RIASTAP Powder for solution for injection or infusion Ref.[9400] Active ingredients: Human fibrinogen

There is a risk of thrombosis when patients with congenital deficiency are treated with human fibrinogen concentrate, particularly with high dose or repeated dosing. Patients given human fibrinogen concentrate should be observed closely for signs or symptoms of thrombosis.

In patients with a history of coronary heart disease or myocardial infarction, in patients with liver disease, in peri- or post-operative patients, in neonates, or in patients at risk of thromboembolic events or disseminated intravascular coagulation, the potential benefit of treatment with human plasma fibrinogen concentrate should be weighed against the risk of thromboembolic complications. Caution and close monitoring should also be performed.

If allergic or anaphylactic-type reactions occur, the injection/infusion should be stopped immediately. In case of anaphylactic shock, standard medical treatment for shock should be implemented.

In the case of replacement therapy with coagulation factors in other congenital deficiencies, antibody reactions have been observed, but there is currently no data with fibrinogen.

Riastap contains up to 164 mg (7.1 mmol) sodium per vial. This correlates with 11.5 mg (0.5 mmol) sodium per kg body weight of the patient if the recommended initial dose of 70 mg/kg body weight is applied. To be taken into consideration by patients on a controlled sodium diet.

Virus safety

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, and for the non-enveloped virus HAV.

The measures taken may be of limited value against non-enveloped viruses such as 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).

Appropriate vaccination (hepatitis A and hepatitis B) should be generally considered for patients in regular/repeated receipt of human plasma-derived products.

It is strongly recommended that every time that Riastap 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.

No interactions of human plasma fibrinogen concentrate with other medicinal products are known.

Pregnancy

Animal reproduction studies have not been conducted with Riastap (see section 5.3). Since the active substance is of human origin, it is catabolised in the same manner as the patient’s own protein. These physiological constituents of the human blood are not expected to induce adverse effects on reproduction or on the foetus.

The safety of Riastap for use in human pregnancy has not been established in controlled clinical trials.

Clinical experience with fibrinogen concentrate in the treatment of obstetric complications suggests that no harmful effects on the course of the pregnancy or health of the foetus or the neonate are to be expected.

Lactation

It is unknown whether Riastap is excreted in human milk. The use of Riastap in lactating women has not been investigated in clinical trials.

A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Riastap therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on fertility available.

Riastap has no or negligible influence on the ability to drive and use machines.

Tabulated list of adverse drug reactions (ADRs)

The table combines the adverse reactions identified from clinical trials and post-marketing experience.

Frequencies presented in the table have been based on pooled analyses across two company sponsored, placebo-controlled clinical trials performed in aortic surgery with or without other surgical procedures [BI3023-2002 (N=61) and BI3023_3002 (N=152)] according to the following convention: 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).

For spontaneous post-marketing ADRs, the reporting frequency is categorised as ‘Unknown’. In view of the fact that these trials were conducted in only the narrow population of aortic surgery, adverse drug reaction rates observed in these trials may not reflect the rates observed in clinical practice and are unknown for clinical settings outside the studied indication.

General Disorders and Administration Site Condition

Very common: Pyrexia

Immune System Disorder

Uncommon: Anaphylactic reactions (including anaphylactic shock)

Unknown: Allergic reactions (including generalised urticaria, rash, dyspnoea, tachycardia, nausea, vomiting, chills, pyrexia, chest pain, cough, blood pressure decreased)

Vascular Disorder

Common**: Thromboembolic events* (see section 4.4)

* Isolated cases have been fatal.
** Based on results of two clinical trials (aortic surgery with or without other surgical procedures), the pooled incidence rate of thromboembolic events was lower in fibrinogen treated subjects (N=8, 7.4%) compared with placebo (N=11, 10.4%).

For safety with respect to transmissible agents, see section 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the UK Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

This product must not be mixed with other medicinal products, diluents or solvents except those mentioned in section 6.6. A standard infusion set is recommended for intravenous application of the reconstituted solution at room temperature.