Posology : מינונים

2        DOSAGE AND ADMINISTRATION
2.1      Administration Precautions

Hydration

Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high-risk of tumor lysis syndrome (TLS) or renal toxicity. Consider hydration with both oral fluids (30 mL per kg at least 48 hours before Cycle 1, Day 1) and intravenous fluids (250 mL to 500 mL of appropriate intravenous fluid prior to each dose in Cycle 1). If needed, give an additional 250 mL to 500 mL of intravenous fluids following Kyprolis administration.
Continue oral and/or intravenous hydration, as needed, in subsequent cycles.

Monitor patients for evidence of volume overload and adjust hydration to individual patient needs, especially in patients with or at risk for cardiac failure [see Warnings and Precautions (5.1, 5.3)].

Electrolyte Monitoring

Monitor serum potassium levels regularly during treatment with Kyprolis [see Adverse Reactions (6.1)].

Premedications and Concomitant Medications

Premedicate with the recommended dose of dexamethasone for monotherapy or dexamethasone administered as part of the combination therapy [see Dosage and Administration (2.2)]. Administer dexamethasone orally or intravenously at least 30 minutes but no more than 4 hours prior to all doses of Kyprolis during Cycle 1 to reduce the incidence and severity of infusion-related reactions [see Warnings and Precautions (5.9)]. Reinstate dexamethasone premedication if these symptoms occur during subsequent cycles.

Provide thromboprophylaxis for patients being treated with Kyprolis in combination with other therapies [see Warnings and Precautions (5.8)].

Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation [see Adverse Reactions (6.1)].

Dose Calculation

For patients with body surface area (BSA) of 2.2 m2 or less, calculate the Kyprolis dose using actual BSA. Dose adjustments do not need to be made for weight changes of 20% or less.

For patients with a BSA greater than 2.2 m2, calculate the Kyprolis dose using a BSA of 2.2 m2.

2.2    Recommended Dosage

Kyprolis in Combination with Lenalidomide and Dexamethasone
Administer Kyprolis intravenously as a 10-minute infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle in combination with lenalidomide and dexamethasone until Cycle 12 as shown in Table 1 [see Clinical Studies (14.1)]. The recommended starting dose of Kyprolis is 20 mg/m2 on Cycle 1, Days 1 and 2. If tolerated, escalate the dose to 27 mg/m2 on Cycle 1, Day 8. From Cycle 13, administer Kyprolis on Days 1, 2, 15, 16 until Cycle 18. Discontinue Kyprolis after Cycle 18. Continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity occurs. Refer to the Prescribing Information for lenalidomide and dexamethasone for additional dosage information.


Table 1: Kyprolis 20/27 mg/m2 Twice Weekly (10-Minute Infusion) in Combination with Lenalidomide and Dexamethasone

Cycle 1
Week 1                     Week 2                      Week 3                 Week 4 Days            Days
Day      Day     Days      Day     Day      Days       Day     Day       17–    Day      23– 1        2      3–7        8       9       10–14       15      16        21     22       28 Kyprolis
(mg/m2)              20       20        -       27      27         -       27       27        -      -            - Dexamethason         40        -        -       40       -         -       40        -        -     40            - e(mg)
Lenalidomide                                 25 mg daily on Days 1-21                                -            - Cycles 2 to 12
Week 1                    Week 2                     Week 3                Week 4 Da Days                   Days
Day      Day     Days      Day     Day      Days        Day   y    17–          Day    23– 1        2      3–7        8       9       10–14        15   16    21           22     28 Kyprolis
(mg/m2)              27       27        -       27      27         -         27      27       -      -            - Dexamethason         40        -        -       40       -         -         40          -    -     40            - e(mg)
Lenalidomide                       25 mg daily on Days 1-21                                          -            - Cycles 13 and latera
Week 1             Week 2                  Week 3                             Week 4 Da Days                                Days
Day Day Days Day        Day     Days     Day     y    17–                       Day    23– 1   2     3–7    8      9     10–14      15     16    21                        22     28 Kyprolis
27       27        -       -        -         -         27      27       -      -            - (mg/m2)
Dexamethason         40        -        -       40       -         -         40          -    -     40            - e(mg)
Lenalidomide                                 25 mg daily on Days 1-21 a Kyprolis is administered through Cycle 18; lenalidomide and dexamethasone continue thereafter.

