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Capecitabine: Drug information

Capecitabine: Drug information
(For additional information see "Capecitabine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Warfarin interaction:

Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or PT) monitored frequently in order to adjust the anticoagulant dose accordingly. A clinically important capecitabine-warfarin drug interaction was demonstrated in a clinical pharmacology trial. Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. Postmarketing reports have shown clinically significant increases in PT and INR in patients who were stabilized on anticoagulants at the time capecitabine was introduced. These events occurred within several days and up to several months after initiating capecitabine therapy and, in a few cases, within 1 month after stopping capecitabine. These events occurred in patients with and without liver metastases. Age >60 years and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.

Brand Names: US
  • Xeloda
Brand Names: Canada
  • ACH-Capecitabine;
  • Mint-Capecitabine;
  • SANDOZ Capecitabine;
  • TARO-Capecitabine;
  • TEVA-Capecitabine [DSC];
  • Xeloda
Pharmacologic Category
  • Antineoplastic Agent, Antimetabolite;
  • Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)
Dosing: Adult

Note: The manufacturer suggests dosing at 5,600 mg/day (in 2 divided doses) in patients with a body surface area of ≥2.18 m2 for labeled indications (refer to product labeling for details). Baseline platelets should be ≥100,000/mm3 and neutrophils should be ≥1,500/mm3 prior to capecitabine initiation.

Anal carcinoma

Anal carcinoma (off-label use): Oral: 825 mg/m2 twice daily 5 days/week (Monday through Friday) (in combination with mitomycin [on day 1 only]) during radiation therapy; radiation therapy occurred over 5 to 6 weeks (Oliveira 2016) or 825 mg/m2 twice daily on radiation therapy days (in combination with mitomycin [on day 1 only] and radiation therapy) (Meulendijks 2014; Thind 2014).

Biliary tract cancer, adjuvant therapy

Biliary tract cancer, adjuvant therapy (off-label use):

Monotherapy (adjuvant): Oral: 1,250 mg/m2 twice daily on days 1 to 14 of a 21-day treatment cycle for 8 cycles (Primrose 2019). Per the American Society of Clinical Oncology guideline for adjuvant therapy for resected biliary tract cancer, the capecitabine dose may be determined by institutional and regional practices (ASCO [Shroff 2019]).

Chemoradiotherapy (adjuvant): Oral: 750 mg/m2 twice daily on days 1 to 14 of a 21-day treatment cycle (in combination with gemcitabine) for 4 cycles, followed by capecitabine 665 mg/m2 twice daily (in combination with concurrent radiotherapy) (Ben-Josef 2015). Refer to protocol for specific details.

Biliary tract cancers, advanced

Biliary tract cancers, advanced (off-label use): Oral: 650 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with gemcitabine) until disease progression or unacceptable toxicity (Knox 2005) or 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with oxaliplatin) until disease progression or unacceptable toxicity (Nehls 2008) or 1,250 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with cisplatin) until disease progression or unacceptable toxicity (Kim 2003).

Breast cancer, adjuvant therapy, HER2-negative, with residual disease after neoadjuvant therapy and surgery

Breast cancer, adjuvant therapy, HER2-negative, with residual disease after neoadjuvant therapy and surgery (off-label use): Oral: 1,250 mg/m2 twice daily on days 1 to 14 of a 21-day treatment cycle for 6 to 8 cycles (Masuda 2017).

Breast cancer, metastatic

Breast cancer, metastatic: Oral: 1,250 mg/m2 twice daily for 2 weeks, every 21 days (as either monotherapy or in combination with docetaxel).

Breast cancer, metastatic (off-label dosing): Adults ≥65 years of age: Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 21-day treatment cycle for at least 2 and up to 6 cycles or longer (Bajetta 2005).

Breast cancer, metastatic (off-label combination): Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with ixabepilone) until disease progression or unacceptable toxicity (Thomas 2007).

Breast cancer, metastatic, HER2+ (off-label combinations): Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with lapatinib) until disease progression or unacceptable toxicity (Geyer 2006) or 1,250 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with trastuzumab) (Bartsch 2007) or 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with tucatinib and trastuzumab) until disease progression or unacceptable toxicity (Murthy 2020) or 750 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with neratinib) until disease progression or unacceptable toxicity (Saura 2020) or 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with margetuximab) until disease progression or unacceptable toxicity (Rugo 2021).

Breast cancer, metastatic, HER2+ with brain metastases, first-line therapy (off-label combination): Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with lapatinib) until disease progression or unacceptable toxicity (Bachelot 2012).

