Basic information Indications and Uses Clinical trials Drug interactions Adverse effects Warnings and precautions Safety Supplier Related
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Capecitabine

Basic information Indications and Uses Clinical trials Drug interactions Adverse effects Warnings and precautions Safety Supplier Related

Capecitabine Basic information

Product Name:
Capecitabine
Synonyms:
  • Capcitabine
  • 5'-DEOXY-5-FLUOROCYTISINE
  • 5'-DEOXY-5-FLUORO-N-[(PENTYLOXY)CARBONYL]CYTIDINE
  • Pentyl (1-((2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1,2-dihydr
  • RO-9-1978
  • pentyl [1-(3,4-dihydroxy-5-methyl-oxolan-2-yl)-5-fluoro-2-oxo-pyrimidin-4-yl]aminoformate
  • XELODA
  • CAPECITABINE
CAS:
154361-50-9
MF:
C15H22FN3O6
MW:
359.35
EINECS:
604-948-1
Product Categories:
  • Inhibitors
  • Cardiovascular Drugs
  • Bases & Related Reagents
  • Anti-cancer
  • API
  • XELODA
  • Active Pharmaceutical Ingredients
  • Antineoplastic
  • Intermediates & Fine Chemicals
  • Nucleotides
  • Pharmaceuticals
  • Antineoplastic drug, 5-FU analog
Mol File:
154361-50-9.mol
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Capecitabine Chemical Properties

Melting point:
110-121°C
Density 
1.49±0.1 g/cm3(Predicted)
Flash point:
87℃
storage temp. 
2-8°C
solubility 
H2O: soluble10mg/mL, clear (warmed)
pka
5.41±0.40(Predicted)
form 
powder
color 
white to beige
Merck 
14,1754
InChIKey
GAGWJHPBXLXJQN-UORFTKCHSA-N
CAS DataBase Reference
154361-50-9(CAS DataBase Reference)
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Safety Information

Hazard Codes 
T
Risk Statements 
45-60-61-68
Safety Statements 
53-22-36/37-45
WGK Germany 
3
RTECS 
HA3852500
HS Code 
29349990
Hazardous Substances Data
154361-50-9(Hazardous Substances Data)

MSDS

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Capecitabine Usage And Synthesis

Indications and Uses

Capecitabine is a new form of oral fluorinated pyrimidine drug. Capecitabine was developed by Roche Pharmaceuticals, and its commercial name is Xeloda. Capecitabine can change in vivo into 5- FU, an anti-metabolizim fluorine pyrimidine deoxynucleoside carbamate drug that targets cancer cells to inhibit cell division and disrupt RNA and protein synthesis. Its effects are significantly tied to the level of TP enzyme expression in neoplastic tissue and to DPD enzyme in vivo expression. It is suitable as further treatment for advanced primary or metastatic breast cancer patients who have not responded to paclitaxel or anthracycline antibiotics. As an anticancer drug, it is mostly used to treat advanced primary or metastatic breast cancer, as well as in treatment for non-small cell lung cancer, pancreatic cancer, bladder cancer, rectal cancer, colon cancer, gastric cancer, and other solid tumors. Many drugs such as taxanes (paclitaxel, docetaxel, mitomycin, cisplatin, etc.) can increase TP enzyme expression in neoplastic tissues and also have curative effects on gastric cancer. When used in combination with Capecitabine, these drugs can also improve Capecitabine’s anticancer abilities and produce synergistic effects.

Clinical trials

Analyses of nearly 400 randomized comparisons of clinical outcomes show that a combination of adriamycin, cisplatin or oxaliplatin with 5-FU, compared to a combination of these drugs with Capecitabine, has a two-fold difference in curative efficacy and lowers toxicty. A large-scale Chinese clinical trial of Capecitabine in combination with DDP in the treatment of stage II gastric cancer also proves its advantages of high efficacy, low toxicity, and affordability.

Drug interactions

Currently, there are no side effects of clinical significance when used in combination with antihistamines, NSAIDs, morphine, paracetamol, aspirin, antiemetic drugs, and H2 receptor antagonist drugs.
Capecitabine’s binding rate with serum protein is relatively low (64%), and its possibility of interacting through substitution with drugs that bind closely with proteins is currently unknown. In external experiments, Capecitabine has not shown any influence on human liver microsomal P450 enzyme.
If any phenytoin and coumarin derivatives anticoagulants are used in combination with Capecitabine, dosages should be lowered.

Adverse effects

Common adverse reactions include nausea, vomiting, oral ulcers, abdominal pain, diarrhea, loss of appetite, and skin changes. There have also been reports of some patients experiencing transient myelosuppression, hair loss, tears, headache, and dizziness.

Warnings and precautions

Capecitabine is a bone marrow inhibitor; a blood exam must be administered before every usage to monitor blood cell and platelet count.
This product poses toxic side effects to the liver, so liver functions must be routinely examined. Additionally, heart functions should also be monitored to prevent irreversible toxic reactions. If venous transfusion of the drug is required, the aforementioned organ functions should be tested for suitability before administration. Capecitabine may cause damage to embryos, thus making it unsuitable for pregnant women. Women using this drug are also not suitable for pregnancy. Even after treatment is ended, this drug may have some impact on fertility.

