Octaplex

/ Dover Medical

The dosage and duration of the substitution therapy depend on the severity of the disorder, on the location and extent of the bleeding and on the patient’s clinical condition.
The amount and the frequency of administration should be calculated on an individual patient basis.
Dosage intervals must be adapted to the different circulating half-life of the different coagulation factors in the prothrombin complex. 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 global tests of the prothrombin complex levels (prothrombin time, INR), and continuous monitoring of the clinical condition of the patient.
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:
The dose will depend on the INR before treatment and the targeted INR. In the following you can see approximate doses (ml/kg body weight of the reconstituted product) required for normalisation of INR (≤ 1.2 within 1 hour) at different initial INR levels are given.
Initial INR: 2 – 2.5 / 2.5 – 3 / 3 – 3.5 / > 3.5
Approximate dose* (ml Octaplex/kg body weight): 0.9 –1.3 / 1.3 – 1.6 / 1.6 – 1.9 / > 1.9.
*The single dose should not exceed 3.000 IU (120 ml Octaplex).
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 the vitamin K dependent coagulation factors II and X 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 II or X per kg body weight raises the plasma factor II or X activity by 0.02 and 0.017 IU/ml, respectively.
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 plasma) or in International Units (relative to the international standard for the specific coagulation factor).
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:
Required units = body weight (kg) x desired factor X rise (IU/ml) x 59
where 59 (ml/kg) is the reciprocal of the estimated recovery.
Required dosage for factor II:
Required units = body weight (kg) x desired factor II rise (IU/ml) x 50
If the individual recovery is known that value should be used for calculation.
Method of administration: Octaplex should be administered intravenously. The infusion should start at a speed of 1 ml per minute, followed by 2-3 ml per minute, using an aseptic technique.

– Treatment of bleeding and perioperative prophylaxis of bleeding in acquired deficiency of the prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists, or in case of overdose of vitamin K antagonists, when rapid correction of the deficiency is required.
– Treatment of bleeding and perioperative prophylaxis in congenital deficiency of the vitamin K dependent coagulation factors II and X when purified specific coagulation factor product is not available.

Hypersensitivity to the active substance or to any of the excipients.
Known allergy to heparin or history of heparin induced thrombocytopenia.

The advice of a specialist experienced in the management of coagulation disorders should be sought.
In patients with acquired deficiency of the vitamin K dependent coagulation factors (e.g. as induced by treatment with vitamin K antagonists), Octaplex should only be used when rapid correction of prothrombin complex levels is necessary, such as major bleeding or emergency surgery. In other cases, reduction of the dose of the vitamin K antagonist and/or administration of vitamin K is usually sufficient.
Patients receiving a vitamin K antagonist may have an underlying hypercoaguable state and infusion of prothrombin complex concentrate may exacerbate this.
In congenital deficiency of any of the vitamin K dependent factors, specific coagulation factor product should be used when available.
If allergic or anaphylactic-type reactions occur, the infusion should be stopped immediately. In case of shock, standard medical treatment for shock should be implemented.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses.
Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV. The measures taken may be of limited value against non-enveloped viruses such as HAV and parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (foetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).
It is strongly recommended that every time Octaplex is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Appropriate vaccination (hepatitis A and B) is recommended for patients in regular/repeated receipt of human plasma-derived prothrombin complex products.
There is a risk of thrombosis or disseminated intravascular coagulation when patients, with either congenital or acquired deficiency are treated with human prothrombin complex particularly with repeated dosing. Patients given human prothrombin complex should be observed closely for signs or symptoms of intravascular coagulation or thrombosis. Because of the risk of thromboembolic
complications, close monitoring should be exercised when administering human prothrombin complex to patients with a history of coronary heart disease, to patients with liver disease, to peri- or postoperative patients, to neonates, or to patients at risk of thromboembolic events or disseminated intravascular coagulation. In each of these situations, the potential benefit of treatment should be weighed against the risk of these complications.
No data are available regarding the use of Octaplex in case of perinatal bleeding due to vitamin K deficiency in the new-born.
Octaplex contains 75 – 125 mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

See prescribing information for full details.

Human prothrombin complex products neutralise the effect of vitamin K antagonist treatment, but no interactions with other medicinal products are known.
Interference with biological testing: When performing clotting tests which are sensitive to heparin in patients receiving high doses of human prothrombin complex, the heparin as a constituent of the administered product must be taken into account.

The safety of human prothrombin complex for use in human pregnancy and during lactation has not been established.
Animal studies are not suitable to assess the safety with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Therefore, human prothrombin complex should be used during pregnancy and lactation only if clearly indicated.

The use of high doses of human prothrombin complex products has been associated with instances of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism. Therefore, in case of overdose, the risk of development of thromboembolic complications or disseminated intravascular coagulation is enhanced.