Cablivi

Treatment with Cablivi should be initiated and supervised by physicians experienced in the management of patients with thrombotic microangiopathies. Posology First dose Intravenous injection of 10 mg of caplacizumab prior to plasma exchange.

Subsequent doses Daily subcutaneous administration of 10 mg of caplacizumab after completion of each plasma exchange for the duration of daily plasma exchange treatment, followed by daily subcutaneous injection of 10 mg of caplacizumab for 30 days after stopping daily plasma exchange treatment.

g. sustained normalisation of ADAMTS13 activity level). 3 In the clinical development program, caplacizumab has been administered daily for up to 71 days consecutively. 1). Missed dose The first dose of caplacizumab should be administered intravenously before the initial plasma exchange.

If the administration of the first intravenous dose of caplacizumab is missed and plasma exchange is already administered, the first caplacizumab dose should still be administered intravenously after the plasma exchange is complete and the next dose should be administered subcutaneously on the following day according to the usual dosing schedule.

If a dose of Cablivi is missed, it can be administered within 12 hours. If more than 12 hours have passed since the dose was to have been given, the missed dose should NOT be administered and the next dose should be administered per the usual dosing schedule.

2). 2). 4 for special considerations in patients with severe hepatic impairment. 2). Paediatric population The safety and efficacy of caplacizumab in the paediatric population have not been established in clinical studies. 2). No recommendations can be made on the posology of Cablivi for paediatric patients below 40 kg of body weight.

Method of administration The first dose of Cablivi is to be administered as an intravenous injection. Subsequent doses are to be administered via subcutaneous injection in the abdomen. Injections into the area around the navel should be avoided and consecutive injections should not be administered in the same abdominal quadrant.

Patients or caregivers may inject the medicinal product after proper training in the subcutaneous injection technique. 6.

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).

6 Table 1 . List of adverse reactions in TITAN and HERCULES studies MedDRA System organ class Very common Common Nervous system disorders Headache Cerebral infarction Eye disorders Eye Haemorrhage* Vascular disorders Haematoma* Respiratory, thoracic and mediastinal disorders Epistaxis* Dyspnoea, Haemoptysis* Gastrointestinal disorders Gingival bleeding* Haematemesis*, haematochezia*, melaena*, upper gastrointestinal haemorrhage*, haemorrhoidal haemorrhage*, rectal haemorrhage *, abdominal wall haematoma* Skin and subcutaneous tissue disorders Urticaria Musculoskeletal and connective tissue disorders Myalgia Renal and urinary disorders Haematuria* Reproductive system and breast disorders Menorrhagia*, vaginal haemorrhage* General disorders and administration site conditions Pyrexia, Fatigue Injection site haemorrhage*, injection site pruritus, injection site erythema, injection site reaction Injury, poisoning and procedural complications 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.

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. 4 and

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. 4 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.

g. alteplase) or heparin requires careful consideration and close clinical monitoring. 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.

1.