Paclitaxel

Renal Impairment No adjustment of the starting paclitaxel protein-bound particles for injectable suspension (albumin-bound) dose is required for patients with mild to moderate renal impairment (estimated creatinine clearance 30 to <90 mL/min) [see Clinical Pharmacology] . There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min).

Dosage Modifications for Hepatic Impairment For patients with moderate or severe hepatic impairment, reduce the starting dose of paclitaxel protein-bound particles for injectable suspension (albumin-bound) as shown in Table 1. [See table below.]

Important Administration Instructions DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS. Paclitaxel protein-bound particles for injectable suspension (albumin-bound) has different dosage and administration instructions from other paclitaxel products. Closely monitor the infusion site for extravasation or drug infiltration during administration.

Limiting the infusion of paclitaxel protein-bound particles for injectable suspension (albumin-bound) to 30 minutes may reduce the risk of infusion-related reactions [see Adverse Reactions]. Consider premedication in patients who have had prior hypersensitivity reactions to paclitaxel protein-bound particles for injectable suspension (albumin-bound).

Do not re-challenge patients who experience a severe hypersensitivity reaction to paclitaxel protein-bound particles for injectable suspension (albumin-bound) [see Contraindications and Warnings and Precautions] .

Preparation for Intravenous Administration Paclitaxel is a cytotoxic drug. Follow applicable special handling and disposal procedures.1 The use of gloves is recommended. If paclitaxel protein-bound particles for injectable suspension (albumin-bound) (lyophilized cake or reconstituted suspension) contacts the skin, wash the skin immediately and thoroughly with soap and water.

Following topical exposure to paclitaxel, events may include tingling, burning, and redness. If paclitaxel protein-bound particles for injectable suspension (albumin-bound) contacts mucous membranes, the membranes should be flushed thoroughly with water. Paclitaxel protein-bound particles for injectable suspension (albumin-bound) is supplied as a sterile lyophilized powder for reconstitution before use.

Read the entire preparation instructions prior to reconstitution . 1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP. 2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over a minimum of 1 minute, using the sterile syringe to direct the solution flow onto the INSIDE WALL OF THE VIAL. 3.

DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized cake as this will result in foaming. 4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of the lyophilized cake/powder. 5. Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/powder occurs.

Avoid generation of foam. 6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides. Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel. The reconstituted suspension should be milky and homogenous without visible particulates. If particulates or settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use.

Discard the reconstituted suspension if precipitates are observed. Discard any unused portion. Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient and slowly withdraw the dosing volume of the reconstituted suspension from the vial(s) into a syringe: Dosing volume (mL)=Total dose (mg)/5 (mg/mL).

Inject the appropriate amount of reconstituted paclitaxel protein-bound particles for injectable suspension (albumin-bound) into an empty, sterile intravenous bag [plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type intravenous bag]. The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer paclitaxel protein-bound particles for injectable suspension (albumin-bound) infusions.

The use of medical devices containing silicone oil as a lubricant (i.e., syringes and intravenous bags) to reconstitute and administer paclitaxel protein-bound particles for injectable suspension (albumin-bound) may result in the formation of proteinaceous strands. Visually inspect the reconstituted paclitaxel protein-bound particles for injectable suspension (albumin‑bound) suspension in the intravenous bag prior to administration.

Discard the reconstituted suspension if proteinaceous strands, particulate matter, or discoloration are observed. Image

Stability Unopened vials of paclitaxel protein-bound particles for injectable suspension (albumin-bound) are stable until the date indicated on the package when stored between 20ºC to 25ºC (68ºF to 77ºF) in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Stability of Reconstituted Suspension in the Vial Reconstituted paclitaxel protein-bound particles for injectable suspension (albumin-bound) in the vial should be used immediately, but may be refrigerated at 2ºC to 8ºC (36ºF to 46ºF) for a maximum of 24 hours if necessary.

If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion. Stability of Reconstituted Suspension in the Infusion Bag The suspension for infusion when prepared as recommended in an infusion bag should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) and protected from bright light for a maximum of 24 hours.

The total combined refrigerated storage time of reconstituted paclitaxel protein-bound particles for injectable suspension (albumin-bound) in the vial and in the infusion bag is 24 hours. This may be followed by storage in the infusion bag at ambient temperature (approximately 25°C) and lighting conditions for a maximum of 4 hours.

Discard any unused portion.