Capetero Special Precautions

General: Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and hand-foot syndrome (hand-foot skin reaction, palmarplantar erythrodysesthesia). Most adverse events are reversible and do not require permanent discontinuation of therapy, although doses may have to be withheld or reduced (see Dosage & Administration).
Cardiotoxicity: Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, dysrhythmias, cardiogenic shock, sudden death and electrocardiographic changes. These adverse reactions may be more common in patients with a prior history of coronary artery disease. Cardiac arrhythmias, 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.
Rarely, unexpected, severe toxicity (e.g. stomatitis, diarrhea, neutropenia and neurotoxicity) associated with 5-FU has been attributed to a deficiency of dihydropyrimidine dehydrogenase (DPD) activity. A link between decreased levels of DPD and increased, potentially fatal toxic effects of 5-FU therefore cannot be excluded.
Capecitabine can induce severe skin reactions such as Stevens-Johnson syndrome and Toxic Epidermal Necrolysis (TEN), [see Adverse Reactions]. Capecitabine should be permanently discontinued in patients who experience a severe skin reaction possibly attributable to Capecitabine treatment.
Capecitabine can induce hand-foot syndrome (palmar-plantar erythrodysesthesia or chemotherapy-induced acral erythema), which is a cutaneous toxicity. For patients receiving Capecitabine monotherapy in the metastatic setting, the median time to onset was 79 days (range 11 to 360 days), with a severity range of Grades 1 to 3. Grade 1 hand-foot syndrome is defined by numbness, dysesthesia/paresthesia, tingling or erythema of the hands and/or feet and/or discomfort which does not disrupt normal activities. Grade 2 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 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, administration of Capecitabine should be interrupted until the event resolves or decreases in intensity to Grade 1. Following Grade 3 hand-foot syndrome, subsequent doses of Capecitabine should be decreased (see Dosage & Administration). When Capecitabine 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.
Capecitabine can induce hyperbilirubinemia. 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.
As this medicinal product contains anhydrous lactose as an excipient, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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. 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 (see Interactions).
Renal Impairment: Physicians should exercise caution when Capecitabine is administered to patients with impaired renal function. As seen with 5-FU the incidence of treatment-related Grade 3 or 4 adverse events was higher in patients with moderate renal impairment (creatinine clearance 30-50 ml/min) (see Dosage & Administration).
Hepatic Impairment: Patients with hepatic impairment should be carefully monitored when Capecitabine is administered. The effect of hepatic impairment not due to liver metastases or severe hepatic impairment on the disposition of Capecitabine is not known (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions and Dosage & Administration).
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.
Use in Elderly: Among patients with colorectal cancer aged 60-79 years receiving Capecitabine monotherapy in the metastatic setting, the incidence of gastrointestinal toxicity was similar to that in the overall population. In patients aged 80 years or older, a larger percentage experienced reversible Grade 3 or 4 gastrointestinal adverse events, such as diarrhea, nausea and vomiting (see Dosage & Administration). When Capecitabine was used in combination with other agents elderly patients (≥65 years) experienced more grade 3 and grade 4 ADRs and ADRs that led to discontinuation than younger patients. An analysis of safety data in patients equal to or greater than 60 years of age treated with Capecitabine plus docetaxel combination therapy showed an increase in the incidence of treatment-related Grade 3 and 4 adverse events, treatment-related serious adverse events and early withdrawals from treatment due to adverse events compared to patients less than 60 years of age.