Xeloda
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Xeloda
SIDE EFFECTS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adjuvant Colon Cancer
Table 4 shows the adverse reactions occurring in ≥ 5% of patients from one phase 3 trial in patients with Dukes' C colon cancer who received at least one dose of study medication and had at least one safety assessment. A total of 995 patients were treated with 1250 mg/m² twice a day of XELODA (capecitabine) administered for 2 weeks followed by a 1-week rest period, and 974 patients were administered 5-FU and leucovorin (20 mg/m² leucovorin IV followed by 425 mg/m² IV bolus 5-FU on days 1-5 every 28 days). The median duration of treatment was 164 days for capecitabine-treated patients and 145 days for 5-FU/LV-treated patients. A total of 112 (11%) and 73 (7%) capecitabine and 5-FU/LV-treated patients, respectively, discontinued treatment because of adverse reactions. A total of 18 deaths due to all causes occurred either on study or within 28 days of receiving study drug: 8 (0.8%) patients randomized to XELODA (capecitabine) and 10 (1.0%) randomized to 5-FU/LV.
Table 5 shows grade 3/4 laboratory abnormalities occurring in ≥ 1% of patients from one phase 3 trial in patients with Dukes' C colon cancer who received at least one dose of study medication and had at least one safety assessment.
Table 4 : Percent Incidence of Adverse Reactions Reported
in ≥ 5% of Patients Treated With XELODA (capecitabine) or 5-FU/LV for Colon Cancer in the
Adjuvant Setting (Safety Population)
| Body System/ Adverse Event | Adjuvant Treatment for Colon Cancer (N=1969) | |||
| XELODA (N=995) | 5-FU/LV (N=974) | |||
| All Grades | Grade 3/4 | All Grades | Grade 3/4 | |
| Gastrointestinal Disorders | ||||
| Diarrhea | 47 | 12 | 65 | 14 |
| Nausea | 34 | 2 | 47 | 2 |
| Stomatitis | 22 | 2 | 60 | 14 |
| Vomiting | 15 | 2 | 21 | 2 |
| Abdominal Pain | 14 | 3 | 16 | 2 |
| Constipation | 9 | - | 11 | < 1 |
| Upper Abdominal Pain | 7 | < 1 | 7 | < 1 |
| Dyspepsia | 6 | < 1 | 5 | - |
| Skin and Subcutaneous Tissue Disorders | ||||
| Hand-and-Foot | 60 | 17 | 9 | < 1 |
| Syndrome | ||||
| Alopecia | 6 | - | 22 | < 1 |
| Rash | 7 | - | 8 | - |
| Erythema | 6 | 1 | 5 | < 1 |
| General Disorders and Administration Site Conditions | ||||
| Fatigue | 16 | < 1 | 16 | 1 |
| Pyrexia | 7 | < 1 | 9 | < 1 |
| Asthenia | 10 | < 1 | 10 | 1 |
| Lethargy | 10 | < 1 | 9 | < 1 |
| Nervous System Disorders | ||||
| Dizziness | 6 | < 1 | 6 | - |
| Headache | 5 | < 1 | 6 | < 1 |
| Dysgeusia | 6 | - | 9 | - |
| Metabolism and Nutrition Disorders | ||||
| Anorexia | 9 | < 1 | 11 | < 1 |
| Eye Disorders | ||||
| Conjunctivitis | 5 | < 1 | 6 | < 1 |
| Blood and Lymphatic System Disorders | ||||
| Neutropenia | 2 | < 1 | 8 | 5 |
| Respiratory Thoracic and Mediastinal Disorders | ||||
| Epistaxis | 2 | - | 5 | - |
Table 5 : Percent Incidence of Grade 3/4 Laboratory Abnormalities
Reported in ≥ 1% of Patients Receiving XELODA (capecitabine) Monotherapy for Adjuvant Treatment
of Colon Cancer (Safety Population)
| Adverse Event | XELODA (n=995) Grade 3/4 % | IV 5-FU/LV (n=974) Grade 3/4 % |
| Increased ALAT (SGPT) | 1.6 | 0.6 |
| Increased calcium | 1.1 | 0.7 |
| Decreased calcium | 2.3 | 2.2 |
| Decreased hemoglobin | 1.0 | 1.2 |
| Decreased lymphocytes | 13.0 | 13.0 |
| Decreased neutrophils* | 2.2 | 26.2 |
