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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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
Dosage and Administration
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
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
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, loss of strength and energy, back pain, or muscle pain. Have patient report immediately to prescriber signs of bleeding (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), signs of a urinary tract infection (blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain), burning or numbness feeling, or shortness of breath (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
