Xeltabine Special Precautions

The drug should be administered with caution in the following patients: In patients with severe renal impairment; In patients hepatic insufficiency; In patients with history of Hypo- or hypercalcaemia; In patients with history of central or peripheral nervous system disease, e.g. brain metastasis or neuropathy; Patients with history of diabetes mellitus or electrolyte disturbances; Elderly patients (see Elderly under Dosage & Administration); Patients with history of coronary disease (myocardiopathy can be occurred); Patients with myelosuppression ( myelosuppression can be aggaravated); Patients with gastrointestinal tract ulcer or gastrointestinal tract bleeding.
General: Capecitabine (Xeltabine) should only be prescribed by a qualified physician experienced in the utilisation of anti-neoplastic agents. Most adverse reactions are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced. (See Dosage & Administration).
In clinical trial of Capecitabine (Xeltabine) in patients with metastatic colorectal cancer, a survival benefit over 5-FU/LV has not been demonstrated with Capecitabine (Xeltabine) monotherapy. Use of Capecitabine (Xeltabine) instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage.
A single agent for adjuvant treatment in patients with Stage III (Dukes' C) colon cancer who have undergone complete resection of the primary tumor: as adjuvant treatment for patients with stage III (Dukes' C) colon cancer who have undergone surgery, Capecitabine (Xeltabine) was approved by reason of being non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS); as adjuvant treatment for patients with stage III (Dukes' C) colon cancer who have undergone surgery, in the primary analysis for DFS in the ITT population, Capecitabine (Xeltabine) was shown to be significantly superior to 5-FU/LV. But after median observation time of 57 months, the analysis for the secondary endpoint of overall survival was not shown to be significant statistically.
Capecitabine (Xeltabine) monotherapy for gastric cancer is approved by reaction rate. And there is no trial result to prove clinical significance like improvement to symptoms or increase of overall survival.
Capecitabine (Xeltabine) is generally administrated in home, patients should be informed of available adverse reactions and what have to do in the case adverse reaction occurring. Patients should be carefully monitored for toxicity.
Hyperbilirubinemia: In 875 patients with either metastatic breast or colorectal cancer who received at least one dose of Capecitabine (Xeltabine) 1250 mg/m² twice daily as monotherapy for 2 weeks followed by a 1-week rest period, grade 3 (1.5-3 x ULN) hyperbilirubinemia occurred in 15.2% (n=133) of patients and grade 4 (>3 x ULN) hyperbilirubinemia occurred in 3.9% (n=34) of patients. Of 566 patients who had hepatic metastases at baseline and 309 patients without hepatic metastases at baseline, grade 3 or 4 hyperbilirubinemia occurred in 22.8% and 12.3%, respectively. Of the 167 patients with grade 3 or 4 hyperbilirubinemia, 18.6% (n=31) also had postbaseline elevations (grades 1 to 4, without elevations at baseline) in alkaline phophatase and 27.5% (n=46) had postbaseline elevations in transaminases at any time (not necessarily concurrent). The majority of these patients, 64.5% (n=20) and 71.7% (n=33), had liver metastases at baseline. In addition, 57.5% (n=96) and 35.3% (n=59) of the 167 patients had elevations (grades 1 to 4) at both prebaseline and postbaseline in alkaline phosphatase or transaminases, respectively. Only 7.8% (n=13) and 3.0% (n=5) had grade 3 or 4 elevations in alkaline phosphatase or transaminases.
In the 596 patients treated with Capecitabine (Xeltabine) as first-line therapy for metastatic colorectal cancer, the incidence of grade 3 or 4 hyperbilirubinemia was similar to the overall clinical trial safety database of Capecitabine (Xeltabine) monotherapy. The median time to onset for grade 3 or 4 hyperbilirubinemia in the colorectal cancer population was 64 days and median total bilirubin increased from 8 μm/L at baseline to 13 μm/L during treatment with Capecitabine (Xeltabine). Of the 136 colorectal cancer patients with grade 3 or 4 hyperbilirubinemia, 49 patients had grade 3 or 4 hyperbilirubinemia as their last measured value, of which 46 had liver metastases at baseline.
In 251 patients with metastatic breast cancer who received a combination of Capecitabine (Xeltabine) and docetaxel, grade 3 (1.5 to 3 x ULN) hyperbilirubinemia occurred in 7% (n=17) and grade 4 (>3 x ULN) hyperbilirubinemia occurred in 2% (n=5).
If drug-related grade 2 to 4 elevations in bilirubin occur, administration of Capecitabine (Xeltabine) should be immediately interrupted until the hyperbilirubinemia resolves or the hyperbilirubinemia decreases to grade 1. NCIC CTC grade 2 hyperbilirubinemia is defined as an 1.5 times of normal, grade 3 hyperbilirubinemia is defined as 1.5~3 times of normal and grade 4 hyperbilirubinemia is defined as more than 3 times of normal (see recommended dose modifications under Dosage & Administration).
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 hemoglobin. In 251 patients with metastatic breast cancer who received a dose of Capecitabine (Xeltabine) 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.
Rarely, unexpected, severe toxicity (eg, stomatitis, diarrhea, neutropenia and neurotoxicity) associated with 5-fluorouracil 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-fluorouracil therefore cannot be excluded.
Effects on Ability to Drive and Use Machine: Capecitabine (Xeltabine) has minor or moderate influence on the ability to drive and use machines. Capecitabine (Xeltabine) may cause dizziness, fatigue and nausea.
Use in Children: There is no experience in children under 18 years.
Use in Elderly: When Capecitabine (Xeltabine) was used elderly patients (≥65 years) experienced more adverse drug reactions compared to younger patients. Careful monitoring of patients ≥65 years of age is advisable.
There is no study between age and Capecitabine (Xeltabine) or its metabolites. elderly patients ≥80 years can experienced more grade 3 and grade 4 adverse drug reactions in gastrointestinal tract compared to younger patients.
As elderly patients can be more sensitive to 5-FU toxicity pharmacologically, careful monitoring to indicate Capecitabine (Xeltabine) of patients ≥60 years of age of is advisable.