Details of the Drug

General Information of Drug (ID: DMTS85L)

• Drug Name: Capecitabine
• Synonyms: Capecitabin; Capecitabina; Capecitabinum; Capecitibine; Capiibine; Caxeta; Xabine; Xeloda; Capecitabine [USAN]; R340;R-340; RG-340; Ro 09-1978; Xeloda (TN); Ro 09-1978/000; Ro-09-1978; Xeloda, Captabin, Capecitabine; Capecitabine (JAN/USAN/INN); Ro-09-1978/000; N(4)-Pentyloxycarbonyl-5'-deoxy-5-fluorocytidine; Pentyl 1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinecarbamate; Pentyl [1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]carbamate; Carbamic acid, (1-(5-deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-, pentyl ester; Pentyl N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate; (1-(5-Deoxy-beta-D-ribofuranosyl)-5-fluoro-1,2-dihydro-2-oxo-4-pyrimidinyl)-carbamic acid pentyl ester; 5'-Deoxy-5-fluoro-N-((pentyloxy)carbonyl)cytidine; 5'-deoxy-5-fluoro-N-[(pentyloxy)carbonyl]cytidine; Capecitabine (Fluoropyrimidine)

Indication

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[1]
Colon adenocarcinoma	N.A.	Approved	[1]
Colorectal cancer	2B91.Z	Approved	[2]
Metastasis from malignant tumor of colon	N.A.	Approved	[1]
Rectal adenocarcinoma	2B92	Approved	[1]
Breast cancer	2C60-2C65	Phase 3	[2]
Colon cancer	2B90.Z	Investigative	[1]
Gastric cancer	2B72	Investigative	[1]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 359.35
  Logarithm of the Partition Coefficient (xlogp); 0.6
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Bioavailability: The bioavailability of drug is 70% []
  Elimination: 3% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 45 - 60 minutes [4]
  Metabolism: The drug is metabolized via thymidine phosphorylase to fluoruracil []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 171.9326 micromolar/kg/day [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 26 mg/mL [3]
• Chemical Identifiers:
  Formula: C15H22FN3O6
  IUPAC Name: pentyl N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate
  Canonical SMILES: CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@H]2[C@@H]([C@@H]([C@H](O2)C)O)O
  InChI: InChI=1S/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1
  InChIKey: GAGWJHPBXLXJQN-UORFTKCHSA-N
• Cross-matching ID:
  PubChem CID: 60953
  ChEBI ID: CHEBI:31348
  CAS Number: 154361-50-9
  DrugBank ID: DB01101
  TTD ID: D00HCQ
  VARIDT ID: DR00380
  INTEDE ID: DR0266
  ACDINA ID: D00095
• 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
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytidine aminohydrolase (CDA)	DEKEDRC	CDD_HUMAN	Substrate	[7]
Thymidine phosphorylase (TYMP)	DE4HCYL	TYPH_HUMAN	Substrate	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)	OT5I4Y9K	PLCB_HUMAN	Drug Response	[9]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1)	OTJISZOX	PLCE1_HUMAN	Drug Response	[9]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1)	OTVKRET0	THIK_HUMAN	Drug Response	[9]
40-kDa huntingtin-associated protein (F8A1)	OTXTQ59R	HAP40_HUMAN	Gene/Protein Processing	[10]
ADP-ribosylation factor-like protein 4D (ARL4D)	OTG5I3KU	ARL4D_HUMAN	Drug Response	[9]
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Drug Response	[9]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Drug Response	[9]
Anterior gradient protein 2 homolog (AGR2)	OTRRZT7W	AGR2_HUMAN	Drug Response	[9]
Aquaporin-8 (AQP8)	OT99JKME	AQP8_HUMAN	Gene/Protein Processing	[10]
B-lymphocyte antigen CD20 (MS4A1)	OTZTVUBX	CD20_HUMAN	Gene/Protein Processing	[10]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Capecitabine and Roflumilast.	Asthma [CA23]	[11]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Capecitabine due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[12]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Capecitabine due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[12]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Capecitabine due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[12]
ABT-492	DMJFD2I	Minor	Decreased absorption of Capecitabine due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[12]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Capecitabine due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[12]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Capecitabine caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[13]
Teriflunomide	DMQ2FKJ	Major	Additive myelosuppressive effects by the combination of Capecitabine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[14]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Capecitabine and Denosumab.	Low bone mass disorder [FB83]	[15]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Capecitabine and Tecfidera.	Multiple sclerosis [8A40]	[16]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Capecitabine and Fingolimod.	Multiple sclerosis [8A40]	[17]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Capecitabine and Ocrelizumab.	Multiple sclerosis [8A40]	[18]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Capecitabine and Ozanimod.	Multiple sclerosis [8A40]	[11]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Capecitabine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[19]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Capecitabine and Canakinumab.	Rheumatoid arthritis [FA20]	[20]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Capecitabine and Rilonacept.	Rheumatoid arthritis [FA20]	[20]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Capecitabine and Golimumab.	Rheumatoid arthritis [FA20]	[21]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Capecitabine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[22]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Capecitabine and Valganciclovir.	Virus infection [1A24-1D9Z]	[23]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Sunset yellow FCF	E00255	17730	Colorant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 1000	E00647	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Capecitabine 150 mg tablet	150 mg	Oral Tablet	Oral
Capecitabine 500 mg tablet	500 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Capecitabine FDA Label
• [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: 6799).
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
• [7] Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805.
• [8] Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45.
• [9] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
• [10] Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
• [11] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [12] Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
• [13] Product Information. Serzone (nefazodone). Bristol-Myers Squibb, Princeton, NJ.
• [14] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [15] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [16] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
• [17] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [18] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [19] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [20] Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
• [21] Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
• [22] CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
• [23] Cerner Multum, Inc. "Australian Product Information.".