CAPELODINE
- Packing6 blister packs of 10 tablets
- Shelf life36 months
- CompositionCapecitabine 500 mg
- Posology and pharmaceutical formFilm-coated tablet
Summary of product characteristic
-
Indications, posology and method of administration
THERAPEUTIC INDICATIONS
Capecitabine is indicated for the treatment of:
- For the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon cancer.
- Metastatic colorectal cancer.
- First-line treatment of advanced gastric cancer in combination with a platinum-based regimen.
- In combination with docetaxel for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.
- As monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline-containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.
POSOLOGY AND METHOD OF ADMINISTRATION
Capecitabine should only be prescribed by a qualified physician experienced in the utilisation of anti-neoplastic medicinal products. Careful monitoring during the first cycle of treatment is recommended for all patients.
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 1 and 2, respectively.
Posology:
- Monotherapy:
Colon, colorectal and breast cancer
Given as monotherapy, the recommended starting dose for 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 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.
- Combination therapy:
Colon, colorectal and gastric cancer
In combination treatment, the recommended starting dose of capecitabine should be reduced to 800 – 1000 mg/m2 when administered twice daily for 14 days followed by a 7-day rest period, or to 625 mg/m2 twice daily when administered continuously. For combination with irinotecan, the recommended starting dose is 800 mg/m2 when administered twice daily for 14 days followed by a 7-day rest period combined with irinotecan 200 mg/m2 on day 1. The inclusion of bevacizumab 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 summary of product characteristics should be started prior to cisplatin administration for patients receiving the capecitabine plus cisplatin combination. Premedication with antiemetics according to the oxaliplatin summary of product characteristics is recommended for patients receiving the capecitabine plus oxaliplatin combination. Adjuvant treatment in patients with stage III colon cancer is recommended for a duration of 6 months.
Breast cancer
In combination with docetaxel, the recommended starting dose of capecitabine in the treatment of metastatic breast cancer is 1250 mg/m2 twice daily for 14 days followed by a 7- day rest period, combined with 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.
Capecitabine dose calculations:
Table 1: Standard and reduced dose calculations according to body surface area for a starting dose of capecitabine of 1250 mg/m2
| |
Dose level 1250 mg/m2 (twice daily) |
| Full dose 1250 mg/m2 |
Number of 150 mg tablets and/or 500 mg tablets per administration (each administration to be given morning and evening) |
Reduced dose (75%)
950 mg/m2 |
Reduced dose (50%)
625 mg/m2 |
Body Surface
Area (m2) |
Dose per administration (mg) |
150 mg |
500 mg |
Dose per administration (mg) |
Dose per administration (mg) |
| < 1,26 |
1500 |
- |
3 |
1150 |
800 |
| 1,27 – 1,38 |
1650 |
1 |
3 |
1300 |
800 |
| 1,39 – 1,52 |
1800 |
2 |
3 |
1450 |
950 |
| 1,53 – 1,66 |
2000 |
- |
4 |
1500 |
1000 |
| 1,67 – 1,78 |
2150 |
1 |
4 |
1650 |
1000 |
| 1,79 – 1,92 |
2300 |
2 |
4 |
1800 |
1150 |
| 1,93 – 2,06 |
2500 |
- |
5 |
1950 |
1300 |
| 2,07 – 2,18 |
2650 |
1 |
5 |
2000 |
1300 |
| > 2,19 |
2800 |
2 |
5 |
2150 |
1450 |
Table 2: Standard and reduced dose calculations according to body surface area for a starting dose of capecitabine of 1000 mg/m2
| |
Dose level 1000 mg/m2 (twice daily) |
| Full dose 1000 mg/m2 |
Number of 150 mg tablets and/or 500 mg tablets per administration (each administration to be given morning and evening) |
Reduced dose (75%)
750 mg/m2 |
Reduced dose (50%)
500 mg/m2 |
| Body Surface Area (m2) |
Dose per administration (mg) |
150 mg |
500 mg |
Dose per administration (mg) |
Dose per administration (mg) |
| < 1,26 |
1150 |
1 |
2 |
800 |
600 |
| 1,27 – 1,38 |
1300 |
2 |
2 |
1000 |
600 |
| 1,39 – 1,52 |
1450 |
3 |
2 |
1100 |
750 |
| 1,53 – 1,66 |
1600 |
4 |
2 |
1200 |
800 |
| 1,67 – 1,78 |
1750 |
5 |
2 |
1300 |
800 |
| 1,79 – 1,92 |
1800 |
2 |
3 |
1400 |
900 |
| 1,93 – 2,06 |
2000 |
- |
4 |
1500 |
1000 |
| 2,07 – 2,18 |
2150 |
1 |
4 |
1600 |
1050 |
| > 2,19 |
2300 |
2 |
4 |
1750 |
1100 |
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 a later time. 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. Patients taking capecitabine should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs.
