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Xeloda

Xeloda is a widely registered antitumour preparation based on capecitabine, with marketing authorisation in 65 countries — a footprint that puts it in front of cancer patients, travellers, and expatriates across every populated continent. Its active ingredient, capecitabine, is classified as an antitumour agent and is used within structured oncology regimens.

Xeloda is prescribed in the management of several cancer indications, including breast cancer, metastatic breast cancer, carcinoma more broadly, and colorectal cancer, and it features in chemotherapy protocols across many national treatment guidelines. The structured indication list further down this page sets out the registered uses recognised across the markets where Xeloda is sold, paraphrased from the regulatory data rather than from any individual treatment plan.

Because Xeloda is so broadly distributed, patients who begin treatment in one country and travel or relocate to another often encounter the same medication abroad — sometimes still under the Xeloda brand, sometimes as a capecitabine-containing generic. Markets where the brand is registered include Australia, Brazil, China, Canada, and Argentina, but regulatory packaging, prescription pathways, and supply arrangements for oncology medications can vary significantly from one country to another. A hospital pharmacist or treating oncologist in the destination country is the right person to confirm continuity of supply.

Other medications in the antitumour category are sold in many of the same markets under different molecules and brand names, although oncology agents within a broad class are not freely interchangeable — they are selected against tumour type, staging, and a patient's full clinical picture. Anyone receiving capecitabine therapy and crossing borders should plan continuity with their oncologist well in advance, and treat any substitution as a clinical decision led by the prescribing team rather than a pharmacy-counter swap.

Countries
Argentina Armenia Australia Austria Bangladesh Belgium Bosnia & Herzegowina Brazil Bulgaria Canada Chile China Colombia Croatia (Hrvatska) Cyprus Czech Republic Denmark Ecuador Egypt Estonia Finland France Georgia Germany Greece Hong Kong Hungary Iceland Indonesia Ireland Israel Italy Japan Latvia Lebanon Liechtenstein Lithuania Luxembourg Malta Mexico Moldova Myanmar Netherlands New Zealand Norway Oman Philippines Poland Portugal Romania Russia Serbia Slovakia Slovenia South Africa Spain Sweden Taiwan Thailand Tunisia Turkey United Kingdom Uruguay USA Vietnam
Diseases
Chemotherapy Carcinoma Metastatic Breast Cancer Cancer Breast Cancer Colorectal cancer
Ingredients
Capecitabine
Drug Actions
Antitumour

Drugs with the same active ingredients

Apecitab Capebina Capecit Capecitabina filaxis Capecitabina techsphere Capecitabina varifarma Capectan Capefas Categor Catepen Derebel Xitabin Ai bin Cabecibine Cansata Cantaloda Capecel Capecitabin actavis Capecitabin al Capecitabin fresenius

Overdose

The manifestations of acute overdose would include nausea, vomiting, diarrhea, gastrointestinal irritation and bleeding, and bone marrow depression. Medical management of overdose should include customary supportive medical interventions aimed at correcting the presenting clinical manifestations. Although no clinical experience using dialysis as a treatment for XELODA overdose has been reported, dialysis may be of benefit in reducing circulating concentrations of 5'-DFUR, a low– molecular-weight metabolite of the parent compound.

Single doses of XELODA were not lethal to mice, rats, and monkeys at doses up to 2000 mg/kg (2.4, 4.8, and 9.6 times the recommended human daily dose on a mg/m2 basis).

Pharmacokinetic properties

Absorption

Following oral administration of 1255 mg/m2 BID to cancer patients, capecitabine reached peak blood levels in about 1.5 hours (Tmax) with peak 5-FU levels occurring slightly later, at 2 hours. Food reduced both the rate and extent of absorption of capecitabine with mean C and AUC decreased by 60% and 35%, respectively. The Cmax and AUC0-8 of 5-FU were also reduced by food by 43% and 21%, respectively. Food delayed Tmax of both parent and 5-FU by 1.5 hours.