Colorectal cancer, metastatic

Colorectal cancer, metastatic: Oral: 1,250 mg/m2 twice daily for 2 weeks, every 21 days. Note: Capecitabine toxicities, particularly hand-foot syndrome, may be higher in North American populations; therapy initiation at doses of 1,000 mg/m2 twice daily (for 2 weeks every 21 days) may be considered (Haller 2008).

Colorectal cancer (off-label combination): Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with oxaliplatin) for 8 or 16 cycles (Cassidy 2008; Haller 2011; Schmoll 2007).

Dukes C colon cancer, adjuvant therapy

Dukes C colon cancer, adjuvant therapy: Oral: 1,250 mg/m2 twice daily for 2 weeks, every 21 days, for a recommended total duration of 24 weeks (8 cycles of 2 weeks of drug administration and 1 week rest period).

Esophageal, gastric, and gastroesophageal cancers

Esophageal, gastric, and gastroesophageal cancers (off-label uses):

Esophageal or gastroesophageal cancers: Preoperative or definitive chemoradiation: Oral: 800 mg/m2 twice daily on days 1 to 5 weekly (in combination with cisplatin and radiation) for 5 weeks (Lee 2007) or 625 mg/m2 twice daily on days 1 to 5 weekly (in combination with oxaliplatin and radiation) for 5 weeks (Javle 2009).

Gastric cancer: Postoperative chemoradiation: Oral: 625 to 825 mg/m2 twice daily during radiation therapy (Lee 2006).

Esophageal, gastric, or gastroesophageal junction cancer: Locally advanced or metastatic: Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with oxaliplatin and nivolumab) until disease progression or unacceptable toxicity (Janjigian 2021).

Gastric or gastroesophageal junction cancer: Locally advanced or metastatic (chemoradiation not indicated): Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with cisplatin for 6 cycles and trastuzumab) (Bang 2010) or 1,250 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (as a single agent) for up to 6 cycles (Hong 2004) or 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with cisplatin) until disease progression or unacceptable toxicity (Kang 2009).

Gastroesophageal cancer, advanced, palliative treatment: Frail and/or elderly patients: Oral: A dose optimization study that examined 60%, 80%, or 100% of a 625 mg/m2 twice daily dose (on days 1 to 21 of a 21-day cycle; in combination with oxaliplatin) found that the 60% dose was not inferior (for progression-free survival) and had less toxicity compared to the full dose (Hall 2021).

Head and neck cancer, squamous cell, recurrent or metastatic; palliative treatment

Head and neck cancer, squamous cell, recurrent or metastatic; palliative treatment (off-label use; based on limited data): Oral: 1,250 mg/m2 twice daily on days 1 to 14 of a 21-day treatment cycle for at least 3 cycles; continue until disease progression or unacceptable toxicity (Martinez-Trufero 2010).

Neuroendocrine pancreatic/islet cell tumors, metastatic or unresectable

Neuroendocrine pancreatic/islet cell tumors, metastatic or unresectable (off-label use) Based on limited data: Oral: 750 mg/m2 twice daily on days 1 to 14 of a 4-week cycle (in combination with temozolomide) until disease progression (Strosberg 2011).

Ovarian, fallopian tube, or peritoneal cancer, platinum-refractory

Ovarian, fallopian tube, or peritoneal cancer, platinum-refractory (off-label use): Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle until disease progression or unacceptable toxicity (Wolf 2006).

Pancreatic cancer, locally advanced or metastatic

Pancreatic cancer, locally advanced or metastatic (off-label use): Oral: 1,250 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (as a single agent) until disease progression or up to 1 year (Cartwright 2002) or 830 mg/m2 twice daily on days 1 to 21 of a 4-week cycle (in combination with gemcitabine) until disease progression or unacceptable toxicity (Cunningham 2009).

Pancreatic cancer, potentially curable, adjuvant therapy

Pancreatic cancer, potentially curable, adjuvant therapy (off-label use; alternative therapy): Note: American Society of Clinical Oncology guidelines for potentially curable pancreatic cancer recommend 6 months of adjuvant therapy if recovery is complete; while first-line therapy with another regimen is preferred, the capecitabine/gemcitabine regimen is an option if toxicity/tolerance are concerns with the preferred therapy (ASCO [Khorana 2019]).

Oral: 830 mg/m2 twice daily on days 1 to 21 every 28 days (in combination with gemcitabine) for 6 cycles beginning within 12 weeks of resection (Neoptolemos 2017).

