human prothrombin complex prothoraas,raas headquarters上海莱士-九游会旗舰厅

date approved:   apr. 02, 2007

date revised:  dec. 22, 2010

prothoraas^®-human prothrombin complex

read the package insert carefully and under the instruction of physician

warning

this product is human-plasma-derived. although the screening and testing measures of infectious agents and viral removal and inactivation added in the manufacture process, theoretically, there is still potential risk in the transmission of some known and even unknown infectious agents. the risk-benefit analysis should be taken before administration.

product name

generic name: human prothrombin complex

ingredients

active ingredients: coagulation factor ⅸ, ⅱ, ⅶ and ⅹ. derived from human plasma of  healthy donors, prothoraas® has been treated with a mixture of   tri-n-butyl-phosphate (tnbp) and polysorbate 80 (tween 80), and the final product has been virus removed by nanofiltration.

excipients: sodium citrate, heparin

characters

prothoraas® is a white or gray-green loose powder. after reconstitution, it should be a clear or slight yellow, or slight blue or yellow-green transparent solution.  

indications

prothoraas® is indicated for the congenital and acquired deficiency of coagulation factorⅱ, ⅶ, ⅸ and ⅹ (single or combined deficiency).

prothoraas®  is mainly appropriate for use in:

1.the deficiency of coagulation factor ⅸ (hemophilia b), and deficiency of coagulation factor ⅱ, ⅶ, and ⅹ

2.the overdosage of anticoagulants, and deficiency of vitamin k

3.treatment of bleeding in patients with hepatic diseases

4.used after heparinization when disseminated intravascular coagulation (dic) occur, coagulation factor ⅱ, ⅶ, ⅸ  and ⅹ are heavily consumed

5.used before surgery for the patients with prolonged prothrombin time caused by various factors. but there may be no effect on patients with deficiency  of coagulation factor v

6.treatment of bleeding episode in the patients with hemophilia a who have inhibitors to factor ⅷ

7.reversal  of  coumarin  anticoagulant  induced hemorrhage

specifications

100 iu, 200 iu, 300 iu, 400 iu, 1000 iu of factor ⅸ per container together with variable  amount of factors ⅱ, ⅶ, and ⅹ. after reconstitution, the volume shall be 10ml per vial.

dosage and administration

administration:

1.prothoraas® should be administered intravenously only, and should be monitored closely by the physician.

2.warm the product, sterile water for injection or 5% dextrose injection to 20-25℃ prior to reconstitution. then, indicated volume of these warmed sterile water for  injection  or 5% dextrose injection will be infused into the product vial. gently swirl the preparation vial  to  dissolve the lyophilized product completely, and avoid foaming.

3.it can also be diluted to 50-100 ml using sodium chloride injection or 5% dextrose injection. infuse only by a transfusion set with filter. initial infusion should be slow, then gradually   increase the infusion rate after 15 minutes. the infusion usually finishes within 30-60 minutes for a vial of 200 iu specification.

dosage:

1.the amount of prothoraas® required depends on the extents of deficiency of coagulation factors. generally 10-20 iu /kg (body weight) is recommended. then it  should be administered every 6 to 8 hours for factor ⅶ deficiency, every 24 hours for factor ⅸ deficiency and every 24 to 48 hours for factor ⅱ and ⅹ deficiency. the dosage can    be reduced according to patient's condition. usually 2 to 3 days treatment is required for  each patient  receiving prothoraas®.

2.for patients with severe hemorrhage or before major surgery, the dosage can be  increased if required.

3.it is also recommended that prothoraas® can be used before surgery for patients    with prolonged prothrombin  time, such as patients who require splenectomy. the    treating physician should determine whether this product should be administered during or after surgery, according to the patient's condition.

adverse reactions

in general, the incidence of adverse reaction is rare. in some patients the rapid   administration of prothoraas® might cause fever, flushing, headache, etc. the above symptoms will disappear when slowing or stopping the infusion.

contraindications

prothoraas®  is contraindicated in individuals who has an anaphylactic response to it.

precautions

1.ensure that a correct diagnosis of deficiency of coagulation factors ⅸ, ⅱ, ⅶ and ⅹ is made prior to administering the product to determine whether the product is needed by the patients, except for patients with severe hepatic haemorrhage. but caution should  be  taken if the patient with coronary heart disease, myocardial infarction, severe hepatic  disease, or  undergone surgical operaiton has tendency of disseminated intravascular coagulation (dic).

2.administer only by intravenous route.

3.do not use if the bottle is broken, or the product is expired, or there is sediment in the solution, etc. if the bottle is not in vacuum condition, do not use.

4.during the infusion, patients should be closely monitored by the physician. if the signs  and symptoms of disseminated intravascular coagulation (dic) or thrombosis are found,  stop using the product immediately,counteract with heparin. prothoraas® contains heparin whose potency is half equivalent of factor ⅸ, which can reduce the risk of thrombosis. however, in case of any suspicious findings the dosage should be markedly reduced even if the treatment cannot be                                                              

discontinued entirely according to patient's condition.

pregnancy and iactation

caution should be taken in pregnancy and iactation women. prothoraas® should be administered under the physician and close monitoring if clearly needed.

pediatric use

no relevant trials were performed, and there is no relevant reference.

geriatric use

the physiological function of elder patients is  usually  declined,  so  prothoraas®   should  be  administered carefully based on patient's condition. 

drug interactions

prothoraas® is not recommended to be administered with other drugs. 

overdosage

there is risk of causing thrombosis when given overdose.

pharmacology and toxicology

pharmacology: prothoraas® is a mixture of vitamin k dependent clotting factor ⅱ, ⅶ, ⅸ and ⅹ that are all synthesized in the liver. the deficiency of vitamin k and severe  hepatic diseases may cause the deficiency of these four clotting factors. the deficiency of any of these four factors may cause clotting disorder. the administration of prothoraas® can increase the level of factor ⅱ, ⅶ,ⅸ and ⅹ in the blood circulation. 

toxicology: no relevant trials were performed, and there is no relevant reference.

pharmacokinetics

no relevant trials of prothoraas® were performed, and no relevant reference of prothoraas®.

storage and shipping

store and ship at 2-8℃, protected from light.

package

glass bottle,one vial per package.

shelf life

24 months.

standard for implementation

volume ⅲ of "pharmacopoeia of the people's republic of china" (2010)

product license no.

100 iu/vial: 国药准字s10950036;

200 iu/vial: 国药准字s10950035;

300 iu/vial: 国药准字s10960071;

400 iu/vial: 国药准字s10950034;

1000 iu/vial: 国药准字s10950033;

shanghai raas blood products co., ltd.