Caplacizumab (Cablivi) is a targeted therapeutic agent classified as a monoclonal antibody fragment (nanobody), primarily indicated for the treatment of adult acquired thrombotic thrombocytopenic purpura (aTTP). 

Caplacizumab (Cablivi):Clinical Uses, Recommended Dosage, Treatment Effect

Currently, this drug has not been launched in China. This article provides a detailed explanation of caplacizumab regarding its indications, dosage and administration, side effects, contraindications, clinical efficacy, and other relevant aspects.

(I) Indications

Caplacizumab (Cablivi) is an antibody fragment targeting von Willebrand factor (vWF). It is used in combination with plasma exchange and immunosuppressive therapy for the treatment of adult acquired thrombotic thrombocytopenic purpura (aTTP).

(II) Dosage and Administration

1. Recommended Dosage and Administration Regimen

First day of treatment: Administer an intravenous bolus of 11 mg at least 15 minutes before plasma exchange; on the same day after the completion of plasma exchange, give a subcutaneous injection of 11 mg.

Subsequent treatment during daily plasma exchange: After daily plasma exchange, administer a subcutaneous injection of 11 mg.

Post-plasma exchange treatment: After the last daily plasma exchange, administer a subcutaneous injection of 11 mg once daily for 30 consecutive days. If there are signs of persistent underlying disease (e.g., suppressed ADAMTS13 activity level) after the initial treatment course, the treatment can be extended for a maximum of 28 days.

Management of recurrence: If a patient experiences more than 2 recurrences of acquired thrombotic thrombocytopenic purpura (aTTP) during treatment with caplacizumab, the drug should be discontinued.

Management of missed doses: If a dose is missed during the plasma exchange period, it should be supplemented as soon as possible; if a dose is missed after the plasma exchange period, administration can be given if it is within 12 hours of the scheduled dose. If more than 12 hours have passed, the missed dose should be skipped, and the next dose should be given according to the regular administration schedule.

2. Discontinuation for Surgery and Other Interventions

Caplacizumab should be discontinued 7 days before elective surgery, dental procedures, or other invasive interventions.

3. Reconstitution and Administration Instructions

The first dose must be administered via intravenous bolus by a healthcare professional. Subsequent doses are given as subcutaneous injections in the abdomen, avoiding the area around the navel, and consecutive injections should not be given in the same abdominal quadrant. Patients or caregivers may administer subcutaneous injections after receiving appropriate training on the preparation and administration of caplacizumab (including aseptic techniques).

Ensure that the caplacizumab vial and diluent syringe are at room temperature. Reconstitute caplacizumab using the accompanying syringe containing 1 mL of Water for Injection (USP) to obtain a single-dose solution with a concentration of 11 mg/mL.

Use aseptic techniques throughout the solution preparation process. Attach the vial adapter to the vial containing caplacizumab, remove the plastic cap of the syringe, and connect it to the vial adapter by rotating clockwise until it can no longer turn. Slowly push the syringe plunger until empty, and do not remove the syringe from the vial adapter. Gently rotate the vial until the cake or powder is completely dissolved; do not shake.

Visually inspect the reconstituted solution to ensure it is clear and colorless. Draw all of the clear and colorless reconstituted solution from the vial into the syringe, label the caplacizumab syringe, and then inject the entire reconstituted solution.

For the initial intravenous injection, if an intravenous infusion set is used, the glass syringe should be connected to a standard Luer lock (not a needle-free connector) and flushed with 0.9% Sodium Chloride Injection (USP) or 5% Dextrose Injection (USP).

The reconstituted caplacizumab solution should be used immediately. If not used immediately, it should be used within 4 hours after reconstitution when stored in a refrigerator at 2°C - 8°C (36°F - 46°F).

(III) Population Applicable

Adults. Pregnant women, lactating women, children, and elderly patients should use the drug under the guidance of a doctor.

(IV) Contraindications

Caplacizumab is contraindicated in patients with a severe hypersensitivity history to caplacizumab or any of its excipients. Hypersensitivity reactions include urticaria, etc.

(V) Side Effects

1. Common Adverse Reactions (Incidence > 15%)

Nasal bleeding, headache, gingival bleeding.

2. Severe Adverse Reactions

Bleeding events: Severe nasal bleeding, subarachnoid hemorrhage, gastrointestinal bleeding, vaginal bleeding.

Others: Injection site bleeding, fever, back pain, urinary tract infection.

3. Post-Marketing Reports

Injection site pain, ecchymosis, erythema.

(VI) Precautions

1. Bleeding Risk

High-risk populations: Patients with coagulation disorders (e.g., hemophilia) and those receiving concurrent anticoagulant/antiplatelet drugs.

Management measures: Discontinue the drug in case of bleeding; if necessary, infuse vWF concentrate to correct hemostatic function. Discontinue the drug 7 days before elective surgery; for emergency surgery, the need for hemostasis should be evaluated.

2. Immunogenicity

Anti-drug antibodies may develop during treatment, but they do not significantly affect efficacy or safety.

3. Patient Education

Guide patients to recognize bleeding symptoms (e.g., abnormal ecchymosis, hematuria, melena) and avoid self-administration of anticoagulant/antiplatelet drugs.

(VII) Therapeutic Efficacy

When used in combination with plasma exchange and immunosuppressive therapy, caplacizumab can effectively treat adult acquired thrombotic thrombocytopenic purpura (aTTP). It can shorten the time required for platelet counts to return to normal and reduce the risk of TTP-related death, recurrence, and at least one major thromboembolic event occurring during treatment.

(VIII) Drug Interactions

1. Concurrent Use with Anticoagulants or Antiplatelet Drugs

Concurrent use of caplacizumab with any anticoagulant or antiplatelet drug may increase the risk of bleeding. Such concurrent use should be avoided if possible; if concurrent use is necessary, the bleeding condition should be evaluated and closely monitored.

(IX) Storage Conditions

Unopened vials: Store refrigerated at 2°C – 8°C, protected from light; freezing is prohibited.

Room temperature storage: Unopened vials can be stored at ≤ 30°C for a maximum of 2 months and must not be refrigerated again.

After reconstitution: Use immediately, or store refrigerated (2°C – 8°C) and use within 4 hours.

【Warm Reminder】: The instructions for some products are updated frequently. Please refer to the actual product for the most accurate information.