Unknown primary cancer

Unknown primary cancer (off-label use): Oral: 1,000 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with oxaliplatin) for up to 6 cycles or until disease progression (Hainsworth 2010) or 800 mg/m2 twice daily on days 1 to 14 of a 3-week cycle (in combination with carboplatin and gemcitabine) for up to 8 cycles or until disease progression or unacceptable toxicity (Schneider 2007).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Kidney impairment prior to treatment initiation:

Altered kidney function:

Note: Capecitabine and its metabolites are primarily (>95%) excreted by the kidneys (manufacturer’s labeling). An increased incidence of drug-limiting toxicity has been observed with declining kidney function, including in patients with eGFR 60 to 90 mL/minute/1.73 m2 as compared to eGFR >90 mL/minute/1.73 m2 (Celik 2021), although another study did not find a difference in toxicity based on CrCl using dose-adjusted capecitabine in patients with breast cancer (Lichtman 2016). As such, monitoring for adverse effects (eg, diarrhea, hematologic, mucositis, hand-foot syndrome/palmar-plantar erythrodysesthesia) is warranted even in mild kidney impairment, and toxicity-related dose reductions may be required. Kidney function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 30 to 50 mL/minute: Administer 75% of the usual indication-specific daily dose (Krens 2019; Poole 2002; manufacturer’s labeling).

CrCl <30 mL/minute: Use is contraindicated (Krens 2019; Poole 2002; manufacturer’s labeling). There are limited case reports demonstrating tolerability in this population following dose reductions of up to 80% (Jhaveri 2012).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):

Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post-trauma or post-major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).

No dosage adjustment necessary (expert opinion).

Hemodialysis, intermittent (thrice weekly): Use not recommended (Krens 2019; manufacturer’s labeling). Tolerability following dose reduction has been observed in several case reports in hemodialysis patients (Jhaveri 2012; Sasaki 2019); however, due to the paucity of data, no specific dosage recommendation can be suggested (expert opinion).

Peritoneal dialysis: Use not recommended (has not been studied) (expert opinion).

CRRT: Use not recommended (has not been studied) (expert opinion).

PIRRT (eg, sustained, low-efficiency diafiltration): Use not recommended (has not been studied) (expert opinion).

Kidney toxicity during treatment:

Capecitabine does not directly damage the kidney (Nemecek 2019). However, its ability to cause diarrhea and dehydration can impact kidney function. Monitor, intensify supportive care, and correct dehydration (Refer to "Dosing: Adjustment for Toxicity").

Dosing: Hepatic Impairment: Adult

Hepatic impairment at treatment initiation:

Mild to moderate impairment: No starting dose adjustment necessary (Eklund 2005; Superfin 2007); however, carefully monitor patients with hepatic dysfunction due to liver metastases.

Severe hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Hepatotoxicity during treatment: Hyperbilirubinemia, grade 3 or 4: Interrupt treatment until bilirubin ≤3 times ULN; refer to dosage adjustment for toxicity for dosage modification recommendations based on toxicity grade.

Dosing: Older Adult

The elderly may be more sensitive to the toxic effects of fluorouracil. Insufficient data are available to provide dosage modifications. Also refer to Adult dosing.

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing with subsequent cycles if cause of toxicity (eg, hepatic or renal impairment) is clearly established and fully resolved (ASCO [Griggs 2021]). The manufacturer suggests dosing at 5,600 mg/day (in 2 divided doses) in patients with a body surface area of ≥2.18 m2 (refer to product labeling for details).

Dosing: Adjustment for Toxicity: Adult

See table (Note: Capecitabine dosing recommendations apply to both monotherapy and when used in combination therapy with docetaxel).

Monitor carefully for toxicity and adjust dose as necessary. Doses reduced for toxicity should not be increased at a later time. For combination therapy, also refer to docetaxel product labeling for docetaxel dose modifications. If treatment delay is required for either capecitabine or docetaxel, withhold both agents until appropriate to resume combination treatment.

Recommended Capecitabine Dose Modifications

Toxicity Grades

During a Course of Therapy

Dose Adjustment for Next Cycle (% of starting dose)

Grade 1

Maintain dose level

Maintain dose level

Grade 2

1st appearance

Interrupt until resolved to grade 0 to 1

100%

2nd appearance

Interrupt until resolved to grade 0 to 1

75%

3rd appearance

Interrupt until resolved to grade 0 to 1

50%

4th appearance

Discontinue treatment permanently

Grade 3

1st appearance

Interrupt until resolved to grade 0 to 1

75%

2nd appearance

Interrupt until resolved to grade 0 to 1

50%

3rd appearance

Discontinue treatment permanently

Grade 4

1st appearance

Discontinue permanently

or

If in the patient's best interest to continue, interrupt until resolved to grade 0 to 1

50%

Specific toxicities (refer to above table for modification recommendations based on toxicity grade):

Dermatologic toxicity: Severe capecitabine-related mucocutaneous toxicity: Permanently discontinue capecitabine.

