Presentation and Status in Health Basket
Haemophilia A or B with inhibitors or expected to have a high anamnestic response.
Dose: NovoSeven RT should be given as early as possible after the start of a bleeding episode. The recommended initial dose, administered by intravenous bolus injection, is 90 g per kg body weight. Following the initial dose of NovoSeven RT further injections may be repeated. The duration of treatment and the interval between injections will vary with the severity of the haemorrhage, the invasive procedures or surgery being performed.
Dosing in children: Current clinical experience does not warrant a general differentiation in dosing between children and adults, although children have faster clearance than adults. Therefore, higher doses of rFVIIa may be needed in paediatric patients to achieve similar plasma concentrations as in adult patients.
Dose interval: Initially 2 – 3 hours to obtain haemostasis. If continued therapy is needed, the dose interval can be increased successively once effective haemostasis is achieved to every 4, 6, 8 or 12 hours for as long as treatment is judged as being indicated.
Mild to moderate bleeding episodes (including home therapy): Early intervention has been shown to be efficacious in the treatment of mild to moderate joint, muscle and mucocutaneous bleeds. Two dosing regimens can be recommended: – Two to three injections of 90 µg per kg body weight administered at threehour intervals If further treatment is required, one additional dose of 90 µg per kg body weight can be administered. – One single injection of 270 µg per kg body weight The duration of the home therapy should not exceed 24 hours. There is no clinical experience with administration of a single dose of 270 µg per kg body weight in elderly patients.
Serious bleeding episodes: An initial dose of 90 µg per kg body weight is recommended and could be administered on the way to the hospital where the patient is usually treated. The following dose varies according to the type and severity of the haemorrhage. Dosing frequency should initially be every second hour until clinical improvement is observed. If continued therapy is indicated, the dose interval can then be increased to 3 hours for 1 – 2 days. Thereafter, the dose interval can be increased successively to every 4, 6, 8 or 12 hours for as long as treatment is judged as being indicated. A major bleeding episode may be treated for 2 – 3 weeks but can be extended beyond this if clinically warranted.
Invasive procedure/surgery: An initial dose of 90 µg per kg body weight should be given immediately before the intervention. The dose should be repeated after 2 hours and then at 2 – 3 hour intervals for the first 24 – 48 hours depending on the intervention performed and the clinical status of the patient. In major surgery, the dose should be continued at 2 – 4 hour intervals for 6 – 7 days. The dose interval may then be increased to 6 – 8 hours for another 2 weeks of treatment. Patients undergoing major surgery may be treated for up to 2 – 3 weeks until healing has occurred.
Dose and dose interval: NovoSeven RT should be given as early as possible after the start of a bleeding episode. The recommended initial dose, administered by intravenous bolus injection, is 90 µg per kg body weight. Following the initial dose of NovoSeven RT further injections may be given if required. The duration of treatment and the interval between injections will vary with the severity of the haemorrhage, the invasive procedures or the surgery being performed. The initial dose interval should be 2 – 3 hours. Once haemostasis has been achieved, the dose interval can be increased successively to every 4, 6, 8 or 12 hours for as long as treatment is judged to be indicated.
Factor VII deficiency
Dose, dose range and dose interval: The recommended dose range for treatment of bleeding episodes and for the prevention of bleeding in patients undergoing surgery or invasive procedures is 15 – 30 μg per kg body weight every 4 – 6 hours until haemostasis is achieved. Dose and frequency of injections should be adapted to each individual.
Dose, dose range and dose interval: The recommended dose for treatment of bleeding episodes and for the prevention of bleeding in patients undergoing surgery or invasive procedures is 90 µg (range 80 – 120 µg) per kg body weight at intervals of two hours (1.5 – 2.5 hours). At least three doses should be administered to secure effective haemostasis. The recommended route of administration is bolus injection as lack of efficacy may appear in connection with continuous infusion. 4For those patients who are not refractory, platelets are the first line treatment for Glanzmann’s thrombasthenia.
For full details see prescribing information.
NovoSeven RT is indicated for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups: – in patients with congenital haemophilia with inhibitors to coagulation factors VIII or IX > 5 Bethesda Units (BU). – in patients with congenital haemophilia who are expected to have a high anamnestic response to factor VIII or factor IX administration. – in patients with acquired haemophilia. – in patients with congenital FVII deficiency. – in patients with Glanzmann’s thrombasthenia with antibodies to GP IIb – IIIa and/or HLA, and with past or present refractoriness to platelet transfusions.