Once weekly 20/70 mg/m2 regimen by 30-minute infusion

Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 8, and 15 of each 28-day cycle in combination with dexamethasone until disease progression or unacceptable toxicity as shown in Table 2 [see Clinical Studies (14.2)]. The recommended starting dose of Kyprolis is 20 mg/m2 on Cycle 1, Day 1. If tolerated, escalate the dose to 70 mg/m2 on Cycle 1, Day 8. Administer dexamethasone 30 minutes to 4 hours before Kyprolis. Refer to Prescribing Information for dexamethasone for additional dosage information.


Table 2: Kyprolis 20/70 mg/m2 Once Weekly (30-Minute Infusion) in Combination with Dexamethasone

Cycle 1
Week 1                Week 2                   Week 3                Week 4 Days                     Days                  Days
Day    Day     Days   Day   Day       10–    Day     Day       17–   Day   Day      24– 1      2       3–7    8     9         14     15      16        21    22    23       28 Kyprolis
20     -       -     70     -         -      70       -       -      -      -       -
(mg/m2)
Dexamethason
40     -       -     40     -         -      40       -       -     40      -       - e (mg)
Cycles 2 to 9
Week 1                Week 2                   Week 3                Week 4 Days                     Days                  Days
Day    Day     Days   Day   Day      10–     Day     Day      17–    Day   Day      24– 1      2      3–7     8     9        14      15      16       21     22    23       28 Kyprolis
70     -       -     70     -         -      70       -       -      -      -       - (mg/m2)
Dexamethason
40     -       -     40     -         -      40       -       -     40              - e (mg)
Cycles 10 and later
Week 1                Week 2                   Week 3                Week 4 Days                     Days                  Days
Day    Day     Days   Day   Day      10–     Day     Day      17–    Day   Day      24– 1      2      3–7     8     9        14      15      16       21     22    23       28 Kyprolis
70     -       -     70     -         -      70       -       -      -      -       - (mg/m2)
Dexamethason
40     -       -     40     -         -      40       -       -      -      -       - e (mg)


Kyprolis in Combination with Dexamethasone
Twice weekly 20/56 mg/m2 regimen by 30-minute infusion

Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle in combination with dexamethasone until disease progression or unacceptable toxicity as shown in Table 3 [see Clinical Studies (14.2)]. The recommended starting dose of Kyprolis is 20 mg/m2 on Cycle 1, Days 1 and 2. If tolerated, escalate the dose to 56 mg/m2 on Cycle 1, Day 8. Administer dexamethasone 30 minutes to 4 hours before Kyprolis. Refer to the Prescribing Information for dexamethasone for additional dosage information.


Table 3: Kyprolis 20/56 mg/m2 Twice Weekly (30-Minute Infusion) in Combination with Dexamethasone

Cycle 1
Week 1              Week 2                 Week 3               Week 4 Day    Day Days     Day    Day Days        Day   Day Days       Day   Day    Days 1      2    3-7     8      9    10-14      15    16    17-21    22    23    24–28 Kyprolis
20    20     -     56     56      -        56    56      -      -      -      -
(mg/m2)
Dexamethason
20    20     -     20     20      -        20    20      -     20     20      - e (mg)
Cycles 2 and later
Week 1              Week 2               Week 3                   Week 4 Day Day Days        Day Day Days Day Day Days                   Day   Day    Days 1   2     3-7       8   9     10-14    15      16  17-21        22    23    24–28 Kyprolis
56    56     -     56     56      -        56    56      -      -      -      - (mg/m2)
Dexamethason
20    20     -     20     20      -        20    20      -     20     20      - e (mg)

Kyprolis in Combination with Daratumumab (I.V. or S.C.) and Dexamethasone 
Twice weekly 20/56 mg/m2 regimen by 30-minute infusion

Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 2, 8, 9, 15 and 16 of each 28-day cycle in combination the daratumumab (I.V. and S.C.) and dexamethasone until disease progression or unacceptable toxicity as shown in Table 4 [see Clinical Studies (14.3)]. The recommended starting dose of Kyprolis is 20 mg/m2 on Cycle 1, Days 1 and 2.
If tolerated, escalate the dose to 56 mg/m2 on Cycle 1, Day 8 and thereafter. Administer dexamethasone 30 minutes to 4 hours before Kyprolis and 1 to 3 hours before daratumumab (I.V. and S.C.). Refer to the Prescribing Information for daratumumab (I.V. and S.C.) and dexamethasone for additional dosage information.