GI toxicity:

Diarrhea, grades 2 to 4: Withhold capecitabine until ≤ grade 1. Subsequent doses should be reduced after grade 3 or 4 diarrhea or recurrence of grade 2 diarrhea. Antidiarrheal therapy (eg, loperamide) is recommended.

Dehydration, ≥ grade 2: Interrupt capecitabine treatment; correct precipitating factors and ensure rehydration prior to resuming therapy; may require dose modification (based on precipitating factor).

Hand-foot syndrome: Grade 2 or 3: Interrupt capecitabine until resolves or decreases in intensity to grade 1. Following grade 3 hand-and-foot syndrome, decrease subsequent capecitabine doses.

Hematologic toxicity: Grade 3 or 4: Withhold capecitabine.

Evidence of acute early-onset or unusually severe toxicity indicative of dihydropyrimidine dehydrogenase deficiency: Withhold or permanently discontinue capecitabine depending on the onset, duration, and severity of toxicity.

Capecitabine dosage adjustments for hematologic toxicity when used in combination therapy with ixabepilone:

Neutrophils <500/mm3 for ≥7 days or neutropenic fever: Hold capecitabine for concurrent diarrhea or stomatitis until neutrophils recover to >1,000/mm3, then continue at same dose.

Platelets <25,000/mm3 (or <50,000/mm3 with bleeding): Hold capecitabine for concurrent diarrhea or stomatitis until platelets recover to >50,000/mm3, then continue at same dose.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Xeloda: 150 mg, 500 mg

Generic: 150 mg, 500 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Xeloda: 150 mg, 500 mg

Generic: 150 mg, 500 mg

Administration: Adult

Oral: Usually administered in 2 divided doses (in the morning and evening). Doses should be administered with water within 30 minutes after a meal. Swallow tablets whole. Avoid cutting or crushing tablets.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Breast cancer (metastatic):

Monotherapy: Treatment of metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing regimen or resistant to paclitaxel in patients for whom further anthracycline therapy is not indicated

Combination therapy: Treatment of metastatic breast cancer (in combination with docetaxel) after failure of a prior anthracycline-containing regimen

Colorectal cancer: First-line treatment of metastatic colorectal cancer when treatment with a fluoropyrimidine alone is preferred; adjuvant therapy of Dukes' C colon cancer after complete resection of the primary tumor when fluoropyrimidine therapy alone is preferred

Use: Off-Label: Adult

Anal carcinoma; Biliary tract cancer (adjuvant therapy); Biliary tract cancers (advanced); Breast cancer (adjuvant therapy); Esophageal, gastric, and gastroesophageal cancers; Head and neck cancer, squamous cell (recurrent or metastatic; palliative treatment); Neuroendocrine (islet cell) tumors (metastatic or unresectable); Ovarian, fallopian tube, or peritoneal cancers (refractory); Pancreatic cancer (locally advanced or metastatic); Pancreatic cancer, potentially curable (adjuvant therapy); Unknown primary cancer

Medication Safety Issues
Sound-alike/look-alike issues:

Capecitabine may be confused with cabozantinib, capmatinib

Xeloda may be confused with Xenical, Xpovio

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence reported for all indications and usage, unless otherwise noted.

>10%:

Cardiovascular: Edema (≤15%)

Central nervous system: Fatigue (≤42%), paresthesia (stage IV breast cancer: 21%), pain (≤12%)

Dermatologic: Palmar-plantar erythrodysesthesia (54% to 60%), dermatitis (27% to 37%)

Gastrointestinal: Diarrhea (47% to 57%), nausea (34% to 43%; stage IV breast cancer: 53%), vomiting (metastatic colorectal cancer, stage IV breast cancer: 27% to 37%; Dukes' C colon cancer: 15%), abdominal pain (metastatic colorectal cancer: 35%; stage IV breast cancer: 20%; Dukes' C colon cancer: 14%), decreased appetite (26%), stomatitis (22% to 25%), anorexia (stage IV breast cancer: 23%; Dukes' C colon cancer: 9%), constipation (9% to 15%)

