Xeltabine Warnings

Diarrhea: Capecitabine (Xeltabine) can induce diarrhea, sometimes severe. Patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. The median time to first occurrence of grade 2 to 4 diarrhea was 31 days (range from 1 to 322 days).
National Cancer Institute of Canada Common Toxicity Criteria (NCIC CTC) defines diarrhea grades as follows.
Grade 2: An increase of 4 to 6 stools/day or nocturnal stools.
Grade 3: An increase of 7 to 9 stools/day incontinence and malabsorption.
Grade 4: An increase of ≥10 stools/day or grossly bloody diarrhea or the need for parenteral support.
If grade 2, 3 or 4 diarrhea occurs, administration of Capecitabine (Xeltabine) should be immediately interrupted until the diarrhea resolves or decreases in intensity to grade 1. Following a reoccurrence of grade 2 diarrhea or occurrence of any grade 3 or 4 diarrhea, subsequent doses of Capecitabine (Xeltabine) should be decreased (see Dosage & Administration). Standard antidiarrheal treatments (eg, loperamide) are recommended. Necrotizing enterocolitis (typhlitis) has been reported.
Dehydration: Dehydration should be prevented or corrected at the onset. Patients with anorexia, asthenia, nausea, vomiting or diarrhoea may rapidly become dehydrated. If Grade 2 (or higher) dehydration occurs, Capecitabine (Xeltabine) treatment should be immediately interrupted and the dehydration corrected. Treatment should not be restarted until the patient is rehydrated and any precipitating causes have been corrected or controlled. Dose modifications applied should be applied for the precipitating adverse event as necessary.
Hand-foot syndrome: Grade 1 hand-foot syndrome is defined as numbness, dysesthesia/paresthesia, tingling, painless swelling or erythema of the hands and/or feet and/or discomfort which does not disrupt the patient's normal activities. Grade 2 hand-foot syndrome is painful erythema and swelling of the hands and/or feet and/or discomfort affecting the patient's activities of daily living. Grade 3 hand-foot syndrome is moist desquamation, ulceration, blistering and severe pain of the hands and/or feet and/or severe discomfort that causes the patient to be unable to work or perform activities of daily living. If grade 2 or 3 hand-foot syndrome occurs, administration of Capecitabine (Xeltabine) should be interrupted until the event resolves or decreases in intensity to grade 1. Following grade 3 hand-foot syndrome, subsequent doses of Capecitabine (Xeltabine) should be decreased. When Capecitabine (Xeltabine) and cisplatin are used in combination, the use of vitamin B6 (pyridoxine) is not advised for symptomatic or secondary prophylactic treatment of hand-foot syndrome, because of published reports that it may decrease the efficacy of cisplatin.
Cardiotoxicity: Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, arrhythmia, cardiogenic shock, dysrhythmias, cardioplegia, heart failure, sudden death and electrocardiographic changes. These adverse reactions may be more common in patients with a prior history of coronary artery disease. Cardiac arrhythmia, angina pectoris, myocardial infarction, heart failure and cardiomyopathy have been reported in patients receiving Capecitabine (Xeltabine). Caution must be exercised in patients with history of significant cardiac disease, arrhythmias and angina pectoris.
Hypo- or hypercalcaemia: Hypo- or hypercalcaemia has been reported during Capecitabine (Xeltabine) treatment. Caution must be exercised in patients with pre-existing hypo- or hypercalcaemia.
Central or peripheral nervous system disease: Caution must be exercised in patients with central or peripheral nervous system disease, e.g. brain metastasis or neuropathy.
Diabetes mellitus or electrolyte disturbances: Caution must be exercised in patients with diabetes mellitus or electrolyte disturbances, as these may be aggravated during Capecitabine (Xeltabine) treatment.
Coumarin-derivative anticoagulation: In a drug interaction study with single-dose warfarin administration, there was a significant increase in the mean AUC (+57%) of S-warfarin. These results suggest an interaction, probably due to an inhibition of the cytochrome P450 2C9 isoenzyme system by Capecitabine (Xeltabine). Patients receiving concomitant Capecitabine (Xeltabine) and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely and the anticoagulant dose adjusted accordingly.
Hepatic impairment: In the absence of safety and efficacy data in patients with hepatic impairment, Capecitabine (Xeltabine) use should be carefully monitored in patients with mild to moderate liver dysfunction, regardless of the presence or absence of liver metastasis. Administration of Capecitabine (Xeltabine) should be interrupted if treatment-related elevations in bilirubin of >3.0 x ULN or treatment-related elevations in hepatic aminotransferases (ALT, AST) of >2.5 x ULN occur. Treatment with Capecitabine (Xeltabine) monotherapy may be resumed when bilirubin decreases to ≤3.0 x ULN or hepatic aminotransferases decrease to ≤2.5 x ULN.
Renal impairment: The incidence of grade 3 or 4 adverse reactions in patients with moderate renal impairment (creatinine clearance 30-50 mL/min) is increased compared to the overall population.