CAPECITABINE ACCORD Film-coated tablet Ref.[6502] Active ingredients: Capecitabine

Capecitabine Accord 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 Accord of 1250 mg/m² and 1000 mg/m² are provided in Tables 1 and 2, respectively.

Posology

Recommended posology (see section 5.1)

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 (see section 5.1). 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 Accord dose calculations

Table 1. Standard and reduced dose calculations according to body surface area for a starting dose of capecitabine of 1250 mg/m²:

Table 2. Standard and reduced dose calculations according to body surface area for a starting dose of Capecitabine of 1000 mg/m²:

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. Doses of capecitabine omitted for toxicity are not replaced. The following are the recommended dose modifications for toxicity:

Capecitabine Accord 150 mg and 500mg film-coated tablets:

Table 3 Capecitabine dose reduction schedule (3-weekly cycle or continuous treatment):

Capecitabine Accord 300 mg film-coated tablets:

Table 4. Capecitabine dose reduction shedule (3-weeklycycle or continuous treatment):

* According to the National Cancer Institute of Canada Clinical Trial Group (NCIC CTG) Common Toxicity Criteria (version 1) or the Common Terminology Criteria for Adverse Events (CTCAE) of the Cancer Therapy Evaluation Program, US National Cancer Institute, version 4.0. For hand-foot syndrome and hyperbilirubinemia, see section 4.4.

Haematology

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 that the neutrophil count drops below 1.0 × 10⁹/L or that the platelet count drops below 75 × 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.

This advice is applicable to all indications and to all special populations.

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).

Posology adjustments for special populations

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 Accord should be discontinued. These dose adjustment recommendations for renal impairment apply both to monotherapy and combination use (see also section “Elderly” below).

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 (see section 5.1). 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 Accord tablets should be swallowed with water within 30 minutes after a meal.

The manifestations of acute overdose include nausea, vomiting, diarrhoea, mucositis, gastrointestinal irritation and bleeding, and bone marrow depression. Medical management of overdose should include customary therapeutic and supportive medical interventions aimed at correcting the presenting clinical manifestations and preventing their possible complications.

Shelf life: 3 years.

Aluminium/aluminium blisters: This medicinal product does not require any special storage conditions.

PVC/PVdC/Aluminium blisters: Do not store above 30°C.

Aluminium/aluminium or PVC/PVdC/Aluminium blister containing 30, 60 or 120 film-coated tablets. Each pack contains 30, 60 or 120 film-coated tablets.

PVC/PVdC/Aluminium perforated unit dose blister containing 30, 60 or 120 film-coated tablets. Each pack contains 30 × 1, 60 × 1 or 120 × 1 film-coated tablets.

Not all pack sizes may be marketed.

No special requirements.