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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 GradesGrade 3/4All GradesGrade 3/4
Gastrointestinal Disorders
  Diarrhea47126514
  Nausea342472
  Stomatitis2226014
  Vomiting152212
  Abdominal Pain143162
  Constipation9-11<1
  Upper Abdominal Pain7<17<1
  Dyspepsia6<15-
Skin and Subcutaneous Tissue Disorders
  Hand-and-Foot Syndrome60179<1
  Alopecia6-22<1
  Rash7-8-
  Erythema615<1
General Disorders and Administration Site Conditions
  Fatigue16<1161
  Pyrexia7<19<1
  Asthenia10<1101
  Lethargy10<19<1
Nervous System Disorders
  Dizziness6<16-
  Headache5<16<1
  Dysgeusia6-9-
Metabolism and Nutrition Disorders
  Anorexia9<111<1
Eye Disorders
  Conjunctivitis5<16<1
Blood and Lymphatic System Disorders
  Neutropenia2<185
Respiratory Thoracic and Mediastinal Disorders
  Epistaxis2-5-
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 EventXELODA
(n=995)
IV 5-FU/LV
(n=974)
Grade 3/4 %Grade 3/4 %
  Increased ALAT (SGPT)1.60.6
  Increased calcium 1.10.7
  Decreased calcium2.32.2
  Decreased hemoglobin1.01.2
  Decreased lymphocytes13.013.0
  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.2.226.2
  Decreased neutrophils/granulocytes2.426.4
  Decreased platelets1.00.7
  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.206.3

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 EventXELODA
(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 9652994459
Body System/Adverse Event
GI
  Diarrhea5513261102
  Nausea434513<1
  Vomiting274<1304<1
  Stomatitis252<162141
  Abdominal Pain359<1315
  Gastrointestinal Motility Disorder10<17<1
  Constipation141<1171
  Oral Discomfort1010
  Upper GI Inflammatory Disorders8<1101
  Gastrointestinal Hemorrhage61<131
  Ileus641521
Skin and Subcutaneous
  Hand-and-Foot Syndrome5417NA61NA
  Dermatitis271261
  Skin Discoloration7<15
  Alopecia621<1
General
  Fatigue/Weakness424464
  Pyrexia181212
  Edema15191
  Pain121101
  Chest Pain6161<1
Neurological
  Peripheral Sensory Neuropathy104
  Headache1017
  DizzinessExcluding vertigo8<18<1
  Insomnia77
  Taste Disturbance6111<11
Metabolism
  Appetite Decreased263<1312<1
  Dehydration72<1831
Eye
  Eye Irritation1310<1
  Vision Abnormal52
Respiratory
  Dyspnea14110<11
  Cough7<118
  Pharyngeal Disorder55
  Epistaxis3<16
  Sore Throat26
Musculoskeletal
  Back Pain1029<1
  Arthralgia8161
Vascular
  Venous Thrombosis83<162
Psychiatric
  Mood Alteration56<1
  Depression54<1
Infections
  Viral5<15<1
Blood and Lymphatic
  Anemia802<1791<1
  Neutropenia131246813
Hepatobiliary
  Hyperbilirubinemia481851733

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 EventXELODA 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
%
– Not observed
NA = Not Applicable
Number of Patients With at Least One Adverse Event 9976.529.19757.631.8
Body System/Adverse Event
GI
  Diarrhea6714<1485<1
  Stomatitis6717<143 5
  Nausea457362
  Vomiting3541242
  Constipation20218
  Abdominal Pain30<3<1242
  Dyspepsia1481
  Dry Mouth6<15
Skin and Subcutaneous
  Hand-and-Foot Syndrome6324NA8 1NA
  Alopecia416427
  Nail Disorder14215
  Dermatitis8111
  Rash Erythematous9<15
  Nail Discoloration64 <1
  Onycholysis5151
  Pruritus4 5
General
  Pyrexia282342
  Asthenia264<1256
  Fatigue224276
  Weakness162112
  Pain in Limb13<1132
  Lethargy762
  Pain7<151
  Chest Pain (non-cardiac)4 <16 2
  Influenza-like Illness55
Neurological
  Taste Disturbance16<114<1
  Headache153152
  Paresthesia12<1161
  Dizziness128<1
  Insomnia810<1
  Peripheral Neuropathy6101
  Hypoaesthesia4 <1 8<1
Metabolism
  Anorexia13111<1
  Appetite Decreased105
  Weight Decreased75
  Dehydration1027<1<1
Eye
  Lacrimation Increased127<1
  Conjunctivitis54
  Eye Irritation51
Musculoskeletal
  Arthralgia152243
  Myalgia15 2 252
  Back Pain12<1113
  Bone Pain8<1102
Cardiac
  Edema33<234<31
Blood
  Neutropenic Fever1631321516
Respiratory
  Dyspnea142<1162
  Cough13122<1
  Sore Throat12211<1
  Epistaxis7<16
  Rhinorrhea53
  Pleural Effusion2 1 74
Infection
  Oral Candidiasis7<18<1
  Urinary Tract Infection6<14
  Upper Respiratory Tract4 51
Vascular
  Flushing55
  Lymphoedema3 <151
Psychiatric
  Depression551
Table 15 Percent of Patients With Laboratory Abnormalities Participating in the XELODA and Docetaxel Combination vs Docetaxel Monotherapy Study
Adverse EventXELODA 1250 mg/m2/bid
With Docetaxel
75 mg/m2/3 weeks
(n=251)
Docetaxel
100 mg/m2/3 weeks

(n=255)
Body System/Adverse EventTotal
%
Grade 3
%
Grade 4
%
Total
%
Grade 3
%
Grade 4
%
Hematologic
  Leukopenia913724884233
  Neutropenia/Granulocytopenia862049871066
  Thrombocytopenia41212312
  Anemia8073835<1
  Lymphocytopenia994841984440
Hepatobiliary
  Hyperbilirubinemia2072622

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 EventPhase 2 Trial in Stage IV Breast Cancer
(n=162)
Body System/Adverse EventTotal
%
Grade 3
%
Grade 4
%
– Not observed
NA = Not Applicable
GI
Diarrhea57123
Nausea534
Vomiting374
Stomatitis247
Abdominal Pain204
Constipation151
Dyspepsia8
Skin and Subcutaneous
Hand-and-Foot Syndrome5711NA
Dermatitis371
Nail Disorder7
General
Fatigue418
Pyrexia121
Pain in Limb61
Neurological
Paresthesia211
Headache91
Dizziness8
Insomnia8
Metabolism
Anorexia233
Dehydration741
Eye
Eye Irritation15
Musculoskeletal
Myalgia9
Cardiac
Edema91
Blood
Neutropenia2622
Thrombocytopenia2431
Anemia7231
Lymphopenia944415
Hepatobiliary
Hyperbilirubinemia2292

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: 2006-06-12

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