CABLIVI Powder and solvent for solution for injection Ref.[7585] Active ingredients: Caplacizumab

Bleeding

Active clinically significant bleeding

In case of active, clinically significant bleeding, treatment with Cablivi should be interrupted. If needed, the use of von Willebrand Factor concentrate could be considered to correct hemostasis. Cablivi should only be restarted upon the advice of a physician experienced in the management of thrombotic microangiopathies.

Increased risk of bleeding

In the setting of concomitant use of oral anticoagulants or high dose heparin

Due to a potential increased risk of bleeding, initiation or continuation of treatment with oral anticoagulants or high dose heparin requires a benefit/risk assessment and close clinical monitoring.

In the setting of concomitant use of anti-platelet agents and/or low molecular weight heparin (LMWH)

While no increased risk of bleeding was observed in clinical trials, concomitant treatment with antiplatelet agents and/or LMWH requires a benefit/risk assessment and close clinical monitoring.

In patients with coagulopathies

Due to a potential increased risk of bleeding, use of Cablivi in patients with underlying coagulopathies (e.g. hemophilia, other coagulation factor deficiencies) is to be accompanied by close clinical monitoring.

In patients undergoing surgery

If a patient is to undergo elective surgery or a dental procedure, the patient should be advised to inform the physician or dentist that they are using Cablivi, and treatment should be stopped at least 7 days before the planned intervention. The patient should also notify the physician who supervises the treatment with Cablivi about the planned procedure.

If emergency surgery is needed, the use of von Willebrand Factor concentrate could be considered to correct hemostasis.

Severe hepatic impairment

No formal study with caplacizumab has been conducted in patients with severe acute or chronic hepatic impairment and no data regarding the use of caplacizumab in these populations are available. Use of Cablivi in this population requires a benefit/risk assessment and close clinical monitoring.

No interaction studies evaluating use of caplacizumab with oral anticoagulants (e.g. vitamin K antagonists, direct oral anticoagulants [DOAC] such as thrombin inhibitors or factor Xa inhibitors) or high dose heparin have been performed (See section 4.4 In the setting of concomitant use of oral anticoagulants or high dose heparin).

Pregnancy

There are no data on the use of caplacizumab in pregnant women. Studies in guinea pigs showed no effect of caplacizumab on the dams or foetuses (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Cablivi during pregnancy.

Breastfeeding

There are no data on the use of caplacizumab in breastfeeding women. It is unknown whether caplacizumab is excreted in human milk. A risk to the child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to abstain/discontinue from therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

The effects of caplacizumab on fertility in humans are unknown. In animal toxicology studies, no impact of caplacizumab on male and female fertility parameters was observed (see section 5.3).

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

Summary of the safety profile

The most frequent adverse reactions in clinical trials were epistaxis, headache and gingival bleeding. The most common serious adverse reaction was epistaxis.

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA system organ class and by frequency. Frequencies are defined as follows: 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), not known (cannot be estimated from the available data).

Nervous system disorders

Very common: Headache

Common: Cerebral infarction

Eye disorders

Common: Eye Haemorrhage*

Vascular disorders

Common: Haematoma*

Respiratory, thoracic and mediastinal disorders

Very common: Epistaxis*

Common: Dyspnoea, Haemoptysis*

Gastrointestinal disorders

Very common: Gingival bleeding*

Common: Haematemesis*, haematochezia*, melaena*, upper gastrointestinal haemorrhage*, haemorrhoidal haemorrhage*, rectal haemorrhage , abdominal wall haematoma

Skin and subcutaneous tissue disorders

Very common: Urticaria

Musculoskeletal and connective tissue disorders

Common: Myalgia

Renal And Urinary Disorders

Common: Haematuria*

Reproductive system and breast disorders

Common: Menorrhagia*, vaginal haemorrhage*

General disorders and administration site conditions

Very common: Pyrexia, Fatigue

Common: Injection site haemorrhage*, injection site pruritus, injection site erythema, injection site reaction

Injury, Poisoning And Procedural Complications

Common: Subarachnoid haemorrhage

* Bleeding events: see below

Description of selected adverse reactions

Bleeding

In clinical studies, bleeding events occurred in different body systems, independent of treatment duration. Although in some cases these events were serious and required medical attention, most were self-limited and all resolved. In case of active clinically significant bleeding, consider actions outlined in sections 4.4 and 4.9.

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 national reporting system listed in Appendix V.

In the absence of compatibility studies, Cablivi must not be mixed with other medicinal products.