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Xeloda (Capecitabine) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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)
Adverse Event XELODA
(n=995)
IV 5-FU/LV
(n=974)
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 neutrophilsThe 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. 2.2 26.2
  Decreased neutrophils/granulocytes 2.4 26.4
  Decreased platelets 1.0 0.7
  Increased bilirubinIt 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. 20 6.3

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
Adverse Event XELODA
(n=596)
5-FU/LV
(n=593)
Total
%
Grade 3
%
Grade 4
%
Total
%
Grade 3
%
Grade 4
%
– Not observed
NA = Not Applicable
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
  DizzinessExcluding vertigo 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

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
Docetaxel
100 mg/m2/3 weeks
(n=251) (n=255)
Total
%
Grade 3
%
Grade 4
%
Total
%
Grade 3
%
Grade 4
%
– Not observed
NA = Not Applicable
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
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 Docetaxel
75 mg/m2/3 weeks
Docetaxel
100 mg/m2/3 weeks
(n=251) (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 Trial in Stage IV Breast Cancer
(n=162)
Body System/Adverse Event Total
%
Grade 3
%
Grade 4
%
– Not observed
NA = Not Applicable
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

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)

Postmarketing: hepatic failure, lacrimal duct stenosis



REPORTS OF SUSPECTED XELODA SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Xeloda. The information is not vetted and should not be considered as verified clinical evidence.

Possible Xeloda side effects / adverse reactions in 52 year old male

Reported by a physician from Germany on 2011-10-03

Patient: 52 year old male weighing 71.3 kg (156.9 pounds)

Reactions: Suture Rupture, Ileus, Wound Infection, Infectious Peritonitis

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Therapeutic Radiopharmaceuticals
    Indication: Rectal Cancer
    Start date: 2011-05-11
    End date: 2011-06-17

Oxaliplatin
    Start date: 2011-06-08
    End date: 2011-06-08

Oxaliplatin
    Indication: Rectal Cancer
    Start date: 2011-05-11
    End date: 2011-05-11

Xeloda
    Administration route: Oral
    Indication: Rectal Cancer
    Start date: 2011-05-11
    End date: 2011-06-17



Possible Xeloda side effects / adverse reactions in 71 year old female

Reported by a physician from United Kingdom on 2011-10-03

Patient: 71 year old female weighing 54.0 kg (118.8 pounds)

Reactions: Vomiting, Diarrhoea, Dehydration, Gastritis Erosive, Lower Gastrointestinal Haemorrhage, Device Related Infection, Gastrooesophageal Reflux Disease, Decreased Appetite

Adverse event resulted in: hospitalization

Suspect drug(s):
Eloxatin
    Indication: Rectal Cancer
    Start date: 2011-03-22
    End date: 2011-03-22

Eloxatin
    Start date: 2011-04-21
    End date: 2011-04-21

Xeloda
    Administration route: Oral
    Indication: Rectal Cancer
    Start date: 2011-03-28
    End date: 2011-04-26

Therapeutic Radiopharmaceuticals
    Dosage: 28 fractions of 1.8 gy, total dose 50.4 gy
    Indication: Rectal Cancer
    Start date: 2011-03-21
    End date: 2011-04-26

Other drugs received by patient: Multi-Vitamins; Mutaflor; Zofran; Lipid Emulsion; Smectite; Smectite; Zofran; Addel N ^baxter^; Sulfasalazine; Mutaflor



Possible Xeloda side effects / adverse reactions in 68 year old female

Reported by a consumer/non-health professional from United States on 2011-10-04

Patient: 68 year old female

Reactions: Vomiting, Diarrhoea, Dehydration, Electrolyte Imbalance

Adverse event resulted in: hospitalization

Suspect drug(s):
Xeloda
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-01-01
    End date: 2009-01-01

Tykerb
    Dosage: 5tab per day
    Administration route: Oral
    Indication: Breast Cancer
    Start date: 2009-01-01
    End date: 2009-01-01

Other drugs received by patient: Multi-Vitamin; Zofran; Coreg; Nexium; Coumadin



See index of all Xeloda side effect reports >>

Drug label data at the top of this Page last updated: 2010-05-20

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