The pharmacokinetics of XELODA and its metabolites have been evaluated in about 200 cancer patients over a dosage range of 500 to 3500 mg/m2 /day. Over this range, the pharmacokinetics of XELODA and its metabolite, 5'-DFCR were dose proportional and did not change over time. The increases in the AUCs of 5'-DFUR and 5-FU, however, were greater than proportional to the increase in dose and the AUC of 5-FU was 34% higher on day 14 than on day 1. The interpatient variability in the Cmax and AUC of 5-FU was greater than 85%.

Distribution

Plasma protein binding of capecitabine and its metabolites is less than 60% and is not concentrationdependent. Capecitabine was primarily bound to human albumin (approximately 35%). XELODA has a low potential for pharmacokinetic interactions related to plasma protein binding.

Bioactivation And Metabolism

Capecitabine is extensively metabolized enzymatically to 5-FU. In the liver, a 60 kDa carboxylesterase hydrolyzes much of the compound to 5'-deoxy-5-fluorocytidine (5'-DFCR). Cytidine deaminase, an enzyme found in most tissues, including tumors, subsequently converts 5'-DFCR to 5'-DFUR. The enzyme, thymidine phosphorylase (dThdPase), then hydrolyzes 5'-DFUR to the active drug 5-FU. Many tissues throughout the body express thymidine phosphorylase. Some human carcinomas express this enzyme in higher concentrations than surrounding normal tissues. Following oral administration of XELODA 7 days before surgery in patients with colorectal cancer, the median ratio of 5-FU concentration in colorectal tumors to adjacent tissues was 2.9 (range from 0.9 to 8.0). These ratios have not been evaluated in breast cancer patients or compared to 5-FU infusion.

Metabolic Pathway of capecitabine to 5-FU

The enzyme dihydropyrimidine dehydrogenase hydrogenates 5-FU, the product of capecitabine metabolism, to the much less toxic 5-fluoro-5, 6-dihydro-fluorouracil (FUH2). Dihydropyrimidinase cleaves the pyrimidine ring to yield 5-fluoro-ureido-propionic acid (FUPA). Finally, β-ureidopropionase cleaves FUPA to a-fluoro-β-alanine (FBAL) which is cleared in the urine.

In vitro enzymatic studies with human liver microsomes indicated that capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5-FU, and FBAL) did not inhibit the metabolism of test substrates by cytochrome P450 isoenzymes 1A2, 2A6, 3A4, 2C19, 2D6, and 2E1.

Excretion

Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose. About 3% of the administered dose is excreted in urine as unchanged drug. The elimination half-life of both parent capecitabine and 5-FU was about 0.75 hour.

Effect Of Age, Gender, And Race On The Pharmacokinetics Of Capecitabine

A population analysis of pooled data from the two large controlled studies in patients with metastatic colorectal cancer (n=505) who were administered XELODA at 1250 mg/m2 twice a day indicated that gender (202 females and 303 males) and race (455 white/Caucasian patients, 22 black patients, and 28 patients of other race) have no influence on the pharmacokinetics of 5'-DFUR, 5-FU and FBAL. Age has no significant influence on the pharmacokinetics of 5'-DFUR and 5-FU over the range of 27 to 86 years. A 20% increase in age results in a 15% increase in AUC of FBAL.

Following oral administration of 825 mg/m2 capecitabine twice daily for 14 days, Japanese patients (n=18) had about 36% lower Cmax and 24% lower AUC for capecitabine than the Caucasian patients (n=22). Japanese patients had also about 25% lower Cmax and 34% lower AUC for FBAL than the Caucasian patients. The clinical significance of these differences is unknown. No significant differences occurred in the exposure to other metabolites (5'-DFCR, 5'-DFUR, and 5-FU).

Effect Of Hepatic Insufficiency

XELODA has been evaluated in 13 patients with mild to moderate hepatic dysfunction due to liver metastases defined by a composite score including bilirubin, AST/ALT and alkaline phosphatase following a single 1255 mg/m2 dose of XELODA. Both AUC0-8 and Cmax of capecitabine increased by 60% in patients with hepatic dysfunction compared to patients with normal hepatic function (n=14). The AUC0-8 and Cmax of 5-FU were not affected. In patients with mild to moderate hepatic dysfunction due to liver metastases, caution should be exercised when XELODA is administered. The effect of severe hepatic dysfunction on XELODA is not known.

