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Caplacizumab

Medically reviewed by Drugs.com. Last updated on Mar 19, 2020.

Pronunciation

(KAP la SIZ ue mab)

Index Terms

  • ALX-0081
  • ALX-0681
  • ALX0081
  • Caplacizumab-yhdp

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Injection [preservative free]:

Cablivi: 11 mg [contains polysorbate 80]

Brand Names: U.S.

  • Cablivi

Pharmacologic Category

  • Anti-von Willebrand Factor (vWF)
  • Monoclonal Antibody

Pharmacology

Caplacizumab is a von Willebrand factor (vWF)-directed monoclonal antibody fragment which targets the A1-domain of vWF, inhibiting the interaction between vWF and platelets, reducing both vWF-mediated platelet adhesion and platelet consumption.

Distribution

Vd: 6.33 L

Metabolism

Caplacizumab is likely catabolized by various proteolytic enzymes; target-bound caplacizumab is metabolized hepatically

Excretion

Unbound caplacizumab is eliminated renally.

Onset of Action

Ristocetin cofactor (RCo) activity levels are decreased to below 20% within 4 hours after a dose.

Time to Peak

SubQ: 6 to 7 hours

Duration of Action

RCo activity returns to baseline within 7 days following discontinuation.

Use: Labeled Indications

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

Contraindications

Previous severe hypersensitivity (eg, urticaria) to caplacizumab or any component of the formulation

Dosing: Adult

Thrombotic thrombocytopenic purpura, acquired: Administer caplacizumab upon initiation of plasma exchange therapy.

First day of treatment: IV followed by SubQ: 11 mg IV at least 15 minutes prior to plasma exchange, followed by 11 mg SubQ after completion of plasma exchange on day 1.

Subsequent treatment days (during daily plasma exchange): SubQ: 11 mg once daily following plasma exchange.

Treatment after plasma exchange period: SubQ: 11 mg once daily, continuing for 30 days following the last daily plasma exchange; if sign(s) of persistent underlying disease remain present (eg, suppressed ADAMTS13 activity levels) after initial treatment course, treatment may be extended up to a maximum of 28 days.

Discontinuation: Discontinue caplacizumab if >2 recurrences of acquired thrombotic thrombocytopenic purpura (aTTP) occur during treatment. Withhold caplacizumab treatment 7 days prior to elective surgery, dental procedures, and/or other invasive interventions.

Missed dose: If a caplacizumab dose is missed during the plasma exchange period, administer as soon as possible. If a caplacizumab dose is missed after the plasma exchange period, administer within 12 hours of the scheduled administration time; beyond 12 hours, the missed dose should be skipped and the next daily dose administered according to the usual dosing schedule.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Bleeding: If clinically significant bleeding occurs, interrupt treatment. If rapid correction of hemostasis is required, von Willebrand factor concentrate may be administered. Monitor closely if caplacizumab is reinitiated.

Reconstitution

Bring vial and diluent to room temperature. Reconstitute (to a concentration of 11 mg/mL) by attaching the vial adapter to the vial, then attach the provided syringe (which contains 1 mL sterile water for injection) to the vial adapter and twist clockwise (until it cannot be further twisted), then slowly push syringe plunger down until syringe is empty (keep syringe attached to the vial adapter). Gently swirl until cake/powder is completely dissolved; do not shake. Withdraw completely dissolved (clear and colorless) solution back into the syringe and label syringe.

Administration

IV: Administer the first (initial) dose as an IV bolus by connecting the glass syringe to a standard luer lock (do not use a needleless connector). Flush with either NS or D5W.

SubQ: Subsequent doses are administered subcutaneously into the abdomen. Avoid injections around the navel. Rotate abdominal quadrants; do not administer consecutive injections into the same quadrant.

The initial IV dose should be administered by a health care provider; subcutaneous doses may be administered by the patient (or caregiver) following appropriate training.

Storage

Store at 2°C to 8°C (36°F to 46°F). Do not freeze. Store in original carton to protect from light. 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 to the refrigerator after it has been stored at room temperature. Use immediately following reconstitution; if not used immediately, store refrigerated (2°C to 8°C [36°F to 46°F]) and use within 4 hours of reconstitution.

Drug Interactions

Anticoagulants: Caplacizumab may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (21%), fatigue (15%), paresthesia (12%)

Dermatologic: Urticaria (14%)

Gastrointestinal: Gingival hemorrhage (16%)

Hematologic & oncologic: Bleeding complications (58%)

Respiratory: Epistaxis (29%)

Miscellaneous: Fever (13%)

1% to 10%:

Cardiovascular: Subarachnoid hemorrhage (2%)

Dermatologic: Injection site pruritus (3%)

Endocrine & metabolic: Heavy menstrual bleeding (4%), intermenstrual bleeding (1%)

Genitourinary: Urinary tract infection (6%), vaginal hemorrhage (5%), hematuria (4%)

Hematologic & oncologic: Rectal hemorrhage (4%), hematoma (3%), upper gastrointestinal hemorrhage (1%)

Immunologic: Antibody development (3%)

Local: Bleeding at injection site (6%), catheter site hemorrhage (6%)

Neuromuscular & skeletal: Back pain (7%), myalgia (6%)

Respiratory: Dyspnea (9%)

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: Caplacizumab increases the risk of bleeding; bleeding events occur commonly. Severe bleeding events (epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia) were reported in a small number of patients in clinical studies. The risk of bleeding is increased in patients with underlying coagulopathies (eg, hemophilia, or other coagulation factor deficiencies) and with concomitant use of caplacizumab with medications affecting hemostasis and coagulation. Interrupt caplacizumab treatment if clinically significant bleeding occurs. If necessary, von Willebrand factor concentrate may be administered to rapidly correct hemostasis. Monitor closely for signs of bleeding if caplacizumab is restarted. Withhold caplacizumab 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 caplacizumab has been resumed, monitor closely for signs of bleeding.

• Hypersensitivity: Urticaria has been reported.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with severe acute or chronic hepatic impairment (due to the potential increased risk of bleeding); monitor closely.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Monitoring Parameters

Consider monitoring ADAMTS13 activity levels (Scully 2019). Monitor for signs/symptoms of bleeding, especially in patients at increased risk (severe hepatic impairment or who are on concurrent medications affecting hemostasis and coagulation).

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

There is a risk of bleeding with caplacizumab; monitor both the mother and the newborn if exposure occurs during pregnancy.

Acquired thrombotic thrombocytopenic purpura, when first diagnosed during pregnancy, is also associated with adverse pregnancy outcomes. Treatment generally follows current recommendations which include plasma exchange, plasma infusion, and/or immunosuppressive therapy (Joly 2017; Scully 2014). Pregnant females were excluded from the initial caplacizumab studies (Scully 2019).

Patient Education

What is this drug used for?

• It is used to treat acquired thrombotic thrombocytopenic purpura (aTTP).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Loss of strength and energy

• Back pain

• Muscle pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.

• Burning or numbness feeling

• Shortness of breath

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.