| Decreased neutrophils/granulocytes | 2.4 | 26.4 |
| Decreased platelets | 1.0 | 0.7 |
| Increased bilirubin** | 20 | 6.3 |
| *The incidence of grade 3/4 white blood
cell abnormalities was 1.3% in the XELODA (capecitabine) arm and 4.9% in the IV 5-FU/LV
arm. **It should be noted that grading was according to NCIC CTC Version 1 (May, 1994). In the NCIC-CTC Version 1, hyperbilirubinemia grade 3 indicates a bilirubin value of 1.5 to 3.0 × upper limit of normal (ULN) range, and grade 4 a value of > 3.0 × ULN. The NCI CTC Version 2 and above define a grade 3 bilirubin value of > 3.0 to 10.0 × ULN, and grade 4 values > 10.0 × ULN. |
||
Metastatic Colorectal Cancer
Monotherapy
Table 6 shows the adverse reactions occurring in ≥ 5% of patients from pooling the two phase 3 trials in first line metastatic colorectal cancer. A total of 596 patients with metastatic colorectal cancer were treated with 1250 mg/m² twice a day of XELODA (capecitabine) administered for 2 weeks followed by a 1-week rest period, and 593 patients were administered 5-FU and leucovorin in the Mayo regimen (20 mg/m² leucovorin IV followed by 425 mg/m² IV bolus 5-FU, on days 1-5, every 28 days). In the pooled colorectal database the median duration of treatment was 139 days for capecitabine-treated patients and 140 days for 5-FU/LV-treated patients. A total of 78 (13%) and 63 (11%) capecitabine and 5-FU/LV-treated patients, respectively, discontinued treatment because of adverse reactions/intercurrent illness. A total of 82 deaths due to all causes occurred either on study or within 28 days of receiving study drug: 50 (8.4%) patients randomized to XELODA (capecitabine) and 32 (5.4%) randomized to 5-FU/LV.
Table 6 : Pooled Phase 3 Colorectal Trials: Percent Incidence
of Adverse Reactions in ≥ 5% of Patients
| Adverse Event | XELODA (n=596) | 5-FU/LV (n=593) | ||||
| Total % | Grade 3 % | Grade 4 % | Total % | Grade 3 % | Grade 4 % | |
| Number of Patients With > One Adverse Event | 96 | 52 | 9 | 94 | 45 | 9 |
| Body System/Adverse Event | ||||||
| GI | ||||||
| Diarrhea | 55 | 13 | 2 | 61 | 10 | 2 |
| Nausea | 43 | 4 | – | 51 | 3 | < 1 |
| Vomiting | 27 | 4 | < 1 | 30 | 4 | < 1 |
| Stomatitis | 25 | 2 | < 1 | 62 | 14 | 1 |
| Abdominal Pain | 35 | 9 | < 1 | 31 | 5 | – |
| Gastrointestinal Motility Disorder | 10 | < 1 | – | 7 | < 1 | – |
| Constipation | 14 | 1 | < 1 | 17 | 1 | – |
| Oral Discomfort | 10 | – | – | 10 | – | – |
| Upper GI Inflammatory Disorders | 8 | < 1 | – | 10 | 1 | – |
| Gastrointestinal Hemorrhage | 6 | 1 | < 1 | 3 | 1 | – |
| Ileus | 6 | 4 | 1 | 5 | 2 | 1 |
| Skin and Subcutaneous | ||||||
| Hand-and-Foot Syndrome | 54 | 17 | NA | 6 | 1 | NA |
| Dermatitis | 27 | 1 | – | 26 | 1 | – |
| Skin Discoloration | 7 | < 1 | – | 5 | – | – |
| Alopecia | 6 | – | – | 21 | < 1 | – |
| General | ||||||
| Fatigue/Weakness | 42 | 4 | – | 46 | 4 | – |
| Pyrexia | 18 | 1 | – | 21 | 2 | – |
| Edema | 15 | 1 | – | 9 | 1 | – |
| Pain | 12 | 1 | – | 10 | 1 | – |
| Chest Pain | 6 | 1 | – | 6 | 1 | < 1 |
| Neurological | ||||||
| Peripheral Sensory Neuropathy | 10 | – | – | 4 | – | – |
| Headache | 10 | 1 | – | 7 | – | – |
| Dizziness* | 8 | < 1 | – | 8 | < 1 | – |
| Insomnia | 7 | – | – | 7 | – | – |
| Taste Disturbance | 6 | 1 | – | 11 | < 1 | 1 |
| Metabolism | ||||||
| Appetite Decreased | 26 | 3 | < 1 | 31 | 2 | < 1 |
| Dehydration | 7 | 2 | < 1 | 8 | 3 | 1 |
| Eye | ||||||
