Details of the Drug

General Information of Drug (ID: DMPUKA7)

• Drug Name: Caplacizumab

Indication

Disease Entry	ICD 11	Status	REF
Thrombotic thrombocytopenic purpura	3B64.14	Approved	[1]

• Drug Type: Antibody
• Sequence:
  EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYY
  PDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQ
  GTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVA
  AISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVR
  TLPSEYTFWGQGTQVTVSS
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 7951 mcgh/L [2]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 528 mcg/L [2]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 6-7 h [2]
  Bioavailability: The bioavailability of drug is 90% [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 16 - 27 hours [3]
  Metabolism: The drug is metabolized via the degraded in the reticuloendothelial system to small peptides and amino acids [4]
  Vd: The volume of distribution (Vd) of drug is 6.33 L [2]
• Cross-matching ID:
  DrugBank ID: DB06081
  TTD ID: DUCA08

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
von Willebrand factor (VWF)	TT3SZBT	VWF_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Thrombotic thrombocytopenic purpura
• ICD Disease Classification: 3B64.14

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
von Willebrand factor (VWF)	DTT	VWF	2.96E-01	2.47	2.08

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Caplacizumab (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Caplacizumab and Levomilnacipran.	Chronic pain [MG30]	[11]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Caplacizumab and Regorafenib.	Colorectal cancer [2B91]	[12]
Intedanib	DMSTA36	Moderate	Increased risk of bleeding by the combination of Caplacizumab and Intedanib.	Colorectal cancer [2B91]	[13]
Ardeparin	DMYRX8B	Major	Increased risk of bleeding by the combination of Caplacizumab and Ardeparin.	Coronary thrombosis [BA43]	[14]
Danaparoid	DM6CLBN	Major	Increased risk of bleeding by the combination of Caplacizumab and Danaparoid.	Deep vein thrombosis [BD71]	[14]
Rivaroxaban	DMQMBZ1	Major	Increased risk of bleeding by the combination of Caplacizumab and Rivaroxaban.	Deep vein thrombosis [BD71]	[14]
Vilazodone	DM4LECQ	Moderate	Increased risk of bleeding by the combination of Caplacizumab and Vilazodone.	Depression [6A70-6A7Z]	[11]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Caplacizumab and Vortioxetine.	Depression [6A70-6A7Z]	[11]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of bleeding by the combination of Caplacizumab and Desvenlafaxine.	Depression [6A70-6A7Z]	[11]
Apigenin	DMI3491	Minor	Increased risk of bleeding by the combination of Caplacizumab and Apigenin.	Discovery agent [N.A.]	[15]
Tazemetostat	DMWP1BH	Major	Increased risk of bleeding by the combination of Caplacizumab and Tazemetostat.	Follicular lymphoma [2A80]	[14]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Caplacizumab and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[12]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of bleeding by the combination of Caplacizumab and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[16]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Caplacizumab and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[17]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Caplacizumab and Ibrutinib.	Mature B-cell lymphoma [2A85]	[18]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Caplacizumab and Ponatinib.	Mature B-cell lymphoma [2A85]	[19]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Caplacizumab and Panobinostat.	Multiple myeloma [2A83]	[14]
Fedratinib	DM4ZBK6	Major	Increased risk of bleeding by the combination of Caplacizumab and Fedratinib.	Myeloproliferative neoplasm [2A20]	[14]
Prasugrel	DM7MT6E	Major	Increased risk of bleeding by the combination of Caplacizumab and Prasugrel.	Myocardial infarction [BA41-BA43]	[14]
Vorapaxar	DMA16BR	Major	Increased risk of bleeding by the combination of Caplacizumab and Vorapaxar.	Myocardial infarction [BA41-BA43]	[14]
Nepafenac	DMYK490	Moderate	Increased risk of bleeding by the combination of Caplacizumab and Nepafenac.	Osteoarthritis [FA00-FA05]	[20]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Caplacizumab and MK-4827.	Ovarian cancer [2C73]	[12]
Curcumin	DMQPH29	Minor	Increased risk of bleeding by the combination of Caplacizumab and Curcumin.	Solid tumour/cancer [2A00-2F9Z]	[21]
Apixaban	DM89JLN	Major	Increased risk of bleeding by the combination of Caplacizumab and Apixaban.	Thrombosis [DB61-GB90]	[14]
Cangrelor	DM8JRH0	Major	Increased risk of bleeding by the combination of Caplacizumab and Cangrelor.	Thrombosis [DB61-GB90]	[14]
Brilinta	DMBR01X	Major	Increased risk of bleeding by the combination of Caplacizumab and Brilinta.	Thrombosis [DB61-GB90]	[14]
Cabozantinib	DMIYDT4	Major	Increased risk of bleeding by the combination of Caplacizumab and Cabozantinib.	Thyroid cancer [2D10]	[22]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Caplacizumab and Betrixaban.	Venous thromboembolism [BD72]	[14]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] Duggan S: Caplacizumab: First Global Approval. Drugs. 2018 Oct;78(15):1639-1642. doi: 10.1007/s40265-018-0989-0.
• [3] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [4] Li K, Xu Y: Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis. Int J Clin Exp Med. 2015 Apr 15;8(4):6578-84. eCollection 2015.
• [5] Clinical pipeline report, company report or official report of Vonvendi.
• [6] 6 Factor VIII Concentrates, Factor VIII/von Willebrand Factor Concentrates, Factor IX Concentrates, Activated Prothrombin Complex Concentrates. Transfus Med Hemother. 2009 December; 36(6): 409-418.
• [7] Clinical pipeline report, company report or official report of Ablynx
• [8] Short-Acting Anti-VWF (von Willebrand Factor) Aptamer Improves the Recovery, Survival, and Hemostatic Functions of Refrigerated Platelets. Arterioscler Thromb Vasc Biol. 2019 Oct;39(10):2028-2037.
• [9] A new oral antiplatelet agent with potent antithrombotic properties: comparison of DZ-697b with clopidogrel a randomised phase I study. Thromb Haemost. 2010 Jan;103(1):205-12.
• [10] Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32.
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• [13] Product Information. Ofev (nintedanib). Boehringer Ingelheim, Ridgefield, CT.
• [14] Cerner Multum, Inc. "Australian Product Information.".
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• [16] Caruso V, Iacoviello L, Di Castelnuovo A, et.al "Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients." Blood 108 (2006): 2216-22. [PMID: 16804111]
• [17] Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [18] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [19] Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
• [20] Product Information. Acular (ketorolac). Allergan Inc, Irvine, CA.
• [21] Abebe W "Herbal medication: potential for adverse interactions with analgesic drugs." J Clin Pharm Ther 27 (2002): 391-401. [PMID: 12472978]
• [22] Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.