Cablivi (Caplacizumab)
Anti-von Willebrand factor nanobody for acquired thrombotic thrombocytopenic purpura (aTTP)
Cablivi (caplacizumab) is a prescription medicine used to treat episodes of acquired thrombotic thrombocytopenic purpura (aTTP) in adults and adolescents aged 12 years and older weighing at least 40 kg. aTTP is a rare and potentially life-threatening blood disorder in which blood clots form in small blood vessels throughout the body. Caplacizumab works by targeting von Willebrand factor (vWF), preventing the abnormal platelet clumping that characterizes this condition. It is always used alongside plasma exchange therapy and immunosuppressive treatment.
Quick Facts
Key Takeaways
- Cablivi (caplacizumab) is the first targeted therapy specifically approved for acquired thrombotic thrombocytopenic purpura (aTTP), a rare and life-threatening blood clotting disorder.
- The first dose is given intravenously before plasma exchange; subsequent doses are self-injected subcutaneously once daily, continuing for at least 30 days after plasma exchange ends.
- The most significant risk is bleeding. Patients should report any unusual or prolonged bleeding to their doctor immediately.
- Caplacizumab has been shown in clinical trials (HERCULES) to significantly reduce time to platelet count normalization, lower the incidence of aTTP-related complications, and reduce the risk of recurrence.
- Special caution is required when using Cablivi alongside anticoagulants or antiplatelet agents due to increased bleeding risk.
What Is Cablivi and What Is It Used For?
Cablivi contains the active substance caplacizumab, a bivalent nanobody (a type of antibody fragment) that targets the A1 domain of von Willebrand factor (vWF). This protein plays a central role in the disease mechanism of acquired thrombotic thrombocytopenic purpura (aTTP), a rare but serious hematological condition characterized by the formation of microthrombi (tiny blood clots) in small blood vessels throughout the body.
In aTTP, autoantibodies develop against the enzyme ADAMTS13, which normally cleaves ultra-large vWF multimers into smaller, less reactive fragments. When ADAMTS13 activity is severely reduced (typically below 10%), these ultra-large vWF multimers accumulate in the bloodstream, causing platelets to stick together excessively, forming microthrombi that can block blood flow to vital organs. This process leads to the hallmark features of aTTP: severe thrombocytopenia (low platelet count), microangiopathic hemolytic anemia (destruction of red blood cells), and organ damage affecting the brain, heart, kidneys, and other tissues.
Caplacizumab works by blocking the interaction between ultra-large vWF multimers and platelet receptors (glycoprotein Ib-IX-V). By preventing this interaction, caplacizumab rapidly inhibits the vWF-mediated platelet adhesion and aggregation that drives microthrombus formation. This mechanism of action is complementary to plasma exchange (which removes autoantibodies and replenishes ADAMTS13) and immunosuppression (which suppresses autoantibody production).
Cablivi is approved for the treatment of aTTP episodes in adults and adolescents aged 12 years and older who weigh at least 40 kg. It was first authorized by the European Medicines Agency (EMA) in 2018 and subsequently approved by the U.S. Food and Drug Administration (FDA) in 2019. The approval was based on the landmark HERCULES trial, a phase 3, randomized, double-blind, placebo-controlled study that demonstrated significant clinical benefits in patients with aTTP.
In the HERCULES trial, caplacizumab-treated patients achieved a significantly faster time to platelet count response (normalization), experienced fewer aTTP-related deaths, recurrences, or major thromboembolic events during the treatment period, and had a lower number of plasma exchange sessions. These results established caplacizumab as a critical addition to the standard of care for aTTP, which previously relied solely on plasma exchange and immunosuppression.
What Should You Know Before Taking Cablivi?
Before beginning treatment with Cablivi, it is essential to have a thorough discussion with your healthcare provider about your medical history, current medications, and any planned procedures. Because caplacizumab affects the blood clotting process, certain conditions and drug combinations require special attention and may influence how your treatment is managed.
