtained EMA marketing authorisation in June 6, 2017.
After nonacog beta pegol is activated by the coagulation factor IXa and tissue-coagulation factor VIIa, the peptide is cleaved off. In preclinical studies, once the peptide is free, there was a restoration of whole blood clotting time activity and the activated-partial thromboplastin time was returned to normal limits. In clinical trials, the administration of nonacog beta pegol significantly increased the levels of factor IX in plasma and temporarily correct the level of activated partial thromboplastin time. The effect of nonacog beta pegol translated into good hemostasis when used to treat bleeds on-demand and in a reduction of annualized bleeding rates when used as prophylaxis without formation of factor IX inhibitors, allergic reactions or thromboembolic complications. The reports in clinical trials have also shown a significant prolongation in the duration of the hemostatic effect.
| Trade Name | Nonacog Beta Pegol |
| Generic | Nonacog beta pegol |
| Nonacog beta pegol Other Names | Coagulation Factor IX (Recombinant), GlycoPEGylated, Nonacog beta pegol |
| Type | |
| Protein binding | Nonavog brta pegol is not expected to bind to plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nonacog Beta Pegol is a recombinant coagulation Factor IX derivative used to treat hemophilia B.
Nonacog Beta Pegol is indicated for the use in adults and children with hemophilia B for control and prevention of bleeding episodes, routine prophylaxis and perioperative management. In the EMA approval, it is also indicated for on-demand treatment of bleeding episodes. Hemophilia B is characterized by a deficiency in the coagulation factor IX which results in prolonged oozing after injuries and delayed or recurring bleeding prior wound healing. Hemophilia B patients present more frequent bleeding episodes during childhood and adolescence than in adulthood.
Nonacog Beta Pegol is also used to associated treatment for these conditions: Bleeding, Perioperative Blood Loss
How Nonacog Beta Pegol works
Nonacog Beta Pegol is activated by the factor IXa and the tissue complex factor VII. When activated, the peptide including the 40kDa PEG moiety is cleaved off leaving an activated recombinant factor IX ready to be part of the coagulation cascade replacing the missing clotting factor IX. Thus, after activation, nonacog beta pegol will present the same mechanism of action than the endogenous coagulation factor IXa. The activated coagulation factor IX function is, in combination with the factor VIIIa, to activate the coagulation factor X to trigger the coagulation cascade that finalizes in the conversion of prothrombin into thrombin and the thrombin-driven conversion of fibrinogen into fibrin for the formation of a clot.
Toxicity
There are reports indicating that long-term administration of nonacog beta pegol results in the development of cross-reacting neutralizing antibodies. Studies regarding carcinogenicity, genotoxicity and reproductive toxicity have not been made.
Food Interaction
No interactions found.Volume of Distribution
The reported volume of distribution for nonacog beta pegol is variable depending on the patient's age. After single administration, the volume of distribution goes from 72 ml/kg when the patient is less than 6 years old, 68 ml/kg between 7-12 years old, 59 ml/kg between 13-17 years old and 47 ml/kg when the patient is over 18 years old. At steady state, the volume of distribution of nonacog beta pegol is 64 ml/kg.
Elimination Route
In preclinical overdose studies, there was reported an AUC of 1200 IU/kg in rats and 3750 IU/kg in monkeys. In clinical studies, the absorption properties of nonacog beta pegol were AUC of 92 IU h/ml at steady state. In precliniacl studies, there was a reduced accumulation of systemic drug after multiple dosing.
Half Life
The terminal half life of nonacog beta pegol is in the range of 96-110 hours which is 5 times longer than an unmodified coagulation factor IX.
Clearance
The registered clearance rate of nonacog beta pegol at steady state is of 0.4 ml h/kg.
Elimination Route
Nonacog Beta Pegol is eliminated from all tissues indicating that it will reach steady state in plasma and tissue but it will not accumulate. The 40 kDa PEG is eliminated by urine and feces taking approximately 49 and 40% of the administered dose respectively. The PEG part of the drug seems to be eliminated with a bi-phasic profile that was registered at 2-3 days and at 15-18 days.
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