Caxeta Special Precautions

The spectrum of cardiotoxicity observed with capecitabine is similar to that of other fluorinated pyrimidines. This includes myocardial infarction, angina, dysrhythmias, cardiac arrest, cardiac failure, and electrocardiographic changes. These ADRs may be more common in patients with a prior history of coronary artery disease.
Capecitabine can induce hand-foot syndrome (palmar-plantar erythrodysesthesia or chemo-therapy-induced acral erythema) which is a cutaneous toxicity. Persistent or severe hand-foot syndrome (grade 2 and above) can eventually lead to loss of fingerprints, which could impact patient identification. 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 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 RECOMMENDED DOSE under Dosage & Administration). When capecitabine and cisplatin are used in combination, use of vitamin B6 (pyridoxine) is not advised for the symptomatic or secondary prophylactic treatment of hand-foot syndrome, because of published reports that it may decrease the efficacy of cisplatin. There is some evidence that dexpanthenol is effective for hand-foot syndrome prophylaxis in patients treated with capecitabine.
Capecitabine can induce hyperbilirubinemia. Administration of capecitabine should be interrupted if treatment-related elevations in bilirubin of >3.0x ULN or treatment-related elevations in hepatic aminotransferases (ALT, AST) of >2.5x ULN occur. Treatment may be resumed when bilirubin decreases to ≤3.0x ULN or hepatic aminotransferases decrease to ≤ 2.5x ULN.
Care should be exercised when capecitabine is co-administered with drugs, which are metabolized by cytochrome P450 2C9 such as for example warfarin or phenytoin. 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. Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations (see INTERACTIONS).
General: Patients treated with capecitabine should be carefully monitored for toxicity. Most ADRs are reversible and do not require permanent discontinuation of therapy, although doses may have to be withheld or reduced (see RECOMMENDED DOSE under Dosage & Administration).
Drug abuse and dependence: Not applicable.
Ability to drive and use machines: Capecitabine has moderate influence on the ability to drive and use machines. Patients should be advised to use caution when driving or using machines if they experience ADRS such as dizziness, fatigue, and or nausea during treatment with capecitabine (see ADVERSE REACTIONS).