Capecitabine Alvogen Special Precautions

Diarrhoea: Patients with severe diarrhoea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. Standard antidiarrhoeal treatments (e.g. loperamide) may be used. NCIC CTC grade 2 diarrhoea 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 (see Dosage & Administration).
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 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: Hand-and-foot syndrome (palmar-plantar erythrodysesthesia or chemotherapy-induced acral erythema) is a cutaneous toxicity. Median time to onset was 79 days (range, 11 to 360 days) with a severity range of grades 1 to 3 for patients receiving capecitabine monotherapy in the metastatic setting. Grade 1 is characterized by any of the following: numbness, dysesthesia/paresthesia, tingling, painless swelling or erythema of the hands and/or feet and/or discomfort that does not disrupt normal activities. Grade 2 hand- foot syndrome is defined as 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 defined as moist desquamation, ulceration, blistering or 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, interrupt administration of Capecitabine until the event resolves or decreases in intensity to grade 1. Following grade 3 handfoot syndrome, decrease subsequent doses of Capecitabine.
Cardiotoxicity: The cardiotoxicity observed with capecitabine includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes and cardiomyopathy. These adverse reaction may be more common in patients with a history of coronary artery disease.
Hematologic: In 875 patients with either metastatic breast or colorectal cancer who received a dose of 1250 mg/m2 administered twice daily as monotherapy for 2 weeks followed by a 1-week rest period, 3.2%, 1.7% and 2.4% of patients had grade 3 or 4 neutropenia, thrombocytopenia, or decreases in haemoglobin, respectively. In 251 patients with metastatic breast cancer who received a dose of capecitabine in combination with docetaxel, 68% had grade 3 or 4 neutropenia, 2.8% had grade 3 or 4 thrombocytopenia, and 9.6% had grade 3 or 4 anemia.
Renal function impairment: Patients with moderate renal impairment at baseline require dose reduction. Carefully monitor patients with mild and moderate renal impairment at baseline for adverse reactions. Prompt in interruption of therapy with subsequent dose adjustments is recommended if a patient develops a grade 2 to 4 adverse reaction. Once the adverse reaction has resolved or decreased in intensity to grade 1, then capecitabine therapy may be restarted at full dose or reduced by 25% for each subsequent appearance of grade 2 toxicity. With the fourth appearance of grade 2 toxicity, discontinue treatment permanently. Interrupt therapy with capecitabine upon the occurrence of a grade 3 adverse experience. Once the adverse reaction has resolved or decreased in intensity to grade 1, then capecitabine therapy may be restarted at 75% of starting dose or reduced by 25% for the second appearance of a grade 3 adverse experience. Discontinue treatment permanently at the third appearance. If a grade 4 experience occurs, discontinue therapy permanently or interrupt until resolved or decreased to grade 1, and then restart at 50% of the original dose if it is in the patient's best interest to continue. Doses of capecitabine omitted for toxicity are not replaced or restored; instead the patient should resume the planned treatment cycles.
Hepatic function impairment: Carefully monitor patients with mild to moderate hepatic dysfunction due to liver metastases when capecitabine is administered. The effect of severe hepatic dysfunction on the disposition of capecitabine is not known.
Use in Elderly: Patients 80 years of age or older may experience a greater incidence of grade 3 or 4 adverse reactions. In 875 patients with either metastatic breast of colorectal cancer who received capecitabine monotherapy, 62% of the 21 patients greater than or equal to 80 years of age treated with capecitabine experienced a treatment-related grade 3 or 4 adverse reaction: Diarrhea in 6 (28.6%), nausea in 3 (14.3%), hand and foot syndrome in 3 (14.3%) and vomiting in 2 (9.5%) patients. Among the 10 patients 70 years of age and older (no patients were older than 80 years of age) treated with capecitabine in combination with docetaxel, 30% (3 out 10) of patients experienced grade 3 or 4 diarrhea and stomatitis, and 40% (4 out of 10) experienced grade 3 hand and foot syndrome.
Effects on ability to drive and use machines: Capecitabine has minor or moderate influence on the ability to drive and use machines. Capecitabine may cause dizziness, fatigue and nausea.