Cablivi

— THERAPEUTIC CATEGORIES —
  • Bleeding disorders
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Cablivi Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Caplacizumab-yhdp 11mg/vial; lyophilized pwd for IV or SC inj after reconstitution; preservative-free.

    Pharmacological Class

    von Willebrand factor (vWF)-directed antibody fragment.

    How Supplied

    Single-dose vial—1 (w. diluent, supplies)

    How Supplied

    Cablivi (caplacizumab-yhdp) for injection is a sterile, white, preservative-free, lyophilized powder in a single-dose vial. 

    Each carton contains:

    • one 11 mg single-dose vial
    • one 1 mL Sterile Water for Injection, USP, prefilled glass syringe (diluent)
    • one sterile vial adapter
    • one sterile hypodermic needle (30 gauge)
    • two individually packaged alcohol swabs

    Storage

    Store refrigerated at 2° C to 8° C (36° F to 46° F) in the original carton to protect from light. 

    Do not freeze. 

    Unopened vials may be stored in the original carton at room temperature up to 30° C (86° F) for a single period of up to 2 months. 

    Do not return Cablivi to the refrigerator after it has been stored at room temperature.

    Manufacturer

    Sanofi Genzyme Company

    Generic Availability

    NO

    Cablivi Indications

    Indications

    Treatment of acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

    Cablivi Dosage and Administration

    Adult

    Administer upon initiation of plasma exchange therapy. 1st bolus IV inj requires administration by healthcare provider. Give subsequent SC inj (after proper training) into the abdomen; rotate inj sites. Avoid inj around the navel. Day 1: Initially 11mg bolus IV inj at least 15mins prior to plasma exchange, then 11mg SC inj after plasma exchange completion. Subsequent Days (during daily plasma exchange): 11mg SC inj once daily following plasma exchange; (after plasma exchange period): 11mg SC inj once daily continuing for 30 days following the last daily plasma exchange; may further extend treatment for max 28 days if signs of persistent underlying disease are present (eg, suppressed ADAMTS13 activity levels). Discontinue if >2 recurrences of aTTP during treatment.

    Children

    Not established.

    Cablivi Contraindications

    Not Applicable

    Cablivi Boxed Warnings

    Not Applicable

    Cablivi Warnings/Precautions

    Warnings/Precautions

    Increased risk of bleeding; interrupt treatment if severe; monitor closely. Withhold treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions. Severe hepatic impairment; monitor closely. Coagulopathy (eg, hemophilia, other coagulation factor deficiencies). Pregnancy, neonates: monitor closely. Nursing mothers.

    Warnings/Precautions

    Cablivi increases the risk of bleeding.

    The risk of bleeding is increased in patients with underlying coagulopathies (eg, hemophilia, other coagulation factor deficiencies). It is also increased with concomitant use of Cablivi with drugs affecting hemostasis and coagulation.

    Interrupt use of Cablivi if clinically significant bleeding occurs. If needed, von Willebrand factor concentrate may be administered to rapidly correct hemostasis. If Cablivi is restarted, monitor closely for signs of bleeding. 

    Withhold Cablivi for 7 days prior to elective surgery, dental procedures or other invasive interventions. If emergency surgery is needed, the use of von Willebrand factor concentrate may be considered to correct hemostasis. After the risk of surgical bleeding has resolved, and Cablivi is resumed, monitor closely for signs of bleeding.

    Pregnancy Considerations

    There are no available data on caplacizumab-yhdp use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. However, there are potential risks of hemorrhage in the mother and fetus associated with use of caplacizumab-yhdp.

    Caplacizumab-yhdp may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding. All patients receiving caplacizumab-yhdp, including pregnant women, are at risk for bleeding. Pregnant women receiving caplacizumab-yhdp should be carefully monitored for evidence of excessive bleeding.

    Nursing Mother Considerations

    There is no information regarding the presence of caplacizumab-yhdp in human milk, the effects on the breastfed child or the effects on milk production. 