Hematologic & oncologic: Lymphocytopenia (stage IV breast cancer: 94%; stage IV breast cancer, grades 3/4: 15% to 44%), anemia (72% to 80%, grades 3/4: ≤3%), neutropenia (≤26%, grades 3/4: ≤3%), thrombocytopenia (stage IV breast cancer: 24%; all: grades 3/4: 1% to 3%)

Hepatic: Hyperbilirubinemia (metastatic colorectal cancer: 48%; stage IV breast cancer: 22%)

Neuromuscular & skeletal: Asthenia (≤42%)

Ophthalmic: Eye irritation (13% to 15%)

Miscellaneous: Fever (7% to 18%)

1% to 10%:

Cardiovascular: Venous thrombosis (8%), chest pain (≤6%), atrial fibrillation (<5%), bradycardia (<5%), cerebrovascular accident (<5%), collapse (<5%), extrasystoles (<5%), hypertension (<5%), hypotension (<5%), myocarditis (<5%), pericardial effusion (<5%), pulmonary embolism (<5%), tachycardia (<5%), ventricular premature contractions (<5%)

Central nervous system: Lethargy (10%), peripheral sensory neuropathy (10%), headache (5% to 10%), insomnia (≤8%), dizziness (6% to 8%), ataxia (<5%), confusion (<5%), depression (≤5%), mood changes (5%), abnormal gait (<5%), dysarthria (<5%), dysphasia (<5%), encephalopathy (<5%), equilibrium disturbance (<5%), irritability (<5%), loss of consciousness (<5%), myasthenia (<5%), sedated state (<5%), vertigo (<5%)

Dermatologic: Nail disease (≤7%), skin discoloration (7%), skin rash (7%), alopecia (6%), erythema of skin (6%), dermal ulcer (<5%), pruritus (<5%)

Endocrine & metabolic: Dehydration (7%), cachexia (<5%), hot flash (<5%), hypertriglyceridemia (<5%), hypokalemia (<5%), hypomagnesemia (<5%), increased thirst (<5%), weight gain (<5%), decreased serum calcium (Dukes' C colon cancer: grades 3/4: 2%), increased serum calcium (Dukes' C colon cancer: grades 3/4: 1%)

Gastrointestinal: Gastrointestinal motility disorder (10%), gastrointestinal inflammation (upper: 8%), oral discomfort (grades 3/4: 10%), dyspepsia (6% to 8%), upper abdominal pain (7%), intestinal obstruction (≤6%), dysgeusia (6%), gastrointestinal hemorrhage (6%), abdominal distention (<5%), dysphagia (<5%), gastric ulcer (<5%), gastroenteritis (<5%), rectal pain (<5%), toxic megacolon (<5%), sore throat (2%)

Hematologic & oncologic: Disorder of hemostatic components of blood (<5%), hemorrhage (<5%), leukopenia (<5%), lymphedema (<5%), pancytopenia (<5%), granulocytopenia (Dukes' C colon cancer: grades 3/4: 3%), immune thrombocytopenia (1%)

Hepatic: Abnormal hepatic function tests (<5%), ascites (<5%), cholestatic hepatitis (<5%), hepatic fibrosis (<5%), hepatitis (<5%), increased serum alanine aminotransferase (Dukes' C colon cancer: grades 3/4: 2%)

Hypersensitivity: Drug-induced hypersensitivity reaction (<5%)

Infection: Viral infection (metastatic colorectal cancer: 5%), fungal infection (<5%), sepsis (<5%)

Neuromuscular & skeletal: Back pain (10%), myalgia (≤9%), arthralgia (8%), limb pain (stage IV breast cancer: 6%), arthritis (<5%), ostealgia (<5%), tremor (<5%)

Ophthalmic: Visual disturbance (metastatic colorectal cancer: 5%), conjunctivitis (≤5%), keratoconjunctivitis (<5%)

Renal: Renal insufficiency (<5%)

Respiratory: Cough (≤7%), pharyngeal disease (metastatic colorectal cancer: 5%), asthma (<5%), bronchitis (<5%), bronchopneumonia (<5%), dyspnea (<5%), flu-like symptoms (<5%), hemoptysis (<5%), hoarseness (<5%), mass (chest; <5%), pneumonia (<5%), respiratory distress (<5%), epistaxis (≤3%), laryngitis (1%)

Miscellaneous: Radiation recall phenomenon (<5%)

Frequency not defined:

