openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS • Bone marrow suppression (particularly neutropenia) and its clinical consequences (febrile neutropenia, neutropenic infections, and death): Monitor blood counts frequently to determine if dosage modification or initiation of G-CSF is needed. Closely monitor patients with hemoglobin <10 g/dL. ( 2.2 , 4 , 5.1 ) • Increased toxicities in elderly patients: Patients ≥65 years of age were more likely to experience fatal outcomes and certain adverse reactions, including neutropenia and febrile neutropenia. Monitor closely. ( 5.2 , 8.5 ) • Hypersensitivity: Severe hypersensitivity reactions can occur. Premedicate with corticosteroids and H2 antagonists. Discontinue infusion immediately if hypersensitivity is observed and treat as indicated. ( 4 , 5.3 ) • Gastrointestinal disorders: Nausea, vomiting, and diarrhea may occur. Mortality related to diarrhea has been reported. Rehydrate and treat with antiemetics and antidiarrheals as needed. If experiencing Grade ≥3 diarrhea, dosage should be modified. ( 2.2 ) Deaths have occurred due to gastrointestinal hemorrhage, perforation and neutropenic enterocolitis. Delay or discontinue Cabazitaxel Injection and treat as indicated. ( 5.4 ) • Renal failure, including cases with fatal outcomes, has been reported. Identify cause and manage aggressively. ( 5.5 ) • Urinary disorders including cystitis: Cystitis, radiation cystitis, and hematuria may occur. Monitor patients who previously received pelvic radiation for signs and symptoms of cystitis. Interrupt or discontinue Cabazitaxel Injection and provide medical or surgical supportive care, as needed, in patients experiencing severe hemorrhagic cystitis. • Respiratory disorders: Interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome, including fatal outcomes, have been reported. Delay or discontinue Cabazitaxel Injection and treat as indicated. ( 5.7 ) • Hepatic impairment: Administer Cabazitaxel Injection at a dose of 20 mg/m 2 in patients with mild hepatic impairment. Administer Cabazitaxel Injection at a dose of 15 mg/m 2 in patients with moderate hepatic impairment. ( 2.3 , 5.8 ) • Embryo-fetal toxicity: Cabazitaxel Injection can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception. ( 5.9 , 8.1 , 8.3 ) 5.1 Bone Marrow Suppression Cabazitaxel Injection is contraindicated in patients with neutrophils ≤1,500/mm 3 [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. 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)] . PROSELICA Trial In the PROSELICA trial comparing two doses of cabazitaxel, 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/m 2 died from infection; of these, 4 deaths on the 20 mg/m 2 arm occurred within the first 30 days of treatment. Clinically important neutropenia-related events occurred and included febrile neutropenia (2.1% on 20 mg/m 2 arm), neutropenic infection/sepsis (2.1% on 20 mg/m 2 arm), and neutropenic deaths (0.3% on 20 mg/m 2 arm). Patients receiving cabazitaxel 20 mg/m 2 were reported to have infectious adverse reactions. Grade 1-4 infections were experienced by 160 patients (28%) on the 20 mg/m 2 arm. Grade 3-4 infections were experienced by 57 patients (10%) on the 20 mg/m 2 arm. 5.2 Increased Toxicities in Elderly Patients In a randomized clinical trial (PROSELICA) comparing two doses of cabazitaxel, deaths due to infection within 30 days of starting cabazitaxel occurred in 0.7% (4/580) patients on the 20 mg/m 2 arm; all of these patients were >60 years of age. In PROSELICA, on the 20 mg/m 2 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 cabazitaxel dose. 5.3 Hypersensitivity Reactions Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of Cabazitaxel Injection, 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 Cabazitaxel Injection [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 cabazitaxel infusion and appropriate therapy. Cabazitaxel Injection 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, anti-diarrheal or anti-emetic 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 cabazitaxel [see Adverse Reactions ( 6.2 )] . Risk may be increased with neutropenia, age, steroid use, concomitant use of NSAIDs, anti-platelet therapy or anti-coagulants, 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. Cabazitaxel Injection 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. 5.5 Renal Failure Renal failure, including with fatal outcome, occurred in patients being treated with cabazitaxel at a higher dose. 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. 5.6 Urinary Disorders Including Cystitis Cystitis, radiation cystitis, and hematuria, including that requiring hospitalization, has been reported with cabazitaxel in patients who previously received pelvic radiation [see Adverse Reactions ( 6.2 )] . In PROSELICA, cystitis and radiation cystitis were reported in 1.2% and 1.5% of patients who received prior radiation, respectively. Hematuria was reported in 19.4% of patients who received prior radiation and in 14.4% of patients who did not receive prior radiation. Cystitis from radiation recall may occur late in treatment with cabazitaxel. Monitor patients who previously received pelvic radiation for signs and symptoms of cystitis while on Cabazitaxel Injection. Interrupt or discontinue Cabazitaxel Injection in patients experiencing severe hemorrhagic cystitis. Medical and/or surgical supportive treatment may be required to treat severe hemorrhagic cystitis. 5.7 Respiratory Disorders Interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome have been reported and may be associated with fatal outcome [see Adverse Reactions ( 6.2 )] . Patients with underlying lung disease may be at higher risk for these events. Acute respiratory distress syndrome may occur in the setting of infection. Interrupt Cabazitaxel Injection if new or worsening pulmonary symptoms develop. Closely monitor, promptly investigate, and appropriately treat patients receiving Cabazitaxel Injection. Consider discontinuation. The benefit of resuming Cabazitaxel Injection treatment must be carefully evaluated. 5.8 Use in Patients with Hepatic Impairment Cabazitaxel is extensively metabolized in the liver. Cabazitaxel Injection is contraindicated in patients with severe hepatic impairment (total bilirubin > 3 × ULN) [see Contraindications ( 4 )] . Dose should be reduced for patients with mild (total bilirubin > 1 to ≤ 1.5 × ULN or AST > 1.5 × ULN) and moderate (total bilirubin > 1.5 to ≤ 3.0 × ULN and any AST) hepatic impairment, based on tolerability data in these patients [see Dosage and Administration ( 2.3 ) and Use in Specific Populations ( 8.7 )] . Administration of Cabazitaxel Injection to patients with mild and moderate hepatic impairment should be undertaken with caution and close monitoring of safety.]. 5.9 Embryo-Fetal Toxicity Based on findings in animal reproduction studies and its mechanism of action, Cabazitaxel Injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, intravenous administration of cabazitaxel in pregnant rats during organogenesis caused embryonic and fetal death at doses lower than the maximum recommended human dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of Cabazitaxel Injection [see Use in Specific Populations ( 8.1 , 8.3 )] .