Cabazitaxel

Source: UK SPC (eMC) 4.2 for Cabazitaxel 20 mg/ml concentrate for solution for infusion (https://www.medicines.org.uk/emc/product/15842/smpc). VERBATIM: 'The recommended dose of Cabazitaxel is 25 mg/m2 administered as a 1-hour intravenous infusion every 3 weeks in combination with oral prednisone or prednisolone 10 mg administered daily throughout treatment.' SETTING: use should be confined to units specialised in the administration of cytotoxics and it should only be administered under the supervision of a physician experienced in the use of anticancer chemotherapy; facilities and equipment for the treatment of serious hypersensitivity reactions such as hypotension and bronchospasm must be available. PREMEDICATION (at least 30 minutes prior to each administration, all intravenous): an antihistamine (dexchlorpheniramine 5 mg or diphenhydramine 25 mg or equivalent), a corticosteroid (dexamethasone 8 mg or equivalent), and an H2 antagonist (ranitidine or equivalent). Antiemetic prophylaxis is recommended and can be given orally or intravenously as needed. Adequate hydration must be ensured throughout treatment to prevent complications such as renal failure. DOSE MODIFICATIONS (CTCAE 4.0): prolonged Grade 3 or higher neutropenia lasting longer than 1 week despite appropriate treatment including G-CSF - delay treatment until the neutrophil count is above 1,500 cells/mm3, then reduce from 25 mg/m2 to 20 mg/m2. Febrile neutropenia or neutropenic infection - delay until improvement or resolution and until the neutrophil count is above 1,500 cells/mm3, then reduce to 20 mg/m2. Grade 3 or higher diarrhoea, or persisting diarrhoea despite appropriate treatment including fluid and electrolyte replacement - delay until improvement or resolution, then reduce to 20 mg/m2. Grade above 2 peripheral neuropathy - delay until improvement, then reduce to 20 mg/m2. If patients continue to experience any of these reactions at 20 mg/m2, further dose reduction to 15 mg/m2 or discontinuation may be considered; data below the 20 mg/m2 dose are limited. HEPATIC IMPAIRMENT: mild impairment (total bilirubin above 1 to 1.5 x ULN or AST above 1.5 x ULN) - reduce the dose to 20 mg/m2 and undertake administration with caution and close monitoring of safety. Moderate impairment (total bilirubin above 1.5 to 3.0 x ULN) - the maximum tolerated dose was 15 mg/m2 and the dose should not exceed 15 mg/m2, though limited efficacy data are available at this dose. Severe hepatic impairment (total bilirubin above 3 x ULN) - must not be given (contraindicated). ELDERLY: no specific dose adjustment recommended. PAEDIATRIC: there is no relevant use in the paediatric population and safety and efficacy in children and adolescents below 18 years have not been established. NOTE: the eMC 4.5 interactions section was not retrieved in this bundle - the CYP3A guidance below is taken from eMC 4.2 (which cross-refers to 4.4 and 4.5) and from the US Jevtana label; source the UK SPC 4.5 separately.