Cardiovascular: Angina pectoris, cardiac arrhythmia, cardiac failure, cardiomyopathy, ECG changes, ischemic heart disease, myocardial infarction

Gastrointestinal: Necrotizing enterocolitis

<1%, postmarketing, and/or case reports: Acute renal failure, bone marrow depression, cutaneous lupus erythematosus, diaphoresis, disorder of hemostatic components of blood, fibrosis, flu-like symptoms, hepatic failure, hypersensitivity reaction, keratitis, lacrimal stenosis, leukoencephalopathy, photophobia, Stevens-Johnson syndrome, swelling of eye, toxic epidermal necrolysis

Contraindications

Known hypersensitivity to capecitabine, fluorouracil, or any component of the formulation; severe renal impairment (CrCl <30 mL/minute)

Canadian labeling: Additional contraindications (not in the US labeling): Known complete absence of dihydropyrimidine dehydrogenase (DPD) activity; concomitant administration with sorivudine or chemically related analogues (eg, brivudine)

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Bone marrow suppression may occur, hematologic toxicity is more common when used in combination therapy.

• Cardiotoxicity: Cardiotoxicity has been observed with capecitabine, including myocardial infarction, ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, ECG changes, and cardiomyopathy. These adverse events may be more common in patients with a history of coronary artery disease. In a scientific statement from the American Heart Association, capecitabine has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate/major) (AHA [Page 2016]).

• Dermatologic toxicity: Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported (some fatal).

• Gastrointestinal toxicity: May cause diarrhea (may be severe); median time to first occurrence of grade 2 to 4 diarrhea was 34 days and median duration of grades 3 or 4 diarrhea was 5 days. Dehydration may occur rapidly in patients with diarrhea, nausea, vomiting, anorexia, and/or weakness; adequately hydrate prior to treatment initiation. Elderly patients may be at higher risk for dehydration. Necrotizing enterocolitis (typhlitis) has been reported.

• Hand-and-foot syndrome: May cause hand-and-foot syndrome (palmar-plantar erythrodysesthesia or chemotherapy-induced acral erythema); characterized by numbness, dysesthesia/paresthesia, tingling, painless or painful swelling, erythema, desquamation, blistering, and severe pain. The median onset is 79 days (range: 11 to 360 days). Persistent hand-and-foot syndrome (grade 2 and higher) could eventually lead to fingerprint loss.

• Hepatotoxicity: Grade 3 and 4 hyperbilirubinemia have been observed in patients with and without hepatic metastases at baseline (median onset: 64 days). Transaminase and alkaline phosphatase elevations have also been reported.

Disease-related concerns:

• Dihydropyrimidine dehydrogenase deficiency: Patients with certain homozygous or heterozygous mutations of the dihydropyrimidine dehydrogenase (DPD) enzyme are at increased risk for acute early-onset (potentially severe, life-threatening, or fatal) toxicity due to total or near total absence of DPD activity. Toxicity may include mucositis/stomatitis, diarrhea, neutropenia, and neurotoxicity. Patients with partial DPD activity are also at risk for severe, life-threatening, or fatal toxicity. May require therapy interruption, reduced doses, and/or permanent discontinuation, depending on the onset, duration, and severity of toxicity observed. No capecitabine dose has been shown to be safe in patients with complete DPD deficiency; data is insufficient to recommend a dose in patients with partial DPD activity.

• Renal impairment: Dehydration may occur, resulting in acute renal failure (may be fatal); concomitant use with nephrotoxic agents and baseline renal dysfunction may increase the risk.

Concurrent drug therapy issues:

• Fluorouracil/leucovorin (FU/LV): In patients with colorectal cancer, treatment with capecitabine immediately following 6 weeks of FU/LV therapy has been associated with an increased incidence of grade ≥3 toxicity, when compared to patients receiving the reverse sequence, capecitabine (two 3-week courses) followed by FU/LV (Hennig 2008).

• Proton pump inhibitors: Concomitant use of proton pump inhibitors and capecitabine may alter capecitabine dissolution and absorption due to higher gastric pH levels. Secondary analysis of a large phase III study comparing capecitabine and oxaliplatin with or without lapatinib for the treatment of gastroesophageal cancer showed decreased overall survival in patients who received concurrent proton pump inhibitors (Chu 2017). Consider avoiding proton pump inhibitors (if possible) in patients receiving capecitabine.