Contraindications
Cablivi must not be used if you are allergic (hypersensitive) to caplacizumab or any of the other ingredients in the medicine. The inactive ingredients include sucrose, anhydrous citric acid, trisodium citrate dihydrate, and polysorbat 80. The solvent is water for injections. If you have experienced an allergic reaction to any of these components previously, inform your doctor before starting treatment.
Warnings and Precautions
Several important warnings and precautions apply to the use of Cablivi. You should tell your doctor if any of the following apply to you:
- Unusual or excessive bleeding: If you experience any unusual bleeding or symptoms such as severe headache, shortness of breath, fatigue, or fainting that could indicate serious internal bleeding, contact your doctor immediately. Your doctor may advise you to discontinue treatment and will tell you when it is safe to resume.
- Use of anticoagulants: If you are taking medications that prevent or treat blood clots, such as warfarin, heparin, rivaroxaban, or apixaban, your doctor will carefully evaluate how to manage your treatment, as combining these drugs with Cablivi increases bleeding risk.
- Use of antiplatelet agents: If you are taking antiplatelet medications such as acetylsalicylic acid (aspirin) or low-molecular-weight heparin, your doctor will determine the appropriate treatment approach.
- Bleeding disorders: If you have an underlying bleeding disorder such as hemophilia, your doctor will assess whether Cablivi is appropriate for you and will closely monitor your condition.
- Severely impaired liver function: Patients with significant liver disease may require dose adjustments or closer monitoring, and your doctor will evaluate your individual situation.
- Planned surgery or dental procedures: If you have an upcoming surgical or dental procedure, tell your doctor. They will decide whether the procedure can be postponed or whether Cablivi should be temporarily discontinued before the procedure.
Cablivi increases the risk of bleeding. Seek immediate medical attention if you experience prolonged or heavy bleeding, severe or sudden headache, vomiting, decreased consciousness, fever, seizures, or neck stiffness. These may indicate serious internal or cerebral hemorrhage.
Children and Adolescents
Cablivi is approved for adolescents aged 12 years and older who weigh at least 40 kg. It is not recommended for use in children under 12 years of age or those weighing less than 40 kg, as safety and efficacy have not been established in this population. Clinical data in pediatric patients are limited, and treatment decisions in adolescents should be made by a hematologist experienced in managing aTTP.
Pregnancy and Breastfeeding
The use of Cablivi during pregnancy is not recommended due to insufficient data on its effects on the developing fetus. If you are pregnant, think you may be pregnant, or are planning to become pregnant, inform your doctor before starting treatment. Your healthcare team will weigh the potential risks and benefits in your individual case, considering the seriousness of untreated aTTP.
It is not known whether caplacizumab passes into human breast milk. If you are breastfeeding, your doctor will help you decide whether to discontinue breastfeeding or discontinue Cablivi, taking into account the benefit of breastfeeding for your child and the benefit of treatment for you. The decision should be individualized based on the clinical urgency of aTTP treatment.
Driving and Operating Machinery
Cablivi is not expected to affect your ability to drive or operate machinery. However, if you experience side effects such as fatigue or dizziness, you should exercise caution when performing activities that require alertness until you know how the medicine affects you.
Cablivi contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.
How Does Cablivi Interact with Other Drugs?
Drug interactions are an important consideration with Cablivi because its mechanism of action directly affects the hemostatic (blood clotting) process. Since caplacizumab inhibits vWF-mediated platelet adhesion, combining it with other drugs that also affect hemostasis can significantly increase the risk of bleeding. Always inform your healthcare provider about all medications you are currently taking, have recently taken, or might take.
The most clinically significant interactions involve anticoagulant and antiplatelet medications. These drugs work through different mechanisms to reduce clotting, and when combined with Cablivi's anti-vWF activity, the cumulative effect on hemostasis can be substantial. Your hematologist will carefully evaluate the risk-benefit ratio of any combination and may adjust dosing or monitoring accordingly.
