化合物详情

Concomitant use of phenytoin and capecitabine may result in toxicity from increased serum phenytoin concentrations. The mechanism of interaction is presumed to be inhibition of the metabolism of phenytoin by capecitabine and/or its metabolites through inhibition of the cytochrome P-450 (CYP) 2C9 isoenzyme. In patients receiving capecitabine, serum concentrations of phenytoin must be monitored carefully, and reduction in the phenytoin dosage may be necessary.

Likelihood score: E* (Unproven but suspected cause of clinically apparent liver injury).

Readily absorbed through the GI tract (~70%)

Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. FdUMP inhibits DNA synthesis by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate.3 The active moiety of capecitabine, fluorouracil, is cell cycle phase-specific (Sphase). Both normal and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-...

/CASE REPORTS/ ... A 65-year-old white woman with stage IV colorectal cancer with liver metastasis was started on a chemotherapy regimen of capecitabine, oxaliplatin, and bevacizumab, given every three weeks. She tolerated the first two treatment cycles fairly well without major toxicities. The capecitabine dosage was started at 2000 mg daily for 14 days during the first cycle and increased to 2500 and 3000 mg daily during the second and the third cycles, respectively. On day 5 of the third cycle, the patient reported increased nausea, fatigue, and sleepiness, and the dosage of capecitabine was subsequently reduced to 2500 mg daily. On day 12 of the fourth treatment cycle, she reported ongoing lightheadedness and progressive gait disturbance with worsening ataxia over the past 3 days. H...

No indication of carcinogenicity to humans (not listed by IARC).

References: DOI:10.1016/j.drudis.2019.09.022

/GENOTOXICITY/ Capecitabine ... was not clastogenic to mouse bone marrow (micronucleus test) in vivo. Capecitabine was not mutagenic in the Ames test or the Chinese hamster V79/HPRT gene mutation assay. Fluorouracil, the biologically active form of capecitabine, has been shown to be mutagenic in some bacteria and yeast. Fluorouracil also causes chromosomal aberrations in the micronucleus test in mice in vivo.

Although the safety and efficacy of capecitabine in geriatric patients have not been specifically studied to date, the manufacturer reports that elderly individuals may experience increased frequency and severity of the toxic effects of capecitabine and its metabolites. Among 21 patients aged 80 years or older receiving capecitabine for metastatic breast cancer or metastatic colorectal cancer in clinical trials, 62% experienced a grade 3 or 4 adverse effect. In particular, severe adverse GI effects (grade 3 or 4 diarrhea, nausea, or vomiting) or severe hand-foot syndrome associated with capecitabine may occur more frequently in such patients. ... Geriatric patients should be monitored closely for the occurrence of capecitabine-induced adverse effects.

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use propar...

◉ Effects on Lactation and Breastmilk