Hypersensitivity to the active substance, or to any of the excipients, or to mouse, hamster or bovine protein.
In pathological conditions in which tissue factor may be expressed more extensively than considered normal, there may be a potential risk of development of thrombotic events or induction of Disseminated Intravascular Coagulation (DIC) in association with NovoSeven RT treatment. Such situations may include patients with advanced atherosclerotic disease, crush injury, septicaemia or DIC. Because of the risk of thromboembolic complications, caution should be excercised when administering NovoSeven RT to patients with a history of coronary heart disease, to patients with liver disease, to patients post-operatively, to neonates, or to patients at risk of thromboembolic phenomena or disseminated intravascular coagulation. In each of these situations, the potential benefit of treatment with NovoSeven RT should be weighed against the risk of these complications. As recombinant coagulation factor VIIa NovoSeven RT may contain trace amounts of mouse IgG, bovine IgG and other residual culture proteins (hamster and bovine serum proteins), the remote possibility exists that patients treated with the product may develop hypersensitivity to these proteins. In such cases treatment with antihistamines i.v. should be considered. If allergic or anaphylactic-type reactions occur, the administration should be discontinued immediately. In case of shock, standard medical treatment for shock should be implemented. Patients should be informed of the early signs of hypersensitivity reactions. If such symptomsoccur, the patient should be advised to discontinue use of the product immediately and contact their physician. In case of severe bleeds the product should be administered in hospitals preferably specialized in treatment of haemophilia patients with coagulation factor VIII or IX inhibitors, or if not possible in close collaboration with a physician specialized in haemophilia treatment. If bleeding is not kept under control hospital care is mandatory. Patients/carers should inform the physician/supervising hospital at the earliest possible opportunity about all usages of NovoSeven RT. Factor VII deficient patients should be monitored for prothrombin time and factor VII coagulant activity before and after administration of NovoSeven RT. In case the factor VIIa activity fails to reach the expected level or bleeding is not controlled after treatment with the recommended doses, antibody formation may be suspected and analysis for antibodies should be performed. The risk of thrombosis in factor VII deficient patients treated with NovoSeven RT is unknown. Patients with rare hereditary problems of fructose intolerance, glucose malabsorption or sucrose-isomaltase insufficiency should not take this medicine
The frequencies of both serious and non-serious adverse drug reactions are listed by system organ classes.
For full details see prescribing information.
The risk of a potential interaction between NovoSeven RT and coagulation factor concentrates is unknown. Simultaneous use of prothrombin complex concentrates, activated or not, should be avoided. Anti-fibrinolytics have been reported to reduce blood loss in association with surgery in haemophilia patients, especially in orthopaedic surgery and surgery in regions rich in fibrinolytic activity, such as the oral cavity. Experience with concomitant administration of anti-fibrinolytics and rFVIIa treatment is however limited.
Pregnancy and Lactation
Pregnancy: As a precautionary measure, it is preferable to avoid use of NovoSeven RT during pregnancy. Data on a limited number of exposed pregnancies within approved indications indicate no adverse effects of rFVIIa on pregnancy or on the health of the foetus/new-born child. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Lactation: It is unknown whether rFVIIa is excreted in human breast milk. The excretion of rFVIIa in milk has not been studied in animals. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with NovoSeven RT should be made taking into account the benefit of breast-feeding to the child and the benefit of NovoSeven RT therapy to the woman.
Dose limiting toxicities of NovoSeven RT have not been investigated in clinical trials. Three cases of overdose have been reported in patients with haemophilia in 13 years. The only complication reported in connection with an overdose was a slight transient increase in blood pressure in a 16 year-old patient receiving 24 mg rFVIIa instead of 5.5 mg. No cases of overdose have been reported in patients with acquired haemophilia or Glanzmann’s thrombasthenia. In patients with factor VII deficiency, where the recommended dose is 15 – 30 µg/kg rFVIIa, one episode of overdose has been associated with a thrombotic event (occipital stroke) in an elderly (> 80 year) male patient treated with 10 – 20 times the recommended dose. In addition, the development of antibodies against NovoSeven RT and FVII has been associated with overdose in one patient with factor VII deficiency. The dose schedule should not be intentionally increased above the recommended doses due to the absence of information on the additional risk that may be incurred.