NovoSeven · 4.8 Undesirable effects · 1

HOS-083086 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most frequently reported adverse drug reactions are decreased therapeutic response, pyrexia, rash, venous thromboembolic events, pruritus and urticaria. These reactions are reported as uncommon (≥ 1/1,000, < 1/100). Tabulated summary of adverse reactions Table 1 lists adverse reactions reported during clinical trials and from spontaneous (post-marketing) reports. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Adverse drug reactions reported post-marketing only (i.e. not in clinical trials) are presented with a frequency of ‘not known’. Clinical trials conducted in 484 patients (including 4297 treatment episodes) with haemophilia A and B, acquired haemophilia, factor VII deficiency or Glanzmann’s thrombasthenia have shown that adverse drug reactions are common (≥ 1/100 to < 1/10). As the total number of treatment episodes in clinical trials is below 10,000, the lowest possible frequency of adverse drug reactions that can be assigned is rare (≥ 1/10,000 to < 1/1,000). The most frequent adverse drug reactions are pyrexia and rash (uncommon: ≥ 1/1,000 to < 1/100), and the most serious adverse drug reactions include venous thromboembolic events (uncommon: ≥ 1/1,000 to < 1/100) and arterial thromboembolic events (rare: ≥ 1/10,000 to < 1/1,000). The frequencies of both serious and non-serious adverse drug reactions are listed by system organ classes in the table below Table 1 Adverse reactions from clinical trials and spontaneous (post-marketing) reports MedDRA system Uncommon (≥1/1,000 to Rare (≥1/10,000 to <1/1,000) Frequency Not Known organ class <1/100) Blood and - Disseminated lymphatic system intravascular coagulation disorders (see section 4.4) - Related laboratory findings, including elevated levels of D- dimer and decreased levels of AT (see section 4.4) - Coagulopathy

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HOS-083082 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to mouse, hamster or bovine protein.

HOS-083081 · has-indication-information · PDF-Seite 2

NovoSeven 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 2 • in patients with congenital FVII deficiency • in patients with Glanzmann’s thrombasthenia with past or present refractoriness to platelet transfusions, or where platelets are not readily available. Severe postpartum haemorrhage NovoSeven is indicated for the treatment of severe postpartum haemorrhage when uterotonics are insufficient to achieve haemostasis.

HOS-083084 · has-interaction-information · PDF-Seite 6

The risk of a potential interaction between NovoSeven and coagulation factor concentrates is unknown. Simultaneous use of prothrombin complex concentrates, activated or not, should be avoided. Antifibrinolytics 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. Antifibrinolytics are also used to reduce blood loss in women with postpartum haemorrhage. Experience with concomitant administration of antifibrinolytics and rFVIIa treatment is, however, limited. Based on a non-clinical study (see section 5.3) it is not recommended to combine rFVIIa and rFXIII. There are no clinical data available on interaction between rFVIIa and rFXIII.

HOS-083085 · has-pregnancy-information · PDF-Seite 6

Pregnancy As a precautionary measure, it is preferable to avoid use of NovoSeven 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 (see section 5.3). Breast-feeding 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 should be made taking into account the benefit of breast-feeding to the child and the benefit of NovoSeven therapy to the woman. 6 Fertility Data from non-clinical studies as well as post-marketing data show no indication that rFVIIa has a harmful effect on male or female fertility.

HOS-083083 · has-warning-information · PDF-Seite 5

In pathological conditions in which tissue factor may be expressed more extensively than considered normal, there may be a risk of development of thrombotic events or induction of Disseminated Intravascular Coagulation (DIC) in association with NovoSeven 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 exercised when administering NovoSeven to patients with a history of coronary heart disease, to patients with liver disease, to post-operative patients, to pregnant or peripartum women, to neonates, or to patients at risk of thromboembolic events or DIC. In each of these situations, the potential benefit of treatment with NovoSeven should be weighed against the risk of these complications. In severe postpartum haemorrhage and pregnancy, the clinical conditions (delivery, severe haemorrhage, transfusion, DIC, surgery/invasive procedures and coagulopathy) are known contributing factors to the thromboembolic risk; and in particular venous thromboembolic risk associated with the administration of NovoSeven (see section 4.8). As recombinant coagulation factor VIIa NovoSeven 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 symptoms occur, the patient should be advised to discontinue use of the product immediately and contact their physician. 5 In case of severe bleeds the product should be administered in hospitals preferably specialised in treatment of haemophilia patients with coagulation factor VIII or IX inhibitors, or if not possible, in close collaboration with a physician specialised 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. Factor VII deficient patients

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