Jevtana

The use of JEVTANA 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. 4). 4). Antiemetic prophylaxis is recommended and can be given orally or intravenously as needed.

3 Throughout the treatment, adequate hydration of the patient needs to be ensured, in order to prevent complications like renal failure. Posology The recommended dose of JEVTANA 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.

0]): Table 1 - Recommended dose modifications for adverse reaction in patients treated with cabazitaxel Adverse reactions Dose modification Prolonged grade ≥3 neutropenia (longer than 1 week) despite appropriate treatment including G-CSF Delay treatment until neutrophil count is >1,500 cells/mm3, then reduce cabazitaxel dose from 25 mg/m2 to 20 mg/m2.

Febrile neutropenia or neutropenic infection Delay treatment until improvement or resolution, and until neutrophil count is >1,500 cells/mm3, then reduce cabazitaxel dose from 25 mg/m2 to 20 mg/m2. Grade ≥3 diarrhoea or persisting diarrhoea despite appropriate treatment, including fluid and electrolytes replacement Delay treatment until improvement or resolution, then reduce cabazitaxel dose from 25 mg/m2 to 20 mg/m2.

Grade >2 peripheral neuropathy Delay treatment until improvement, then reduce cabazitaxel dose from 25 mg/m2 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 of JEVTANA may be considered.

Data in patients below the 20 mg/m2 dose are limited. Special populations Patients with hepatic impairment Cabazitaxel is extensively metabolised by the liver. 5 x ULN), should have cabazitaxel dose reduced to 20 mg/m2. Administration of cabazitaxel to patients with mild hepatic impairment should be undertaken with caution and close monitoring of safety.

0 x ULN), the maximum tolerated dose (MTD) was 15 mg/m2. If the treatment is envisaged in patients with moderate hepatic impairment the dose of cabazitaxel should not exceed 15 mg/m2. However, limited efficacy data are available at this dose.

Summary of safety profile The safety of JEVTANA in combination with prednisone or prednisolone was evaluated in 3 randomized, open label, controlled studies (TROPIC, PROSELICA and CARD), totaling 1092 patients with metastatic castration resistant prostate cancer who were treated with 25 mg/m² cabazitaxel once every 3 weeks.

Patients received a median of 6 to 7 cycles of cabazitaxel. The incidences from the pooled analysis of these 3 trials are presented below and in the tabulated list. 7%). 8% in CARD) in patients receiving cabazitaxel. 0%) leading to cabazitaxel discontinuation were hematuria, fatigue and neutropenia.

Tabulated list of adverse reactions Adverse reactions are listed in table 2 according to MedDRA system organ class and frequency categories. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

0 (grade ≥3 = G≥3). Frequencies are based on all grades and defined as: 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); not known (cannot be estimated from the available data).

4) 0 Aspartate aminotransferase […]

2). Patients should be observed closely for hypersensitivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of cabazitaxel, thus facilities and equipment for the treatment of hypotension and bronchospasm should be available.

Severe reactions can occur and may include generalised rash/erythema, hypotension and bronchospasm. Severe hypersensitivity reactions require immediate discontinuation of cabazitaxel and appropriate therapy. 3). 4 below). Risk of neutropenia Patients treated with cabazitaxel may receive prophylactic G-CSF, as per American Society of Clinical Oncology (ASCO) guidelines and/or current institutional guidelines, to reduce the risk or manage neutropenia complications (febrile neutropenia, prolonged neutropenia or neutropenic infection).

Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features (age >65 years, poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities) that predispose them to increased complications from prolonged neutropenia.

The use of G-CSF has been shown to limit the incidence and severity of neutropenia. 8). Monitoring of complete blood counts is essential on a weekly basis during cycle 1 and before each treatment cycle thereafter so that the dose can be adjusted, if needed.

2). 3). Gastrointestinal disorders Symptoms such as abdominal pain and tenderness, fever, persistent constipation, diarrhoea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly.

Cabazitaxel treatment delay or discontinuation may be necessary. Risk of nausea, vomiting, diarrhoea and dehydration If patients experience diarrhoea following administration of cabazitaxel they may be treated with commonly used anti-diarrhoeal medicinal products.

1. • Neutrophil counts less than 1,500/mm3. • Severe hepatic impairment (total bilirubin >3 x ULN). 5).