Major Interactions
| Drug / Class | Type of Interaction | Clinical Significance |
|---|---|---|
| Warfarin (Vitamin K antagonist) | Increased bleeding risk | Combined anticoagulant and anti-vWF effects; close INR monitoring required |
| Heparin (Unfractionated) | Increased bleeding risk | Both affect different parts of the coagulation cascade; physician-supervised use only |
| Rivaroxaban (Direct factor Xa inhibitor) | Increased bleeding risk | Additive anticoagulant effect; careful benefit-risk assessment needed |
| Apixaban (Direct factor Xa inhibitor) | Increased bleeding risk | Additive anticoagulant effect; careful benefit-risk assessment needed |
Minor Interactions
| Drug / Class | Type of Interaction | Clinical Significance |
|---|---|---|
| Acetylsalicylic acid (Aspirin) | Increased bleeding risk | Antiplatelet effect combined with anti-vWF; physician to determine management |
| Low-molecular-weight heparin (e.g., enoxaparin) | Increased bleeding risk | Prophylactic doses may be used with caution under specialist supervision |
| NSAIDs (e.g., ibuprofen, naproxen) | Potential increased bleeding risk | NSAIDs affect platelet function; use with caution and inform your doctor |
No formal drug interaction studies have been conducted with caplacizumab beyond anticoagulants and antiplatelet agents. However, it is biologically plausible that any medication affecting hemostasis could interact with Cablivi. Always provide your healthcare team with a complete medication list, including over-the-counter drugs and herbal supplements. Fish oil, vitamin E supplements, and certain herbal products (such as ginkgo biloba) may also affect bleeding risk.
What Is the Correct Dosage of Cablivi?
Cablivi treatment should always be initiated and supervised by a physician experienced in the management of blood disorders, specifically thrombotic thrombocytopenic purpura. The dosing regimen is designed to work alongside plasma exchange (PEX) therapy and immunosuppressive treatment as part of a comprehensive aTTP management strategy.
Adults and Adolescents (12 years and older, weighing at least 40 kg)
The recommended dose is one vial (10 mg) administered as follows:
Phase 1: Initial Dose (Day 1)
One 10 mg dose administered intravenously (into a vein) by a healthcare professional. This initial IV dose must be given before the first plasma exchange treatment. The IV route ensures rapid onset of action during this critical phase.
Phase 2: During Plasma Exchange
One 10 mg dose administered subcutaneously (under the skin of the abdomen) once daily, after each daily plasma exchange session. This phase continues for the duration of daily plasma exchange therapy.
Phase 3: Post-Plasma Exchange
Once daily plasma exchange has been completed, continue subcutaneous injections of 10 mg once daily for at least 30 days. Your doctor may extend this treatment period if the underlying signs of the disease (such as suppressed ADAMTS13 activity levels) have not resolved.
After appropriate training, patients or their caregivers may perform the subcutaneous injections at home. The injection site on the abdomen should be rotated daily, and the area around the navel should be avoided. Each injection requires using a new, single-use injection kit to prepare the solution from the powder and solvent provided.
Children Under 12 Years
Cablivi is not recommended for children under 12 years of age or those weighing less than 40 kg. Safety and efficacy in this age group have not been established.
Elderly Patients
No dose adjustment is required for elderly patients. However, older adults may be at increased risk of bleeding due to age-related factors such as impaired renal or hepatic function, concurrent medications, and comorbidities. Close monitoring for signs of bleeding is recommended throughout treatment.
Missed Dose
If you miss a dose, take it as soon as you remember, provided it is within 12 hours of the scheduled time. If more than 12 hours have passed since the scheduled dose, skip the missed dose and take the next dose at the usual time. Do not inject a double dose to make up for a missed one. Maintaining consistent daily dosing is important for optimal treatment outcomes.
