Xeloda
SIDE EFFECTS
Adjuvant Colon Cancer
Table 11 shows the adverse events 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 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 events. 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 and 10 (1.0%) randomized to 5-FU/LV.
Table 12 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 11: Percent Incidence of Adverse Events Reported in
≥ 5% of Patients Treated With XELODA or 5-FU/LV for Colon Cancer in the Adjuvant
Setting (Safety Population)
| Adjuvant Treatment for Colon Cancer (N=1969) | ||||
| XELODA (N=995) |
5-FU/LV (N=974) |
|||
| Body System/Adverse Event | 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 Syndrome | 60 | 17 | 9 | <1 |
| 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 12: Percent Incidence of Grade 3/4 Laboratory Abnormalities
Reported in ≥ 1% of Patients Receiving XELODA Monotherapy for Adjuvant Treatment
of Colon Cancer (Safety Population)
| XELODA (n=995) |
IV 5-FU/LV (n=974) |
|
| Adverse Event | Grade 3/4 % | 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 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 abilirubin value of 1.5 to3.0 × upper limit of normal (ULN) range, and grade 4 a value of > 3.0 × ULN. The NCI CTC Version 2 andabove define a grade 3 bilirubin value of >3.0 to 10.0 × ULN, and grade 4 values >10.0 × ULN. |
||
Metastatic Colorectal Cancer
Table 13 shows the adverse events 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 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 events/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 and 32 (5.4%) randomized to 5-FU/LV.
Table 13: Pooled Phase 3 Colorectal Trials: Percent Incidence
of Adverse Events in ≥ 5% of Patients Breast Cancer Combination
| 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 Combination
The following data are shown for the combination study with XELODA and docetaxel in patients with metastatic breast cancer in Table 14 and Table 15. In the XELODA and docetaxel combination arm the treatment was XELODA 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 events. The percentage of patients requiring dose reductions due to adverse events was 65% in the combination arm and 36% in the monotherapy arm. The percentage of patients requiring treatment interruptions due to adverse events 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 14: Percent Incidence of Adverse Events Considered
Related or Unrelated to Treatment in ≥ 5% of Patients Participating in the
XELODA and Docetaxel Combination vs Docetaxel Monotherapy Study
| Adverse Event | XELODA 1250 mg/m2/bid With Docetaxel
75 mg/m2/3 weeks (n=251) |
Docetaxel 100 mg/m2/3 weeks (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 15: Percent of Patients With Laboratory Abnormalities
Participating in the XELODA and Docetaxel Combination vs Docetaxel Monotherapy
Study
| Adverse Event | XELODA 1250 mg/m2/bid With Docetaxe l75 mg/m2/3 weeks (n=251) | Docetaxel 100 mg/m2/3 weeks (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 |
Breast Cancer XELODA 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 events/intercurrent illness.
Table 16: Percent Incidence of Adverse Events 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 Trialin 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 |
|||
XELODA and Docetaxel in Combination
Shown below by body system are the clinically relevant adverse events in < 5% of patients in the overall clinical trial safety database of 251 patients (Study Details) reported as related to the administration of XELODA in combination with docetaxel and that were clinically at least remotely relevant. In parentheses is the incidence of grade 3 and 4 occurrences of each adverse event.
It is anticipated that the same types of adverse events observed in the XELODA monotherapy studies may be observed in patients treated with the combination of XELODA plus docetaxel.
Gastrointestinal: ileus (0.39), necrotizing enterocolitis (0.39), esophageal ulcer (0.39), hemorrhagic diarrhea (0.80)
Neurological: ataxia (0.39), syncope (1.20), taste loss (0.80), polyneuropathy (0.39), migraine (0.39)
Cardiac: supraventricular tachycardia (0.39)
Infection: neutropenic sepsis (2.39), sepsis (0.39), bronchopneumonia (0.39) Blood and Lymphatic: agranulocytosis (0.39), prothrombin decreased (0.39)
Vascular: hypotension (1.20), venous phlebitis and thrombophlebitis (0.39), postural hypotension (0.80)
Renal: renal failure (0.39)
Hepatobiliary: jaundice (0.39), abnormal liver function tests (0.39), hepatic failure (0.39), hepatic coma (0.39), hepatotoxicity (0.39)
Immune System: hypersensitivity (1.20)
XELODA Monotherapy Metastatic Breast and Colorectal Cancer
Shown below by body system are the clinically relevant adverse events in < 5% of patients in the overall clinical trial safety database of 875 patients (phase 3 colorectal studies — 596 patients, phase 2 colorectal study — 34 patients, phase 2 breast cancer studies — 245 patients) reported as related to the administration of XELODA and that were clinically at least remotely relevant. In parentheses is the incidence of grade 3 or 4 occurrences of each adverse event.
Gastrointestinal: abdominal distension, dysphagia, proctalgia, ascites (0.1), gastric ulcer (0.1), ileus (0.3), toxic dilation of intestine, gastroenteritis (0.1)
Skin and Subcutaneous: 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 and 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)
DRUG INTERACTIONS
Drug-Food Interaction
In all clinical trials, patients were instructed to administer XELODA within 30 minutes after a meal. Since current safety and efficacy data are based upon administration with food, it is recommended that XELODA be administered with food (see DOSAGE AND ADMINISTRATION).
Drug-Drug Interactions
Antacid
The effect of an aluminum hydroxide- and magnesium hydroxide-containing antacid (Maalox) on the pharmacokinetics of XELODA was investigated in 12 cancer patients. There was a small increase in plasma concentrations of XELODA and one metabolite (5'-DFCR); there was no effect on the 3 major metabolites (5'-DFUR, 5-FU and FBAL).
Anticoagulants
Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely with great frequency and the anticoagulant dose should be adjusted accordingly (see BOXED WARNING and CLINICAL PHARMACOLOGY). Altered coagulation parameters and/or bleeding have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. 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. In a drug interaction study with single-dose warfarin administration, there was a significant increase in the mean AUC of S-warfarin. 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 (see CLINICAL PHARMACOLOGY).
CYP2C9 substrates
Other than warfarin, no formal drug-drug interaction studies between XELODA and other CYP2C9 substrates have been conducted. Care should be exercised when XELODA is coadministered with CYP2C9 substrates.
Phenytoin
The level of phenytoin should be carefully monitored in patients taking XELODA and phenytoin dose may need to be reduced (see DOSAGE AND ADMINISTRATION: Dose Management Guidelines). Postmarketing reports indicate that some patients receiving XELODA 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 (see PRECAUTIONS: Drug-Drug Interactions: Anticoagulants).
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.
Generic Name: Capecitabine
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Cancer
Get the latest treatment options.
Cancer and Exercise
Resting to conserve energy may not be the best remedy for fatigue during radiation therapy. See more WebMD Videos »
Xeloda
Health Resources
2008 Election & Health Care on WebMD. Get Informed.
Updated & New
RxList does not provide medical advice, diagnosis or treatment.