    The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for caplacizumab-yhdp and any potential adverse effects on the breastfed child from caplacizumab-yhdp, or from the underlying maternal condition.

    Pediatric Considerations

    The safety and effectiveness of caplacizumab-yhdp in pediatric patients have not been established.

    Geriatric Considerations

    Clinical studies of caplacizumab-yhdp did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

    Hepatic Impairment Considerations

    No formal studies with caplacizumab-yhdp have been conducted in patients with severe acute or chronic hepatic impairment and no data regarding the use of caplacizumab-yhdp in these populations are available. Due to a potential increased risk of bleeding, use of caplacizumab-yhdp in patients with severe hepatic impairment requires close monitoring for bleeding.

    Cablivi Pharmacokinetics

    Absorption

    The bioavailability of subcutaneous caplacizumab-yhdp is approximately 90%. The maximum concentration was observed 6 to 7 hours after subcutaneous dosing of 10 mg caplacizumab-yhdp once daily in healthy subjects.

    Distribution

    Caplacizumab-yhdp central volume of distribution is 6.33 L in patients with aTTP.

    Metabolism

    The available data suggest target-bound caplacizumab-yhdp is metabolized within the liver. Because caplacizumab-yhdp is a monoclonal antibody fragment, it is expected to be catabolized by various proteolytic enzymes.

    Elimination

    The available nonclinical data suggest unbound caplacizumab-yhdp is cleared renally.

    Cablivi Interactions

    Interactions

    Avoid concomitant anticoagulants or antiplatelet agents; may increase risk of bleeding; monitor closely if needed.

    Cablivi Adverse Reactions

    Adverse Reactions

    Epistaxis, headache, gingival bleeding, fatigue, urticaria, pyrexia, paresthesia, dyspnea.

    Cablivi Clinical Trials

    Clinical Trials

    The efficacy of Cablivi for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy was established in a pivotal multicenter, randomized, double-blind, placebo-controlled trial (HERCULES) (NCT02553317). 

    A total of 145 patients were enrolled in the HERCULES study. Patients were randomized to either Cablivi (n=72) or placebo (n=73). Patients in both groups received plasma exchange and immunosuppressive therapy. Patients were stratified according to the severity of neurological involvement (Glasgow Coma Scale score ≤12 or 13 to 15).

    Patients received a single 11 mg Cablivi bolus intravenous injection or placebo prior to the first plasma exchange on study, followed by a daily subcutaneous injection of 11 mg Cablivi or placebo after completion of plasma exchange, for the duration of the daily plasma exchange period and for 30 days thereafter. If after the initial treatment course, sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels remained present, treatment was extended for 7 day intervals for a maximum of 28 days. 

    The median treatment duration with Cablivi was 35 days. 

    The efficacy of Cablivi in patients with aTTP was established based on time to platelet count response (platelet count ≥150,000/µL followed by cessation of daily plasma exchange within 5 days). Time to platelet count response was shorter among patients treated with Cablivi, compared to placebo (Stratified log-rank test: P =0.01; Hazard Ratio: 1.55 [1.10; 2.20]).

    Treatment with Cablivi resulted in a lower number of patients with aTTP-related death, recurrence of aTTP, or at least one treatment-emergent major thromboembolic event (a composite endpoint) during the treatment period vs plasma exchange and immunosuppression alone (12.7% vs 49.3%; P <.0001), as well as a significantly lower percentage of aTTP recurrences in the overall study period (13% vs 38%; P <.001).

    Cablivi Note

    Not Applicable

    Cablivi Patient Counseling

    Patient Counseling

    Bleeding  

    • Patients should be informed that bruising and bleeding may occur more easily, that nosebleeds and bleeding of gums may occur, and that it may take them longer than usual to stop bleeding. 

    • Patients should contact their healthcare provider immediately if symptoms of excessive bruising, excessive bleeding, or major bleeding occur. 

    • Patients should inform their healthcare provider before scheduling any elective surgery, dental procedure or other invasive interventions.

    Cost Savings Program

    The Cablivi savings program is available here.

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