Jevtana

Taxanes

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Low
Administer routine antiemetic prophylaxis prior to treatment.

Administer as an intravenous infusion.
Prior to administration, patients should have absolute neutrophil counts greater than 1,500 cells/mm3.
Do not use PVC infusion containers and polyurethane infusion sets for preparation and administration of cabazitaxel.
To prevent hypersensitivity reactions, all patients should be premedicated intravenously at least 30 minutes before cabazitaxel with an antihistamine (dexchlorpheniramine 5 mg, diphenhydramine 25 mg, or equivalent), a corticosteroid (dexamethasone 8 mg or equivalent), and an H2-antagonist. Antiemetic prophylaxis is also recommended.
Primary prophylaxis of neutropenia with G-CSF is recommended for high risk patients (e.g., older patients and those with poor performance status, previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities); also consider primary prophylaxis for all patients treated with a cabazitaxel dose of 25 mg/m2.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. If properly stored, undiluted cabazitaxel is a clear, yellow to brownish viscous solution.
If the cabazitaxel first diluted or second diluted solution is not clear or appears to have precipitation, discard the solution.
If the undiluted injection or the first or second diluted dilution comes into contact with mucosa, immediately and thoroughly wash with soap and water.

Cabazitaxel requires two dilutions prior to administration.
Both the cabazitaxel injection and the diluent vials contain an overfill to compensate for liquid loss during preparation; after dilution with the entire contents of the accompanying diluent, the initial diluted solution should have a concentration of 10 mg/mL.
First dilution:
Mix each vial of cabazitaxel injection (60 mg/1.5 mL) with the entire contents of the supplied diluent. After reconstitution, the resultant solution will have a cabazitaxel concentration of 10 mg/mL.
When transferring the diluent, direct the needle onto the inside wall of the vial and inject slowly to limit foaming. Remove the syringe and needle and gently mix by repeated inversions for at least 45 seconds to ensure complete mixing. Do not shake.
Let the solution stand for a few minutes to allow any foam to dissipate. Check that the solution is homogenous. It is not required that all foam dissipate prior to continuing the preparation process.
The resulting cabazitaxel solution (10 mg/mL) requires further dilution before administration. The second dilution should be done immediately (within 30 minutes) to obtain the final infusion.
Second dilution:
Withdraw the recommended dose from the vial containing the cabazitaxel solution after the initial dilution (10 mg/mL). Further dilute the withdrawn volume into a sterile 250 mL PVC-free container of either 0.9% Sodium Chloride injection or 5% Dextrose solution injection. If a cabazitaxel dose of 65 mg or greater is required, use a larger volume of the infusion vehicle so the concentration of the final infusion solution does not exceed 0.26 mg/mL.
The concentration of the final infusion solution should be 0.1 to 0.26 mg/mL.
Remove the syringe and needle and thoroughly mix the final infusion solution by gently inverting the bag or bottle.
Do not mix cabazitaxel with any other drugs.
The final solution is supersaturated and may crystallize over time. Discard the solution if this occurs.
The final infusion solution should be used within 8 hours (including the one-hour infusion) if stored at room temperature or within 24 hours (including the one-hour infusion) if stored under refrigeration.
Administration:
Administer cabazitaxel as an intravenous infusion over 1 hour at room temperature.
Use an in-line filter of 0.22 micrometer nominal pore size (0.2 micrometer) during infusion.

neutropenia / Delayed / 42.0-97.0
leukopenia / Delayed / 29.0-69.0
lymphopenia / Delayed / 0-27.0
infection / Delayed / 2.0-20.0
anemia / Delayed / 8.0-14.0
diarrhea / Early / 1.0-6.0
fatigue / Early / 3.0-5.0
asthenia / Delayed / 2.0-5.0
hematuria / Delayed / 0.8-4.0
back pain / Delayed / 0.9-4.0
thrombocytopenia / Delayed / 3.0-4.0
bone fractures / Delayed / 0-3.2
spinal cord compression / Delayed / 0-3.2
renal failure (unspecified) / Delayed / 0-2.4
hypertension / Early / 0-2.4
vomiting / Early / 0-2.0
nausea / Early / 0-2.0
dehydration / Delayed / 0-2.0
bone pain / Delayed / 0-2.0
abdominal pain / Early / 0.5-2.0
musculoskeletal pain / Early / 0-1.6
peripheral neuropathy / Delayed / 0-1.6
pulmonary embolism / Delayed / 0-1.6
arthralgia / Delayed / 0.5-1.0
dyspnea / Early / 0-1.0
anorexia / Delayed / 0-1.0
fever / Early / 0-1.0
peripheral edema / Delayed / 0-1.0
hyperbilirubinemia / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
constipation / Delayed / 0-1.0
hypotension / Rapid / 0-1.0
dysuria / Early / 0-0.3
stomatitis / Delayed / 0-0.3
headache / Early / 0-0.2
weight loss / Delayed / 0-0.2
hemorrhagic cystitis / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
atrial flutter / Early / Incidence not known
AV block / Early / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
palpitations / Early / Incidence not known
bradycardia / Rapid / Incidence not known
ventricular fibrillation / Early / Incidence not known
atrial tachycardia / Early / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
bronchospasm / Rapid / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
pulmonary edema / Early / Incidence not known
pancytopenia / Delayed / Incidence not known
enterocolitis / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known
ileus / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
hypertensive crisis / Early / Incidence not known