Table 4: Kyprolis 20/56 mg/m2 Twice Weekly (30-Minute Infusion) in Combination with Daratumumab (I.V. and S.C.) and Dexamethasone

Cycle 1
Week 1                   Week 2                       Week 3                    Week 4 Da                        Da
Day       Day     Days   Day       Day     Days       Day       y       Days    Day        y      Days 1         2       3–7    8         9      10–14       15       16      17–21    22       23      24–28 Kyprolis
20        20      -      56        56       -         56       56        -       -        -          -
(mg/m2)
Dexamethasone
20        20      -      20        20       -         20       20        -      20       20          -
(mg)*
 with intravenous daratumumab

Daratumumab intravenous       8        8       -      16         -       -         16        -        -      16        -          - (mg/kg)

OR with subcutaneous daratumumab

Daratumumab
1,800/                   1,800/                       1,800/ subcutaneous                                                                                    1,800/ 30,00      -       -     30,00       -       -        30,00      -        -     30,000 -          -
(mg/units)         0                        0                            0 
Cycle 2
Week 1                   Week 2                       Week 3                    Week 4 Da                        Da
Day       Day     Days   Day       Day     Days       Day       y       Days    Day        y      Days 1         2      3–7     8         9      10–14       15       16      17–21    22       23      24–28 Kyprolis
56        56      -      56        56       -         56       56        -       -        -          - (mg/m2)
Dexamethasone
20        20      -      20        20       -         20       20        -      20       20          -
(mg)*
 with intravenous daratumumab

Daratumumab intravenous      16        -       -      16         -       -         16        -        -      16        -          - (mg/kg)

OR with subcutaneous daratumumab

Daratumumab
1,800/                   1,800/                       1,800/ subcutaneous                                                                                    1,800/ 30,00      -       -     30,00       -       -        30,00      -        -     30,000 -          -
(mg/units)         0                        0                            0 
Cycles 3-6
Week 1                   Week 2                       Week 3                    Week 4 
Da                            Da
Day       Day     Days      Day       Day      Days        Day      y       Days        Day        y     Days 1         2      3–7        8         9       10–14        15      16      17–21        22       23     24–28 Kyprolis
56        56        -       56        56         -         56       56        -          -        -         - (mg/m2)
Dexamethasone
20        20        -       20        20         -         20       20        -         40        -         - (mg)*
 with intravenous daratumumab

Daratumumab intravenous           16        -         -        -         -         -         16        -        -          -        -         - (mg/kg)

OR with subcutaneous daratumumab

Daratumumab
1,800/                                                    1,800/ subcutaneous
30,00      -         -        -         -         -       30,00       -        -          -        -         - (mg/units)              0                                                         0 
Cycles 7 and onwards
Week 1                      Week 2                        Week 3                       Week 4 Da                            Da
Day       Day     Days      Day       Day      Days        Day      y       Days        Day        y     Days 1         2      3–7        8         9       10–14        15      16      17–21        22       23     24–28 Kyprolis
56        56        -       56        56         -         56       56        -          -        -         - (mg/m2)
Dexamethasone
20        20        -       20        20         -         20       20        -         40        -         - (mg)*
 with intravenous daratumumab

Daratumumab intravenous           16        -         -        -         -         -          -        -        -          -        -         - (mg/kg)

OR with subcutaneous daratumumab

Daratumumab
1,800/ subcutaneous
30,00      -         -        -         -         -          -        -        -          -        -         - (mg/units)              0

*For patients > 75 years of age, administer 20 mg of dexamethasone orally or intravenously weekly after the first week.

