Jevtana (Page 2 of 8)

3 DOSAGE FORMS AND STRENGTHS

JEVTANA (cabazitaxel) injection is supplied as a kit consisting of the following:

  • Cabazitaxel injection: 60 mg/1.5 mL; a clear yellow to brownish-yellow viscous solution
  • Diluent: 5.7 mL of 13% (w/w) ethanol in water; a clear colorless solution

4 CONTRAINDICATIONS

JEVTANA is contraindicated in patients with:

5 WARNINGS AND PRECAUTIONS

5.1 Bone Marrow Suppression

JEVTANA is contraindicated in patients with neutrophils ≤1,500/mm3 [see Contraindications (4)]. Closely monitor patients with hemoglobin <10 g/dL.

Bone marrow suppression manifested as neutropenia, anemia, thrombocytopenia and/or pancytopenia may occur. Neutropenic deaths have been reported.

TROPIC Trial (JEVTANA 25 mg/m2)

In the TROPIC trial with G-CSF administered only at the investigator’s discretion, 5 patients (1.3%) died from neutropenic infection (sepsis or septic shock); 4 of these patients died in the first 30 days of treatment. One additional patient’s death was attributed to neutropenia without a documented infection. Twenty-two (6%) patients discontinued JEVTANA treatment due to neutropenia, febrile neutropenia, infection, or sepsis. Grade 3–4 neutropenia occurred in 82% of patients treated with JEVTANA in the randomized trial [see Adverse Reactions (6.1)].

PROSELICA Trial (comparison of JEVTANA 20 mg/m2 versus 25 mg/m2)

In the PROSELICA trial comparing two doses of JEVTANA, primary prophylaxis with G-CSF was not allowed, but could be administered after development of neutropenia at investigators discretion. Eight patients (1%) on the 20 mg/m2 arm and 15 patients (3%) on the 25 mg/m2 arm died from infection; of these, 4 deaths on the 20 mg/m2 arm and 8 deaths on the 25 mg/m2 arm occurred within the first 30 days of treatment. Clinically important neutropenia-related events occurred and included febrile neutropenia (2.1% on 20 mg/m2 arm and 9.2% on 25 mg/m2 arm), neutropenic infection/sepsis (2.1% on 20 mg/m2 arm and 6.4% on 25 mg/m2 arm), and neutropenic deaths (0.3% on 20 mg/m2 arm and 0.7% on 25 mg/m2 arm).

Fewer patients receiving JEVTANA 20 mg/m2 were reported to have infectious adverse reactions. Grade 1–4 infections were experienced by 160 patients (28%) on the 20 mg/m2 arm and 227 patients (38%) on the 25 mg/m2 arm. Grade 3–4 infections were experienced by 57 patients (10%) on the 20 mg/m2 arm and 120 patients (20%) on the 25 mg/m2 arm. Noninferiority for overall survival was demonstrated between these two arms [see Adverse Reactions (6.1)].

CARD Trial (JEVTANA 25 mg/m2 + primary prophylaxis G-CSF)

In the CARD trial where JEVTANA 25 mg/m2 was administered with primary prophylaxis of G-CSF, 1 patient (0.8%) died from sepsis within the first 30 days of treatment. Grade 1–4 neutropenia-related adverse reactions were experienced in 33 patients (26%). Grade 3–4 neutropenias were experienced by 26 patients (21%). Clinically important neutropenia-related events occurred and included febrile neutropenia (3.2%), neutropenic infection/sepsis (0.8%) and neutropenic deaths (0.8%) [see Adverse Reactions (6.1)].

Based on guidelines for the use of G-CSF and the adverse reactions profile of JEVTANA, primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features (older patients, 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. Consider primary prophylaxis with G-CSF in all patients receiving JEVTANA 25 mg/m2.

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 [see Dosage and Administration (2.2)].