Overdose
An overdose is unlikely because each pre-filled syringe contains only a single dose. There is limited experience with overdose of caplacizumab in clinical settings. If you believe you have taken more than the prescribed dose, contact your healthcare provider or local poison control center immediately. In the event of overdose, monitoring for signs of bleeding is essential, and supportive care should be provided as needed.
To achieve the best possible outcome, it is critical to take Cablivi exactly as prescribed and for the full duration recommended by your doctor. Stopping treatment prematurely may increase the risk of aTTP recurrence. If you are considering discontinuing treatment, discuss this with your doctor first.
What Are the Side Effects of Cablivi?
Like all medicines, Cablivi can cause side effects, although not everyone experiences them. Because caplacizumab works by inhibiting platelet-vWF interactions, the majority of side effects are related to an increased tendency to bleed. Most bleeding events observed in clinical trials were mild to moderate in severity; however, serious bleeding events can occur, and patients should be aware of the warning signs.
Contact your doctor immediately if you experience prolonged or heavy bleeding. Your doctor may decide to monitor you more closely or adjust your treatment. In cases of serious bleeding, treatment may need to be temporarily interrupted.
The following side effects were reported in clinical trials with the frequencies indicated below:
Very Common
May affect more than 1 in 10 people
- Bleeding gums (gingival bleeding)
- Fever (pyrexia)
- Fatigue
- Headache
- Nosebleed (epistaxis)
- Hives (urticaria)
Common
May affect up to 1 in 10 people
- Bleeding in the eye (ocular hemorrhage)
- Vomiting blood (hematemesis)
- Blood in stools or black, tarry stools (melena)
- Stomach bleeding (gastrointestinal hemorrhage)
- Hemorrhoidal bleeding
- Rectal bleeding
- Injection site reactions: redness, itching, bleeding
- Cerebral hemorrhage (bleeding in the brain), presenting as sudden severe headache, vomiting, decreased consciousness, fever, seizures, or neck stiffness
- Muscle pain (myalgia)
- Stroke
- Blood in urine (hematuria)
- Heavy menstrual bleeding (menorrhagia)
- Vaginal hemorrhage
- Coughing up blood (hemoptysis)
- Shortness of breath (dyspnea)
- Bruising (ecchymosis)
It is important to note that some of these side effects, particularly cerebral hemorrhage and stroke, are also potential complications of aTTP itself. Your medical team will carefully differentiate between disease-related events and drug-related adverse effects. Throughout your treatment, regular blood tests and clinical assessments will help monitor for both the efficacy of treatment and the occurrence of adverse events.
If you experience any side effects, whether listed above or not, talk to your doctor, pharmacist, or nurse. Reporting side effects helps regulatory agencies continuously monitor the benefit-risk balance of medicines. In the European Union, side effects can be reported through national pharmacovigilance systems. In the United States, adverse events can be reported to the FDA MedWatch program. In the United Kingdom, reports can be made via the Yellow Card Scheme.
How Should You Store Cablivi?
Proper storage of Cablivi is essential to maintain its effectiveness and safety. Incorrect storage can cause degradation of the active substance, potentially reducing its efficacy or introducing safety concerns. Follow these storage guidelines carefully:
- Primary storage: Keep in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
- Light protection: Store in the original packaging to protect from light.
- Room temperature storage: Cablivi may be stored at room temperature (not exceeding 25°C / 77°F) for a single continuous period of up to two months, but not beyond the printed expiry date.
- No re-refrigeration: Once removed from the refrigerator for room-temperature storage, do not return it to the refrigerator.
- Temperature limit: Never expose Cablivi to temperatures above 30°C (86°F).
- Expiry date: Do not use after the expiry date printed on the label and carton (the expiry date refers to the last day of that month).
- Visual inspection: Before use, do not use the medicine if you observe particles, discoloration, or any other visible abnormality in the prepared solution.
- Keep out of reach: Store out of the sight and reach of children.
