Capetero Dosage/Direction for Use

Standard Dosage: Capecitabine should only be prescribed by a qualified physician experienced in the utilisation of anti-neoplastic agents. Capecitabine tablets should be swallowed with water within 30 minutes after a meal. Treatment should be discontinued if progressive disease or intolerable toxicity is observed. Standard and reduced dose calculations according to body surface area for starting doses of Capecitabine of 1250 mg/m² and 1000 mg/m² are provided in Tables 4 and 5, respectively.
Monotherapy: Colon, colorectal and breast cancer: The recommended monotherapy starting dose of Capecitabine in the adjuvant treatment of colon cancer, in the treatment of metastatic colorectal cancer or of locally advanced or metastatic breast cancer is 1250 mg/m² administered twice daily (morning and evening; equivalent to 2500 mg/m² total daily dose) for 2 weeks followed by a 7-day rest period.
Adjuvant treatment in patients with stage III colon cancer is recommended for a total of 6 months.
Combination therapy: Breast cancer: In combination with docetaxel, the recommended starting dose of Capecitabine is 1250 mg/m² twice daily for 2 weeks followed by a 7-day rest period, combined with docetaxel at 75 mg/m² as a 1-hour intravenous infusion every 3 weeks.
Pre-medication with an oral corticosteroid such as dexamethasone according to the docetaxel summary of product characteristics should be started prior to docetaxel administration for patients receiving the Capecitabine plus docetaxel combination.
Colon and colorectal cancer: In combination treatment, the recommended starting dose of Capecitabine should be reduced to 1000 mg/m² administered twice daily for 2 weeks followed by a 7-day rest period. The inclusion of biological agents in a combination regimen has no effect on the starting dose of Capecitabine.
Premedication to maintain adequate hydration and anti-emesis according to the cisplatin and oxaliplatin product information should be started prior to cisplatin administration for patients receiving the Capecitabine plus cisplatin or oxaliplatin combination.
Adjuvant treatment in patients with stage III colon cancer is recommended fora total of 6 months.
Capecitabine dose is calculated according to body surface area. The following tables show examples of the standard and reduced dose calculations (see Dosage adjustments during treatment as follows) for a starting dose of Capecitabine of either 1250 mg/m² or 1000 mg/m². (See Tables 4 and 5.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Dosage adjustments during treatment: General: Toxicity due to Capecitabine administration may be managed by symptomatic treatment and/or modification of the Capecitabine dose (treatment interruption or dose reduction). Once the dose has been reduced it should not be increased at a later time.
For those toxicities considered by the treating physician to be unlikely to become serious or life-threatening treatment can be continued at the same dose without reduction or interruption.
Patients taking Capecitabine should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs. Doses of Capecitabine omitted for toxicity are not replaced.
Hematology: Patients with baseline neutrophil counts of <1.5 x 10⁹/l and/or thrombocyte counts of <100 x 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.
If the neutrophil count drops below 1.0 x 10⁹/L or if the platelet count drops below 75 x 10⁹/L, discontinue capecitabine. At recovery, restart capecitabine at full dose.
The following table shows the recommended dose modifications following toxicity related to Capecitabine: (See Table 6.)

Click on icon to see table/diagram/image

General combination therapy: Dose modifications for toxicity when Capecitabine is used in combination with other therapies should be made according to the previously mentioned Table 6 for Capecitabine and according to the appropriate Prescribing Information for the other agent(s).
At the beginning of a treatment cycle, if a treatment delay is indicated for either Capecitabine or the other agent(s), then administration of all agents should be delayed until the requirements for restarting all drugs are met. During a treatment cycle for those toxicities considered by the treating physician not to be related to Capecitabine, Capecitabine should be continued and the dose of the other agent adjusted according to the appropriate Prescribing Information.
If the other agent(s) have to be discontinued permanently, Capecitabine treatment can be resumed when the requirements for restarting Capecitabine are met.
This advice is applicable to all indications and to all special populations.
Special Dosage Instructions: Patients with hepatic impairment due to liver metastases: In patients with mild to moderate hepatic impairment due to liver metastases, no starting dose adjustment is necessary. However, such patients should be carefully monitored (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions and Precautions). Patients with severe hepatic impairment have not been studied.
Patients with renal impairment: In patients with moderate renal impairment (creatinine clearance 30 - 50 ml/min [Cockroft and Gault]) at baseline, a dose reduction to 75% for a starting dose of 1250 mg/m² is recommended. In patients with mild renal impairment (creatinine clearance 51 - 80 ml/min), no adjustment in starting dose is recommended.
Careful monitoring and prompt treatment interruption is recommended if the patient develops a Grade 2, 3, or 4 adverse event with subsequent dose adjustment as outlined in Table 6 above (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions). If the calculated creatinine clearance decreases during treatment to a value below 30 ml/min, Capecitabine should be discontinued. The dose adjustment recommendations for patients with moderate renal impairment apply both to monotherapy and combination use. For dosage calculations, see Tables 4 and 5.
Children: The safety and efficacy of Capecitabine in children have not been established.
Elderly: For Capecitabine monotherapy, no adjustment of the starting dose is needed. However, severe grade 3 or 4 treatment-related adverse events were more frequent in patients over 80 years of age compared to younger patients. When Capecitabine was used in combination with otheragents, elderly patients (= 65 years) experienced more grade 3 and grade 4 adverse drug reactions (ADRs) and ADRs that led to discontinuation, than younger patients. Careful monitoring of elderly patients is advisable.
In combination with docetaxel: an increased incidence of grade 3 or 4 treatment-related adverse events and treatment-related serious adverse events was observed in patients 60 years of age or more. For patients 60 years of age or more treated with the combination of Capecitabine plus docetaxel, a starting dose reduction of Capecitabine to 75% (950 mg/m² twice daily) is recommended. For dosage calculations, see Table 5.
In combination with irinotecan: for patients 65 years of age or more, a starting dose reduction of Capecitabine to 800 mg/m² twice daily is recommended.