PADCEV EJFV Powder for solution for injection Ref.[10213] Active ingredients: Enfortumab vedotin

Source: FDA, National Drug Code (US)  Revision Year: 2020 

1. Indications and Usage

PADCEV is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.

This indication is approved under accelerated approval based on tumor response rate [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

2. Dosage and Administration

2.1 Recommended Dosage

The recommended dose of PADCEV is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) administered as an intravenous infusion over 30 minutes on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

2.2 Dose Modifications

Table 1. Dose Modifications:

Adverse Reaction Severity* Dose Modification*
Hyperglycemia [see Warnings and Precautions (5.1)] Blood glucose >250 mg/dL Withhold until elevated blood glucose has improved to ≤250 mg/dL, then resume treatment at the same dose level.
Peripheral Neuropathy [see Warnings and Precautions (5.2)] Grade 2 Withhold until Grade ≤1, then resume treatment at the same dose level (if first occurrence). For a recurrence, withhold until Grade ≤1 then, resume treatment reduced by one dose level.
Grade ≥3 Permanently discontinue.
Skin Reactions [see Warnings and Precautions (5.4)] Grade 3 (severe) Withhold until Grade ≤1, then resume treatment at the same dose level or consider dose reduction by one dose level.
Grade 4 or recurrent Grade 3 Permanently discontinue.
Other nonhematologic toxicity Grade 3 Withhold until Grade ≤1, then resume treatment at the same dose level or consider dose reduction by one dose level
Grade 4 Permanently discontinue.
Hematologic toxicity Grade 3, or Grade 2 thrombocytopenia Withhold until Grade ≤1, then resume treatment at the same dose level or consider dose reduction by one dose level.
Grade 4 Withhold until Grade ≤1, then reduce dose by one dose level or discontinue treatment.

Table 2. Recommended Dose Reduction Schedule

 Dose Level
Starting dose 1.25 mg/kg up to 125 mg
First dose reduction 1.0 mg/kg up to 100 mg
Second dose reduction 0.75 mg/kg up to 75 mg
Third dose reduction 0.5 mg/kg up to 50 mg

2.3 Instructions for Preparation and Administration

  • Administer PADCEV as an intravenous infusion only.
  • PADCEV is a cytotoxic drug. Follow applicable special handling and disposal procedures1.

Prior to administration, the PADCEV vial is reconstituted with Sterile Water for Injection (SWFI). The reconstituted solution is subsequently diluted in an intravenous infusion bag containing either 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer’s Injection, USP.

Reconstitution in single-dose vial

  • Follow procedures for proper handling and disposal of anticancer drugs.
  • Use appropriate aseptic technique for reconstitution and preparation of dosing solutions.
  • Calculate the recommended dose based on the patient’s weight to determine the number and strength (20 mg or 30 mg) of vials needed.
  • Reconstitute each vial as follows and, if possible, direct the stream of SWFI along the walls of the vial and not directly onto the lyophilized powder:
    • 20 mg vial: Add 2.3 mL of SWFI, resulting in 10 mg/mL PADCEV.
    • 30 mg vial: Add 3.3 mL of SWFI, resulting in 10 mg/mL PADCEV.
  • Slowly swirl each vial until the contents are completely dissolved. Allow the reconstituted vial(s) to settle for at least 1 minute until the bubbles are gone. DO NOT SHAKE THE VIAL. Do not expose to direct sunlight.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be clear to slightly opalescent, colorless to light yellow and free of visible particles. Discard any vial with visible particles or discoloration.
  • Based upon the calculated dose amount, the reconstituted solution from the vial(s) should be added to the infusion bag immediately. This product does not contain a preservative. If not used immediately, reconstituted vials may be stored for up to 4 hours in refrigeration at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE. Discard unused vials with reconstituted solution beyond the recommended storage time.

Dilution in infusion bag

  • Withdraw the calculated dose amount of reconstituted solution from the vial(s) and transfer into an infusion bag.
  • Dilute PADCEV with either 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection. The infusion bag size should allow enough diluent to achieve a final concentration of 0.3 mg/mL to 4 mg/mL PADCEV.
  • Mix diluted solution by gentle inversion. DO NOT SHAKE THE BAG. Do not expose to direct sunlight.
  • Visually inspect the infusion bag for any particulate matter or discoloration prior to use. The reconstituted solution should be clear to slightly opalescent, colorless to light yellow and free of visible particles. DO NOT USE the infusion bag if particulate matter or discoloration is observed.
  • Discard any unused portion left in the single-dose vials.

Administration

  • Immediately administer the infusion over 30 minutes through an intravenous line.
  • If the infusion is not administered immediately, the prepared infusion bag should not be stored longer than 8 hours at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE.

DO NOT administer PADCEV as an intravenous push or bolus.

DO NOT mix PADCEV with, or administer as an infusion with, other medicinal products.

16.2. Storage and Handling

Store PADCEV vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Do not shake.

Special Handling

PADCEV is a cytotoxic drug. Follow applicable special handling and disposal procedures.

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