hypokalemia / Delayed / 0-3.2
cystitis / Delayed / 1.2-1.5
urinary retention / Early / Incidence not known
urinary incontinence / Early / Incidence not known
angina / Early / Incidence not known
interstitial lung disease / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
infusion-related reactions / Rapid / Incidence not known
erythema / Early / Incidence not known
bone marrow suppression / Delayed / Incidence not known
colitis / Delayed / Incidence not known
gastritis / Delayed / Incidence not known

cough / Delayed / 6.0-11.0
dysgeusia / Early / 7.0-11.0
dizziness / Early / 0.8-10.0
alopecia / Delayed / 3.0-10.0
dyspepsia / Early / 0-10.0
muscle cramps / Delayed / 0-7.0
paresthesias / Delayed / 0-6.0
insomnia / Early / 0-3.2
influenza / Delayed / Incidence not known
urinary urgency / Early / Incidence not known
nocturia / Early / Incidence not known
myalgia / Early / Incidence not known
malaise / Early / Incidence not known
lethargy / Early / Incidence not known
rash / Early / Incidence not known
gastroesophageal reflux / Delayed / Incidence not known

Cabazitaxel is contraindicated for use in patients with severe neutropenia (an absolute neutrophil count (ANC) 1,500 cells/mm3 or less); administer with caution to patients with a hemoglobin less than 10 g/dL. Monitor complete blood counts weekly during the first cycle and prior to each cycle thereafter; an interruption of therapy or dose reduction may be necessary. Bone marrow suppression, including severe neutropenia with some fatalities, anemia, and thrombocytopenia have been reported with cabazitaxel treatment. Primary prophylaxis of neutropenia is recommended in patients with high-risk features (older patients, poor performance status, poor nutritional status, previous febrile neutropenia, extensive prior radiation ports, or other serious comorbidities); consider primary prophylaxis with G-CSF in all patients receiving a cabazitaxel dose of 25 mg/m2.

Jevtana

Rx

Microtubule stabilizer; semi-synthetic taxane made from a precursor extracted from yew needles
Used for the treatment of metastatic hormone-refractory prostate cancer previously treated with docetaxel
Contraindicated in patients with severe hypersensitivity to cabazitaxel or other drugs formulated with polysorbate 80, ANC less than or equal to 1,500 cells/mm3, and severe hepatic impairment

20 mg/m2 IV over 1 hour on day 1 in combination with prednisone (10 mg PO once daily continuously); repeat cycles every 3 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. At least 30 minutes prior to each dose, premedicate with an IV antihistamine (dexchlorpheniramine 5 mg, diphenhydramine 25 mg, or equivalent), IV corticosteroid (dexamethasone 8 mg or equivalent), and IV H2 antagonist to reduce the risk of hypersensitivity; primary prophylaxis with G-CSF is recommended in older patients or those with poor performance status, previous febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities. A cabazitaxel dose of 25 mg/m2 IV can be used in select patients at the discretion of the treating healthcare provider; consider primary prophylaxis with G-CSF in all patients receiving this dose as it is associated with a higher incidence of hematologic toxicities. In a randomized clinical trial (the TROPIC study), overall survival was significantly increased in patients with metastatic castration-resistant prostate cancer (CRPC) treated with cabazitaxel 25 mg/m2 plus prednisone compared with mitoxantrone plus prednisone (15.1 vs. 12.7 months). A cabazitaxel dose of 20 mg/m2 was found to be non-inferior in terms of overall survival when compared with cabazitaxel 25 mg/m2 (13.4 vs. 14.5 months) in a separate multicenter, randomized, open-label clinical trial (PROSELICA).

Mild hepatic impairment (total bilirubin 1.1 to 1.5 times the upper limit of normal (ULN) or AST greater than 1.5 times the ULN): Administer cabazitaxel 20 mg/m2 IV.
Moderate hepatic impairment (total bilirubin 1.6 to 3 times the ULN and any AST): Reduce the starting dose of cabazitaxel to 15 mg/m2 based on tolerability data; the efficacy of this dose is unknown.
Severe hepatic impairment (total bilirubin greater than 3 times the ULN): Do not use cabazitaxel. Cabazitaxel treatment is contraindicated in patients with severe hepatic impairment.

