Capecitabine should only be prescribed by a qualified physician experienced in the utilization of antineoplastic 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 dose capecitabine of 1,250 mg/m2
and 1,000 mg/m2
are provided in tables 1 and 2, respectively. (See Tables 1 and 2).
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image
Recommended posology: Colon and colorectal cancer:
The recommended dose for capecitabine in the adjuvant treatment in colon cancer or in the treatment of metastatic colorectal cancer is 1,250 mg/m2
administered twice daily (morning and evening; equivalent to 2,500 mg/m2
total daily dose) for 14 days followed by a 7-day rest period. Adjuvant treatment in patients with stage III colon cancer is recommended for a total of 6 months, i.e. capecitabine 1,250 mg/m2
administered twice daily for 14 days followed by a 7-day rest period, given as 3-week cycles for a total of 8 cycles (24 weeks).
Advanced gastric cancer:
In combination with a platinum-based compound, the recommended dose of capecitabine for the treatment of advanced gastric cancer is 1,000 mg/m2
administered twice daily for 14 days followed by a 7-day rest period. The first dose of capecitabine should be given on the evening of day 1 and the last dose should be given on the morning of day 15.
Premedication to maintain adequate hydration and anti-emesis according to the cisplatin summary product characteristics should be started prior to cisplatin administration for patients receiving in the capecitabine plus cisplatin combination.
Given as a single agent, the recommended dose of capecitabine in treatment of locally advanced or metastatic breast cancer is 1,250 mg/m2
twice daily for 14 days followed by a 7-day rest period.
In combination with docetaxel, the recommended dose of capecitabine in the treatment of metastatic breast cancer is 1,250 mg/m2
twice daily for 14 days followed by a 7-day rest period, combined with a docetaxel at 75 mg/m2
as a 1-hour intravenous infusion every 3 weeks. Premedication 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.
Posology adjustments during treatment: General:
Toxicity due to capecitabine administration may be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced, it should not be increased at later time. Patients taking capecitabine should be informed of the need to interrupt treatment immediately if moderate or worse toxicity occurs. Doses of capecitabine omitted for toxicity are not replaced or restored, instead the patient should resume the planned treatment cycle. (See Table 3.)
Click on icon to see table/diagram/image
Dose modification for toxicity when capecitabine is used as a 3-weekly cycle in combination with other agents:
Dose modifications for toxicity when capecitabine is used as a 3-weekly cycle in combination with other agents should be made according to Table 3 for capecitabine and according to the appropriate summary of product characteristics for the other agent.
At the beginning of a treatment cycle, if a treatment delay is indicated for either capecitabine or the other agent, then administration of both agents should be delayed until the requirements for restarting both drugs are met.
During a treatment cycle for those toxicities considered by the treating physician not to be related to capecitabine (for example, neurotoxicity or ototoxicity), then capecitabine should be continued and the other agent should be discontinued 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 starting capecitabine are met.
This advice is applicable to all indications and to all special populations.
For those toxicities considered by the treating physician to be unlikely to become serious or life threatening, e.g. alopecia, altered taste, nail changes, treatment can be continued at the same dose without reduction or interruption.
Dose modifications for toxicity when capecitabine is used continuously in combination with other agents:
Dose modification for toxicity when capecitabine is used continuously in combination with other agents should be made according to Table 3 for capecitabine and according to the appropriate summary of product characteristics for the other agents(s).
Capecitabine treatment may continue throughout a grade 3 neutropenic episode. However, the patient should be closely monitored and administration of capecitabine should be interrupted if any grade 2 clinical event (e.g. diarrhea, stomatitis, fever) coincides with the grade 3 neutropenic episode. If grade 4 neutropenia occurs, treatment with capecitabine should be interrupted until recovery to grade 0-1. Treatment should only be re-administered when the neutrophil count is ≥1.5 x 109
/L (grade 0-1).
Patients with baseline neutrophil counts <1.5 x 109
/L and/or thrombocyte counts of <100 x 109
/L should not be treated with the capecitabine.
If the neutrophil counts drops below 1.0 x 109
/L or if the platelet count drops below 75 x 109
/L, stop capecitabine. At recovery, restart capecitabine at full dose.
Dehydration should be prevented or corrected at the onset. Patients with anorexia, asthenia, nausea, vomiting or diarrhea may rapidly become dehydrated. If grade 2 (or higher) dehydration occurs, capecitabine treatment should be immediately interrupted and the dehydration corrected. Treatment should not be restarted until the patient is rehydrated and any precipitating causes have been corrected or controlled. Dose modification applied should be those for the precipitating adverse event in accordance with the above guidelines.
Posology adjustments for special populations: Hepatic impairment:
Insufficient safety and efficacy data are available in patients with hepatic impairment to provide dose adjustment recommendation. No information is available on hepatic impairment due to cirrhosis or hepatitis.
Capecitabine is contraindicated in patients with severe renal impairment (creatinine clearance below 30 mL/min at baseline). The incidence of grade 3 or 4 adverse reactions in patients with moderate renal impairment (creatinine clearance 30-50 mL/min at baseline) is increased compared to the overall population.
In patients with moderate renal impairment at baseline, a dose reduction to 75% for a starting dose of 1,250 mg/m2
is recommended. In patients with moderate renal impairment at baseline, no dose reduction is required for a starting dose of 1,000 mg/m2
. 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 during treatment and subsequent dose adjustment as outlined in the table previously. These dose adjustment recommendations for renal impairment apply both to monotherapy and combination use.
There is no experience in children (under 18 years).
No adjustment of the starting dose is needed during capecitabine monotherapy. However, severe grade 3 or 4 treatment-related adverse events were more frequent in patients ≥ 60 years of age compared to younger patients. Careful monitoring of elderly patients is advisable. In combination with docetaxel, an increased incidence of grade 3 or 4 treatment-related adverse reactions and treatment-related serious adverse reactions were 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. If no toxicity is observed in patients ≥ 60 years of age treated with a reduced capecitabine starting dose in combination with docetaxel, the dose of capecitabine may be cautiously escalated to 1,250 mg/m2