Posology: Except for the therapy of bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist treatment, only general dosage guidelines are given as follows. Treatment should be initiated under the supervision of a physician experienced in the treatment of coagulation disorders.
The dosage and duration of the substitution therapy depend on the severity of the coagulation disorder, on the location and extent of the bleeding and on the patient's clinical condition. Dosage and frequency of administration should be calculated on an individual patient basis. Dosage intervals must be adjusted to the different circulating half-lives of the various coagulation factors in the prothrombin complex (see PHARMACOLOGY: Pharmacokinetics under Actions).
Individual dosage requirements can only be identified on the basis of regular determinations of the individual plasma levels of the coagulation factors of interest or on the global test of the prothrombin complex level (e.g. Quick's time value, INR, prothrombin time) and continuous monitoring of the patient's clinical condition.
In case of major surgical interventions precise monitoring of the substitution therapy by means of coagulation assays is essential (specific coagulation factor assays and/or global tests for prothrombin complex levels).
Bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist treatment: In severe haemorrhages or before operations with a high risk of bleeding, normal values (Quick's time value 100%, INR 1.0) are to be aimed for. The following rule of thumb applies: 1 IU factor IX/kg body weight raises the Quick's time value by about 1%. If Prothromplex TOTAL 600 IU administration is based on the INR measurement the dose will depend on the INR before treatment and the targeted INR.
The dosing in the table as follows should be followed according to the recommendation made in the publication. (See Table 3.)
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The correction of the vitamin K antagonist induced impairment of haemostasis persists for approximately 6 - 8 hours. However, the effects of vitamin K, if administered simultaneously, are usually achieved within 4 - 6 hours. Thus, repeated treatment with human prothrombin complex is not usually required when vitamin K has been administered.
As these recommendations are empirical and recovery and the duration of effect may vary, monitoring of INR during treatment is mandatory.
Bleeding and perioperative prophylaxis in congenital deficiency of any of the vitamin K-dependent coagulation factors when specific coagulation factor product is not available: The calculated required dosage for treatment is based on the empirical finding that approximately 1 IU of factor IX per kg body weight raises the plasma factor IX activity by about 0.015 IU/ml; and 1 IU of factor VII per kg body weight raises the plasma factor VII activity by about 0.024 IU/ml. One IU of factor II or X per kg body weight raises the plasma factor II or X activity by 0.021 IU/ml.
The dose of a specific factor administered is expressed in International Units (IU), which are related to the current WHO standard for each factor. The activity in plasma of a specific coagulation factor is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to the international standard for specific factor concentrates).
One International Unit (IU) of a coagulation factor activity is equivalent to the quantity in one ml of normal human plasma. For example, the calculation of the required dosage of factor X is based on the empirical finding that 1 International Unit (IU) of factor X per kg body weight raises the plasma factor X activity by 0.017 IU/ml. The required dosage is determined using the following formula: See equation.
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Where 60 (ml/kg) is the reciprocal of the estimated recovery. If the individual recovery is known that value should be used for calculation.
Maximum single dose: In order to correct the INR, it is not necessary to exceed the dose of 50 IU/kg. If the severity of bleeding requires a higher dose the risk/benefit has to be evaluated by the treating physician.
Paediatric population: The safety and efficacy of the use of Prothromplex TOTAL 600 IU in paediatric patients have not been established in clinical trials.
Method of administration: Intravenous use.
Prothromplex TOTAL 600 IU should be administered via the intravenous route slowly. It is recommended not to administer more than 2 ml per minute (60 IU/min).
For instructions on reconstitution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.