Description

Capecitabine is a new oral fluoropyrimidine carbamate for patients with advanced neoplastic disease, approved as Xeloda for the treatment of refractory metastatic breast cancer after failure on Paclitaxel and an anthracycline-based chemotherapy regimen ; it is a prodrug of doxifluridine (5-fluorouracil ; 5-FU) activated by a cascade of 3 enzymes concentrated in human liver and cancer tissue, resulting in the selective release of 5-FU at the tumor site and offering a prolonged tumour exposure to 5-FU. Oral Capecitabine passes intact through the intestinal mucosa, is converted first by carboxylesterase to 5'-deoxy-5- fluorocytidine in the liver, then by cytidine deaminase to 5'-deoxy-5-fluorouridine in the liver and tumour tissues and finally by thymidine phosphorylase to 5-FU in tumors. Therefore, Xeloda is much safer and more effective than 5-FU (for example, in the HCT116 human colon cancer and the MX-1 breast cancer xenograft .models).

Chemical Properties

Colourless solid

Originator

Roche (Switzerland)

Uses

An antineoplastic agent. A prodrug of doxifluridine.

Uses

Capecitabine is an antineoplastic agent. Capecitabine is a prodrug of Doxifluridine (D556750).

Uses

An antiproliferative 5-fluorouracil releasing compound

Definition

ChEBI: A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted to its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agen used in the treatment of cancers.

Manufacturing Process

5-Deoxy-5-fluoro-N4-((n-pentyloxy)carbonyl)cytidine may be prepared according to US Patent No. 6,114,520.
From 2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-fluorocytidine and n-pentylchloroformate in dichloromethane and pyridine may be obtained 2',3'- bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-fluoro-N4-((pentyloxy)carbonyl) cytidine.From 2',3'-bis-O-(tert-butyldimethylsilyl)-5'-deoxy-5-fluoro-N4- ((pentyloxy)carbonyl)cytidineand tetrabutylammonium fluoride in tetrahydrofuran at room temperature for 2 hours may be prepared the product which by hydrolyses may be converted to 5-deoxy-5-fluoro-N4- ((pentyloxy)carbonyl)cytidine. Purification of the product may be carried out by silica gel chromatography (using dichloromethane:methanol = 20:1 as an eluent).

brand name

Xeloda (Roche).

Therapeutic Function

Antitumor

General Description

The drug is available in a 150- and 500-mg tablets for oraluse. This drug is a fluoropyrimidine carbamate prodrugform of 5-fluorouracil (5-FU). It is used to treat breast cancerand colorectal cancer. The drug is converted to 5-FU bythe enzyme thymidine phosphorylase following esterase activity to hydrolyze the carbamate moiety and deamination.Capecitabine is readily absorbed by the GI tract, and peakplasma levels of 5-FU occur about 2 hours after oral administration.Indications, drug interactions, and toxicities areequivalent to those of 5-FU.

Clinical Use

Capecitabine is indicated for use as first-line therapy in patients with colorectal cancer. It also is used alone or in combination with docetaxel in patients with metastatic breast cancer who have experienced disease progression or recurrence after anthracycline therapy. Given b.i.d. in tablet form, the total daily dose is calculated based on patient body surface area and is taken 30 minutes after eating to avoid food-induced decreases in absorption. In addition to bone marrow suppression, nausea, and vomiting, the drug can induce severe diarrhea and a potentially disabling disorder termed “hand-and-foot syndrome” (palmar-plantar erythrodysethesia). Capecitabine inhibits CYP2C9 and, along with competition for serum protein binding sites, results in clinically significant drug–drug interactions with both warfarin and phenytoin.

Metabolism

Although capecitabine is a carbamylated analogue of cytidine , the drug actually is another 5-fluoro-dUMP prodrug. Given orally, it is extensively metabolized to fluorouracil, which is then converted to the active fluorinated deoxyribonucleotide as previously described. Thymidine phosphorylase, an enzyme involved in this biotransformation, is much more active in tumors than in normal tissue, which improves the tumor-selective generation of fluorouracil. Levels of active drug in the tumor can be up to 3.5-fold higher than in surrounding tissue, leading to a lower incidence of side effects compared to fluorouracil therapy. Because capecitabine is biotransformed to fluorouracil, it follows the same catabolic and elimination pathways reported for 5-fluorouracil.

CapecitabineSupplier

Shandong Platinum Pharmaceutical Co., Ltd. Gold
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0531-88963280- ;531-88963280-
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Absin Bioscience Inc. Gold
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Wisdom Drugs Co., Ltd. Gold
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J & K SCIENTIFIC LTD.
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010-82848833- ;010-82848833-
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jkinfo@jkchemical.com;market6@jkchemical.com
INTATRADE GmbH
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+49 3493/605464
Email
sales@intatrade.de