Cabazitaxel

Use should be confined to units specialised in the administration of cytotoxics and only under the supervision of a physician experienced in the use of anticancer chemotherapy; facilities and equipment for treating serious hypersensitivity reactions such as hypotension and bronchospasm must be available. PREMEDICATION, at least 30 minutes before each administration, with the following intravenous medicines: 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 neutrophils above 1,500 cells/mm³, then reduce to 20 mg/m²; grade 3 or higher or persisting diarrhoea despite appropriate treatment — 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 reactions continue at 20 mg/m², further reduction to 15 mg/m² or discontinuation may be considered; data below 20 mg/m² are limited. HEPATIC IMPAIRMENT: mild (total bilirubin above 1 to 1.5 x ULN, or AST above 1.5 x ULN) — reduce to 20 mg/m² with caution and close safety monitoring; moderate (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, with limited efficacy data; severe (total bilirubin above 3 x ULN) — must not be given. Concomitant strong CYP3A inducers or inhibitors should be avoided; if a strong CYP3A inhibitor is required, a 25% cabazitaxel dose reduction should be considered. Monitor complete blood counts weekly during cycle 1 and before each subsequent cycle; prophylactic G-CSF may be given, and primary G-CSF prophylaxis should be considered in high-risk patients (age over 65, poor performance status, previous febrile neutropenia, extensive prior radiation ports, poor nutritional status, other serious comorbidities). PVC infusion containers and polyurethane infusion sets should not be used, and cabazitaxel must not be mixed with other medicinal products. PAEDIATRIC: there is no relevant use in the paediatric population and safety and efficacy below 18 years have not been established — no per-kg dose in the SPC, hence paedDose is null. CROSS-LABEL DISCREPANCY the clinician must reconcile: the US Jevtana prescribing information recommends 20 mg/m² every three weeks as the standard dose, with 25 mg/m² used in select patients at the discretion of the treating healthcare provider; the UK SPC figure of 25 mg/m² has been used here because eMC is the preferred source. Some sections of the product information we used were incomplete — check the full SPC.