Skip to content
ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Bypass Agent — Haemophilia with Inhibitors Pregnancy: §4.6: 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/newborn; animal studies do not indicate direct or indirect harmful effects. Breast-feeding: it is unknown whether rFVIIa is excreted in human breast milk — a decision to continue or discontinue should weigh the benefit of breast-feeding against the benefit of therapy. Fertility: non-clinical and post-marketing data show no indication of a harmful effect. Note §4.4: pregnant or peripartum women are among the groups in whom thromboembolic risk warrants caution.

Recombinant Factor VIIa

Brand names: NovoSeven

Recombinant factor VIIa (eptacog alfa) is a bypassing agent used to treat and prevent bleeding in haemophilia A or B with inhibitors, and in certain other rare bleeding disorders such as factor VII deficiency and Glanzmann thrombasthenia.

Adult dose

Dose: HAEMOPHILIA A OR B WITH INHIBITORS, or expected to have a high anamnestic response (this page's primary indication) — NovoSeven should be given as early as possible after the start of a bleeding episode. §4.2 verbatim: 'The recommended initial dose, administered by intravenous bolus injection, is 90 µg per kg body weight. Following the initial dose of NovoSeven further injections may be repeated.' MILD TO MODERATE bleeding episodes (joint, muscle and mucocutaneous bleeds, including home therapy) — two regimens are recommended: '1) Two to three injections of 90 µg per kg body weight administered at three-hour intervals. If further treatment is required, one additional dose of 90 µg per kg body weight can be administered. 2) One single injection of 270 µg per kg body weight.' Home therapy should not exceed 24 hours. SERIOUS bleeding episodes: initial dose 90 µg/kg, then every second hour until clinical improvement is observed, then 3-hourly for 1-2 days. INVASIVE PROCEDURE/SURGERY: 90 µg/kg immediately before the intervention, repeated after 2 hours and then at 2-3 hour intervals for the first 24-48 hours; in major surgery continue at 2-4 hour intervals for 6-7 days, then 6-8 hourly for another 2 weeks.
Route: Intravenous bolus injection over 2-5 minutes, after reconstitution. §4.2 verbatim: 'Administer the solution as an intravenous bolus injection over 2 – 5 minutes.'
Frequency: Initially every 2-3 hours to obtain haemostasis. §4.2 verbatim: '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.' A major bleeding episode may be treated for 2-3 weeks, or longer if clinically warranted.
Max: No absolute maximum dose is stated for this indication. The highest single dose stated for haemophilia with inhibitors is 270 µg/kg, as the alternative single-injection regimen for mild-to-moderate bleeds; duration of home therapy should not exceed 24 hours, and continued home treatment only after consultation with the haemophilia treatment centre.
Source: UK SPC (eMC) for NovoSeven 1 mg (50KIU) powder and solvent for solution for injection, §4.2 posology plus §4.3, §4.4, §4.6 and §4.8 (https://www.medicines.org.uk/emc/product/6360/smpc). The §4.2 POSOLOGY SECTION IS COMPLETE in this bundle (it runs to the end of 'Monitoring of treatment – laboratory tests'). Some sections of the product information we used were incomplete — check the full SPC. SPECIALIST SUPERVISION: §4.2 — 'Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia and/or bleeding disorders.' 'Maintenance of adequate fibrinogen concentration and platelet count is recommended in order to optimise the benefit of NovoSeven treatment.' §4.4 — '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.' OTHER LICENSED INDICATIONS IN THE SAME §4.2, each with its OWN dose — these are NOT this page's primary indication and their figures must not be applied to it: ACQUIRED HAEMOPHILIA — 90 µg/kg IV bolus initially, interval 2-3 hours then increased successively to 4, 6, 8 or 12 hours. FACTOR VII DEFICIENCY — 15-30 µg/kg every 4-6 hours until haemostasis is achieved, in adults and children. GLANZMANN'S THROMBASTHENIA — 90 µg/kg (range 80-120 µg/kg) at intervals of two hours (1.5-2.5 hours), at least three doses, by bolus injection (platelets are first-line for patients who are not refractory). SEVERE POSTPARTUM HAEMORRHAGE — 60-90 µg/kg IV bolus, peak coagulant activity expected at 10 minutes, a second dose may be given after 30 minutes if the haemostatic response is insufficient. NOTE ON SOURCES: providers.openfda and providers.who are both null in this bundle — no US label and no WHO entry were used.

Paediatric dose

Dose: 90 micrograms/kg
Route: Intravenous bolus injection over 2-5 minutes
Frequency: Initially every 2-3 hours to obtain haemostasis; once effective haemostasis is achieved the interval can be increased successively to every 4, 6, 8 or 12 hours for as long as treatment is judged to be indicated
Max: No absolute paediatric maximum is stated. As in adults, the highest single dose stated for haemophilia with inhibitors is 270 µg/kg (the single-injection alternative for mild-to-moderate bleeds); there is no clinical experience with a single 270 µg/kg dose in elderly patients.
This is the LABEL'S OWN paediatric figure, not an adult dose scaled down. §4.2 verbatim: 'Paediatric population. 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 (see section 5.2).' So the initial dose in children is the same 90 µg per kg body weight by IV bolus injection as in adults, and higher doses may be required. Note for factor VII deficiency (a DIFFERENT indication): 'Limited clinical experience in long term prophylaxis has been gathered in the paediatric population below 12 years of age, with a severe clinical phenotype... Dose and frequency of injections for prophylaxis should be based on clinical response and adapted to each individual.' §4.4 lists neonates among the groups in whom caution is needed because of thromboembolic risk. Verify against a children's formulary and the local haemophilia centre before use.