No dose adjustment is necessary in patients with renal impairment not requiring hemodialysis. Carefully monitor patients with end-stage renal disease (ESRD; CrCL less than 15 mL/min/1.73 m2) during treatment.

Adagrasib: (Major) Avoid coadministration of cabazitaxel with adagrasib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A and adagrasib is a strong CYP3A inhibitor. In a drug interaction study, coadministration with another strong CYP3A inhibitor increased cabazitaxel exposure by 25%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of cabazitaxel with clarithromycin if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and clarithromycin is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Atazanavir: (Major) Avoid coadministration of cabazitaxel with atazanavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and atazanavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Atazanavir; Cobicistat: (Major) Avoid coadministration of cabazitaxel with atazanavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and atazanavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%. (Major) Avoid coadministration of cabazitaxel with cobicistat if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Ceritinib: (Major) Avoid coadministration of cabazitaxel with ceritinib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ceritinib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Chloramphenicol: (Major) Avoid coadministration of cabazitaxel with chloramphenicol if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and chloramphenicol is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Major) Avoid coadministration of cabazitaxel with clarithromycin if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and clarithromycin is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cobicistat: (Major) Avoid coadministration of cabazitaxel with cobicistat if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Darunavir: (Major) Avoid coadministration of cabazitaxel with darunavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and darunavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Darunavir; Cobicistat: (Major) Avoid coadministration of cabazitaxel with cobicistat if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%. (Major) Avoid coadministration of cabazitaxel with darunavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and darunavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of cabazitaxel with cobicistat if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%. (Major) Avoid coadministration of cabazitaxel with darunavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and darunavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Delavirdine: (Major) Avoid coadministration of cabazitaxel with delavirdine if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and delavirdine is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of cabazitaxel with cobicistat if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of cabazitaxel with cobicistat if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Erlotinib: (Moderate) The use of taxane-based chemotherapy with erlotinib appears to be one of the risk factors for gastrointestinal (GI) perforation with erlotinib. Monitor for symptoms of GI perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with a taxane chemotherapy agent is necessary.
Fosamprenavir: (Major) Avoid coadministration of cabazitaxel with fosamprenavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and fosamprenavir is a strong CYP3A4 inhibitor; data also suggest that fosamprenavir has the potential to induce CYP3A4. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%; concomitant use with a strong CYP3A4 inducer decreased cabazitaxel exposure by 17%.
Grapefruit juice: (Major) Avoid coadministration of cabazitaxel with grapefruit juice due to increased cabazitaxel exposure. Cabazitaxel is primarily metabolized by CYP3A4 and grapefruit juice is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Idelalisib: (Major) Avoid coadministration of cabazitaxel with idelalisib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Indinavir: (Major) Avoid coadministration of cabazitaxel with indinavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and indinavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Itraconazole: (Major) Avoid use of cabazitaxel during and for 2 weeks after discontinuation of itraconazole due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and itraconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Ketoconazole: (Major) Avoid coadministration of cabazitaxel with ketoconazole if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ketoconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ketoconazole increased cabazitaxel exposure by 25%.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of cabazitaxel with clarithromycin if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and clarithromycin is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Letermovir: (Moderate) A clinically significant increase in cabazitaxel exposure is not expected when coadministered with letermovir; however, if the patient is also receiving cyclosporine, increased cabazitaxel concentrations are possible. Consider a 25% reduction in the dose of cabazitaxel in patients who are also receiving cyclosporine. Cabazitaxel is a substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration of cabazitaxel with a moderate CYP3A4 inhibitor did not modify cabazitaxel exposure; however, when given with a strong CYP3A4 inhibitor, the cabazitaxel exposure increased by 25%.
Levoketoconazole: (Major) Avoid coadministration of cabazitaxel with ketoconazole if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ketoconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ketoconazole increased cabazitaxel exposure by 25%.
Lonafarnib: (Major) Avoid coadministration of cabazitaxel with lonafarnib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and lonafarnib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Lopinavir; Ritonavir: (Major) Avoid coadministration of cabazitaxel with ritonavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Mifepristone: (Major) Avoid coadministration of cabazitaxel with mifepristone if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Cabazitaxel is primarily metabolized by CYP3A4 and mifepristone is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Nefazodone: (Major) Avoid coadministration of cabazitaxel with nefazodone if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and nefazodone is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Nelfinavir: (Major) Avoid coadministration of cabazitaxel with nelfinavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and nelfinavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of cabazitaxel with ritonavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Posaconazole: (Major) Avoid coadministration of cabazitaxel with posaconazole if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and posaconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Ribociclib: (Major) Avoid coadministration of cabazitaxel with ribociclib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ribociclib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Ribociclib; Letrozole: (Major) Avoid coadministration of cabazitaxel with ribociclib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ribociclib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Ritonavir: (Major) Avoid coadministration of cabazitaxel with ritonavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Saquinavir: (Major) Avoid coadministration of cabazitaxel with saquinavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and saquinavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tipranavir: (Major) Avoid coadministration of cabazitaxel with tipranavir if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and tipranavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Tucatinib: (Major) Avoid coadministration of cabazitaxel with tucatinib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and tucatinib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of cabazitaxel with clarithromycin if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and clarithromycin is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Voriconazole: (Major) Avoid coadministration of cabazitaxel with voriconazole if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and voriconazole is a strong CYP3A4 inhibitor; however, the inhibitory potential is less with voriconazole than with ketoconazole and itraconazole. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.

