Information for Patients / Medical Professionals

Xeloda® (capecitabine)

• Full Prescribing Information including boxed WARNINGS
• Healthcare Provider Letters

  1 letter

  Alternative Packaging Configuration for XELODA® - March 2011
• Material Safety Data Sheet

Indication

XELODA is indicated as a single agent for adjuvant treatment in patients with Dukes’ C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. XELODA was non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS). Physicians should consider results of combination chemotherapy trials, which have shown improvement in DFS and OS, when prescribing single-agent XELODA in the adjuvant treatment of Dukes’ C colon cancer.

XELODA is indicated as first-line treatment of patients with metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. Combination chemotherapy has shown a survival benefit compared to 5-FU/LV alone. A survival benefit over 5-FU/LV has not been demonstrated with XELODA monotherapy. Use of XELODA instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage.

XELODA monotherapy is indicated for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated, e.g., patients who have received cumulative doses of 400 mg/m2 of doxorubicin or doxorubicin equivalents. Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen.

XELODA in combination with docetaxel is indicated for the treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing chemotherapy.

Important Safety Information and BOXED WARNINGS

Warfarin Interaction - Coagulopathy

• Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly.
• A clinically important XELODA-Warfarin drug interaction was demonstrated in a clinical pharmacology trial.
• Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.
• Postmarketing reports have shown clinically significant increases in prothrombin time (PT) and INR have been observed in patients who were stabilized on anticoagulants at the time

XELODA was introduced. These events occurred within several days and up to several months after initiating XELODA therapy, and in a few cases within 1 month after stopping XELODA.

These events occurred in patients with and without liver metastases.

• Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.
• XELODA is also contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency, or severe renal impairment. XELODA is contraindicated in patients with known hypersensitivity to capecitabine or to any of its components or to 5-fluorouracil.
• Additional serious adverse reactions include diarrhea, cardiotoxicity, hand-and-foot syndrome, and hyperbilirubinemia. XELODA can cause fetal harm. Advise women of the potential risk to the fetus. Do not treat patients with neutrophil counts <1.5 x 109/L or thrombocyte counts <100x 109/L
• The most common adverse reactions (≥30%) reported were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, including serious adverse reactions, have been reported.

Additional serious adverse reactions include diarrhea, cardiotoxicity, hand-and-foot syndrome, and hyperbilirubinemia. Xeloda can cause fetal harm. Advise women of the potential risk to the fetus. Do not treat patients with neutrophil counts <1.5 x 109/L or thrombocyte counts <100 x 109/L

Most Common Adverse Reactions

The most common adverse reactions (≥30%) were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, have been reported.

Important safety information – Monotherapy in Adjuvant Colon Cancer

In a phase 3 study of XELODA monotherapy in colon cancer in the adjuvant setting, serious adverse events (grade 3/4) occurring in ≥5% of patients receiving either XELODA or 5-FU/LV (%;%) were increase in bilirubin (20;6), hand-foot syndrome (17;<1), decrease in lymphocytes (13;13), diarrhea (12;14), decrease in neutrophils/granulocytes (2;26), stomatitis (2;14), and neutropenia (<1;5).

Important safety information – Monotherapy in MCRC

In two phase 3 trials of XELODA monotherapy in metastatic colorectal cancer, serious adverse events (grade 3/4) occurring in ≥5% of patients receiving either XELODA or 5-FU/LV (%;%) were hyperbilirubinemia (23;6), hand-foot syndrome (17;1), diarrhea (15;12), abdominal pain (<10;5), vomiting (<5;<5), ileus (5;3), stomatitis (<3;15), and neutropenia (3;21).

Important safety information – Monotherapy in MBC

In a single-arm study of XELODA monotherapy in metastatic breast cancer, serious adverse events (grade 3/4) occurring in ≥5% of patients receiving XELODA (%) were lymphopenia (59), diarrhea (15), hand-foot syndrome (11), hyperbilirubinemia (11), fatigue (8), stomatitis (7), and dehydration (5).

Important safety information – Combination Therapy with Docetaxel in MBC

In a phase 3 study of XELODA combination therapy (XELODA plus docetaxel) in metastatic breast cancer, serious adverse events (grade 3/4) occurring at a ≥2% higher incidence in patients receiving XELODA plus docetaxel vs. docetaxel alone (%;%) were lymphocytopenia (89;84), hand-foot syndrome (24;1), stomatitis (<18;5), diarrhea (<15;<6), anemia (10;<6), hyperbilirubinemia (9;4), nausea (7;2), vomiting (5;2), constipation (2;0), and nail disorder (2;0).

Important treatment considerations—Women of childbearing potential

XELODA may cause fetal harm when given to a pregnant woman. There are no adequate and well-controlled studies in pregnant women using XELODA. If the drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with XELODA.

For additional safety information, please see the full prescribing information, including BOXED WARNINGS at www.xeloda.com.