| Eye Irritation | 13 | – | – | 10 | < 1 | – |
| Vision Abnormal | 5 | – | – | 2 | – | – |
| Respiratory | ||||||
| Dyspnea | 14 | 1 | – | 10 | < 1 | 1 |
| Cough | 7 | < 1 | 1 | 8 | – | – |
| Pharyngeal Disorder | 5 | – | – | 5 | – | – |
| Epistaxis | 3 | < 1 | – | 6 | – | – |
| Sore Throat | 2 | – | – | 6 | – | – |
| Musculoskeletal | ||||||
| Back Pain | 10 | 2 | – | 9 | < 1 | – |
| Arthralgia | 8 | 1 | – | 6 | 1 | – |
| Vascular | ||||||
| Venous Thrombosis | 8 | 3 | < 1 | 6 | 2 | – |
| Psychiatric | ||||||
| Mood Alteration | 5 | – | – | 6 | < 1 | – |
| Depression | 5 | – | – | 4 | < 1 | – |
| Infections | ||||||
| Viral | 5 | < 1 | – | 5 | < 1 | – |
| Blood and Lymphatic | ||||||
| Anemia | 80 | 2 | < 1 | 79 | 1 | < 1 |
| Neutropenia | 13 | 1 | 2 | 46 | 8 | 13 |
| Hepatobiliary | ||||||
| Hyperbilirubinemia | 48 | 18 | 5 | 17 | 3 | 3 |
| – Not observed * Excluding vertigo NA = Not Applicable |
||||||
Breast Cancer
In Combination with Docetaxel
The following data are shown for the combination study with XELODA (capecitabine) and docetaxel in patients with metastatic breast cancer in Table 7 and Table 8. In the XELODA (capecitabine) and docetaxel combination arm the treatment was XELODA (capecitabine) administered orally 1250 mg/m² twice daily as intermittent therapy (2 weeks of treatment followed by 1 week without treatment) for at least 6 weeks and docetaxel administered as a 1-hour intravenous infusion at a dose of 75 mg/m² on the first day of each 3-week cycle for at least 6 weeks. In the monotherapy arm docetaxel was administered as a 1-hour intravenous infusion at a dose of 100 mg/m² on the first day of each 3-week cycle for at least 6 weeks. The mean duration of treatment was 129 days in the combination arm and 98 days in the monotherapy arm. A total of 66 patients (26%) in the combination arm and 49 (19%) in the monotherapy arm withdrew from the study because of adverse reactions. The percentage of patients requiring dose reductions due to adverse reactions was 65% in the combination arm and 36% in the monotherapy arm. The percentage of patients requiring treatment interruptions due to adverse reactions in the combination arm was 79%. Treatment interruptions were part of the dose modification scheme for the combination therapy arm but not for the docetaxel monotherapy-treated patients.
Table 7 : Percent Incidence of Adverse Events Considered
Related or Unrelated to Treatment in ≥ 5% of Patients Participating in the
XELODA (capecitabine) and Docetaxel Combination vs Docetaxel Monotherapy Study
| Adverse Event | XELODA 1250 mg/m²/bid With Docetaxel 75 mg/m²/ 3 weeks (n=251) | Docetaxel 100mg/m²/ 3weeks (n=255) | ||||
| Total % | Grade 3 % | Grade 4 % | Total % | Grade 3 % | Grade 4 % | |
| Number of Patients With at Least One Adverse Event | 99 | 76.5 | 29.1 | 97 | 57.6 | 31.8 |
| Body System/Adverse Event | ||||||
| GI | ||||||
| Diarrhea | 67 | 14 | < 1 | 48 | 5 | < 1 |
| Stomatitis | 67 | 17 | < 1 | 43 | 5 | – |
| Nausea | 45 | 7 | – | 36 | 2 | – |
| Vomiting | 35 | 4 | 1 | 24 | 2 | – |
| Constipation | 20 | 2 | – | 18 | – | – |
| Abdominal Pain | 30 | < 3 | < 1 | 24 | 2 | – |
| Dyspepsia | 14 | – | – | 8 | 1 | – |
| Dry Mouth | 6 | < 1 | – | 5 | – | – |
| Skin and Subcutaneous | ||||||
| Hand-and-Foot Syndrome | 63 | 24 | NA | 8 | 1 | NA |
| Alopecia | 41 | 6 | – | 42 | 7 | – |
| Nail Disorder | 14 | 2 | – | 15 | – | – |
