INCITABINE FILM COATED TABLET 500MG

TABLET, FILM COATED

**4.2 Posology and method of administration** INCITABINE should only be prescribed by a qualified physician experienced in the utilisation of anti-neoplastic agents. INCITABINE tablets should be swallowed whole with water within 30 minutes after a meal. INCITABINE tablets should not be crushed or cut. If patients cannot swallow INCITABINE tablets whole and tablets must be crushed or cut, this should be done by a professional trained in the safe handling of cytotoxic drugs. 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 INCITABINE of 1250 mg/m2 and 1000 mg/m2 are provided in tables 1 and 2, respectively. Monotherapy _Colon, colorectal and breast cancer:_ The recommended monotherapy starting dose of INCITABINE 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 INCITABINE 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 INCITABINE plus docetaxel combination. _Colon, colorectal and gastric cancer:_ In combination treatment, the recommended starting dose of INCITABINE should be reduced to 1000 mg/m2 administered twice daily for 2 weeks followed by a 7-day rest period. The inclusion of bevacizumab in a combination regimen has no effect on the starting dose of INCITABINE. 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 INCITABINE plus cisplatin or oxaliplatin combination. Adjuvant treatment in patients with stage III colon cancer is recommended for a total of 6 months. Dose calculation INCITABINE dose is calculated according to body surface area. The following tables show examples of the standard and reduced dose calculations (see section “Dosage adjustments during treatment”) for a starting dose of INCITABINE of either 1250 mg/m2 or 1000 mg/m2.   Dosage adjustments during treatment _General:_ Toxicity due to INCITABINE administration may be managed by symptomatic treatment and/or modification of the INCITABINE 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 INCITABINE should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs. Doses of INCITABINE 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 INCITABINE. If unscheduled laboratory assessments during a treatment cycle show grade 3 or 4 hematologic toxicity, treatment with INCITABINE 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, capecitabine. At recovery, restart capecitabine at full dose. The following table shows the recommended dose modifications following toxicity related to INCITABINE:  General combination therapy Dose modifications for toxicity when INCITABINE is used in combination with other therapies should be made according to Table 3 above for INCITABINE 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 INCITABINE 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 INCITABINE, INCITABINE 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, INCITABINE treatment can be resumed when the requirements for restarting INCITABINE are met. This advice is applicable to all indications and to all special populations. **4.2.1 Special Dosage Instructions** _Pediatric use_ The safety and efficacy of INCITABINE in children and adolescents (<18 years) have not been established. _Geriatric use_ For INCITABINE monotherapy, no adjustment of the starting dose is needed. However, severe grade 3 or 4 treatment-related adverse drug reactions (ADRs) were more frequent in patients over 80 years of age compared to younger patients. When INCITABINE was used in combination with other antineoplastic agents, geriatric patients (≥ 65 years) experienced more grade 3 and grade 4 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 ADRs and treatment-related serious ADRs was observed in patients 60 years of age or more. For patients 60 years of age or more treated with the combination of INCITABINE plus docetaxel, a starting dose reduction of INCITABINE to 75% (950 mg/m2 twice daily) is recommended. For dosage calculations, see Table 2. In combination with irinotecan: for patients 65 years of age or more, a starting dose reduction of INCITABINE to 800 mg/m2 twice daily is recommended. _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 ADRs with subsequent dose adjustment as outlined in Table 3 above. If the calculated creatinine clearance decreases during treatment to a value below 30 ml/min, INCITABINE 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 1 and 2. _Hepatic Impairment_ 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. Patients with severe hepatic impairment have not been studied.