Table 3: Capecitabine dose reduction schedule (3 weekly cycle or continuous treatment)
| Toxicity grades |
Dose changes within a treatment cycle |
Dose adjustment for next cycle/dose (% of starting dose) |
| Grade 1 |
Maintain dose level |
Duy trì liều |
| Grade 2 |
| 1st appearance |
Interrupt until resolved to grade 0-1 |
100% |
| 2nd appearance |
75% |
| 3rd appearance |
50% |
| 4th appearance |
Discontinue treatment permanently |
Not applicable |
| Grade 3 |
| 1st appearance |
Interrupt until resolved to grade 0-1 |
75% |
| 2nd appearance |
50% |
| 3rd appearance |
Discontinue treatment permanently |
Not applicable |
| Grade 4 |
| 1st appearance |
Discontinue permanently or If physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1 |
50% |
| 2nd appearance |
Discontinue permanently |
Not applicable |
Haematology:
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 that the neutrophil count drops below 1,0 x 109/L or that the platelet count drops below 75 x 109/L, treatment with capecitabine should be interrupted.
Dose modifications for toxicity when capecitabine is used as a 3 weekly cycle in combination with other medicinal products:
Dose modifications for toxicity when capecitabine is used as a 3 weekly cycle in combination with other medicinal products should be made according to table 3 above for capecitabine and according to the appropriate summary of product characteristics for the other medicinal product(s).
At the beginning of a treatment cycle, if a treatment delay is indicated for either capecitabine or the other medicinal product(s), then administration of all therapy should be delayed until the requirements for restarting all medicinal products 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 medicinal product should be adjusted according to the appropriate Prescribing Information.
If the other medicinal product(s) have to be discontinued permanently, capecitabine treatment can be resumed when the requirements for restarting capecitabine are met.
Dose modifications for toxicity when capecitabine is used continuously in combination with other medicinal products:
Dose modifications for toxicity when capecitabine is used continuously in combination with other medicinal products should be made according to table 3 above for capecitabine and according to the appropriate summary of product characteristics for the other medicinal product(s).
Hepatic impairment
Insufficient safety and efficacy data are available in patients with hepatic impairment to provide a dose adjustment recommendation. No information is available on hepatic impairment due to cirrhosis or hepatitis.
Renal impairment
Capecitabine is contraindicated in patients with severe renal impairment (creatinine clearance below 30 mL/min [Cockcroft and Gault] 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 1250 mg/m2 is recommended. In patients with moderate renal impairment at baseline, no dose reduction is required for a starting dose of 1000 mg/m2. In patients with mild renal impairment (creatinine clearance 51 – 80 mL/min at baseline) no adjustment of the 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 table 3 above. If the calculated creatinine clearance decreases during treatment to a value below 30 mL/min, capecitabine should be discontinued. These dose adjustment recommendations for renal impairment apply both to monotherapy and combination use.
Elderly
During capecitabine monotherapy, no adjustment of the starting dose is needed. However, grade 3 or 4 treatment – related adverse reactions were more frequent in patients ≥ 60 years of age compared to younger patients.
When capecitabine was used in combination with other medicinal products, elderly patients (≥ 65 years) experienced more grade 3 and grade 4 adverse drug reactions, including those leading to discontinuation, compared to younger patients. Careful monitoring of patients ≥ 60 years of age 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, 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 1250 mg/m2 twice daily.
Paediatric population
There is no relevant use of capecitabine in the paediatric population in the indications colon, colorectal, gastric and breast cancer.
Method of administration:
Capecitabine tablets should be swallowed whole with water within 30 minutes after a meal.
For lower dosages, refer to other products with the same active ingredient.
CONTRAINDICATIONS
- History of severe and unexpected reactions to fluoropyrimidine therapy.
- Hypersensitivity to capecitabine or to any of the excipients.
- Known complete dihydropyrimidine dehydrogenase (DPD) deficiency.
- During pregnancy and lactation.
- In patients with severe leukopenia, neutropenia, or thrombocytopenia.
- In patients with severe hepatic impairment.
- In patients with severe renal impairment (creatinine clearance below 30 mL/min).
- Treatment with sorivudine or chemically similar agents, such as brivudine.
- If contraindications exist to any of the medicinal products in the combination regimen, that medicinal product should not be used.
This information is for reference only. Please read the leaflet inside.
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