Once weekly 20/70 mg/m2 regimen by 30-minute infusion

Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 8 and 15 of each     28-day cycle in combination with daratumumab (I.V. and S.C.) and dexamethasone until disease progression or unacceptable toxicity as shown in Table 5 [see Clinical Studies 
(14.3)]. The recommended starting dose of Kyprolis is 20 mg/m2 on Cycle 1, Day 1. If tolerated, escalate the dose to 70 mg/m2 on Cycle 1, Day 8 and thereafter. Administer dexamethasone 30 minutes to 4 hours before Kyprolis and 1 to 3 hours before daratumumab (I.V and S.C). Refer to the Prescribing Information for daratumumab (I.V and S.C) and dexamethasone for additional dosage information.

Table 5: Kyprolis 20/70 mg/m2 Once Weekly (30-Minute Infusion) in Combination with Daratumumab (I.V. and S.C.) and Dexamethasone

Cycle 1
Week 1                   Week 2                      Week 3                    Week 4 Day      Day      Days   Day       Day     Days       Day     Day      Days    Day      Day      Days 1        2        3–7    8         9      10–14       15      16      17–21    22       23      24–28 Kyprolis
20        -       -      70        -        -         70      -         -       -        -          -
(mg/m2)
Dexamethasone
20       20       -      20        20       -         20      20        -      20       20          -
(mg)* with intravenous daratumumab
Daratumumab intravenous       8        8       -      16        -        -         16      -         -      16        -          - (mg/kg)
OR with subcutaneous daratumumab
Daratumumab
1,800/ subcutaneous                             1,800/                      1,800/                    1,800/ 30,00      -       -     30,000
-        -       30,000
-         -     30,000
-          -
(mg/units)         0

Cycle 2
Week 1                   Week 2                      Week 3                    Week 4 Day      Day      Days   Day       Day     Days       Day     Day      Days    Day      Day      Days 1        2       3–7     8         9      10–14       15      16      17–21    22       23      24–28 Kyprolis
70        -       -      70        -        -         70      -         -       -        -          - (mg/m2)
Dexamethasone
20       20       -      20        20       -         20      20        -      20       20          -
(mg)* with intravenous daratumumab
Daratumumab intravenous      16        -       -      16        -        -         16      -         -      16        -          - (mg/kg)
OR with subcutaneous daratumumab
Daratumumab
1,800/ subcutaneous                             1,800/                      1,800/                    1,800/ 30,00      -       -     30,000
-        -       30,000
-         -     30,000
-          -
(mg/units)         0


Cycles 3-6
Week 1                       Week 2                        Week 3                        Week 4 Day      Day      Days       Day      Day      Days        Day      Day      Days        Day      Day     Days 1        2       3–7         8        9       10–14        15       16      17–21        22       23     24–28 Kyprolis
70        -        -         70        -         -         70        -         -          -        -         - (mg/m2)
Dexamethasone
20       20        -         40        -         -         20       20         -         40        -         - (mg)* with intravenous daratumumab
Daratumumab intravenous          16        -        -          -        -         -         16        -         -          -        -         - (mg/kg)
OR with subcutaneous daratumumab
Daratumumab subcutaneous
1,800/
(mg/units)                                                                    1,800/ 30,00       -        -          -        -         -       30,000
-         -          -        -         -
0


Cycles 7 and onwards
Week 1                       Week 2                        Week 3                        Week 4 
Day      Day      Days       Day      Day      Days        Day      Day      Days        Day      Day     Days 1        2       3–7         8        9       10–14        15       16      17–21        22       23     24–28 Kyprolis
70        -        -         70        -         -         70        -         -          -        -         - (mg/m2)
Dexamethasone
20       20        -         40        -         -         40        -         -         40        -         - (mg)* with intravenous daratumumab
Daratumumab intravenous          16        -        -          -        -         -          -        -         -          -        -         - (mg/kg)
OR with subcutaneous daratumumab
Daratumumab
1,800/ subcutaneous
30,00       -        -          -        -         -          -        -         -          -        -         - (mg/units)            0

*For patients > 75 years of age, administer 20 mg of dexamethasone orally or intravenously weekly after the first week.