• Warfarin: Capecitabine may increase the anticoagulant effects of warfarin; bleeding events, including death, have occurred with concomitant use. Clinically significant increases in PT and INR have occurred within several days to months after capecitabine initiation (in patients previously stabilized on anticoagulants) and may continue up to 1 month after capecitabine discontinuation. May occur in patients with or without liver metastases. An increased risk of coagulopathy is correlated with a cancer diagnosis and age >60 years.

Special populations:

• Elderly: Use with caution in patients ≥60 years of age; the incidence of treatment-related adverse events may be higher.

Other warnings/precautions:

• Fluoropyrimidine overdose: Uridine triacetate (formerly called vistonuridine), has been studied in cases of fluoropyrimidine overdose. In a clinical study of 98 patients who received uridine triacetate for fluorouracil toxicity (due to overdose, accidental capecitabine ingestion, or possible DPD deficiency), 96 patients recovered fully (Bamat 2013). Of 17 patients receiving uridine triacetate beginning within 8 to 96 hours after fluorouracil overdose, all patients fully recovered (von Borstel 2009). An additional case report describes accidental capecitabine ingestion by a 22-month-old child; uridine triacetate was initiated approximately 7 hours after exposure. The patient received uridine triacetate every 6 hours for a total of 20 doses through nasogastric tube administration; he was asymptomatic throughout his course and was discharged with normal laboratory values (Kanie 2011). Refer to Uridine Triacetate monograph.

Metabolism/Transport Effects

Inhibits CYP2C9 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Allopurinol: May decrease serum concentrations of the active metabolite(s) of Fluorouracil Products. Risk X: Avoid combination

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine [INT]: May enhance the adverse/toxic effect of Fluorouracil Products. Risk X: Avoid combination

Cedazuridine: May increase the serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

CloZAPine: Fluorouracil Products may enhance the myelosuppressive effect of CloZAPine. CloZAPine may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA vaccine at least 28 days after the primary vaccine dose. Patients should also receive 2 booster doses of mRNA vaccine - one 2 months after the 2nd (additional) dose and another 4 months after the first booster dose. Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series, and a booster dose 3 months after the 3rd dose in the primary series, to patients taking immunosuppressive medications. Patients 12 years of age and older should also receive a 2nd booster 4 months after the first booster. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Fexinidazole: Fluorouracil Products may enhance the myelosuppressive effect of Fexinidazole. Fexinidazole may enhance the QTc-prolonging effect of Fluorouracil Products. Risk X: Avoid combination

Fluorouracil Products: May enhance the QTc-prolonging effect of other Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Folic Acid: May enhance the adverse/toxic effect of Fluorouracil Products. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: CYP2C9 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Gimeracil: May increase the serum concentration of Fluorouracil Products. Risk X: Avoid combination

Haloperidol: May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Capecitabine. Risk C: Monitor therapy

Interferons (Alfa): May increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Leucovorin Calcium-Levoleucovorin: May enhance the adverse/toxic effect of Fluorouracil Products. Risk C: Monitor therapy

Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

MetroNIDAZOLE (Systemic): May increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Ondansetron: May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification

Pentamidine (Systemic): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Antidepressants (Moderate Risk): Fluorouracil Products may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): Fluorouracil Products may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Telotristat Ethyl: May decrease serum concentrations of the active metabolite(s) of Capecitabine. Risk C: Monitor therapy

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Vitamin K Antagonists (eg, warfarin): Fluorouracil Products may increase the serum concentration of Vitamin K Antagonists. Management: Monitor INR and for signs/symptoms of bleeding closely when a fluorouracil product is combined with a vitamin K antagonist (eg, warfarin). Anticoagulant dose adjustment will likely be necessary. Risk D: Consider therapy modification

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Food Interactions

Food reduced the rate and extent of absorption of capecitabine. Management: Administer within 30 minutes after a meal.

Reproductive Considerations

Evaluate pregnancy status prior to therapy in patients who can become pregnant. Patients who can become pregnant should use effective contraception during treatment and for 6 months after the last dose. Patients with partners who can become pregnant should use effective contraception during treatment and for 3 months after the last dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to capecitabine may cause fetal harm.

Information related to the use of capecitabine in pregnancy is limited (Cardonick 2010; Castellanos 2020; Sharma 2016).

Breastfeeding Considerations

It is not known if capecitabine is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 2 weeks after the last dose. Other guidance suggests waiting at least 24 hours after the last dose of capecitabine and feeding with breast milk; however, actual recommendations should be individualized. Patients may maintain milk supply by expressing during treatment; however, milk supply is expected to be decreased by systemic chemotherapy (ABM [Johnson 2020]).