After reconstitution (dissolving the powder in the solvent), the solution should be used immediately. The reconstituted solution should be clear and colorless to slightly yellowish. If the solution appears cloudy, contains lumps, or looks abnormal in any way, do not use it and contact your pharmacist or nurse.
Do not dispose of unused medicines in household waste or via the sewage system. Ask your pharmacist how to dispose of medicines you no longer use. Proper disposal helps protect the environment and prevents accidental exposure.
What Does Cablivi Contain?
Active Ingredient
Each vial of powder contains 10 mg of caplacizumab. Caplacizumab is a humanized bivalent nanobody produced in Escherichia coli by recombinant DNA technology. Nanobodies are the smallest functional antibody fragments, derived from the variable domains of heavy-chain-only antibodies found in camelids (llamas and camels). Their small size (approximately 28 kDa for caplacizumab) allows for unique pharmacological properties, including rapid tissue penetration and high target specificity.
Inactive Ingredients (Excipients)
Powder vial:
- Sucrose (as a stabilizer)
- Anhydrous citric acid (pH adjustment)
- Trisodium citrate dihydrate (buffering agent)
- Polysorbat 80 (surfactant)
Pre-filled syringe:
- Water for injections (1 mL)
Appearance and Packaging
Cablivi is supplied as a white powder for injection in a glass vial, together with a pre-filled syringe containing 1 mL of water for injections (solvent). After reconstitution, the solution should be clear, colorless to slightly yellowish.
Cablivi is available in the following pack sizes:
- Single-dose pack: 1 vial of caplacizumab powder, 1 pre-filled syringe of solvent, 1 vial adapter, 1 needle, and 2 alcohol swabs
- Multi-dose pack (7-day supply): 7 vials of caplacizumab powder, 7 pre-filled syringes of solvent, 7 vial adapters, 7 needles, and 14 alcohol swabs
Not all pack sizes may be marketed in every country. Your pharmacist will dispense the appropriate pack size based on your prescription and local availability.
Frequently Asked Questions About Cablivi
Medical References
- Scully M, Cataland SR, Peyvandi F, et al. (2019). "Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura." New England Journal of Medicine. 380(4):335-346. DOI: 10.1056/NEJMoa1806311 Pivotal HERCULES phase 3 trial. Evidence level: 1A
- European Medicines Agency (EMA) (2024). "Cablivi - Summary of Product Characteristics." EMA - Cablivi EPAR Official European regulatory documentation for Cablivi.
- Peyvandi F, Scully M, Kremer Hovinga JA, et al. (2016). "Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura." New England Journal of Medicine. 374(6):511-522. DOI: 10.1056/NEJMoa1505533 TITAN phase 2 trial demonstrating proof-of-concept.
- Zheng XL, Vesely SK, Cataland SR, et al. (2020). "ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura." Journal of Thrombosis and Haemostasis. 18(10):2486-2495. International Society on Thrombosis and Haemostasis diagnostic guidelines.
- Coppo P, Bubenheim M, Azoulay E, et al. (2021). "A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP." Blood. 137(6):733-742. Real-world evidence supporting caplacizumab in aTTP management.
- Scully M, Knoebl P, Engert A, et al. (2023). "Post-authorization experience with caplacizumab in the management of acquired TTP." Blood Advances. Long-term safety and efficacy data from post-marketing surveillance.
- British Society for Haematology (BSH) (2023). "Guidelines on the Diagnosis and Management of Thrombotic Thrombocytopenic Purpura." UK national guidelines incorporating caplacizumab into aTTP treatment algorithms.
Evidence grading: This article uses the GRADE framework (Grading of Recommendations Assessment, Development and Evaluation) for evidence-based medicine. Evidence level 1A represents the highest quality of evidence, based on systematic reviews of randomized controlled trials.
iMedic Medical Editorial Team
Specialists in hematology, pharmacology and internal medicine
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