Kyprolis Monotherapy

20/27 mg/m2 twice weekly regimen by 10-minute infusion

Administer Kyprolis intravenously as a 10-minute infusion [see Clinical Studies (14.4)]. In Cycles 1 through 12, administer Kyprolis on Days 1, 2, 8, 9, 15 and 16 of each 28-day cycle as shown in Table 6. From Cycle 13, administer Kyprolis on Days 1, 2, 15 and 16 of each 28-day cycle. Premedicate with dexamethasone 4 mg orally or intravenously 30 minutes to
4 hours before each Kyprolis dose in Cycle 1, then as needed to minimize infusion-related reactions [see Dosage and Administration (2.1)]. The recommended starting dose of Kyprolis is 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m2 on Day 8 of Cycle 1 and thereafter. Continue Kyprolis until disease progression or unacceptable toxicity.

Table 6: Kyprolis Monotherapy 20/27 mg/m2 Twice Weekly (10-Minute Infusion) 
Cycle 1
Week 1                     Week 2                  Week 3         Week 4 Day    Day    Days        Day     Day    Days      Day    Day    Days     Days 1      2     3–7          8       9     10–14      15     16    17–21   22–28 
Kyprolis (mg/m2)a          20      20        -       27      27        -       27    27      -       - Cycles 2 to 12
Week 1                        Week 2                  Week 3         Week 4 Day Day    Days           Day     Day     Days      Day   Day    Days     Days 1   2     3–7             8        9     10–14      15    16    17–21   22–28 
Kyprolis (mg/m2)          27      27        -       27   27        -       27       27      -       - Cycles 13 and later
Week 1                     Week 2                     Week 3         Week 4 Day  Da    Days            Day  Day     Days     Day      Day    Days     Days 1    y    3–7              8    9      10–14     15       16    17–21   22–28 2
Kyprolis (mg/m2)          27      27        -         -        -        -    27     27      -       - a   Dexamethasone premedication is required for each Kyprolis dose in Cycle 1.

2.3         Dosage Modifications for Adverse Reactions

Recommended actions and dosage modifications for Kyprolis are presented in Table 7. Dose level reductions are presented in Table 8. See the lenalidomide, intravenous daratumumab, and dexamethasone Prescribing Information respectively for recommended dosage modifications associated with each product.


Table 7: Dosage Modifications for Adverse Reactionsa

Hematologic Toxicity
[see Warnings and Precautions (5.11),                         Recommended Action Adverse Reactions (6.1)]
•     ANC less than 0.5 × 109/L            •   Withhold dose •    If recovered to greater than or equal to 0.5 × 109/L,
continue at the same dose level
•   For subsequent drops to less than 0.5 × 109/L, follow the same recommendations as above and consider 1 dose level reduction when restarting Kyprolisa
•    Febrile neutropenia: ANC less         •   Withhold dose than 0.5 × 109/L and an oral              •    If ANC returns to baseline grade and fever resolves, temperature more than 38.5°C or                resume at the same dose level two consecutive readings of more than 38.0°C for 2 hours
•    Platelets less than 10 × 109/L or     •   Withhold dose evidence of bleeding with                 •    If recovered to greater than or equal to 10 × 109/L thrombocytopenia                               and/or bleeding is controlled, continue at the same dose level
•   For subsequent drops to less than 10 × 109/L, follow the same recommendations as above and consider 1 dose level reduction when restarting Kyprolisa
Renal Toxicity
Recommended Action
[see Warnings and Precautions (5.2)]
•    Serum creatinine greater than or      •    Withhold dose and continue monitoring renal function equal to 2 × baseline, or                  (serum creatinine or creatinine clearance)
•    Creatinine clearance less                 • If attributable to Kyprolis, resume when renal function than 15 mL/min, or creatinine                  has recovered to within 25% of baseline; start at 1 dose clearance decreases to less than or            level reductiona equal to 50% of baseline, or need         • If not attributable to Kyprolis, dosing may be resumed at for hemodialysis                               the discretion of the healthcare provider •    For patients on hemodialysis receiving Kyprolis, the dose is to be administered after the hemodialysis procedure
Other Non-hematologic Toxicity
Recommended Action
[see Adverse Reactions (6.1)]
•    All other severe or life-             •   Withhold until resolved or returned to baseline threateningb non-hematological        •   Consider restarting the next scheduled treatment at 1 dose toxicities                                level reductiona
ANC = absolute neutrophil count a See Table 8 for dose level reductions.
b Grade 3 and 4.


