Jevtana Adverse Reactions

Summary of Safety Profile: The safety of JEVTANA in combination with prednisone or prednisolone was evaluated in 371 patients with metastatic castration resistant prostate cancer who were treated with 25 mg/m² cabazitaxel once every three weeks in a randomised open label, controlled phase III study. Patients received a median duration of 6 cycles of cabazitaxel.
The most commonly (≥ 10%) occurring adverse reactions in all grades were anaemia (97.3%), leukopenia (95.7%), neutropenia (93.5%), thrombocytopenia (47.4%), and diarrhoea (46.6%). The most commonly (≥ 5%) occurring grade ≥ 3 adverse reactions in the cabazitaxel group were neutropenia (81.7%), leukopenia (68.2%), anaemia (10.5%), febrile neutropenia (7.5%), diarrhoea (6.2%).
Discontinuation of treatment due to adverse reactions occurred in 68 patients (18.3%) receiving cabazitaxel. The most common adverse reactions leading to cabazitaxel discontinuation was neutropenia.
Tabulated List of Adverse Reactions: Adverse reactions are listed in Table 5 according to MedDRA system organ class and frequency categories. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Intensity of the adverse reactions is graded according to CTCAE 4.0 (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). (See Table 5.)

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Description of Selected Adverse Reactions: Neutropenia, and Associated Clinical Events: Incidence of grade ≥ 3 neutropenia based on laboratory data was 81.7%. The incidence of grade ≥ 3 clinical neutropenia and febrile neutropenia adverse reactions were 21.3% and 7.5% respectively. Neutropenia was the most common adverse reaction leading to medicinal product discontinuation (2.4%).
Neutropenic complications included neutropenic infections (0.5%), neutropenic sepsis (0.8%), and septic shock (1.1%), which in some cases resulted in a fatal outcome.
The use of G-CSF has been shown to limit the incidence and severity of neutropenia (see Dosage & Administration and Precautions).
Cardiac Disorders and Arrhythmias: All Grade events among cardiac disorders were more common on cabazitaxel of which 6 patients (1.6%) had Grade ≥ 3 cardiac arrhythmias. The incidence of tachycardia on cabazitaxel was 1.6%, none of which were Grade ≥ 3. The incidence of atrial fibrillation was 1.1% in the cabazitaxel group. Cardiac failure events were more common on cabazitaxel, the event term being reported for 2 patients (0.5%). One patient in the cabazitaxel group died from cardiac failure. Fatal ventricular fibrillation was reported in 1 patient (0.3%), and cardiac arrest in 2 patients (0.5%). None were considered related by the investigator.
Haematuria: Haematuria all grades frequency was 20.8% at 25 mg/m² in EFC11785 study (see Pharmacology: Pharmacodynamics under Actions). Confounding causes such as disease progression, instrumentation, infection or anticoagulation/NSAID/aspirin therapy were identified in nearly two thirds of the cases.
Other Laboratory Abnormalities: The incidence of grade ≥ 3 anaemia, increased AST, ALT, and bilirubin based on laboratory abnormalities were 10.5%, 0.7%, 0.9%, and 0.6%, respectively.
Gastrointestinal Disorders: Colitis, enterocolitis, gastritis, neutropenic enterocolitis have been observed. Gastrointestinal hemorrhage and perforation, ileus and intestinal obstruction have also been reported (see Precautions).
Respiratory disorders: Cases of interstitial pneumonia/pneumonitis and interstitial lung disease, sometimes fatal have been reported with an unknown frequency (cannot be estimated from the available data) (see Precautions).
Renal and urinary disorders: Cystitis due to radiation recall phenomenon, including haemorrhagic cystitis, were reported uncommonly.
Paediatric Population: (see Dosage & Administration).
Other Special Populations: Elderly Population: Among the 371 patients treated with cabazitaxel in the prostate cancer study, 240 patients were 65 years or over including 70 patients older than 75 years.
The following adverse reactions reported at rates ≥ 5% higher in patients 65 years of age or greater compared to younger patients: fatigue (40.4% versus 29.8%), clinical neutropenia (24.2% versus 17.6%), asthenia (23.8% versus 14.5%), pyrexia (14.6% versus 7.6%), dizziness (10.0% versus 4.6%), urinary tract infection (9.6% versus 3.1%) and dehydration (6.7% versus 1.5%), respectively.
The incidence of the following grade ≥ 3 adverse reactions were higher in patients ≥ 65 years of age compared to younger patients; neutropenia based on laboratory abnormalities (86.3% versus 73.3%), clinical neutropenia (23.8% versus 16.8%) and febrile neutropenia (8.3% versus 6.1%) (see Dosage & Administration and Precautions).
Of the 595 patients treated with cabazitaxel 25 mg/m² in the prostate cancer EFC 11785 study, 420 patients were 65 years or over. The adverse reactions reported at rates of at least 5% higher in patients 65 years of age or greater compared to younger patients were diarrhoea (42.9% vs. 32.6%), fatigue (30.2% vs. 19.4%), asthenia (22.4% vs. 13.1%), constipation (20.2% vs. 12.6%), clinical neutropenia (12.9% vs. 6.3%), febrile neutropenia (11.2% vs. 4.6%) and dyspnoea (9.5% vs. 3.4%).