Capiibine Dosage/Direction for Use

Standard dosage: CAPIIBINE tablets should be swallowed whole with water within 30 minutes after a meal. CAPIIBINE tablets should not be crushed or cut. If patients cannot swallow CAPIIBINE tablets whole and tablets must be crushed or cut, this should be done by a professional trained in the safe handling of cytotoxic drugs.
Monotherapy: Colon, Colorectal, and Breast cancer: The recommended monotherapy starting dose of CAPIIBINE 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.
Combination therapy Breast Cancer: In combination with docetaxel: In combination with docetaxel, the recommended dose of CAPIIBINE 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 according to the docetaxel labelling should be started prior to docetaxel administration for patients receiving the CAPIIBINE plus docetaxel combination.
In combination with lapatinib ditosylate: In combination with lapatinib ditosylate, the recommended dose of CAPIIBINE is 2000 mg/m²/day administered orally in 2 doses 12 hours apart for 14 days (Day 1-14) in a repeating 21-day cycle combined with lapatinib ditosylate 1250 mg (5 tablets) given orally once daily from Day 1-21. (See manufacturer's prescribing information for lapatinib ditosylate for further information).
Colon, Colorectal cancer: In combination with oxaliplatin and/or bevacizumab: In combination with oxaliplatin and/or bevacizumab, the recommended dose of CAPIIBINE is 1000 mg/m² twice daily for 2 weeks followed by a 7-day rest period. The first dose of CAPIIBINE is given on the evening of day 1 and the last dose is given on the morning of day 15. Given as a 3-weekly schedule, on day 1 every 3 weeks, bevacizumab is administered as a 7.5 mg/kg intravenous infusion over 30-90 minutes, followed by oxaliplatin administered as a 130 mg/m² intravenous infusion over 2 hours.
Premedication to maintain adequate hydration and anti-emesis according to the oxaliplatin product information should be started prior to oxaliplatin administration for patients receiving the CAPIIBINE plus oxaliplatin combination. Adjuvant treatment in patients with stage III colon cancer is recommended for a total of 6 months.
Gastric Cancer: In combination with platinum-based regimen: In combination with a platinum-based compound, the recommended dose of CAPIIBINE for the treatment of advanced gastric cancer is 1000 mg/m² administered twice daily for 14 days, followed by a 7-day rest period. The first dose of CAPIIBINE should be given on the evening of day 1, and the last dose should be given on the morning of day 15. If epirubicin is added to this regimen, the recommended dose of CAPIIBINE is 625 mg/m² twice daily continuously. Epirubicin at a dose of 50 mg/m² should be given as a bolus on day 1 every 3 weeks. The platinum-based compound (cisplatin at a dose of 60 mg/m² (triple regimen) - 80 mg/m² (double regimen) or oxaliplatin at a dose of 130 mg/m²) should be given on day 1 as a 2-hour intravenous infusion every 3 weeks.
Premedication to maintain adequate hydration and anti-emesis according to the cisplatin/oxaliplatin summary of product characteristics should be started prior to cisplatin/oxaliplatin administration for patients receiving the CAPIIBINE plus cisplatin/oxaliplatin combination.
Dose calculation: CAPIIBINE dose is calculated according to body surface area. The following tables show the standard and reduced dose calculations (see "Dosage adjustments during treatment" as follows) for a starting dose of CAPIIBINE of either 1250 mg/m² or 1000 mg/m². (See Tables 1 & 2.)

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Dosage adjustments during treatment: General: Toxicity due to CAPIIBINE administration may be managed by symptomatic treatment and/or modification of the CAPIIBINE 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.
Dosage modifications are not recommended for Grade 1 events. Therapy with CAPIIBINE should be interrupted if a Grade 2 or 3 adverse drug reaction (ADR) occurs. Once the ADR has resolved or decreased in intensity to Grade 1, CAPIIBINE therapy may be restarted at full dose or as adjusted according to Table 3. If a Grade 4 ADR occurs, therapy should be discontinued or interrupted until the ADR has resolved or decreased to Grade 1, and therapy should be restarted at 50% of the original dose. Patients taking CAPIIBINE should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs. Doses of CAPIIBINE omitted for toxicity are not replaced.
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 CAPIIBINE. If unscheduled laboratory assessments during a treatment cycle show grade 3 or 4 haematologic toxicity, treatment with CAPIIBINE should be interrupted.
The following table shows the recommended dose modifications following toxicity related to with CAPIIBINE: (See Table 3.)

