Posology : מינונים

2. DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage

The recommended dosages for IMFINZI as a single agent and IMFINZI in
combination with chemotherapy are presented in Table 1 [see Clinical

Studies (14)].
IMFINZI is administered as an intravenous infusion over 60 minutes.


Table 1. Recommended Dosages of IMFINZI

Indication                   Recommended IMFINZI                  Duration of Therapy dosage
Urothelial Carcinoma         Patients with a body weight of 30 Until disease kg and more:                         progression or
10 mg/kg every 2 weeks               unacceptable toxicity
or
1500 mg every 4 weeks


Patients with a body weight of
less than 30 kg:
10 mg/kg every 2 weeks
Patients with a body weight of 30    Until disease
kg and more:                         progression,
Unresectable stage III
10 mg/kg every 2 weeks               unacceptable toxicity,
NSCLC                        Or                                   or a maximum of 12 1500 mg every 4 weeks                months

Patients with a body weight of
less than 30 kg:
10 mg/kg every 2 weeks
or
20 mg/kg every 4 weeks

Patients with a body weight of 30 Until disease
kg and more:                      progression or
ES-SCLC                           1500 mg in combination with       unacceptable toxicity chemotherapy1 every 3 weeks
(21 days) for 4 cycles,
followed by 1500 mg every 4
weeks as a single agent

Patients with a body weight of
less than 30 kg:
20 mg/kg in combination with
chemotherapy every 3 weeks
(21 days) for 4 cycles, followed
by 20 mg/kg every 4 weeks as a
single agent
1 Administer IMFINZI prior to   chemotherapy on the same day. When IMFINZI is administered in combination with chemotherapy, refer to the Prescribing Information for etoposide and carboplatin or cisplatin for dosing information.


2.2 Dose Modifications for Adverse Reactions
No dose reductions are recommended. Withhold and/or discontinue IMFINZI to manage adverse reactions as described in Table 2.
Table 2. Recommended Treatment Modifications for IMFINZI
Adverse Reactions           Severity1                     Dosage Modification Pneumonitis [see            Grade 2                       Withhold dose until Grade 1 or resolved Warnings and                                              and corticosteroid dose is less than or Precautions (5.1)]                                        equal to prednisone 10 mg per day (or equivalent).
Grade 3 or 4                  Permanently discontinue



Hepatitis [see             For ALT or AST               Withhold dose until Grade 1 or resolved Warnings and               greater than 3 but less      and corticosteroid dose is less than or Precautions (5.2)]         than or equal to 8           equal to prednisone 10 mg per day (or times the ULN or Total       equivalent).
bilirubin greater than
1.5 but less than or
equal to 5 times the
ULN



ALT or AST greater           Permanently discontinue
than 8 times the ULN
or total bilirubin greater
than 5 times the ULN
or Concurrent ALT or
AST greater than 3
times the ULN and
total bilirubin greater
than 2 times the ULN
with no other cause
Colitis or diarrhea [see   Grade 2                      Withhold dose until Grade 1 or resolved Warnings and                                            and corticosteroid dose is less than or Precautions (5.3)]                                      equal to prednisone 10 mg per day (or equivalent).
Grade 3 or 4                 Permanently discontinue
Hyperthyroidism or         Grade 2-4                    Withhold dose until clinically stable thyroiditis [see
Warnings and
Precautions (5.4)]


Adrenal insufficiency or    Grade 2-4                Withhold dose until clinically stable Hypophysitis/Hypopitui
tarism [see Warnings
and Precautions (5.4)]



Type 1 Diabetes Mellitus    Grade 2-4                Withhold dose until clinically stable [see Warnings and
Precautions (5.4)]
Nephritis [see              For       Creatinine     Withhold dose until Grade 1 or resolved Warnings and                greater than 1.5 to 3    and corticosteroid dose is less than or Precautions (5.5)]          times the ULN            equal to prednisone 10 mg per day (or equivalent).
For Creatinine           Permanently discontinue
greater than 3
times the ULN



Rash or dermatitis          Grade 2 for longer       Withhold dose until Grade 1 or resolved (including Pemphigoid)      than 1 week or           and corticosteroid dose is less than or [see Warnings and           Grade 3                  equal to prednisone 10 mg per day (or Precautions (5.6)]                                   equivalent).


Grade 4                  Permanently discontinue
Infection [see              Grade 3 or 4             Withhold dose until clinically stable Warnings and
Precautions (5.8)]
Infusion-related reactions   Grade 1 or 2            Interrupt or slow the rate of infusion [see Warnings and            Grade 3 or 4            Permanently discontinue Precautions (5.9)]


Other immune- mediated Grade 3                                        Withhold dose until Grade 1 or resolved adverse reactions [see                                                and corticosteroid dose is less than or Warnings and                                                          equal to prednisone 10 mg per day (or Precautions (5.7)]                                                    equivalent)2 .
Grade 4                           Permanently discontinue
Persistent Grade 2 or            Grade 2 or 3 adverse              Permanently discontinue 3 adverse reaction               reaction that does not
(excluding                       recover to Grade 0 or 1
endocrinopathies)                within 12 weeks after
last IMFINZI dose
Inability to taper               Inability to reduce to            Permanently discontinue corticosteroid                   less than or equal to
prednisone 10 mg per
day (or equivalent)
within 12 weeks after
the last IMFINZI dose
Recurrent Grade 3 or 4 Recurrent Grade 3 or 4 Permanently discontinue adverse reaction                 (severe or life-
threatening) adverse
reaction
1National   Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal.
2 For   myasthenia gravis permanently discontinue IMFINZI if the adverse reaction does not resolve to ≤ Grade 1 within 30 days or if there are
signs of respiratory and/or autonomic insufficiency.


2.4 Preparation and Administration
Preparation
•       Visually inspect drug product for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the vial if the solution is cloudy, discolored, or visible particles are observed.
•     Do not shake the vial.
•     Withdraw the required volume from the vial(s) of IMFINZI and transfer into an intravenous bag 
containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix diluted solution by gentle inversion. Do not shake the solution. The final concentration of the diluted solution should be between 1 mg/mL and 15 mg/mL.
•   Discard partially used or empty vials of IMFINZI.


Storage of Infusion Solution
•   IMFINZI does not contain a preservative.
•   Administer infusion solution immediately once prepared. If infusion solution is not administered immediately and needs to be stored, the total time from vial puncture to the start of the administration should not exceed:
o 30 days in a refrigerator at 2°C to 8°C
o 12 hours at room temperature up to 25°C
•   Do not freeze.
•   Do not shake.


Administration
•   Administer infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
•   Do not co-administer other drugs through the same infusion line.