Jevtana Infusion

Metastatic prostate cancer

Prostate Cancer Indicated in combination with prednisone for metastatic castration-resistant prostate cancer in patients previously treated with a docetaxel-containing treatment regimen Injection 20 mg/m2 is administered every three weeks as a one-hour intravenous infusion in combination with oral prednisone 10 mg administered daily throughout Cabazitaxel Injection treatment. A dose of 25 mg/m2 can be used in select patients at the discretion of the treating healthcare provider. Dosage reductions If at 20 mg/m2: Reduce to 15 mg/m2 If at 25 mg/m2: Reduce to 20 mg/m2; once additional dose reduction to 15 mg/m2 may be considered Neutropenia Prolonged grade >3 neutropenia (>1 week) despite appropriate medication including G-CSF: Delay treatment until neutrophil count >1,500 cells/mm3, then reduce dose by 1 level; use G-CSF for secondary prophylaxis Febrile neutropenia or neutropenic infection: Delay treatment until improvement or resolution, and until neutrophil count >1,500 cells/mm3, then reduce dose by 1 level; use G-CSF for secondary prophylaxis Diarrhea Grade >3 or persisting despite appropriate medication, fluid, and electrolyte replacement: Delay treatment until improvement or resolution, then reduce dose by 1 level Peripheral neuropathy Grade 2: Delay treatment until improvement or resolution, then reduce dose by 1 level Grade >3: Discontinue Strong CYP3A4 inhibitors Avoid coadministration If unavoidable, consider reducing dose by 25%

Safety and efficacy not established

Renal impairment All severities (not requiring hemodialysis): No dosage adjustment necessary End-stage renal disease (CrCl <15 mL/min): Carefully monitor

No overall differences in effectiveness were observed between patients >65 years of age and younger patients. Elderly patients (>65 years of age) may be more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia The incidence of death due to causes other than disease progression within 30 days of the last cabazitaxel dose were higher in patients who were 65 years of age or greater compared to younger patients

Hepatic impairment Mild (total bilirubin [TB] >1 to <1.5x ULN or AST >1.5x ULN): Administer at a dose of 20 mg/m2 Moderate (TB >1.5 to ≤3x ULN and any AST): Reduce dose to 15 mg/m2; based on tolerability; efficacy of this dose is unknown Severe (TB >3x ULN): Contraindicated

IV Preparation Cytotoxic anticancer drug; follow applicable special handling and disposal procedure If diluted solutions come into contact with skin or mucous, immediately and thorough wash with soap and water Visually inspect single-dose vials; solution should be a clear yellow to brownish-yellow viscous solution Cabazitinib (20 mg/mL vial) Only requires 1 dilution Withdraw dose from the vial and further dilute into a sterile 250 mL PVC-free container of either 0.9% NaCl or D5W for infusion; concentration of final infusion solution should be 0.1-0.26 mg/mL For doses >65 mg, use a larger infusion bag (>250 mL PVC-free container) to assure 0.26 mg/mL concentration not exceeded Gently invert bag or bottle to thoroughly mix Final infusion solution is supersaturated and may crystallize over time; do not use if this occurs and discard IV Administration Visually inspect for particulate matter, any crystals, and discoloration before administering; discard dilution if not clear or appears to have precipitated Use an in-line filter of 0.22 micrometer nominal pore size (or 0.2 micrometer) Infuse over 1 hr at room temperature Premedication IV regimen Antihistamine (dexchlorpheniramine 5 mg, diphenhydramine 25 mg, or equivalent antihistamine) Corticosteroid (dexamethasone 8 mg or equivalent steroid) H2-antagonist (ranitidine 50-mg or equivalent H2-antagonist) Administer 30 minute before each cabazitaxel dose Primary prophylaxis with G-CSF Recommended in patients with high-risk clinical features Consider in all patients receiving 25 mg/m2

Patients with neutrophil counts of > 1,500/mm3. Patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80. Severe hepatic impairment (total bilirubin >3x ULN)