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The following are the recommended dose modifications for toxicity when CAPIIBINE and docetaxel are used in combination: (See Table 4.)

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Specific dose adjustment in combination with docetaxel: CAPIIBINE and/or docetaxel dose modifications should be made according to the general dose modification scheme as previously mentioned, if nothing else is stated regarding specific dose adjustments. For those toxicities considered 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. At the beginning of a treatment cycle, if either a docetaxel or a CAPIIBINE treatment delay is indicated, both docetaxel and CAPIIBINE administration should be delayed until the requirements for restarting both drugs are met. If docetaxel has to be discontinued, CAPIIBINE treatment can be resumed when the requirements for restarting CAPIIBINE are met.
Hematology: Treatment should only be re-administered when the neutrophil count is ≥1.5 x 10⁹/l (Grade 0-1). Patients with neutropenia <0.5 x 10⁹/l (Grade 4) for more than 1 week, or febrile (>38°C) neutropenia, should have the docetaxel dosage reduced from 75 mg/m² to 55 mg/m². If Grade 4 neutropenia or febrile neutropenia occurs at 55 mg/m² docetaxel, docetaxel should be discontinued. Patients with baseline neutrophil counts of <1.5 x 10⁹/l and/or thrombocyte counts of <1.0 x 10⁹/l should not be treated with the CAPIIBINE/docetaxel combination.
Hypersensitivity: Patients who develop severe hypersensitivity reactions (hypotension with a decrease of ≥20 mmHg, or bronchospasm, or generalised rash/erythema) should stop treatment immediately and be given appropriate therapy. These patients should not be re-challenged with the drug suspected to have caused hypersensitivity.
Peripheral neuropathy: For 1st appearance of Grade 2 toxicity, reduce the docetaxel dose to 55 mg/m². If Grade 3 toxicity appears, discontinue docetaxel treatment. In both instances, follow the previously mentioned dose modification scheme for CAPIIBINE.
Fluid retention: Severe (Grade 3 or 4) toxicity, such as pleural effusion, pericardial effusion, or ascites, which is possibly related to docetaxel, should be closely monitored. In case of appearance of such toxicity, docetaxel treatment should be discontinued, CAPIIBINE treatment may be continued without dose modification.
Hepatic impairment: Docetaxel should generally not be given to patients with serum bilirubin above the upper limit of normal. The following modifications should be applied to the docetaxel dose in the event of abnormal values for ASAT, ALAT, and/or alkaline phosphatase levels: (See Table 5.)

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Once the docetaxel dose is reduced for a given cycle, no further dose reduction is recommended for subsequent cycles unless worsening of the parameters is observed. In case of recovery of liver function tests after previous reduction of the docetaxel dose, the docetaxel dose can be re-escalated to the previous dose level.
Dehydration: 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, CAPIIBINE 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 modifications applied should be those for the precipitating adverse event in accordance with the previously mentioned guidelines.
Reductions to 75% and 50% of CAPIIBINE dose: For patients receiving CAPIIBINE monotherapy or CAPIIBINE in combination with docetaxel, the following tables show the dosage at 75% and 50%, calculated according to the body surface area: (See Table 6.)

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Special dosage instructions: Pediatric use: The safety and efficacy of CAPIIBINE in children and adolescents (<18 years) have not been established.
Geriatric use: For CAPIIBINE monotherapy, no adjustment of the starting dose is needed. However, severe Grade 3 or 4 treatment-related ADRs were more frequent in patients over 80 years of age compared to younger patients.
When CAPIIBINE 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 CAPIIBINE plus docetaxel, a starting dose reduction of CAPIIBINE to 75% (950 mg/m² twice daily) is recommended. For dosage calculations, see Table 1 as previously mentioned.
In combination with irinotecan: for patients 65 years of age or more, a starting dose reduction of CAPIIBINE 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 as previously mentioned (see also Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions). If the calculated creatinine clearance decreases during treatment to a value below 30 mL/min, CAPIIBINE should be discontinued. The dose adjustment recommendations for patients with moderate renal impairment apply both to monotherapy and combination use. For dosage calculations, see Table 1 and Table 2 as previously mentioned.
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 (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions and Precautions). Patients with severe hepatic impairment have not been studied.
Mode of Administration: Oral.