Capecitabine SUN

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. 1): MonotherapyMedicinal product no longer authorised 3 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. 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.

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.

Summary of the safety profile The overall safety profile of capecitabine is based on data from over 3000 patients treated with capecitabine as monotherapy or capecitabine in combination with different chemotherapy regimens in multiple indications.

The safety profiles of capecitabine monotherapy for the metastatic breast cancer, metastatic colorectal cancer and adjuvant colon cancer populations are comparable. 1 for details of major studies, including study designs and major efficacy results.

The most commonly reported and/or clinically relevant treatment-related adverse drug reactions (ADRs) were gastrointestinal disorders (especially diarrhoea, nausea, vomiting, abdominal pain, stomatitis), hand-foot syndrome (palmar-plantar erythrodysesthesia), fatigue, asthenia, anorexia, cardiotoxicity, increased renal dysfunction on those with preexisting compromised renal function, and thrombosis/embolism.

Tabulated summary of adverse reactions ADRs considered by the investigator to be possibly, probably, or remotely related to the administration of capecitabine are listed in table 4 for capecitabine given as a monotherapy and in table 5 for capecitabine given in combination with different chemotherapy regimens in multiple indications.

The following headings are used to rank the ADRs by frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). Medicinal product no longer authorised 11 Capecitabine monotherapy Table 4 lists ADRs associated with the use of capecitabine monotherapy based on a pooled analysis of safety data from three major studies including over 1900 patients (studies M66001, SO14695, and SO14796).

ADRs are added to the appropriate frequency grouping according to the overall incidence from the pooled analysis. 4) Muskulo- skeletal and connective tissue disorders - Pain in extremity, Back pain, Arthralgia Joint swelling, Bone pain, Facial pain, Musculoskeletal stiffness, Muscular weaknessMedicinal product no longer authorised 13 Body System Very Common All grades Common All grades Uncommon Severe and/or Life- threatening (grade 3- 4) or considered medically relevant Rare/Very Rare (Post-Marketing Experience) Renal and urinary disorders - - Hydronephrosis, Urinary incontinence, Haematuria, Nocturia, Blood creatinine increased Reproductive system and breast disorders - - Vaginal haemorrhage General disorders and […]

4. 5 x 109/L and/or thrombocyte counts of <100 x 109/L should not be treated with capecitabine. 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. 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.

1 or fluorouracil. - History of severe and unexpected reactions to fluoropyrimidine therapy. 4). - 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). 5). - If contraindications exist to any of the medicinal products in the combination regimen, that medicinal product should not be used.