| Dermatitis | 8 | – | – | 11 | 1 | – |
| Rash Erythematous | 9 | < 1 | – | 5 | – | – |
| Nail Discoloration | 6 | – | – | 4 | < 1 | – |
| Onycholysis | 5 | 1 | – | 5 | 1 | – |
| Pruritus | 4 | – | – | 5 | – | – |
| General | ||||||
| Pyrexia | 28 | 2 | – | 34 | 2 | – |
| Asthenia | 26 | 4 | < 1 | 25 | 6 | – |
| Fatigue | 22 | 4 | – | 27 | 6 | – |
| Weakness | 16 | 2 | – | 11 | 2 | – |
| Pain in Limb | 13 | < 1 | – | 13 | 2 | – |
| Lethargy | 7 | – | – | 6 | 2 | – |
| Pain | 7 | < 1 | – | 5 | 1 | – |
| Chest Pain (non-cardiac) | 4 | < 1 | – | 6 | 2 | – |
| Influenza-like Illness | 5 | – | – | 5 | – | – |
| Neurological | ||||||
| Taste Disturbance | 16 | < 1 | – | 14 | < 1 | – |
| Headache | 15 | 3 | – | 15 | 2 | – |
| Paresthesia | 12 | < 1 | – | 16 | 1 | – |
| Dizziness | 12 | – | – | 8 | < 1 | – |
| Insomnia | 8 | – | – | 10 | < 1 | – |
| Peripheral Neuropathy | 6 | – | – | 10 | 1 | – |
| Hypoaesthesia | 4 | < 1 | – | 8 | < 1 | – |
| Metabolism | ||||||
| Anorexia | 13 | 1 | – | 11 | < 1 | – |
| Appetite Decreased | 10 | – | – | 5 | – | – |
| Weight Decreased | 7 | – | – | 5 | – | – |
| Dehydration | 10 | 2 | – | 7 | < 1 | < 1 |
| Eye | ||||||
| Lacrimation Increased | 12 | – | – | 7 | < 1 | – |
| Conjunctivitis | 5 | – | – | 4 | – | – |
| Eye Irritation | 5 | – | – | 1 | – | – |
| Musculoskeletal | ||||||
| Arthralgia | 15 | 2 | – | 24 | 3 | – |
| Myalgia | 15 | 2 | – | 25 | 2 | – |
| Back Pain | 12 | < 1 | – | 11 | 3 | – |
| Bone Pain | 8 | < 1 | – | 10 | 2 | – |
| Cardiac | ||||||
| Edema | 33 | < 2 | – | 34 | < 3 | 1 |
| Blood | ||||||
| Neutropenic Fever | 16 | 3 | 13 | 21 | 5 | 16 |
| Respiratory | ||||||
| Dyspnea | 14 | 2 | < 1 | 16 | 2 | – |
| Cough | 13 | 1 | – | 22 | < 1 | – |
| Sore Throat | 12 | 2 | – | 11 | < 1 | – |
| Epistaxis | 7 | < 1 | – | 6 | – | – |
| Rhinorrhea | 5 | – | – | 3 | – | – |
| Pleural Effusion | 2 | 1 | – | 7 | 4 | – |
| Infection | ||||||
| Oral Candidiasis | 7 | < 1 | – | 8 | < 1 | – |
| Urinary Tract Infection | 6 | < 1 | – | 4 | – | – |
| Upper Respiratory Tract | 4 | – | – | 5 | 1 | – |
| Vascular | ||||||
| Flushing | 5 | – | – | 5 | – | – |
| Lymphoedema | 3 | < 1 | – | 5 | 1 | – |
| Psychiatric | ||||||
| Depression | 5 | – | – | 5 | 1 | – |
| – Not observed NA = Not Applicable |
||||||
Table 8 : Percent of Patients With Laboratory Abnormalities
Participating in the XELODA (capecitabine) and Docetaxel Combination vs Docetaxel Monotherapy
Study
| Adverse Event | XELODA (capecitabine) 1250 mg/m²/bid With Docetaxel
75 mg/m²/ 3 weeks (n=251) |
Docetaxel 100 mg/m²/ 3weeks (n=255) |
||||
| Body System/Adverse Event | Total % | Grade 3 % | Grade 4 % | Total % | Grade 3 % | Grade 4 % |
| Hematologic | ||||||
| Leukopenia | 91 | 37 | 24 | 88 | 42 | 33 |
| Neutropenia/Granulocytopenia | 86 | 20 | 49 | 87 | 10 | 66 |
| Thrombocytopenia | 41 | 2 | 1 | 23 | 1 | 2 |
| Anemia | 80 | 7 | 3 | 83 | 5 | < 1 |
| Lymphocytopenia | 99 | 48 | 41 | 98 | 44 | 40 |
| Hepatobiliary | ||||||
| Hyperbilirubinemia | 20 | 7 | 2 | 6 | 2 | 2 |
Monotherapy
The following data are shown for the study in stage IV breast cancer patients who received a dose of 1250 mg/m² administered twice daily for 2 weeks followed by a 1-week rest period. The mean duration of treatment was 114 days. A total of 13 out of 162 patients (8%) discontinued treatment because of adverse reactions/intercurrent illness.
