CABLIVI

Other Hematological Agents

Visually inspect parenteral products for particulate matter and discoloration whenever solution and container permit. The reconstituted solution should be clear and colorless.
If a dose is missed during the plasma exchange period, give the dose as soon as possible. If a dose is missed after the plasma exchange period, administer the dose within 12 hours of the scheduled time of administration; beyond 12 hours, skip the dose and administer the next daily dose according to the usual dosing schedule.[63940]
 
Reconstitution
Ensure the caplacizumab vial and diluent syringe are at room temperature.
Reconstitute the caplacizumab vial using the provided syringe containing 1 mL of Sterile Water for Injection to yield an 11 mg/mL single-dose solution.
Attach the vial adapter to the caplacizumab vial.
Attach the syringe to the vial adapter by twisting it clockwise until it cannot twist any further.
Slowly push the syringe plunger down until the syringe is empty. Do not remove the syringe from the vial adapter.
Gently swirl the vial until the cake or powder is completely dissolved; do not shake.
Withdraw all the reconstituted solution from the vial into the syringe.
Storage: Use immediately. If not, use within 4 hours after reconstitution when stored in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F).[63940]

The first dose of caplacizumab should be administered by a healthcare provider as a bolus IV injection.
Connect the glass syringe to a standard Luer lock (and not a needleless connector), and flush with either 0.9% Sodium Chloride Injection or 5% Dextrose Injection.[63940]

After the first IV dose, administer subsequent caplacizumab doses subcutaneously in the abdomen.
Avoid injections around the navel. Do not administer consecutive injections in the same abdominal quadrant.
Patients or caregivers may inject caplacizumab subcutaneously after proper training on preparation and administration techniques.[63940]

epistaxis / Delayed / 1.0-4.0
GI bleeding / Delayed / 1.0-1.0

bleeding / Early / 58.0-58.0
dyspnea / Early / 9.0-9.0
vaginal bleeding / Delayed / 5.0-5.0
hematuria / Delayed / 4.0-4.0
hematoma / Early / 3.0-3.0
erythema / Early / Incidence not known
antibody formation / Delayed / Incidence not known

headache / Early / 21.0-21.0
fatigue / Early / 15.0-15.0
urticaria / Rapid / 14.0-14.0
fever / Early / 13.0-13.0
paresthesias / Delayed / 12.0-12.0
back pain / Delayed / 7.0-7.0
myalgia / Early / 6.0-6.0
infection / Delayed / 6.0-6.0
injection site reaction / Rapid / 3.0-6.0
menorrhagia / Delayed / 4.0-4.0
pruritus / Rapid / 3.0-3.0

CABLIVI

Rx

Parenteral von Willebrand factor-directed antibody fragment
Used for acquired thrombotic thrombocytopenic purpura, in combination with plasma exchange and immunosuppressive therapy
Associated with increased risk of bleeding

11 mg IV once at least 15 minutes prior to plasma exchange on the first day of treatment.

11 mg subcutaneously once daily starting after the completion of plasma exchange on day 1 and continuing for 30 days after the last daily plasma exchange. Treatment may be extended for a maximum of 28 days after the initial treatment course if signs of persistent underlying disease remain present (e.g., suppressed ADAMTS13 activity concentrations). Discontinue caplacizumab if more than 2 recurrences of aTTP occur while on therapy.[63940]

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abciximab: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Acetaminophen; Aspirin: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Acetaminophen; Aspirin; Diphenhydramine: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Anagrelide: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Anticoagulants: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Antithrombin III: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Apixaban: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Argatroban: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Caffeine: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Carisoprodol: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Dipyridamole: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs. (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Omeprazole: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Aspirin, ASA; Oxycodone: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Betrixaban: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Bivalirudin: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Cangrelor: (Major) Avoid concomitant use of caplacizumab and cangrelor when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Cilostazol: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Clopidogrel: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Dabigatran: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Dalteparin: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Desirudin: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Dipyridamole: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Edoxaban: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Enoxaparin: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Eptifibatide: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Fondaparinux: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Heparin: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Pentosan: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Platelet Inhibitors: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Prasugrel: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Rivaroxaban: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Ticagrelor: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Ticlopidine: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Tirofiban: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Vorapaxar: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Warfarin: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.

CABLIVI Intravenous Inj Pwd: 11mg
CABLIVI Subcutaneous Inj Pwd: 11mg

11 mg/dose IV or subcutaneously.

11 mg/dose IV or subcutaneously.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Caplacizumab targets the A1-domain of von Willebrand factor (vWF) and inhibits the interaction between vWF and platelets, thus reducing both vWF-mediated platelet adhesion and platelet consumption.[63940] In acquired thrombotic thrombocytopenic purpura (aTTP), autoantibodies inhibit activity of the vWF-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), which leads to unrestrained adhesion of vWF to platelets and microvascular thrombosis.[63946]

Caplacizumab is administered intravenously as an initial bolus, then subcutaneously thereafter. Caplacizumab pharmacokinetics depend on the expression of the target von Willebrand factor (vWF) and are not dose proportional. Higher concentrations of vWF antigen increase the fraction of drug-target complex retained in the circulation. Central volume of distribution is 6.33 L. Available data suggest target-bound caplacizumab is hepatically metabolized. Because caplacizumab is a monoclonal antibody fragment, it is expected to be catabolized by various proteolytic enzymes. Nonclinical data suggest unbound caplacizumab is renally eliminated. The half-life is concentration and target-level dependent.[63940]
 
Ristocetin cofactor (RICO) activity was used to assess vWF activity during clinical trials. Caplacizumab decreased RICO activity concentrations to below 20% approximately 4 hours after subcutaneous administration. RICO activity returned to baseline values within 7 days of drug discontinuation. Caplacizumab also decreased vWF antigen factor and factor VIII:C concentrations; these reductions were transient and returned to baseline upon drug discontinuation.[63940]
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Steady-state was attained after the first administration of caplacizumab in healthy subjects, with minimal accumulation. The initial dose of caplacizumab is administered via IV bolus.[63940]

The bioavailability of subcutaneous caplacizumab is approximately 90%. Tmax occurs 6 to 7 hours after subcutaneous administration. Mean Cmax was 528 ng/mL and AUC was 7,951 ng x hour/mL after a single subcutaneous dose of 10 mg in healthy subjects. After once daily dosing for 14 days, mean Cmax was 348 ng/mL and AUC was 6,808 ng x hour/mL.

All patients receiving caplacizumab, including pregnant women, are at risk for bleeding. In utero exposure may also increase the risk of bleeding in the fetus and neonate. Closely monitor pregnant women and neonates born to those receiving the drug for bleeding. There are no available data on caplacizumab use in human pregnancy to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, there was no evidence of adverse developmental outcomes in guinea pigs at exposures approximately 30 times the AUC in humans at the recommended dose.

There is no information regarding the presence of caplacizumab in human milk, the effects on the breast-fed child, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for caplacizumab and any potential adverse effects on the breast-fed child from caplacizumab or the underlying maternal condition.[63940]