Details of the Drug

General Information of Drug (ID: DM6AUHV)

• Drug Name: Fostamatinib
• Synonyms: 901119-35-5; R788; Tavalisse; UNII-SQ8A3S5101; R-788 Free acid; R 788; R-788; R-935788 Free acid; SQ8A3S5101; R7935788; Fostamatinib [USAN:INN]

Indication

Disease Entry	ICD 11	Status	REF
Immune thrombocytopenic purpura	3B64.13	Approved	[1]
Rheumatoid arthritis	FA20	Phase 3	[2]

• ATC Code:
  B02BX09: Fostamatinib
  B02BX: Other systemic hemostatics
  B02B: VITAMIN K AND OTHER HEMOSTATICS
  B02: ANTIHEMORRHAGICS
  B: BLOOD AND BLOOD FORMING ORGANS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 580.5
  Logarithm of the Partition Coefficient (xlogp); 1.6
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 15
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.5 h [3]
  Bioavailability: The bioavailability of drug is 55% [3]
  Clearance: The apparent oral clearance of drug is 300 mL/min [3]
  Elimination: About 80% of R406 is excreted in the feces, primarily as the O-glucuronide conjugate and the O-desmethyl metabolite produced by gut bacteria []
  Half-life: The concentration or amount of drug in body reduced by one-half in 406 hours [3]
  Metabolism: The drug is metabolized via the alkaline phosphatase to the active metabolite R406 [4]
  Vd: The volume of distribution (Vd) of drug is 400 L [3]
• Chemical Identifiers:
  Formula: C23H26FN6O9P
  IUPAC Name: [6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl dihydrogen phosphate
  Canonical SMILES: CC1(C(=O)N(C2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)COP(=O)(O)O)C
  InChI: InChI=1S/C23H26FN6O9P/c1-23(2)21(31)30(11-38-40(32,33)34)20-14(39-23)6-7-17(28-20)27-19-13(24)10-25-22(29-19)26-12-8-15(35-3)18(37-5)16(9-12)36-4/h6-10H,11H2,1-5H3,(H2,32,33,34)(H2,25,26,27,28,29)
  InChIKey: GKDRMWXFWHEQQT-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 11671467
  CAS Number: 901119-35-5
  UNII: SQ8A3S5101
  DrugBank ID: DB12010
  TTD ID: D0V8HJ
  VARIDT ID: DR00300
  INTEDE ID: DR0754
  ACDINA ID: D01107
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tyrosine-protein kinase SYK (SYK)	TTOU65C	KSYK_HUMAN	Modulator	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
ATP-binding cassette sub-family B member 5 (ABCB5)	DTKVEXO	ABCB5_HUMAN	Substrate	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[7]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[]
Alkaline phosphatase (ALPL) Main DME	DEVEFKM	PPBT_HUMAN	Substrate	[]

Molecular Expression Atlas of This Drug

• The Studied Disease: Immune thrombocytopenic purpura
• ICD Disease Classification: 3B64.13

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase SYK (SYK)	DTT	SYK	3.05E-05	0.29	0.43
ATP-binding cassette sub-family B member 5 (ABCB5)	DTP	ABCB5	3.35E-01	-2.42E-02	-1.22E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	6.90E-01	2.35E-02	7.88E-02

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Fostamatinib

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Fostamatinib due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[8]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Fostamatinib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[9]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Fostamatinib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[10]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Fostamatinib due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[11]
Oliceridine	DM6MDCF	Moderate	Decreased metabolism of Fostamatinib caused by Oliceridine mediated inhibition of CYP450 enzyme.	Acute pain [MG31]	[10]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Fostamatinib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[10]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Fostamatinib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[12]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Fostamatinib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[10]
Ripretinib	DM958QB	Moderate	Decreased clearance of Fostamatinib due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[9]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Fostamatinib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[10]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Fostamatinib due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[13]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Fostamatinib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[14]
Upadacitinib	DM32B5U	Moderate	Decreased metabolism of Fostamatinib caused by Upadacitinib mediated inhibition of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[10]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Fostamatinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[10]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Fostamatinib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[15]
Larotrectinib	DM26CQR	Moderate	Decreased clearance of Fostamatinib due to the transporter inhibition by Larotrectinib.	Solid tumour/cancer [2A00-2F9Z]	[9]
Fluticasone	DMGCSVF	Moderate	Decreased metabolism of Fostamatinib caused by Fluticasone mediated inhibition of CYP450 enzyme.	Vasomotor/allergic rhinitis [CA08]	[10]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of Fostamatinib due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[10]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Sodium bicarbonate	E00424	516892	Alkalizing agent; Diluent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Fostamatinib 100 mg tablet	100 mg	Tablet	Oral
Fostamatinib 150 mg tablet	150 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7796).
• [3] Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies. Br J Clin Pharmacol. 2013 Jul;76(1):78-88. doi: 10.1111/bcp.12048.
• [4] Fohner AE, McDonagh EM, Clancy JP, Whirl Carrillo M, Altman RB, Klein TE: PharmGKB summary: ivacaftor pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics. 2017 Jan;27(1):39-42. doi: 10.1097/FPC.0000000000000246.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2230).
• [6] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB12010)
• [7] Effects of CYP3A4 inhibitors ketoconazole and verapamil and the CYP3A4 inducer rifampicin on the pharmacokinetic parameters of fostamatinib: results from In vitro and phase I clinical studies. Drugs R D. 2016 Mar;16(1):81-92.
• [8] EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
• [9] Cerner Multum, Inc. "Australian Product Information.".
• [10] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
• [11] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [12] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [13] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [14] Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
• [15] Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.