Monitoring Parameters

Renal function should be estimated at baseline to determine initial dose. During therapy, monitor CBC with differential, hepatic function, and renal function. Monitor INR closely if receiving concomitant warfarin. Evaluate pregnancy status prior to treatment initiation (in females of reproductive potential). Monitor for signs/symptoms of diarrhea, dehydration, hand-foot syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, stomatitis, and cardiotoxicity. Promptly evaluate any symptoms suggestive of cardiotoxicity. Consider monitoring ECG in patients on concomitant QT-prolonging medications. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Capecitabine is a prodrug of fluorouracil. It undergoes hydrolysis in the liver and tissues to form fluorouracil which is the active moiety. Fluorouracil is a fluorinated pyrimidine antimetabolite that inhibits thymidylate synthetase, blocking the methylation of deoxyuridylic acid to thymidylic acid, interfering with DNA, and to a lesser degree, RNA synthesis. Fluorouracil appears to be phase specific for the G1 and S phases of the cell cycle.

Pharmacokinetics

Absorption: Rapid and extensive (rate and extent reduced by food)

Protein binding: <60%; ~35% to albumin

Metabolism:

Hepatic: Inactive metabolites: 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine

Tissue: Enzymatically metabolized to fluorouracil, which is then metabolized to active metabolites, 5-fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-2’-deoxyuridine-5’-O-monophosphate (F-dUMP)

Half-life elimination: ~0.75 hour

Time to peak: 1.5 hours; Fluorouracil: 2 hours

Excretion: Urine (96%, 57% as α-fluoro-β-alanine; <3% as unchanged drug); feces (<3%)

Pharmacokinetics: Additional Considerations

Renal function impairment: In moderate to severe renal function impairment, there is increased exposure to inactive metabolites (FBAL and 5’-DFUR) and a 25% increase in exposure to capecitabine.

Hepatic function impairment: In mild to moderate hepatic dysfunction due to liver metastases, capecitabine AUC and Cmax increased 60%; 5-FU was not affected. The effect of severe hepatic dysfunction is not known.

Geriatric: In a study of patients ranging from ages 27 to 86 years, age had no significant influence on the pharmacokinetics of 5’-DFUR, 5-FU; a 20% increase in age resulted in a 15% increase in the AUC of alpha-fluoro-beta-alanine (FBAL).

Race: 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 compared to White patients (n = 22). Japanese patients had also about 25% lower Cmax and 34% lower AUC for alpha-fluoro-beta-alanine than White patients, although the clinical significance of these differences is unknown.

Pricing: US

Tablets (Capecitabine Oral)

150 mg (per each): $3.30 - $14.63

500 mg (per each): $6.50 - $48.75

Tablets (Xeloda Oral)

150 mg (per each): $16.27

500 mg (per each): $54.22

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Aceda (LB);
  • Actabi (PL);
  • Ai Bin (CN);
  • Arxeda (RO);
  • Binoda (PL);
  • Capebina (VN);
  • Capecitabina (PE);
  • Capecite (IN);
  • Capectan (AR);
  • Capeda (LB, TW);
  • Capefas (CL);
  • Capeoda (IT);
  • Capetero (SG);
  • Capexa (ZA);
  • Capibine (IN);
  • Capit (LK);
  • Caprcel (AT);
  • Captabine (BD, LK);
  • Capvex (PH);
  • Catacibin (PH);
  • Categor (AR, CL);
  • Caxeta (IN, LK, PH);
  • Coloxet (CZ, HU, NL, PL);
  • Ecansya (CZ, HR, MT);
  • Intacape (TH);
  • Kapeda (TR);
  • Kapetral (TW);
  • Naprocap (PH);
  • Pecaset (ZA);
  • Skemca (MX);
  • Skemka (MX);
  • Tutabin (RU);
  • Xelabine (AU);
  • Xelazor (GR);
  • Xelcip (ES);
  • Xelobig (KR);
  • Xelocan (KR);
  • Xelocitabine (AU);
  • Xeloda (AE, AR, AT, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CU, CY, CZ, DE, DO, EC, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, IE, IL, IS, IT, JM, JO, JP, KE, KR, KW, LB, LK, LR, LT, LU, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, PA, PH, PK, PL, PT, PY, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TW, UA, UG, UY, VE, VN, ZA, ZM, ZW);
  • Xeltabin (TR);
  • Xeltabine (PH, VN);
  • Xitabin (AR, BD, HK, LK)


For country abbreviations used in Lexicomp (show table)
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