Effect Of Renal Insufficiency

Following oral administration of 1250 mg/m2 capecitabine twice a day to cancer patients with varying degrees of renal impairment, patients with moderate (creatinine clearance = 30 to 50 mL/min) and severe (creatinine clearance <30 mL/min) renal impairment showed 85% and 258% higher systemic exposure to FBAL on day 1 compared to normal renal function patients (creatinine clearance >80 mL/min). Systemic exposure to 5'-DFUR was 42% and 71% greater in moderately and severely renal impaired patients, respectively, than in normal patients. Systemic exposure to capecitabine was about 25% greater in both moderately and severely renal impaired patients.

Effect Of Capecitabine On The Pharmacokinetics Of Warfarin

In four patients with cancer, chronic administration of capecitabine (1250 mg/m2 bid) with a single 20 mg dose of warfarin increased the mean AUC of S-warfarin by 57% and decreased its clearance by 37%. Baseline corrected AUC of INR in these 4 patients increased by 2.8-fold, and the maximum observed mean INR value was increased by 91%.

Effect Of Antacids On The Pharmacokinetics Of Capecitabine

When Maalox® (20 mL), an aluminum hydroxide- and magnesium hydroxide-containing antacid, was administered immediately after XELODA (1250 mg/m2 , n=12 cancer patients), AUC and Cmax increased by 16% and 35%, respectively, for capecitabine and by 18% and 22%, respectively, for 5'-DFCR. No effect was observed on the other three major metabolites (5'-DFUR, 5-FU, FBAL) of XELODA.

Effect Of Capecitabine On The Pharmacokinetics Of Docetaxel And Vice Versa

A Phase 1 study evaluated the effect of XELODA on the pharmacokinetics of docetaxel (Taxotere®) and the effect of docetaxel on the pharmacokinetics of XELODA was conducted in 26 patients with solid tumors. XELODA was found to have no effect on the pharmacokinetics of docetaxel (Cmax and AUC) and docetaxel has no effect on the pharmacokinetics of capecitabine and the 5-FU precursor 5'- DFUR.

Date of revision of the text

Mar 2015

Frequently asked questions

What conditions does Xeloda treat?

Xeloda is prescribed in oncology, with registered indications spanning chemotherapy regimens for carcinoma, metastatic breast cancer, breast cancer more broadly, and colorectal cancer. It is classified as an antitumour agent and is typically used as part of a structured cancer treatment plan rather than as a standalone short course. The structured indication block further down this page lists every registered use recognised across the markets where Xeloda is sold.

What is the active ingredient in Xeloda?

Xeloda contains capecitabine, an antitumour agent used in oncology. Capecitabine is the same molecule whether dispensed under the Xeloda brand or as a generic — internationally, the same active ingredient circulates under multiple commercial names, particularly in markets where the original patent has expired and several manufacturers produce capecitabine products in parallel.

In how many countries is Xeloda available?

Xeloda is registered in 65 countries across a broad international footprint, including Australia, Brazil, Canada, China, Belgium, Argentina, and Bangladesh. The full country list is shown in the structured section below this introduction. If your country is not represented there, a local oncology pharmacist or treating physician can usually confirm whether capecitabine is available in that market under a different brand name or as a generic.

Are there other medications with the same active ingredient as Xeloda?

Capecitabine is sold under several brand names worldwide, particularly in markets where the original patent has expired and generic manufacturers have entered. Other medications within the broader antitumour category also exist, although they are not interchangeable — oncology agents are selected against tumour type, staging, and a patient's full clinical picture. To identify a local capecitabine-containing product, search the active ingredient on Pill2Trip or ask an oncology pharmacist.

Should I consult a doctor before taking Xeloda?

Yes. Xeloda is a prescription oncology medication, and any treatment plan involving capecitabine is built around a specific cancer diagnosis, staging, concurrent therapies, and individual clinical circumstances. This is particularly relevant for patients who travel or relocate mid-treatment, since prescription pathways, available brands, and supply arrangements differ between countries. Continuity of an oncology regimen should always be coordinated with the treating oncologist and a local healthcare provider.

Xeloda

Available in 65 countries