X

BIOSTATE FOR INJECTION 50 IU/ML

Product Information

Registration Status: Active

SIN12180P

BIOSTATE FOR INJECTION 50 IU/ML is approved to be sold in Singapore with effective from 2003-01-31. It is marketed by BLOOD SERVICES GROUP, HEALTH SCIENCES AUTHORITY, with the registration number of SIN12180P.

This product contains Human Coagulation Factor VIII 50 iu/mL, and Von Willebrand Factor 100 iu/mL in the form of INJECTION, POWDER, FOR SOLUTION. It is approved for INTRAVENOUS use.

This product is manufactured by CSL Behring (Australia) Pty Ltd in GERMANY, andCSL Behring GmbH (Manufacturer of Solvent) in AUSTRALIA.

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.

Product Reference
Loading...


Description

Antihemophilic factor human, also known as Coagulation Factor VIII or Anti-Hemophilic Factor (AHF), is a non-recombinant, lyophilized concentrate of coagulation factor VIII, an endogenous protein and essential component of the coagulation cascade. Antihemophilic factor is manufactured with reduced amounts of von Willebrand Factor antigen (VWF:Ag) and purified from extraneous plasma-derived protein by affinity chromatography. The small amount of VWF:Ag is used to purify factor VIII complex and then removed from the final preparation. The final purified concentrate contains albumin as a stabilizer.[L1053]. The complex was developed by CSL Behring or Baxter Healthcare Corporation and approved in the 90s. Endogenous Factor VIII is essential to the clotting process in the body due to its involvement in the clotting cascade where it is responsible for acting as a co-factor to Factor IX. Activation of Factor IX leads to a cascade of signals that results in activation of Factor X, which then results in the conversion of prothrombin to thrombin, and as a result, leads to the conversion of fibrinogen to fibrin, the fibrous protein that creates the scaffold of the clot. Replacement of Factor VIII is essential for the treatment of Hemophilia A, which is caused by mutations in the Factor VIII gene, leading to a functional deficiency or complete loss of protein. Congenital loss or deficiency of Factor VIII results in the physiologic impairment of the coagulation clotting cascade, and as a result, leads to easy bruising and bleeding. Bleeding can range in severity from minor concerns, such as nosebleeds, to more serious events such as hemorrhaging in the joints, brain, or digestive tract [A32280]. Exogenous replacement of Factor VIII is currently the cornerstone of Hemophilia treatment and is used for the prophylaxis and control of bleeding episodes. Treatment has drastically improved since the 1960s when Factor VIII protein was primarily purified from human plasma, rather than being produced through recombinant DNA technology. Unfortunately, purification of protein from human plasma carries an increased risk of transmission of blood-borne diseases such as HIV and Hepatitis, which in part contributed to the Tainted Blood Scandal in the 1980s and 1990s [A31551, A32272]. Other drug products with similar structure and function to Antihemophilic factor human include [DB13999], which is produced by recombinant DNA technology and is identical in sequence to endogenously produced Factor VIII, but does not contain the B-domain, which has no known biological function and [DB11607], which is a fully recombinant factor VIII-Fc fusion protein which has an extended half-life compared with conventional factor VIII due to conjugation to the dimeric Fc domain of human immunoglobulin G1, a long-lived plasma protein [A31551]. Antihemophilic factor human is approved by the Food and Drug Administration for use in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes [FDA Label].

Indication

The human antihemophilic factor is indicated for the cases of hemophilia A, also known as classical hemophilia for the prevention and control of hemorrhagic episodes.[L1055] If surgery is needed in patients with hemophilia A there is a need of correction of the clotting abnormality. In this cases, the human antihemophilic factor may be administered followed by intermittent maintenance doses.[L1053] The hemophilia A is characterized by the deficiency of the coagulation factor VIII that results in prolonged blood flow after injury or surgery as well as recurrent bleeding.[T56]

Mechanism of Action

The human antihemophilic factor replaces the coagulation factor VIII. It acts as a co-factor for factor IX to activate factor X in the intrinsic pathway of blood coagulation.[L1056, L1057]