Dose adjustments

Renal

Not stated in the product information we used — check the full SPC.

Hepatic

No hepatic dose adjustment is stated. §4.4 advises caution in patients with liver disease because of the risk of thromboembolic complications.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

This is the LABEL'S OWN paediatric figure, not an adult dose scaled down. §4.2 verbatim: 'Paediatric population. 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 (see section 5.2).' So the initial dose in children is the same 90 µg per kg body weight by IV bolus injection as in adults, and higher doses may be required. Note for factor VII deficiency (a DIFFERENT indication): 'Limited clinical experience in long term prophylaxis has been gathered in the paediatric population below 12 years of age, with a severe clinical phenotype... Dose and frequency of injections for prophylaxis should be based on clinical response and adapted to each individual.' §4.4 lists neonates among the groups in whom caution is needed because of thromboembolic risk. Verify against a children's formulary and the local haemophilia centre before use.

Verify in a children's formulary

Contraindications

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

Side effects

  • Most frequently reported (uncommon, 1/1,000 to 1/100): decreased therapeutic response, pyrexia, rash, venous thromboembolic events, pruritus and urticaria
  • Most serious: venous thromboembolic events (uncommon) — deep vein thrombosis, thrombosis at the IV site, pulmonary embolism, thromboembolic events of the liver including portal vein thrombosis, renal vein thrombosis, thrombophlebitis, superficial thrombophlebitis and intestinal ischaemia
  • Arterial thromboembolic events (rare, 1/10,000 to 1/1,000) — myocardial infarction, cerebral infarction, cerebral ischaemia, cerebral artery occlusion, cerebrovascular accident, renal artery thrombosis (the list was cut at the fetch limit)
  • Blood: disseminated intravascular coagulation and related laboratory findings including elevated D-dimer and decreased antithrombin; coagulopathy
  • Immune: hypersensitivity; anaphylactic reaction (frequency not known)
  • General: injection site reaction including injection site pain; nausea; headache; flushing; angioedema
  • Investigations: increased fibrin degradation products; increases in alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and prothrombin
  • This side-effect list may be incomplete — check the full SPC.

Interactions

  • §4.4: in pathological conditions in which tissue factor may be expressed more extensively than normal there may be a risk of thrombotic events or induction of DIC — such situations may include advanced atherosclerotic disease, crush injury, septicaemia or DIC
  • §4.4: caution when administering to patients with a history of coronary heart disease, liver disease, post-operative patients, pregnant or peripartum women, neonates, or patients at risk of thromboembolic events or DIC
  • This interaction list may be incomplete — check the full SPC.

Monitoring

  • §4.2 verbatim: 'There is no requirement for monitoring of NovoSeven therapy. Severity of bleeding condition and clinical response to NovoSeven administration must guide dosing requirements.'
  • §4.2: after administration of rFVIIa, prothrombin time (PT) and activated partial thromboplastin time (aPTT) have been shown to shorten, however no correlation has been demonstrated between PT/aPTT and clinical efficacy of rFVIIa
  • §4.2: maintain adequate fibrinogen concentration and platelet count to optimise the benefit of treatment
  • §4.4 (factor VII deficiency, a different indication): monitor prothrombin time and factor VII coagulant activity before and after administration; if factor VIIa activity fails to reach the expected level or bleeding is not controlled at the recommended doses, suspect antibody formation and analyse for antibodies
  • Watch for thromboembolic complications and for early signs of hypersensitivity; discontinue immediately if allergic or anaphylactic-type reactions occur

Clinical monograph

How it works

In pharmacological amounts it activates the coagulation cascade on the surface of activated platelets, generating thrombin and a fibrin clot largely independently of factors VIII and IX, thereby bypassing inhibitors.

Prescribing in practice

  • Thromboembolic events, including arterial and venous thrombosis, are a recognised risk, particularly in patients with predisposing cardiovascular factors, so it should be used with caution and for the shortest effective duration.
  • It is administered by intravenous injection and dosing for bleeding episodes is repeated according to response under haematology guidance.
  • Management of bleeding in inhibitor patients should follow specialist advice and current prescribing references.

Monitoring

Monitor clinical haemostatic response and remain vigilant for signs of thrombosis, as routine coagulation tests do not reliably reflect efficacy.

Counselling the patient

  • Explain that this medicine helps blood to clot when standard factor replacement does not work because of inhibitors.
  • Advise reporting symptoms suggesting a clot, such as chest pain, breathlessness or limb swelling.

Evidence & guidelines

Recombinant factor VIIa is an established bypassing agent for haemophilia with inhibitors in UK haematology practice and the SPC.

Reference: FAST Trial (Mayer et al. NEJM 2008); BSH Haemophilia with Inhibitors Guidelines; UKHCDO; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways