Bdocin 500 Special Precautions

Dose-limiting toxicities: Dose-limiting toxicities include diarrhea, abdominal pain, nausea, stomatitis and hand-foot syndrome (hand-foot skin reaction, palmar-plantar erythrodysesthesia). Most adverse reactions are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced.
Diarrhea: Patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. Standard antidiarrheal treatments (e.g. loperamide) may be used. NCIC CTC grade 2 diarrhea is defined as an increase of 4 to 6 stools/day or nocturnal stools, grade 3 diarrhoea as an increase of 7 to 9 stools/day or incontinence and malabsorption. Grade 4 diarrhoea is an increase of ≥10 stools/day or grossly bloody diarrhoea or the need for parenteral support. Dose reduction should be applied as necessary.
Dehydration: Dehydration should be prevented or corrected at the onset. Patients with anorexia, asthenia, nausea, vomiting or diarrhea may rapidly become dehydrated. Dehydration may cause acute renal failure, especially in patients with pre-existing compromised renal function or when Capecitabine is given concomitantly with known nephrotoxic medicinal products. Acute renal failure secondary to dehydration might be potentially fatal. If grade 2 (or higher) dehydration occurs, Capecitabine 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 (also known as hand-foot skin reaction or palmar-plantar erythrodysesthesia or chemotherapy induced acral erythema): 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.
Cardiotoxicity: Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, dysrhythmias, cardiogenic shock, sudden death and electrocardiographic changes (including very rare cases of QT prolongation). These adverse reactions may be more common in patients with a prior history of coronary artery disease. Cardiac arrhythmias (including ventricular fibrillation, torsades de pointes, and bradycardia), angina pectoris, myocardial infarction, heart failure and cardiomyopathy have been reported in patients receiving Capecitabine. 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 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 treatment.
Coumarin-derivative anticoagulation: In an 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. Patients receiving concomitant Capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely and the anticoagulant dose adjusted accordingly.
Brivudine: Brivudine must not be administered concomitantly with Capecitabine. Fatal cases have been reported following this drug interaction. There must be at least a 4-week waiting period between end of treatment with brivudine and start of Capecitabine therapy. Treatment with brivudine can be started 24 hours after the last dose of Capecitabine. In the event of accidental administration of brivudine to patients being treated with Capecitabine, effective measures should be taken to reduce the toxicity of Capecitabine. Immediate admission to hospital is recommended. All measures should be initiated to prevent systemic infections and dehydration.
Dihydropyrimidine dehydrogenase (DPD) deficiency: Rarely, unexpected, severe toxicity (e.g. stomatitis, diarrhoea, mucosal inflammation, neutropenia and neurotoxicity) associated with 5-FU has been attributed to a deficiency of DPD activity.
Ophthalmologic complications: Patients should be carefully monitored for ophthalmological complications such as keratitis and corneal disorders, especially if they have a prior history of eye disorders. Treatment of eye disorders should be initiated as clinically appropriate.
Severe skin reactions: Capecitabine can induce severe skin reactions such as Stevens-Johnson syndrome and Toxic Epidermal Necrolysis. Capecitabine should be permanently discontinued in patients who experience a severe skin reaction during treatment.
Patients with Hepatic Impairment: Caution should be exercised when patients with mild to moderate hepatic dysfunction due to liver metastases are treated with Capecitabine.
In the absence of safety and efficacy data in patients with hepatic impairment, Capecitabine 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 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 monotherapy may be resumed when bilirubin decreases to ≤3.0 x ULN or hepatic aminotransferases decrease to ≤2.5 x ULN.
Patients with Renal Impairment: Patients with moderate (creatinine clearance=30 to 50 mL/min) and severe (creatinine clearance <30 mL/min) renal impairment showed higher exposure for Capecitabine, 5-FDUR, and FBAL than in those with normal renal function.
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.
Use in Children: The safety and effectiveness of Capecitabine in pediatrics have not been established.
Use in the Elderly: Geriatric population must be monitored for adverse effects of Capecitabine.