Bortezomib

Renal Impairment No starting dosage adjustment of bortezomib is recommended for patients with renal impairment. In patients requiring dialysis, bortezomib should be administered after the dialysis procedure [see Clinical Pharmacology] .

Dosage in Patients with Hepatic Impairment Do not adjust the starting dose for patients with mild hepatic impairment. Start patients with moderate or severe hepatic impairment at a reduced dose of 0.7 mg/m 2 per injection during the first cycle, and consider subsequent dose escalation to 1 mg/m 2 or further dose reduction to 0.5 mg/m 2 based on patient tolerance (see Table 6) [see Use in Specific Populations, Clinical Pharmacology] . [See table below.] None Moderate More than 1.5 x to 3 x ULN Any Reduce bortezomib for injection to 0.7 mg/m 2 in the first cycle.

Consider dose escalation to 1 mg/m 2 or further dose reduction to 0.5 mg/m 2 in subsequent cycles based on patient tolerability. Severe More than 3 x ULN Any

Administration Precautions The drug quantity contained in one vial (3.5 mg) may exceed the usual dose required. Caution should be used in calculating the dose to prevent overdose [ see Dosage and Administration ]. When administered subcutaneously, sites for each injection (thigh or abdomen) should be rotated. New injections should be given at least one inch from an old site and never into areas where the site is tender, bruised, erythematous, or indurated.

If local injection site reactions occur following bortezomib for injection administration subcutaneously, a less concentrated bortezomib for injection solution (1 mg/mL instead of 2.5 mg/mL) may be administered subcutaneously [see Dosage and Administration] . Alternatively, consider use of the intravenous route of administration [see Dosage and Administration] .

Bortezomib for injection is a hazardous drug. Follow applicable special handling and disposal procedures. 1 .

Reconstitution/Preparation for Intravenous and Subcutaneous Administration Use proper aseptic technique. Reconstitute only with 0.9% sodium chloride . The reconstituted product should be a clear and colorless solution. Different volumes of 0.9% sodium chloride are used to reconstitute the product for the different routes of administration.

The reconstituted concentration of bortezomib for subcutaneous administration (2.5 mg/mL) is greater than the reconstituted concentration of bortezomib for intravenous administration (1 mg/mL). Because each route of administration has a different reconstituted concentration, use caution when calculating the volume to be administered [see Dosage and Administration] .

For each 3.5 mg single-dose vial of bortezomib, reconstitute with the following volume of 0.9% sodium chloride based on route of administration ( Table 7 ): [See table below.] Dose must be individualized to prevent overdosage. After determining patient body surface area (BSA) in square meters, use the following equations to calculate the total volume (mL) of reconstituted bortezomib for injection to be administered: Intravenous Administration [1 mg/mL concentration ] Subcutaneous Administration [2.5 mg/mL concentration] Stickers that indicate the route of administration are provided with each bortezomib for injection vial.

These stickers should be placed directly on the syringe of bortezomib for injection once bortezomib for injection is prepared to help alert practitioners of the correct route of administration for bortezomib for injection. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

If any discoloration or particulate matter is observed, the reconstituted product should not be used. Stability Unopened vials of bortezomib for injection are stable until the date indicated on the package when stored in the original package protected from light. Bortezomib for injection contains no antimicrobial preservative.

Administer reconstituted bortezomib for injection within eight hours of preparation. When reconstituted as directed, bortezomib for injection may be stored at 25°C (77°F). The reconstituted material may be stored in the original vial and/or the syringe prior to administration. The product may be stored for up to eight hours in a syringe; however, total storage time for the reconstituted material must not exceed eight hours when exposed to normal indoor lighting.