Neutropenia Neutropenic deaths reported Monitor for neutropenia with frequent blood cell counts Contraindicated with neutrophil counts <1,500 cell/mm3 Primary prophylaxis with G-CSF is recommended in high-risk patients Consider G-CSF prophylaxis with dose of 25 mg/m2 Severe hypersensitivity Severe hypersensitivity reactions can occur and may include generalized rash/erythema, hypotension, and bronchospasm Premedicate with IV antihistamine, corticosteroid, and H2 antagonist Contraindicated with history of severe hypersensitivity reactions to cabazitaxel or other drugs formulated with polysorbate 80 Immediately discontinue therapy if hypersensitivity occurs and initiate supportive treatment as indicated 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. 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. Hypersensitivity: Severe hypersensitivity reactions can occur. Premedicate with corticosteroids and H2 antagonists. Discontinue infusion immediately if hypersensitivity is observed and treat as indicated. 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. Deaths have occurred due to gastrointestinal hemorrhage, perforation and neutropenic enterocolitis. Delay or discontinue Cabazitaxel Injection and treat as indicated. Renal failure, including cases with fatal outcomes, has been reported. Identify cause and manage aggressively. Urinary disorders including cystitis: Cystitis, r

Not Classi Pregnancy Safety and efficacy not established in females No human data available on use in pregnant females Contraception Males with female partners of reproductive potential: Use effective contraception during treatment and for 4 months after final dose Infertility Fertility in males of reproductive potential may be impaired Animal data IV administration in pregnant rats during organogenesis cause embryonic and fetal death at doses lower than maximum recommended human dose Lactation Not indicated for use in females No data available on presence in human milk, effects on breastfed infants, or on milk production Drug or drug metabolites are excreted in maternal milk of lactating rats

Increased conc w/ strong CYP3A inhibitors (eg ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) & decreased conc w/ CYP3A inducers (eg phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarb). Serious or fatal infections w/ live or live attenuated vaccines. Risk of interaction w/ OATP1B1 substrates (eg statins, valsartan, repaglinide) during 1-hr & 20 min after infusion. Contraindicated (0) Serious (29) adenovirus types 4 and 7 live, oral BCG intravesical live BCG vaccine live clarithromycin conivaptan eslicarbazepine acetate etrasimod imatinib influenza virus vaccine quadrivalent, adjuvanted influenza virus vaccine trivalent, adjuvanted isoniazid itraconazole ketoconazole levoketoconazole lopinavir measles mumps and rubella vaccine, live measles, mumps, rubella and varicella vaccine, live nefazodone nicardipine palifermin posaconazole ropeginterferon alfa 2b rotavirus oral vaccine, live smallpox and mpox (vaccinia) vaccine, live typhoid vaccine live varicella virus vaccine live voriconazole yellow fever vaccine zoster vaccine live

>10% Anemia (11-98%),Leukopenia (69-96%),Neutropenia (82-94%),Thrombocytopenia (4-48%),Diarrhea (6-47%),Fatigue (5-37%),Nausea (2-34%),Vomiting (2-22%),Asthenia (5-20%),Constipation (1-20%),Abdominal pain (2-17%),Hematuria (2-17%),Anorexia (1-16%),Back pain/arthralgia (11-16%),Peripheral neuropathy (1-13%),Pyrexia (1-12%),Dyspnea (1-12%),Cough (11%),Dysgeusia (11%) 1-10% Dyspepsia (10%),Alopecia (10%),Peripheral edema (1-9%),Weight loss (9%),Dizziness (8%),Headache (8%),UTI (2-8%),Dysuria (7%),Febrile neutropenia (1-7%),Mucosal inflammation (1-6%),Hypotension (5%),Arrhythmia (1-5%)

Microtubule inhibitor; binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly; this results in microtubule stabilization, which results in the inhibition of mitotic and interphase cellular functions.

Jevtana 60 mg/1.5 ml Infusion manufactured by Synovia Pharma PLC. Its generic name is Cabazitaxel accton solvate.