PROTHROMPLEX TOTAL

Posology Except for the therapy of bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist treatment, only general dosage guidelines are given below. 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.

2). 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).

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.

0 50 The correction of the vitamin K antagonist induced impairment of hemostasis 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. 024 IU/ml. Haematol. 2001; 114: 271-280 2 Ostermann H, Haertel S, Knaub S, Kalina U, Jung K, Pabinger I.

Pharmacokinetics of Beriplex P/N prothrombin complex concentrate in healthy volunteers. Thromb Haemost. 2007;98(4):790-797. 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.

Summary of the safety profile Replacement therapy with human prothrombin complex concentrates, including therapy with Prothromplex TOTAL 600 IU, may result in the formation of circulating antibodies inhibiting one or more of the human prothrombin complex factors.

If such inhibitors occur, the condition will manifest itself as a poor clinical response. 4). 4. Tabulated list of adverse reactions The acute myocardial infarction, venous thrombosis and pyrexia presented in the tabulated list of adverse reactions below have been reported in one clinical study with Prothromplex TOTAL 600 IU in oral anticoagulant reversal in patients (n=61) with acquired prothrombin complex coagulation factors (II, VII, IX, X) deficiency.

The other adverse reactions included in the table have been reported from post-marketing experience only and the frequency category was assigned by statistics based on the assumption that each adverse reaction could have occurred in the clinical trial with 61 patients.

1). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from the available data).

System Organ Class (SOC) Undesirable effect Frequency Blood and lymphatic system disorders Disseminated intravascular coagulation Inhibitors to one or more of the prothrombin complex factors (Factors II, VII, IX, X)* Common Immune system Disorders Anaphylactic shock Anaphylactic reaction Hypersensitivity Common Nervous system disorders Cerebrovascular accident Headache Common Cardiac disorders Heart failure Acute myocardial infarction** Tachycardia Common Vascular disorders Arterial thrombosis Venous thrombosis** Hypotension Flushing Common Respiratory thoracic and mediastinal disorders Pulmonary embolism Dyspnoea Wheezing Common Gastrointestinal disorders Vomiting Nausea Common Skin and subcutaneous tissue disorders Urticaria Rash erythematous Pruritus Common Renal and urinary disorders Nephrotic syndrome Common General and administration site conditions Pyrexia** Common * Development in patients with congenital deficient factors.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. The advice of a specialist experienced in the management of coagulation disorders should be sought.

g. as induced by treatment with vitamin K antagonists) Prothromplex TOTAL 600 IU should only be used when rapid correction of the prothrombin complex levels is necessary, such as major bleeding or emergency surgery. In other cases, reduction of the dose of vitamin K antagonist and/or administration of vitamin K is usually sufficient.

Patients receiving a vitamin K antagonist may have an underlying hypercoagulable state and infusion of human prothrombin complex may exacerbate this. In congenital deficiency of any vitamin K-dependent factors, specific coagulation factor product should be used when available.

Allergic-type hypersensitivity reactions including anaphylactic reactions and anaphylactic shock have been reported with Prothromplex TOTAL 600 IU. If allergic or anaphylactic-type reactions occur, the injection/infusion should be stopped immediately.

In the case of shock standard medical treatment for shock should be implemented. Thromboembolism, DIC, Fibrinolysis There is a risk of thrombosis and disseminated intravascular coagulation (DIC) when patients, with either congenital or acquired deficiency are treated with human prothrombin complex concentrates, including Prothromplex TOTAL 600 IU, particularly with repeated dosing.

g. stroke), pulmonary embolism as well as DIC have been reported with Prothromplex TOTAL 600 IU. The risk may be higher in treatment of isolated F VII deficiency, since the other vitamin K-dependent coagulation factors, with longer half-lives, may accumulate to levels considerably higher than normal Patients given human prothrombin complex concentrates should be observed closely for signs and symptoms of intravascular coagulation or thrombosis.

1. - Known allergy to heparin or history of heparin-induced thrombocytopenia.