Cabazitaxel

Deaths due to neutropenia have been reported. Monitor blood counts frequently. Cabazitaxel is contraindicated in patients with neutrophil count ≤1,500/mm3. Primary prophylaxis with filgrastim is recommended in patients with high-risk clinical features. Neutropenia, anemia, thrombocytopenia, and/or pancytopenia may occur; grade 3 and 4 neutropenia was observed in over 80% of patients treated with cabazitaxel in a clinical trial. Deaths due to neutropenia, neutropenic fever, or infection have been reported, and some have occurred during the first 30 days of therapy; the incidence of fatal neutropenic events was lower with the 20 mg/m2 dose. Treatment delay and dose reduction is recommended following neutropenic fever or prolonged neutropenia. Administration of WBC growth factors may reduce the risk of complications due to neutropenia. Although the efficacy of primary prophylaxis with WBC growth factor with cabazitaxel has not been studied, use is recommended in high-risk patients (eg, older patients, poor performance status, history of neutropenic fever, extensive prior radiation, poor nutrition status, other serious comorbidities); secondary prophylaxis and therapeutic WBC growth factors should be considered in all patients at increased risk for neutropenic complications. Closely monitor patients with hemoglobin • Gastrointestinal toxicity: Nausea, vomiting and diarrhea may occur. Diarrhea may be severe and may result in dehydration and electrolyte imbalance; fatalities have b

Severe hypersensitivity reactions, including generalized rash, erythema, hypotension, and bronchospasm may occur. Immediate discontinuation is required if hypersensitivity is severe; administer appropriate supportive medications. Premedicate with an IV antihistamine, corticosteroid, and H2 antagonist prior to infusion. Use in patients with history of severe hypersensitivity to cabazitaxel or other medications formulated with polysorbate 80 is contraindicated. Observe closely during infusion, especially during the first and second infusions; reaction may occur within minutes. Do not rechallenge after severe hypersensitivity reactions.

Interstitial pneumonia/pneumonitis, interstitial lung disease, and acute respiratory distress syndrome have been observed; may be fatal. Patients with underlying pulmonary disease may be at higher risk for these events. Acute respiratory distress syndrome may occur in the setting of infection. If new or worsening pulmonary symptoms develop, interrupt cabazitaxel treatment, monitor closely and promptly investigate and manage symptoms. May require discontinuation (carefully evaluate the potential benefits of treatment resumption).

Renal failure (including rare fatalities) has been reported from clinical trials; generally associated with dehydration, sepsis, or obstructive uropathy. Use with caution in patients with severe renal impairment (CrCl • Urinary disorders: Cystitis, radiation cystitis, and hematuria may occur in patients with prior history of pelvic radiation; hospitalizations have been reported. Cystitis due to radiation recall may occur late in cabazitaxel treatment. Monitor for signs/symptoms of cystitis in patients who received prior pelvic radiation. Interrupt or discontinue cabazitaxel in patients who experience severe hemorrhagic cystitis; may require medical and/or surgical supportive therapy. Disease-related concerns:

Use is contraindicated in patients with severe hepatic impairment (total bilirubin >3 times ULN). Use with caution and monitor closely in patients with mild impairment (total bilirubin >1 to ≤1.5 times ULN or AST >1.5 times ULN) and moderate impairment (total bilirubin >1.5 to ≤3 times ULN and any AST); reduce the initial dose in patients with moderate impairment. Due to extensive hepatic metabolism, cabazitaxel exposure is increased in patients with hepatic impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling. Special populations:

Patients ≥65 years of age are more likely to experience certain adverse reactions, neutropenia (including grades 3 and 4), and neutropenic fever. Fatigue, asthenia, pyrexia, dizziness, dyspnea, urinary tract infection, dehydration, diarrhea, and constipation also occurred more frequently in elderly patients compared to younger patients. Death due to infection within 30 days of starting treatment and due to causes other than disease progression (within 30 days of the last cabazitaxel dose) was higher in elderly patients versus younger patients. Other warnings/precautions:

Failure to properly reconstitute the concentrated vial of cabazitaxel with the correct amount of diluent may lead to higher dosage being administered and increased risk of toxicity. Follow manufacturer instructions carefully.