caplacizumab

Action and Spectrum

Actions and Spectrum: 

Action: caplacizumab is a bivalent anti-von Willebrand factor (vWF) nanobody that inhibits the interaction between vWF and platelets. It binds to the A1 domain of vWF and prevents the formation of large vWF-platelet aggregates responsible for the microvascular thrombosis seen in aTTP. By inhibiting this interaction, drug reduces platelet adhesion and prevents the formation of blood clots. 

Spectrum: The drug is specifically approved for the therapy of acquired thrombotic thrombocytopenic purpura (aTTP) in the adults. It is used as an adjunct therapy to plasma exchange and immunosuppressive therapy to decrease the time to platelet count normalization and reduce the incidence of major thromboembolic events during episodes of aTTP. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

Paresthesia (12%) 

Pyrexia (13%) 

Urticaria (14%) 

Fatigue (15%) 

Gingival bleeding (16%) 

Headache (21%) 

Epistaxis (29%) 

1-10% 

Abdominal wall hematoma (3%) 

Menorrhagia (4%) 

Hematuria (4%) 

Rectal hemorrhage (4%) 

Vaginal hemorrhage (5%) 

Urinary tract infection (6%) 

Myalgia (6%) 

Back pain (7%) 

Dyspnea (9%) 

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: caplacizumab is contraindicated in individuals with a known hypersensitivity or allergic reaction to the medication or any of its components. Allergic reactions may include symptoms such as rash, itching, swelling, or difficulty breathing. 

Major bleeding risk: caplacizumab can increase the risk of bleeding. Therefore, it should be used cautiously or avoided in patients with an increased susceptibility to bleeding or those at high risk of major bleeding events, such as patients with a history of gastrointestinal bleeding or recent surgery. 

Concurrent anticoagulant use: Drug should not be used concomitantly with other anticoagulant medications, such as vitamin K antagonists (e.g., warfarin) or direct oral anticoagulants (e.g., apixaban, rivaroxaban). Combining caplacizumab with these agents can further increase the risk of bleeding. 

Surgical procedures: Drug should be used cautiously in patients scheduled to undergo surgery or invasive procedures.  

Pregnancy and breast-feeding: The safety and efficacy of caplacizumab in pregnant and breastfeeding women have not been established. Therefore, it is generally not recommended during pregnancy or breastfeeding unless the potential benefits outweigh the potential risks. Healthcare providers should assess the individual situation and make an informed decision. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology: caplacizumab is a medication used to treat acquired thrombotic thrombocytopenic purpura (aTTP).  

Pharmacodynamics:  

caplacizumab acts by binding to the A1 domain of vWF, thereby inhibiting the interaction between vWF and platelets. It prevents the formation of platelet-rich thrombi in small blood vessels.   

Pharmacokinetics: 

Absorption 

Since caplacizumab is given as an IV infusion, it bypasses the absorption phase that is typical for orally administered drugs. Instead, it directly enters the bloodstream and is distributed throughout the body to exert its effects on vWF and platelet interactions. 

Distribution 

The volume of distribution is approximately equal to the plasma volume, indicating that caplacizumab is primarily distributed within the blood. 

Metabolism 

caplacizumab is not metabolized by the liver or other metabolic pathways 

Excretion and Elimination 

The clearance of caplacizumab is primarily through the reticuloendothelial system, resulting in a relatively long elimination half-life. 

Adminstartion

Administration:  

Injection: caplacizumab is administered as a subcutaneous injection, which means it is injected into the fatty tissue just beneath the skin. The most common injection site is the abdomen, although other sites may be used as well. The healthcare professional will determine the appropriate injection site and provide instructions on administering the injection. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: caplacizumab 

Why do we use caplacizumab?  

Treatment of aTTP: caplacizumab is specifically approved for treating acquired thrombotic thrombocytopenic purpura. It is combined with standard plasma exchange therapy to reduce the time to platelet normalization and prevent major thrombotic events in patients with aTTP. 

Reduction of treatment duration: Drug can help shorten the duration of plasma exchange treatment in patients with aTTP. It has been shown to reduce the time to normalize platelet count and decrease the risk of disease-related complications. 

Prevention of major thrombotic events: By inhibiting the vWF-platelet interaction, caplacizumab helps prevent the formation of blood clots and reduces the risk of major thrombotic events such as stroke, heart attack, and organ damage in patients with aTTP.