Caplacizumab – Uses, Dosage, Side Effects, Interaction

Caplacizumab is a von Willebrand factor (vWF)-directed antibody fragment used to treat acquired thrombotic thrombocytopenic purpura (aTTP). Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019, and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression

Mechanism of action

Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.[rx]

In vitro studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.[rx]

In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP[rx] as well as a significant reduction in the median time to response of about 39%. However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.[rx]

The last clinical trial prior to approval showed the production of a platelet count of more than 150,000 per MCL after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.[rx]

Ristocetin cofactor (RICO) activity was used to assess vWF activity. Subcutaneous doses of caplacizumab-yhdp at greater than or equal to the approved recommended dosage to healthy subjects and patients with aTTP decreased RICO activity levels to below 20% approximately hours post-dose. RICO activity returned to baseline values within 7 days of drug discontinuation. Caplacizumab-yhdp decreased vWF antigen and factor VIII:C levels. These reductions were transient and returned to baseline upon cessation of treatment.


  • Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.[rx]
  • aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia, and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Willebrand factor. The lack of this process produces the generation of ultra-large von Willebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.[rx]
  • Previously, bevacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.[rx]
  • Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
  • Treatment of patients with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange and immunosuppressive therapy

Use in Cancer

Caplacizumab-yhdp is approved to treat:


  • contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of the excipients. Hypersensitivity reactions have included urticaria


Strengths: yhdp 11 mg

Thrombocytopenic Purpura

Initial dose:

  • First day of treatment: 11 mg bolus IV injection at least 15 minutes prior to plasma exchange followed by an 11 mg subcutaneous injection after completion of plasma exchange on Day

Maintenance dose:

  • Subsequent days of treatment during daily plasma exchange: 11 mg subcutaneous injection once a day following plasma exchange
  • Treatment after plasma exchange period: 11 mg subcutaneous injection once a day continuing for 30 days following the last daily plasma exchange. If after initial treatment course sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels remain present, treatment may be extended for a maximum of 28 days.
  • Discontinue this drug if the patient experiences more than 2 recurrences of acquired thrombotic thrombocytopenic purpura (aTTP) during treatment with this drug.
  • Withhold this drug 7 days prior to elective surgery, dental procedures, or other invasive interventions.

Side Effects

The Most Common

  • headache
  • extreme tiredness
  • back pain
  • muscle pain
  • tingling, prickling, or numb feeling on the skin
  • itching near the spot the medication was injected
  • shortness of breath
  • fever
  • hives
  • heavy bleeding that won’t stop including bleeding from rectum, vagina, nose, gums or place where the medication was injected
  • vomiting blood
  • red, or black, tarry stools
  • blood in urine
  • sudden severe headache, nausea, vomiting
  • sudden, sharp abdominal pain, nausea, vomiting
  • frequent, painful, or urgent urination

More Common

  • easy bruising or bleeding (nosebleeds, bleeding gums);
  • unusual vaginal bleeding;
  • any bleeding that will not stop; or
  • signs of stomach bleeding–bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds.
  • nosebleeds, bleeding gums; or
  • headache.


  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • easy bruising,
  • unusual bleeding (nosebleeds, bleeding gums),
  • unusual vaginal bleeding,
  • any bleeding that will not stop,
  • bloody or tarry stools,
  • coughing up blood, and
  • vomit that looks like coffee grounds


Pregnancy and Lactation

US FDA pregnancy category: Not assigned.


There are no available data on CABLIVI use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. However, there are potential risks of hemorrhage in the mother and fetus associated with the use of CABLIVI. In animal reproduction studies, there was no evidence of adverse developmental outcomes with intramuscular administration of caplacizumab-yhdp during organogenesis in guinea pigs at exposures approximately 30 times the AUC in humans at the recommended subcutaneous injection dose of 11 mg (see Data).

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background rate of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background rate of major birth defects and
miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.


There is no information regarding the presence of caplacizumab-yhdp in human milk, the effects on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CABLIVI and any potential adverse effects on the breastfed child from CABLIVI, or from the underlying maternal condition

How should this medicine be used?

Caplacizumab-yhdp comes as a powder to be dissolved in liquid and given by intravenous (into the vein) or subcutaneous (under the skin) injection. It is usually given on the first day of treatment as an intravenous injection at least 15 minutes before plasma exchange, and then again as a subcutaneous injection after plasma exchange is finished. After the first day of treatment, it is usually given as a once-daily subcutaneous injection following plasma exchange for as long as you receive plasma exchange therapy, and then once daily for an additional 30 to 58 days after stopping plasma exchange therapy. Use caplacizumab-yhdp at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use caplacizumab-yhdp exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.

Your doctor may allow you or a caregiver to perform the injections at home. Ask your doctor or pharmacist to show you or the person who will be performing the injections how to prepare and inject caplacizumab-yhdp. Before you use caplacizumab-yhdp injection yourself for the first time, read the written instructions that come with it. Ask your pharmacist or doctor for a copy of the manufacturer’s instructions for use information for the patient.

You should inject caplacizumab-yhdp injection subcutaneously in the abdominal (stomach) area but avoid your navel and the area 2 inches (5 centimeters) around it. Do not inject in the same spot two days in a row.

Dispose of used needles, syringes, and vials in a puncture-resistant container. Talk to your doctor or pharmacist about how to dispose of the puncture-resistant container.

What special precautions should I follow?

Before receiving caplacizumab-yhdp,

  • tell your doctor and pharmacist if you are allergic to caplacizumab-yhdp, any other medications, or any of the ingredients in caplacizumab-yhdp injection. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: apixaban (Eliquis), clopidogrel (Plavix), dabigatran (Pradaxa), dipyridamole (Persantine, in Aggrenox), edoxaban (Savaysa), enoxaparin (Lovenox), fondaparinux (Arixtra), heparin, prasugrel (Effient), rivaroxaban (Xarelto), ticagrelor (Brilinta), or warfarin (Coumadin, Jantoven). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had hemophilia (a genetic disorder in which the body can’t stop bleeding properly) or other bleeding problems, or liver disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while receiving caplacizumab-yhdp, call your doctor.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are using caplacizumab-yhdp. Your doctor or dentist may tell you not to use caplacizumab-yhdp for 7 days before the surgery.