Jevtana Intravenous Inj Sol: 1.5mL, 60mg

25 mg/m2 IV once every 3 weeks.

25 mg/m2 IV once every 3 weeks.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Cabazitaxel is a taxane derivative of the natural taxoid 10-deacetylbaccatin III prepared semi-synthetically with a precursor extracted from yew needles. Cabazitaxel binds to tubulin and promotes its assembly into microtubules. Simultaneously, cabazitaxel inhibits microtubule disassembly by stabilizing tubulin. This results in inhibition of microtubule depolymerization and cell division, cell cycle arrest (G2/M phase), and the inhibition of tumor cell proliferation. Unlike other taxanes, cabazitaxel is a poor substrate for the multidrug resistance P-glycoprotein efflux pump and may be useful for treating multidrug-resistant tumors. In addition, cabazitaxel penetrates the blood-brain barrier, where Pgp efflux pumps may serve as barriers.

Cabazitaxel is administered as an intravenous infusion. It is 89% to 92% protein bound, primarily to albumin (82%) and lipoproteins (HDL, 88%; LDL, 70%; VLDL, 56%); protein binding was not saturable at the maximum concentrations observed in clinical trials. In vitro blood-to-plasma concentrations indicate it is equally distributed between blood and plasma. The volume of distribution (Vd) at steady-state was 4,864 L (2,643 L/m2). Cabazitaxel is extensively metabolized in the liver (more than 95%), mainly by CYP3A4/5 (80% to 90%), and to a lesser extent by CYP2C8. Cabazitaxel is the main circulating moiety in human plasma. Seven metabolites were detected in plasma (including 3 active metabolites issued from O-demethylation), with the main one accounting for 5% of cabazitaxel exposure. Based on a population pharmacokinetic analysis, the plasma clearance of cabazitaxel is 48.5 L/hour (coefficient of variation (CV), 39%; 26.4 L/hour/m2). Approximately 80% of cabazitaxel is eliminated within 2 weeks of a 25 mg/m2 1-hour infusion. It is mainly (76%) eliminated in the feces as numerous metabolites, renal elimination accounts for 3.7% of a dose, with 2.3% as unchanged drug. Elimination is characterized by a 3-compartment pharmacokinetic model after a 1-hour infusion with alpha-, beta-, and gamma-half-lives of 4 minutes, 2 hours, and 95 hours, respectively.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4/5, CYP2C8, P-glycoprotein (P-gp)
Cabazitaxel is primarily metabolized by CYP3A, and to a lesser extent by CYP2C8; cabazitaxel is also a substrate of P-gp. Concomitant use with strong CYP3A inhibitors should be avoided if possible; if not possible, a 25% dose reduction of cabazitaxel should be considered. In a drug interaction study, coadministration with a strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%; however, concomitant use with a moderate CYP3A inhibitor did not affect cabazitaxel exposure. Coadministration with a strong CYP3A inducer decreased exposure by cabazitaxel by 17%. While cabazitaxel inhibits P-gp, BCRP, OATP1B1, and OATP1B3 in vitro, the in vivo risk is low at the recommended dose of 25 mg/m2; additionally, the risk of inhibition of CYP isoenzymes is low based on in vitro studies. Cabazitaxel did not affect exposure of midazolam, a probe substrate of CYP3A, in a drug interaction study.

Based on a population pharmacokinetic analysis, the mean Cmax in patients with metastatic prostate cancer was 226 ng/mL (CV, 107%), reached at the end of a 1-hour infusion (Tmax) of cabazitaxel 25 mg/m2; the mean AUC was 991 mL*ng/hour (CV, 34%). In patients with advanced solid tumors, no major deviation from dose proportionality was observed from 10 to 30 mg/m2.

Cabazitaxel should not be used in women who are breast-feeding; the safety and efficacy of cabazitaxel have not been established in females. Cabazitaxel and cabazitaxel metabolites are excreted in the breast milk of lactating rats; it is not known whether cabazitaxel is excreted in human breast milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from cabazitaxel, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.