Pharmacokinetics

Absorption
After intravenous administration of the human antihemophilic factor the values of Cmax, AUC and Tmax were 100 IU/ml, 1450 IU h/ml and 0.43 h respectively. In a second clinical trial, the treatment was administered for six months and the values of Cmax, AUC and Tmax were 99 units/ 100 ml, 1471 units h/ 100ml and 16 h, respectively.[L1057]
Distribution
The pharmacokinetic profile of the human antihemophilic factor needed to be studied by the two-compartment theory as not all of it stays just in blood plasma. The central and peripheral volume of distribution in adults weight an average of 68 kg were 2.81 L and 1.90 L respectively.[A31392]
Metabolism
The metabolism of the human antihemophilic factor is identical to the normal inactivation and elimination pathway of the natural coagulation factor VIII. After activation, the human antihemophilic factor gets metabolized by activated protein C in R336 and R562 and this action inactivates this cofactor. The proteolysis generates two major fragments which are recognized by an anti-factor VIII A2 domain antibody. This process is followed by a further degradation into smaller fragments.[A31393]
Elimination

Clearance

The reported clearance for the administration of antihemophilic factor is 0.15 L/h in adults with an average weight of 68 kg. In the same study, there was a separation of the intercompartment clearance which is 0.16 L/h. The clearance rate was reported to be significantly decreased with increasing age and significantly increased in patients that presented a blood type of gourp O.[A31392]

Toxicity

The highest toxicity is the risk of viral hepatitis transmition as well as intravascular hemolyisis can occur if large or frequent doses are used in blood groups A, B or AB.[T57]

Active Ingredient/Synonyms

Antihemophilic factor VIII human | Antihemophilic factor, human | Antihemophilic factor, human (monoclonal) | Antihemophilic factor,human | F8 protein, human | Factor VIII (antihaemophilic factor) | Factor VIII (human) | Human coagulation factor VIII | Antihemophilic factor human |


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

von Willebrand Factor (vWF) is a multimeric glycoprotein that consists of disulfide-bridge linked dimers. It is usually circulating in plasma as a stable complex with the coagulation factor VIII. The human vWF, as a drug product, is a complex that also contains the coagulation factor VIII.[A32268] This complex was developed by Octapharma Pharmazeutika Produktionsges and FDA approved on August 21, 2015.[L1878]

Indication

The vWF and Factor VIII complex is indicated for the prevention of excessive bleeding during and after minor and major surgery in adult and pediatric von Willebrand disease patients. It is also indicated for the on-demand treatment and control of bleeding episodes.[L1880] The von Willebrand disease is an inherited disorder characterized by the deficiency or misfunction of the von Willebrand factor (vWF). Due to this deficiency, the blood cannot clot properly and the patients that present this disease are prone to prolonged or excessive bleeding. There are three types of this disease, and type 3 is an autosomal recessive inherited disorder marked by very low or absent levels of vWF.[L1867]

Mechanism of Action

The vWF is involved in primary and secondary homeostasis and it is also a carrier and stabilizing protein that protects the coagulation factor VIII from proteolysis and clearance.[A32268] vWF also presents an adhesive function in which it mediates the binding between platelets and subendothelial tissues.[A32289] The external human vWF acts as the endogenous vWF and thus, it presents all the functions abovementioned.[L1880]

Pharmacokinetics

Absorption
According to clinical trials in patients with von Willebrand disease, the AUC, Cmax and mean residence time was approximately 1119 h.IU/dL, 76 IU/dL and 20.6 hours, respectively.[A32270]
Distribution
The volume of distribution of the human concentrate vWF is 69.7 ml/kg.[A32270]
Metabolism
The endogenous regulator of the vWF is ADAMTS13. The interaction between these two proteins results in the proteolysis of vWF. This proteolysis occurs primarily in the cleavage site at the domain A2 which is a target domain for ADAMTS13.[A32290]
Elimination

Clearance

The clearance rate of the human concentrate vWF is 3.9 ml.h/kg.[A32270]

Toxicity

The administration of human vWF seems to be very well accepted.

Active Ingredient/Synonyms

Human von willebrand factor | Von willebrand factor | Von willebrand factor (human) | Von willebrand factor complex (human) | von Willebrand factor, human | Von willebrand's factor | Von Willebrand Factor Human |


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.

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank

Pharmfair.com uses cookies to improve your browsing experience. We'll assume you're ok with this, but you can opt-out if you wish. Peace!