Cabazitaxel

Renal Impairment No dose adjustment is necessary in patients with renal impairment not requiring hemodialysis. Patients presenting with end-stage renal disease (creatinine clearance CL CR <15 mL/min/1.73 m 2 ), should be monitored carefully during treatment [see Clinical Pharmacology ] .

Dose Modifications for Hepatic Impairment Mild hepatic impairment (total bilirubin >1 to ≤1.5 × Upper Limit of Normal (ULN) or AST >1.5 × ULN): Administer JEVTANA at a dose of 20 mg/m 2 . Moderate hepatic impairment (total bilirubin >1.5 to ≤3 × ULN and AST = any): Administer JEVTANA at a dose of 15 mg/m 2 based on tolerability data in these patients; however, the efficacy of this dose is unknown.

Severe hepatic impairment (total bilirubin >3 × ULN): JEVTANA is contraindicated in patients with severe hepatic impairment [see Warning and Precautions and Clinical Pharmacology ] .

Preparation and Administration JEVTANA is a hazardous anticancer drug. Follow applicable special handling and disposal procedures [see References ] . If JEVTANA first diluted solution, or second (final) dilution for intravenous infusion should come into contact with the skin or mucous, immediately and thoroughly wash with soap and water.

Do not use PVC infusion containers or polyurethane infusions sets for preparation and administration of JEVTANA infusion solution. JEVTANA should not be mixed with any other drugs. Preparation Read this entire section carefully before mixing and diluting. JEVTANA requires two dilutions prior to administration. Follow the preparation instructions provided below, as improper preparation may lead to overdose [see Overdosage ].

Note: Both the JEVTANA injection and the diluent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the entire contents of the accompanying diluent, there is an initial diluted solution containing 10 mg/mL JEVTANA. Inspect the JEVTANA injection and supplied diluent vials.

The JEVTANA injection is a clear yellow to brownish-yellow viscous solution. Step 1 – first dilution Each vial of JEVTANA (cabazitaxel) 60 mg/1.5 mL must first be mixed with the entire contents of supplied diluent. Once reconstituted, the resultant solution contains 10 mg/mL of JEVTANA. When transferring the diluent, direct the needle onto the inside wall of JEVTANA vial and inject slowly to limit foaming.

Remove the syringe and needle and gently mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full mixing of the drug and diluent. Do not shake. Let the solution stand for a few minutes to allow any foam to dissipate, and check that the solution is homogeneous and contains no visible particulate matter.

It is not required that all foam dissipate prior to continuing the preparation process. The resulting initial diluted JEVTANA solution (cabazitaxel 10 mg/mL) requires further dilution before administration. The second dilution should be done immediately (within 30 minutes) to obtain the final infusion as detailed in Step 2.

Step 2 – second (final) dilution Withdraw the recommended dose from the JEVTANA solution containing 10 mg/mL as prepared in Step 1 using a calibrated syringe and further dilute into a sterile 250 mL PVC-free container of either 0.9% sodium chloride solution or 5% dextrose solution for infusion. If a dose greater than 65 mg of JEVTANA is required, use a larger volume of the infusion vehicle so that a concentration of 0.26 mg/mL JEVTANA is not exceeded.

The concentration of the JEVTANA final infusion solution should be between 0.10 mg/mL and 0.26 mg/mL. Remove the syringe and thoroughly mix the final infusion solution by gently inverting the bag or bottle. As the final infusion solution is supersaturated, it may crystallize over time. Do not use if this occurs and discard.

Fully prepared JEVTANA infusion solution (in either 0.9% sodium chloride solution or 5% dextrose solution) should be used within 8 hours at ambient temperature (including the one-hour infusion), or for a total of 24 hours (including the one-hour infusion) under the refrigerated conditions. Discard any unused portion. Administration Inspect visually for particulate matter, any crystals and discoloration prior to administration.

If the JEVTANA first diluted solution or second (final) infusion solution is not clear or appears to have precipitation, it should be discarded. Use an in-line filter of 0.22 micrometer nominal pore size (also referred to as 0.2 micrometer) during administration. The final JEVTANA infusion solution should be administered intravenously as a one-hour infusion at room temperature.