Capecitabine API Manufacturers & Suppliers

Capecitabine (CAS 154361-50-9) is used in the treatment of colorectal, breast, gastric, esophageal, gastroesophageal junction, and pancreatic cancers. It is indicated as monotherapy or in combination regimens for stage III colon cancer, unresectable or metastatic colorectal cancer, locally advanced rectal cancer, and metastatic breast cancer after anthracycline failure. It is also used for gastrointestinal malignancies, including HER2‑overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, and as adjuvant therapy in pancreatic adenocarcinoma.

Capecitabine belongs to the following therapeutic categories: Antimetabolites, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Cardiotoxic antineoplastic agents, Cytidine Deaminase Substrates. This positioning helps teams compare alternative APIs, anticipate pharmacology expectations, and align early research priorities.

The primary indications for Capecitabine: Capecitabine is indicated as treatment for a variety of cancer types, For colorectal cancer, Capecitabine is indicated as a single agent or a component of a combination chemotherapy regiment for the adjuvant treatment of stage III colon cancer and treatment unresectable or metastatic colorectal cancer, It can also be used as a part of a combination chemotherapy perioperative treatment of adult locally advanced rectal cancer, For breast cancer, Capecitabine is indicated for advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated or as a regimen with docetaxel after disease progression on prior anthracycline-containing chemotherapy. These use cases frame the target patient populations and help prioritize formulation and safety evaluations.

Capecitabine is metabolized to 5-fluorouracil in vivo by carboxylesterases, cytidine deaminase, and thymidine phosphorylase/uridine phosphorylase sequentially.5-fluorouracil is further metabolized through a series of enzymatic reactions into 3 main active metabolites: 5-fluorouridine triphosphate (5-FUTP), 5-fluoro-2’-deoxyuridine monophosphate (5-FdUMP), and 5-fluorodeoxyuridine triphosphate (5-FdUTP).. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate (CH₂THF), bind to thymidylate synthase (TS) to form a covalently bound ternary complex.TS is an enzyme that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).Under normal physiological conditions, dUMP binds to TS first before CH₂THF, followed by a 1,4 or Michael addition from the pyrimidine C (6)atom to the Cys146 nucleophile.If correctly positioned, dUMP, CH₂THF, and TS would form a ternary complex to facilitate the donation of the methyl group from CH₂THF to dUMP.However, the substitution of dUMP with FdUMP results in a new time-dependent TS–FdUMP–CH2THF complex. Since the fluorine group prevents dissociation of FdUMP from the pyrimidine ring, the whole complex is rendered irreversibly deactivated, terming this reaction "suicide inhibition".TS inhibition prevents the conversion of dUMP to dTMP, depleting the pool of dTMP that could be phosphorylated into dTTP to be incorporated as DNA nucleotides. This disrupts the nucleotides balance, particularly the the ATP/dTTP ratio, thus impairing DNA synthesis and repair and causing apoptosis. 5-FdUMP can also be phosphorylated into 5-FdUTP, further increasing the pool of dUTP base to potentially overwhelm the activity of dUTPase.Coupled with the decrease in dTTP, 5-FdUMP, and 5-FdUTP increase the probability of mistakenly incorporating a uracil base into DNA strands in place of thymine. Although this mistake can often be resolved by the nucleotide excision repair enzyme uracil-DNA-glycosylase (UDG), the high (F)dUTP/dTTP ratio would result in re-incorporation of uracil into DNA, leading to a futile cycle of misincorporation, excision, and repair.Repeated base excision repair can result in abasic sites, which can lead to DNA mutagenesis and thus protein miscoding, replication forks collapse, and DNA fragmentation through single or double strand breaks However, several reports have found that the incorporation of uracil in genomic DNA does not significantly affect the cytotoxicity of 5-FU, suggesting that the cytotoxic effect of 5-FU is dominated by the perturbation of RNA through 5-FUTP.Similar to 5-dFUTP, 5-FUTP can be mistakenly incorporated into RNA in place of regular UTP and disrupt regular RNA biology through various mechanisms. 5-FUTP can be incorporated into the spliceosomal U2 snRNA at pseudouridylated sites to prevent further pseudouridylation and thus pre-mrNA splicing. 5-FUTP can also change the structure of U4 and U6 snRNA and reduce the turnover rate of U1 snrNA once incorporated.For tRNA, 5-FUTP can affect tRNA's post-transcriptional RNA modifications activity, particularly by inhbiting pseudouridine synthase through formation of covalent complex.Recently, the effect of 5-FUTP on miRNAs and lncRNA was also observed through profound changes in expression, although the precise mechanism is still unknown. Although the main mechanism of 5-FU cytotoxicity was thought to be attributed to DNA damages, recent reports have shown that the majority of 5-FU pharmacological action is mediated through RNA, since 5-FU is accumulated ~3000- to 15 000-fold more in RNA compared to that of DNA.

Capecitabine’s safety profile reflects its conversion to 5‑fluorouracil, with systemic exposure linked to myelosuppression, gastrointestinal toxicity, hyperbilirubinemia, cardiotoxicity, and severe reactions in individuals with dihydropyrimidine dehydrogenase deficiency. Genotoxicity has been demonstrated through in‑vitro clastogenicity and in‑vivo chromosomal abnormalities associated with 5‑fluorouracil. High-dose animal studies showed reproductive toxicity, including estrous disruption, testicular degeneration, embryolethality, and teratogenic effects during organogenesis. These findings support a mechanism‑based risk for developmental toxicity.

Capecitabine is a moisture‑sensitive prodrug, so solid‑state control and protection from humidity are important during manufacturing and storage. Its low aqueous solubility requires attention to particle size, solid‑state form, and dissolution performance to ensure consistent oral absorption. The API is intended for intact film‑coated tablets; crushing or splitting should be avoided due to stability and exposure considerations. Handling should minimize degradation and maintain uniformity of this enzymatically activated nucleoside derivative.

Capecitabine is classified as a small molecule. That classification shapes process design, impurity profiling, and analytical control strategies.

Capecitabine tablets are moisture‑sensitive, so the film coating helps maintain solid‑state stability and protect the low‑solubility prodrug. The tablets should be swallowed intact because crushing or splitting can compromise stability and alter exposure. Administration with food affects absorption, so maintaining the intended oral dosage form and conditions of intake is important for consistent performance.