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

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Bleeding

Cablivi increases the risk of bleeding. Cases of major bleeding, including life-threatening and fatal bleeding have been reported in patients receiving caplacizumab, mainly in those using concomitant anti-platelet agents or anticoagulants. Caplacizumab should be used with caution in patients with underlying conditions that may predispose them to a higher risk of bleeding.

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

In the setting of concomitant use of oral anticoagulants, anti-platelet agents, thrombolytic agents or heparin

The risk of bleeding is increased with concomitant use of Cablivi with other medicinal products affecting haemostasis and coagulation. Initiation or continuation of treatment with oral anticoagulants (e.g., vitamin K antagonists or direct oral anticoagulants [DOAC] such as thrombin inhibitors or factor Xa inhibitors), anti-platelet agents, thrombolytic agents such as urokinase, tissue plasminogen activator (t-PA) (e.g. alteplase) or heparin requires careful consideration 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. haemophilia, other coagulation factor deficiencies) must be accompanied by close clinical monitoring.

In patients undergoing surgery

If a patient is to undergo elective surgery, an invasive dental procedure or other invasive interventions, the patient must be advised to inform the physician or dentist that they are using caplacizumab and it is recommended to withhold treatment for at least 7 days before the planned intervention. The patient must also notify the physician who supervises the treatment with caplacizumab about the planned procedure. After the risk of surgical bleeding has resolved, and caplacizumab is resumed, the patient should be monitored closely for signs of bleeding.

If emergency surgery is needed, the use of von Willebrand Factor concentrate is recommended to correct haemostasis.

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.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

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), antiplatelet agents, thrombolytic agents such as urokinase, tPA (e.g. alteplase) or heparin have been performed (see section 4.4 In the setting of concomitant use of oral anticoagulants, anti-platelet agents, thrombolytic agents or 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 the TITAN and HERCULES clinical studies 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).

Table 1. List of adverse reactions in TITAN and HERCULES studies:

Description of selected adverse reactions

Bleeding

In clinical studies, bleeding events occurred in different body systems, independent of treatment duration. In the postmarketing setting, cases of major bleeding, including life-threatening and fatal bleeding have been reported in patients receiving caplacizumab, mainly in those using concomitant anti-platelet agents or anticoagulants. In case of 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.