Table 8: Dose Level Reductions for Adverse Reactions

First Dose   Second Dose   Third Dose
Regimen                          Dose
Reduction     Reduction    Reduction
Kyprolis and Dexamethasone
OR
Kyprolis, Daratumumab and                 70 mg/m2            56 mg/m2      45 mg/m2     36 mg/m2a Dexamethasone (once weekly)

Kyprolis and Dexamethasone
OR
Kyprolis, Daratumumab, and                   56 mg/m2            45 mg/m2      36 mg/m2     27 mg/m2a Dexamethasone
(twice weekly)
Kyprolis, Lenalidomide, and
Dexamethasone
OR                                        27 mg/m2            20 mg/m2      15 mg/m2a       — Kyprolis Monotherapy (twice weekly)
Note: Infusion times remain unchanged during dose reduction(s).
a If toxicity persists, discontinue Kyprolis treatment.



2.4       Recommended Dosage for End Stage Renal Disease

For patients with end stage renal disease who are on hemodialysis, administer Kyprolis after the hemodialysis procedure.

2.5       Preparation and Administration

Kyprolis vials contain no antimicrobial preservatives and are intended for single-dose only.
The reconstituted solution contains carfilzomib at a concentration of 2 mg/mL.
Read the complete preparation instructions prior to reconstitution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstitution/Preparation Steps:

1.        Remove vial from refrigerator just prior to use.
2.        Calculate the dose (mg/m2) and number of vials of Kyprolis required using the patient’s BSA at baseline.
3.        Aseptically reconstitute each Kyprolis vial only with Sterile Water for Injection, USP using the volumes described in Table 9. Use a 21-gauge or larger needle (0.8 mm or smaller external diameter needle) to reconstitute each vial by slowly injecting Sterile Water for Injection, USP through the stopper and directing the Sterile Water for Injection, USP onto the INSIDE WALL OF THE VIAL to minimize foaming. There is no data to support the use of closed system transfer devices with Kyprolis.

Table 9: Reconstitution Volumes

Strength                   Amount of Sterile Water for Injection, USP required for reconstitution

10 mg vial                                         5 mL

30 mg vial                                        15 mL
60 mg vial                                        29 mL


4.     Gently swirl and/or invert the vial slowly for about 1 minute, or until complete dissolution. DO NOT SHAKE to avoid foam generation. If foaming occurs, allow the solution to settle in the vial until foaming subsides (approximately 5 minutes) and the solution is clear.
5.     Visually inspect for particulate matter and discoloration prior to administration. The reconstituted product should be a clear, colorless solution and should not be administered if any discoloration or particulate matter is observed.
6.     Discard any unused portion left in the vial. DO NOT pool unused portions from the vials. DO NOT administer more than one dose from a vial.
7.     Administer Kyprolis directly by intravenous infusion or in a 50 mL to 100 mL intravenous bag containing 5% Dextrose Injection, USP. Do not administer as an intravenous push or bolus.
8.     When administering in an intravenous bag, use a 21-gauge or larger gauge needle (0.8 mm or smaller external diameter needle) to withdraw the calculated dose from the vial and dilute into 50 mL or 100 mL intravenous bag containing only 5% Dextrose Injection, USP (based on the calculated total dose and infusion time).
9.     Flush the intravenous administration line with normal saline or 5% Dextrose Injection, USP immediately before and after Kyprolis administration.
10.    Do not mix Kyprolis with or administer as an infusion with other medicinal products.

The stabilities of reconstituted Kyprolis under various temperature and container conditions are shown in Table 10.


Table 10: Stability of Reconstituted Kyprolis

Stabilitya per Container
Intravenous Bag
Storage Conditions of Reconstituted Kyprolis                    Vial              Syringe             (D5Wb) Refrigerated 2°C to 8°C                                            24 hours            24 hours          24 hours Room Temperature 15°C to 30°C                                       4 hours            4 hours           4 hours a   Total time from reconstitution to administration should not exceed 24 hours.
b   5% Dextrose Injection, USP.