Posology : מינונים

3 DOSAGE AND ADMINISTRATION
3.1 Recommended Dosage
The recommended dose of PADCEVTM 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.



3.2 Dose Modifications

Table 1. Dose Modifications
Adverse Reaction         Severity*                 Dose Modification* 
Immediately withhold, consult a specialist
Suspected SJS or to confirm the diagnosis. If not SJS/TEN,
TEN see Grade 3 skin reactions.
Skin Reactions
Confirmed SJS or
[see Boxed
TEN; Grade 4 or
Warning, Warnings                                  Permanently discontinue.
recurrent Grade 3 and Precautions skin reactions
(5.1)]
Withhold until Grade ≤ 1, then resume
Grade 3 (severe) treatment at the same dose level or skin reactions consider dose reduction by one dose level.
Hyperglycemia                                      Withhold until elevated blood glucose has Blood glucose
[see Warnings and                                  improved to ≤ 250 mg/dL, then resume > 250 mg/dL
Precautions (5.2)]                                 treatment at the same dose level.
Withhold until Grade < 1 for persistent or
Pneumonitis              Grade 2                   recurrent Grade 2 pneumonitis, consider [see Warnings and                                  dose reduction by one dose level.
Precautions (5.3)]
Grade > 3                 Permanently discontinue.
Withhold until Grade ≤ 1, then resume
Peripheral                                         treatment at the same dose level (if first Neuropathy               Grade 2                   occurrence). For a recurrence, withhold [see Warnings and                                  until Grade ≤ 1 then, resume treatment Precautions (5.4)]                                 reduced by one dose level.
Grade ≥ 3                 Permanently discontinue.
Withhold until Grade ≤ 1, then resume
Other                    Grade 3                   treatment at the same dose level or nonhematologic                                     consider dose reduction by one dose level.
toxicity
[see Adverse
Reactions (6)]           Grade 4                   Permanently discontinue.


Withhold until Grade ≤ 1, then resume
Grade 3, or Grade 2
Hematologic                                        treatment at the same dose level or thrombocytopenia toxicity                                           consider dose reduction by one dose level.
[see Adverse                                       Withhold until Grade ≤ 1, then reduce Reactions (6)]           Grade 4                   dose by one dose level or discontinue treatment.
*Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening 


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

3.3 Instructions for Preparation and Administration
•   Administer PADCEV as an intravenous infusion only.
•   PADCEV is a hazardous drug. Follow applicable special handling and disposal procedures.1 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, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection.
Reconstitution in single-dose vial
1. Follow procedures for proper handling and disposal of anticancer drugs.
2. Use appropriate aseptic technique for reconstitution and preparation of dosing solutions.
3. Calculate the recommended dose based on the patient’s weight to determine the number and strength (20 mg or 30 mg) of vials needed.
4. 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: a. 20 mg vial: Add 2.3 mL of SWFI, resulting in 10 mg/mL PADCEV.
b. 30 mg vial: Add 3.3 mL of SWFI, resulting in 10 mg/mL PADCEV.
5. 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.
6. 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.
7. 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 24 hours in refrigeration at 2°C to 8°C. DO NOT FREEZE.
Discard unused vials with reconstituted solution beyond the recommended storage time.
Dilution in infusion bag
8. Withdraw the calculated dose amount of reconstituted solution from the vial(s) and transfer into an infusion bag.

9. 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.
10. Mix diluted solution by gentle inversion. DO NOT SHAKE THE BAG. Do not expose to direct sunlight.
11. 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.
12. Discard any unused portion left in the single-dose vials.
Administration
13. Immediately administer the infusion over 30 minutes through an intravenous line.
14. 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. 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.