Capiibine Adverse Reactions

Summary of the safety profile: The safety profiles of capecitabine monotherapy for the metastatic breast cancer, metastatic colorectal cancer and adjuvant colon cancer populations are comparable.
The most commonly reported and/or clinically relevant treatment-related adverse drug reactions (ADRs) were gastrointestinal disorders (especially diarrhoea, nausea, vomiting, abdominal pain, stomatitis), hand-foot syndrome (palmar-plantar erythrodysesthesia), fatigue, asthenia, anorexia, cardiotoxicity, increased renal dysfunction on those with preexisting compromised renal function, and thrombosis/embolism.
Tabulated list of adverse reactions: ADRs considered to be possibly, probably, or remotely related to the administration of capecitabine are listed in table 7 for capecitabine given as monotherapy and in table 8 for capecitabine given in combination with different chemotherapy regimens in multiple indications. The following headings are used to rank the ADRs by frequency: very common, common, uncommon, rare, very rare. Within each frequency grouping, ADRs are presented in order of decreasing seriousness.
Capecitabine Monotherapy: (See Table 7.)

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Capecitabine in Combination therapy: (See Table 8.)

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Description of selected adverse reactions: Hand-foot syndrome: For the capecitabine dose of 1250 mg/m² twice daily on days 1 to 14 every 3 weeks, a frequency of 53% to 60% of all-grades HFS was observed in capecitabine monotherapy and a frequency of 63% was observed in the capecitabine/docetaxel for the treatment of metastatic breast cancer. For the capecitabine dose of 1000 mg/m² twice daily on days 1 to 14 every 3 weeks, a frequency of 22% to 30% of all-grade HFS was observed in capecitabine combination therapy.
The following covariates were statistically significantly associated with an increased risk of developing HFS: increasing capecitabine starting dose (gram), decreasing cumulative capecitabine dose (0.1*kg), increasing relative dose intensity in the first six weeks, increasing duration of study treatment (weeks), increasing age (by 10 year increments), female gender, and good ECOG performance status at baseline (0 versus ≥1).
Diarrhoea: Capecitabine can induce the occurrence of diarrhoea, which has been observed in patients.
The following covariates were statistically significantly associated with an increased risk of developing diarrhoea: increasing capecitabine starting dose (gram), increasing duration of study treatment (weeks), increasing age (by 10 year increments), and female gender. The following covariates were statistically significantly associated with a decreased risk of developing diarrhoea: increasing cumulative capecitabine dose (0.1*kg) and increasing relative dose intensity in the first six weeks.
Cardiotoxicity: In addition to the ADRs described in tables 7 and 8, the following ADRs were associated with the use of capecitabine monotherapy: cardiomyopathy, cardiac failure, sudden death, and ventricular extrasystoles.
Encephalopathy: In addition to the ADRs described in tables 7 and 8, encephalopathy was also associated with the use of capecitabine monotherapy.
Exposure to crushed or cut capecitabine tablets: In the instance of exposure to crushed or cut capecitabine tablets, the following adverse drug reactions have been reported: eye irritation, eye swelling, skin rash, headache, paresthesia, diarrhoea, nausea, gastric irritation, and vomiting.
Special populations: Elderly patients: It has been shown an increase in the incidence of treatment-related grade 3 and 4 adverse reactions and treatment-related serious adverse reactions in patients ≥60 years of age compared to patients <60 years of age. Patients ≥60 years of age treated with capecitabine plus docetaxel also had more early withdrawals from treatment due to adverse reactions compared to patients <60 years of age.
Further, with increasing age (by 10 year increments), it was statistically significantly associated with an increased risk of developing HFS and diarrhoea and with a decreased risk of developing neutropenia.
Gender: Female gender was statistically significantly associated with an increased risk of developing HFS and diarrhoea and with a decreased risk of developing neutropenia.
Patients with renal impairment: It has been shown an increase in the incidence of treatment-related grade 3 and 4 adverse reactions compared to patients with normal renal function. Patients with moderately impaired renal function show an increased rate of dose reduction and patients with no or mild renal impairment and an increase in early withdrawals from treatment and in patients with no or mild renal impairment.