5.2 Increased Toxicities in Elderly Patients

In a randomized trial (TROPIC), 2% of patients (3/131) <65 years of age and 6% (15/240) ≥65 years of age died of causes other than disease progression within 30 days of the last JEVTANA dose. Patients ≥65 years of age are more likely to experience certain adverse reactions, including neutropenia and febrile neutropenia. The incidence of the following grade 3–4 adverse reactions was higher in patients ≥65 years of age compared to younger patients; neutropenia (87% vs 74%), and febrile neutropenia (8% vs 6%).

In a randomized clinical trial (PROSELICA) comparing two doses of JEVTANA, deaths due to infection within 30 days of starting JEVTANA occurred in 0.7% (4/580) patients on the 20 mg/m2 arm and 1.3% (8/595) patients on the 25 mg/m2 arm; all of these patients were >60 years of age.

In PROSELICA, on the 20 mg/m2 arm, 3% (5/178) of patients <65 years of age and 2% (9/402) ≥65 years of age died of causes other than disease progression within 30 days of the last JEVTANA dose. On the 25 mg/m2 arm, 2% (3/175) patients <65 years of age and 5% (20/420) ≥65 years of age died of causes other than disease progression within 30 days of the last JEVTANA dose [see Adverse Reactions (6) and Use in Specific Populations (8.5)].

In CARD, a death due to infection within 30 days of starting JEVTANA occurred in 0.8% (1/126) patient who was >75 years of age. There were 2.4% (3/126) of patients who died of causes other than disease progression within 30 days of the last JEVTANA dose; all of these patients were >75 years of age.

5.3 Hypersensitivity Reactions

Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of JEVTANA, thus facilities and equipment for the treatment of hypotension and bronchospasm should be available. Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension and bronchospasm.

Premedicate all patients prior to the initiation of the infusion of JEVTANA [see Dosage and Administration (2.1)]. Observe patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions require immediate discontinuation of the JEVTANA infusion and appropriate therapy. JEVTANA is contraindicated in patients with a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80 [see Contraindications (4)].

5.4 Gastrointestinal Adverse Reactions

Nausea, vomiting and severe diarrhea, at times, may occur. Deaths related to diarrhea and electrolyte imbalance occurred in the randomized clinical trials. Intensive measures may be required for severe diarrhea and electrolyte imbalance. Antiemetic prophylaxis is recommended. Treat patients with rehydration, antidiarrheal or antiemetic medications as needed. Treatment delay or dosage reduction may be necessary if patients experience Grade ≥3 diarrhea [see Dosage and Administration (2.2)].

Gastrointestinal (GI) hemorrhage and perforation, ileus, enterocolitis, neutropenic enterocolitis, including fatal outcome, have been reported in patients treated with JEVTANA [see Adverse Reactions (6.2)]. Risk may be increased with neutropenia, age, steroid use, concomitant use of NSAIDs, antiplatelet therapy or anticoagulants, and patients with a prior history of pelvic radiotherapy, adhesions, ulceration and GI bleeding.

Abdominal pain and tenderness, fever, persistent constipation, diarrhea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly. JEVTANA treatment delay or discontinuation may be necessary.

The incidence of gastrointestinal adverse reactions is greater in the patients who have received prior radiation. In PROSELICA, diarrhea was reported in 41% (297/732) of patients who had received prior radiation and in 27% (118/443) of patients without prior radiation. Of the patients who had previously received radiation, more patients on the 25 mg/m2 arm reported diarrhea, compared to patients on the 20 mg/m2 arm.

5.5 Renal Failure

In the randomized clinical trial (TROPIC), renal failure of any grade occurred in 4% of the patients being treated with JEVTANA, including four cases with fatal outcome. Most cases occurred in association with sepsis, dehydration, or obstructive uropathy [see Adverse Reactions (6.1)]. Some deaths due to renal failure did not have a clear etiology. Appropriate measures should be taken to identify causes of renal failure and treat aggressively.

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