Table 9 : Percent Incidence of Adverse Reactions Considered
Remotely, Possibly or Probably Related to Treatment in ≥ 5% of Patients Participating
in the Single Arm Trial in Stage IV Breast Cancer
| Adverse Event | Phase 2 Trial in Stage IV Breast Cancer (n=162) | ||
| Body System/Adverse Event | Total % | Grade 3 % | Grade 4 % |
| GI | |||
| Diarrhea | 57 | 12 | 3 |
| Nausea | 53 | 4 | – |
| Vomiting | 37 | 4 | – |
| Stomatitis | 24 | 7 | – |
| Abdominal Pain | 20 | 4 | – |
| Constipation | 15 | 1 | – |
| Dyspepsia | 8 | – | – |
| Skin and Subcutaneous | |||
| Hand-and-Foot Syndrome | 57 | 11 | NA |
| Dermatitis | 37 | 1 | – |
| Nail Disorder | 7 | – | – |
| General | |||
| Fatigue | 41 | 8 | – |
| Pyrexia | 12 | 1 | – |
| Pain in Limb | 6 | 1 | – |
| Neurological | |||
| Paresthesia | 21 | 1 | – |
| Headache | 9 | 1 | – |
| Dizziness | 8 | – | – |
| Insomnia | 8 | – | – |
| Metabolism | |||
| Anorexia | 23 | 3 | – |
| Dehydration | 7 | 4 | 1 |
| Eye | |||
| Eye Irritation | 15 | – | – |
| Musculoskeletal | |||
| Myalgia | 9 | – | – |
| Cardiac | |||
| Edema | 9 | 1 | – |
| Blood | |||
| Neutropenia | 26 | 2 | 2 |
| Thrombocytopenia | 24 | 3 | 1 |
| Anemia | 72 | 3 | 1 |
| Lymphopenia | 94 | 44 | 15 |
| Hepatobiliary | |||
| Hyperbilirubinemia | 22 | 9 | 2 |
| – Not observed NA = Not Applicable |
|||
Clinically Relevant Adverse Events in < 5% of Patients
Clinically relevant adverse events reported in < 5% of patients treated with XELODA (capecitabine) either as monotherapy or in combination with docetaxol that were considered at least remotely related to treatment are shown below; occurrences of each grade 3 and 4 adverse event are provided in parentheses.
Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer)
Gastrointestinal: abdominal distension, dysphagia, proctalgia, ascites (0.1%), gastric ulcer (0.1%), ileus (0.3%), toxic dilation of intestine, gastroenteritis (0.1%)
Skin & Subcutan.: nail disorder (0.1%), sweating increased (0.1%), photosensitivity reaction (0.1%), skin ulceration, pruritus, radiation recall syndrome (0.2%)
General: chest pain (0.2%), influenza-like illness, hot flushes, pain (0.1%), hoarseness, irritability, difficulty in walking, thirst, chest mass, collapse, fibrosis (0.1%), hemorrhage, edema, sedation
Neurological: insomnia, ataxia (0.5%), tremor, dysphasia, encephalopathy (0.1%), abnormal coordination, dysarthria, loss of consciousness (0.2%), impaired balance
Metabolism: increased weight, cachexia (0.4%), hypertriglyceridemia (0.1%), hypokalemia, hypomagnesemia
Eye: conjunctivitis
Respiratory: cough (0.1%), epistaxis (0.1%), asthma (0.2%), hemoptysis, respiratory distress (0.1%), dyspnea
Cardiac: tachycardia (0.1%), bradycardia, atrial fibrillation, ventricular extrasystoles, extrasystoles, myocarditis (0.1%), pericardial effusion
Infections: laryngitis (1.0%), bronchitis (0.2%), pneumonia (0.2%), bronchopneumonia (0.2%), keratoconjunctivitis, sepsis (0.3%), fungal infections (including candidiasis) (0.2%)
Musculoskeletal: myalgia, bone pain (0.1%), arthritis (0.1%), muscle weakness
Blood & Lymphatic: leukopenia (0.2%), coagulation disorder (0.1%), bone marrow depression (0.1%), idiopathic thrombocytopenia purpura (1.0%), pancytopenia (0.1%)
Vascular: hypotension (0.2%), hypertension (0.1%), lymphoedema (0.1%), pulmonary embolism (0.2%), cerebrovascular accident (0.1%)
Psychiatric: depression, confusion (0.1%)
Renal: renal impairment (0.6%)
Ear: vertigo
Hepatobiliary: hepatic fibrosis (0.1%), hepatitis (0.1%), cholestatic hepatitis (0.1%), abnormal liver function tests
Immune System: drug hypersensitivity (0.1%)
Postmarketing: hepatic failure, lacrimal duct stenosis
XELODA (capecitabine) In Combination With Docetaxel (Metastatic Breast Cancer)
Gastrointestinal: ileus (0.4%), necrotizing enterocolitis (0.4%), esophageal ulcer (0.4%), hemorrhagic diarrhea (0.8%)
Neurological: ataxia (0.4%), syncope (1.2%), taste loss (0.8%), polyneuropathy (0.4%), migraine (0.4%)
Cardiac: supraventricular tachycardia (0.4%)
Infection: neutropenic sepsis (2.4%), sepsis (0.4%), bronchopneumonia (0.4%)
Blood & Lymphatic: agranulocytosis (0.4%), prothrombin decreased (0.4%)
Vascular: hypotension (1.2%), venous phlebitis and thrombophlebitis (0.4%), postural hypotension (0.8%)
Renal: renal failure (0.4%)
Hepatobiliary: jaundice (0.4%), abnormal liver function tests (0.4%), hepatic failure (0.4%), hepatic coma (0.4%), hepatotoxicity (0.4%)
Immune System: hypersensitivity (1.2%)
Read the Xeloda (capecitabine) Side Effects Center for a complete guide to possible side effects »
DRUG INTERACTIONS
Drug-Drug Interactions
Anticoagulants
Altered coagulation parameters and/or bleeding have been reported in patients taking XELODA (capecitabine) concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon [see BOXED WARNING]. These events occurred within several days and up to several months after initiating XELODA (capecitabine) therapy and, in a few cases, within 1 month after stopping XELODA (capecitabine) . These events occurred in patients with and without liver metastases. In a drug interaction study with single-dose warfarin administration, there was a significant increase in the mean AUC of S-warfarin [see CLINICAL PHARMACOLOGY]. The maximum observed INR value increased by 91%. This interaction is probably due to an inhibition of cytochrome P450 2C9 by capecitabine and/or its metabolites.
Phenytoin
The level of phenytoin should be carefully monitored in patients taking XELODA (capecitabine) and phenytoin dose may need to be reduced [see DOSAGE AND ADMINISTRATION]. Postmarketing reports indicate that some patients receiving XELODA (capecitabine) and phenytoin had toxicity associated with elevated phenytoin levels. Formal drug-drug interaction studies with phenytoin have not been conducted, but the mechanism of interaction is presumed to be inhibition of the CYP2C9 isoenzyme by capecitabine and/or its metabolites.
Leucovorin
The concentration of 5-fluorouracil is increased and its toxicity may be enhanced by leucovorin. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil.
CYP2C9 substrates
Other than warfarin, no formal drug-drug interaction studies between XELODA (capecitabine) and other CYP2C9 substrates have been conducted. Care should be exercised when XELODA (capecitabine) is coadministered with CYP2C9 substrates.
Drug-Food Interaction
Food was shown to reduce both the rate and extent of absorption of capecitabine [see CLINICAL PHARMACOLOGY]. In all clinical trials, patients were instructed to administer XELODA (capecitabine) within 30 minutes after a meal. It is recommended that XELODA be administered with food [see DOSAGE AND ADMINISTRATION].
Last reviewed on RxList: 4/6/2011
This monograph has been modified to include the generic and brand name in many instances.
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