Description

Simple

A medication used to treat a rare blood disorder called acquired Thrombotic thrombocytopenic purpura (TTP).

Clinical

A von Willebrand factor (vWF)-directed antibody fragment used to treat acquired thrombotic thrombocytopenic purpura (aTTP).

Overview

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,[6] and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.[1]

Pharmacology

Indication

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.[ Read more

Pharmacodynamic

_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 a... Read more

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 b... Read more

Absorption

After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-... Read more

Protein binding

This antibody acts directly on plasma proteins and thus, this parameter is not significant for drug description.

Volume of distribution

The reported volume of distribution of caplacizumab is 6.33 L.[1]

Clearance

As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description.

Half life

The reported half-life is reported to be in the range of 16-27 hours.[9]

Route of elimination

The elimination of caplacizumab is divided between target-driven disposition which is driven by the binding to the von Willebrand factor and non-target disposition driven by the combination of catabolism and renal elimination.[ Read more

Toxicity

Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.[FDA label]

To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity

Adverse Effects

Contraindications

  • Route:
    • Intravenous
    • Subcutaneous
  • Dose Form:
    • Injection
  • Hypersensitivity:
    • true
  • Regions: US

Food Interactions

    Information currently not available.

Interactions

Type in a drug name to check for interaction with Caplacizumab
Type a drug name in the box above to get started
  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The risk or severity of bleeding can be increased when Caplacizumab is combined with (R)-warfarin.
(S)-Warfarin
The risk or severity of bleeding can be increased when Caplacizumab is combined with (S)-Warfarin.
4-hydroxycoumarin
The risk or severity of bleeding can be increased when Caplacizumab is combined with 4-hydroxycoumarin.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of bleeding and hemorrhage can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Caplacizumab.
Abciximab
The risk or severity of bleeding can be increased when Caplacizumab is combined with Abciximab.
Abituzumab
The risk or severity of adverse effects can be increased when Caplacizumab is combined with Abituzumab.
Abrilumab
The risk or severity of adverse effects can be increased when Caplacizumab is combined with Abrilumab.
Aceclofenac
The risk or severity of bleeding can be increased when Aceclofenac is combined with Caplacizumab.
Acemetacin
The risk or severity of bleeding can be increased when Acemetacin is combined with Caplacizumab.
Acenocoumarol
The risk or severity of bleeding can be increased when Caplacizumab is combined with Acenocoumarol.
Acetylsalicylic acid
Acetylsalicylic acid may increase the antiplatelet activities of Caplacizumab.
Adalimumab
The risk or severity of adverse effects can be increased when Adalimumab is combined with Caplacizumab.
Adecatumumab
The risk or severity of adverse effects can be increased when Adecatumumab is combined with Caplacizumab.
Aducanumab
The risk or severity of adverse effects can be increased when Caplacizumab is combined with Aducanumab.
Afelimomab
The risk or severity of adverse effects can be increased when Afelimomab is combined with Caplacizumab.
Alaproclate
The risk or severity of hemorrhage can be increased when Alaproclate is combined with Caplacizumab.
Alclofenac
The risk or severity of bleeding can be increased when Alclofenac is combined with Caplacizumab.
Aldesleukin
The risk or severity of bleeding can be increased when Caplacizumab is combined with Aldesleukin.
Alemtuzumab
The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Caplacizumab.
Alirocumab
The risk or severity of adverse effects can be increased when Caplacizumab is combined with Alirocumab.
9 References
  1. 1 . Duggan S: Caplacizumab: First Global Approval. Drugs. 2018 Oct;78(15):1639-1642. doi: 10.1007/s40265-018-0989-0.PubMed: 30298461
  2. 2 . Coppo P, Cuker A, George JN: Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine. Res Pract Thromb Haemost. 2018 Nov 16;3(1):26-37. doi: 10.1002/rth2.12160. eCollection 2019 Jan.PubMed: 30656273
  3. 3 . Peyvandi F, Scully M, Kremer Hovinga JA, Knobl P, Cataland S, De Beuf K, Callewaert F, De Winter H, Zeldin RK: Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2017 Jul;15(7):1448-1452. doi: 10.1111/jth.13716. Epub 2017 Jun 5.PubMed: 28445600
  4. 4 . Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knobl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D: Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2016 Feb 11;374(6):511-22. doi: 10.1056/NEJMoa1505533.PubMed: 26863353
  5. 5 . Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X.PubMed: 16478695
  6. 6 . FDA news Link
  7. 7 . Guide to Pharmacology Link
  8. 8 . Clinical trials Link
  9. 9 . Cablivi (caplacizumab) EMA label File