Naprocap Special Precautions

General: Patients receiving therapy with Capecitabine should be monitored by a physician experienced in the use of cancer chemotherapeutic agents. Most adverse reactions are reversible and do not need to result in discontinuation, although doses may need to be withheld or reduced.
Diarrhea: Capecitabine can induce diarrhea, sometimes severe. Patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. If grade 2, 3 or 4 diarrheas occurs, administration of Capecitabine should be immediately interrupted until the diarrhea resolves or decreases in intensity to grade 1. Following are occurrence of grade 2 diarrheas or occurrence of any grade 3 or 4 diarrhea, subsequent doses of Capecitabine should be decreased. Standard antidiarrheal treatments (e.g. loperamide) are recommended. Necrotizing enterocolitis (typhlitis) has been reported.
Coagulopathy: Patients receiving concomitant Capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely with great frequency and the anticoagulant dose should be adjusted accordingly.
Cardiotoxicity: The cardiotoxicity observed with Capecitabine includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. These adverse reactions may be more common in patients with a prior history of coronary artery disease.
Dihydropyrimidine Dehydrogenase Deficiency: Rarely, unexpected, severe toxicity (e.g. stomatitis, diarrhea, neutropenia and neurotoxicity) associated with 5-fluorouracil has been attributed to a deficiency of dihydropyrimidinedehydrogenase (DPD) activity. A link between decreased levels of DPD and increased, potentially fatal toxic effects of 5-fluorouracil therefore cannot be excluded.
Renal Insufficiency: Patients with moderate renal impairment at baseline require dose reduction. Patients with mild and moderate renal impairment at baseline should be carefully monitored for adverse reactions. Prompt interruption of therapy with subsequent dose adjustments is recommended if a patient develops a grade 2 to 4 adverse event outlined in Table 2.
Hand-and-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 from 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 which does not disrupt normal activities.
Grade 2 hand-and-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-and-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-and-foot syndrome occurs, administration of Capecitabine should be interrupted until the event resolves or decreases in intensity to grade 1. Following grade 3 hand-and-foot syndrome, subsequent doses of Capecitabine should be decreased.
Hyperbilirubinemia: Patients with either metastatic breast or colorectal cancer who received at least one dose of Capecitabine 1250 mg/m² twice daily as monotherapy for 2 weeks followed by a 1-week rest period, grade 3 (1.5-3×ULN) and grade 4 (>3×ULN) Hyperbilirubinemia have been reported some of patients. Patients who had hepatic metastases at baseline and those who were without hepatic metastases, grade 3 or 4 Hyperbilirubinemia have been reported in some patients.
Some patients also had postbaseline elevations (grades 1 to 4 without elevations at baseline) in alkaline phosphatase and had postbaseline elevations in transaminases at any time (not necessarily concurrent). The majority of these patients, had liver metastases at baseline. In addition, some patients had elevations (grades 1 to 4) at both prebaseline and postbaseline in alkaline phosphatase or transaminases, respectively. Few patients had grade 3 or 4 elevations in alkaline phosphatase or transaminases. If drug-related grade 3 to 4 elevations in bilirubin occur, administration of Capecitabine should be immediately interrupted until the hyperbilirubinemia decreases to ≤3.0 X ULN.
Hematologic: In 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, may have grade 3 or 4 neutropenia, thrombocytopenia or decreases in hemoglobin. In patients with metastatic breast cancer who received a dose of Capecitabine in combination with docetaxel, may show grade 3 or 4 neutropenia, grade 3 or 4 thrombocytopenia, and grade 3 or 4 anemia.
Patients with baseline neutrophil counts of <1.5×10⁹/L and/or thrombocyte counts of <100×10⁹/L should not be treated with Capecitabine. If unscheduled laboratory assessments during a treatment cycle show grade 3 or 4 hematologic toxicity, treatment with Capecitabine should be interrupted.
Hepatic Insufficiency: Patients with mild to moderate hepatic dysfunction due to liver metastases should be carefully monitored when Capecitabine is administered. The effect of severe hepatic dysfunction on the disposition of Capecitabine is not known.
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation for further information.
Use in Children: The safety and effectiveness of Capecitabine tablets in persons <18 years of age have not been established.