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Kyprolis Dosage

Medically reviewed by Drugs.com. Last updated on Aug 26, 2020.

Generic name: CARFILZOMIB 60mg in 30mL
Dosage form: injection, powder, lyophilized, for solution

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.

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

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

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 3 [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 3: Kyprolis 20/70 mg/m2 Once Weekly (30-Minute Infusion) in Combination with Dexamethasone
Cycle 1
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis (mg/m2) 20 - - 70 - - 70 - - - - -
Dexamethasone (mg) 40 - - 40 - - 40 - - 40 - -
Cycles 2 to 9
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis (mg/m2) 70 - - 70 - - 70 - - - - -
Dexamethasone (mg) 40 - - 40 - - 40 - - 40 -
Cycles 10 and later
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis (mg/m2) 70 - - 70 - - 70 - - - - -
Dexamethasone (mg) 40 - - 40 - - 40 - - - - -

Kyprolis in Combination with Intravenous Daratumumab 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 intravenous daratumumab 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 intravenous daratumumab. Refer to the Prescribing Information for intravenous daratumumab and dexamethasone for additional dosage information.

Table 4: Kyprolis 20/56 mg/m2 Twice Weekly (30-Minute Infusion) in Combination with Intravenous Daratumumab and Dexamethasone
*
For patients > 75 years of age, administer 20 mg of dexamethasone orally or intravenously weekly after the first week.
Cycle 1
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis
(mg/m2)
20 20 - 56 56 - 56 56 - - - -
Dexamethasone
(mg)
*
20 20 - 20 20 - 20 20 - 40 - -
Daratumumab
(mg/kg)
8 8 - 16 - - 16 - - 16 - -
Cycle 2
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis
(mg/m2)
56 56 - 56 56 - 56 56 - - - -
Dexamethasone
(mg)
*
20 20 - 20 20 - 20 20 - 40 - -
Daratumumab
(mg/kg)
16 - - 16 - - 16 - - 16 - -
Cycles 3-6
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis
(mg/m2)
56 56 - 56 56 - 56 56 - - - -
Dexamethasone
(mg)
*
20 20 - 20 20 - 20 20 - 40 - -
Daratumumab
(mg/kg)
16 - - - - - 16 - - - - -
Cycles 7 and onwards
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis
(mg/m2)
56 56 - 56 56 - 56 56 - - - -
Dexamethasone
(mg)
*
20 20 - 20 20 - 20 20 - 40 - -
Daratumumab
(mg/kg)
16 - - - - - - - - - - -

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 intravenous daratumumab 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 intravenous daratumumab. Refer to the Prescribing Information for intravenous daratumumab and dexamethasone for additional dosage information.

Table 5: Kyprolis 20/70 mg/m2 Once Weekly (30-Minute Infusion) in Combination with Intravenous Daratumumab and Dexamethasone
*
For patients > 75 years of age, administer 20 mg of dexamethasone orally or intravenously weekly after the first week.
Cycle 1
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis (mg/m2) 20 - - 70 - - 70 - - - - -
Dexamethasone (mg)* 20 20 - 20 20 - 20 20 - 20 20 -
Daratumumab (mg/kg) 8 8 - 16 - - 16 - - 16 - -
Cycle 2
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis (mg/m2) 70 - - 70 - - 70 - - - - -
Dexamethasone (mg)* 20 20 - 20 20 - 20 20 - 20 20 -
Daratumumab (mg/kg) 16 - - 16 - - 16 - - 16 - -
Cycles 3-6
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis (mg/m2) 70 - - 70 - - 70 - - - - -
Dexamethasone (mg)* 20 20 - 40 - - 20 20 - 40 - -
Daratumumab (mg/kg) 16 - - - - - 16 - - - - -
Cycles 7 and thereafter
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Day
22
Day
23
Days
24-28
Kyprolis (mg/m2) 70 - - 70 - - 70 - - - - -
Dexamethasone (mg)* 20 20 - 40 - - 40 - - 40 - -
Daratumumab (mg/kg) 16 - - - - - - - - - - -

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)
*
Dexamethasone premedication is required for each Kyprolis dose in Cycle 1.
Cycle 1
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Days
22–28
Kyprolis (mg/m2)* 20 20 - 27 27 - 27 27 - -
Cycles 2 to 12
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Days
22–28
Kyprolis (mg/m2) 27 27 - 27 27 - 27 27 - -
Cycles 13 and later
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Days
22–28
Kyprolis (mg/m2) 27 27 - - - - 27 27 - -

20/56 mg/m2 twice weekly regimen by 30-minute infusion

Administer Kyprolis intravenously as a 30-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 7. From Cycle 13, administer Kyprolis on Days 1, 2, 15 and 16 of each 28-day cycle. Premedicate with dexamethasone 8 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 56 mg/m2 on Day 8 of Cycle 1. Continue Kyprolis until disease progression or unacceptable toxicity.

Table 7: Kyprolis Monotherapy 20/56 mg/m2 Twice Weekly (30-Minute Infusion)
*
Dexamethasone premedication is required for each Kyprolis dose in Cycle 1.
Cycle 1
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Days
22–28
Kyprolis (mg/m2)* 20 20 - 56 56 - 56 56 - -
Cycles 2 to 12
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Days
22–28
Kyprolis (mg/m2) 56 56 - 56 56 - 56 56 - -
Cycles 13 and later
Week 1 Week 2 Week 3 Week 4
Day
1
Day
2
Days
3–7
Day
8
Day
9
Days
10–14
Day
15
Day
16
Days
17–21
Days
22–28
Kyprolis (mg/m2) 56 56 - - - - 56 56 - -

Dosage Modifications for Adverse Reactions

Recommended actions and dosage modifications for Kyprolis are presented in Table 8. Dose level reductions are presented in Table 9. See the lenalidomide, intravenous daratumumab, and dexamethasone Prescribing Information respectively for recommended dosage modifications associated with each product.

Table 8: Dosage Modifications for Adverse Reactions*
ANC = absolute neutrophil count
*
See Table 9 for dose level reductions.
Grade 3 and 4.
Hematologic Toxicity
[see Warnings and Precautions (5.11), Adverse Reactions (6.1)]
Recommended Action
  • 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 Kyprolis*
  • Febrile neutropenia: ANC less than 0.5 × 109/L and an oral temperature more than 38.5°C or two consecutive readings of more than 38.0°C for 2 hours
  • Withhold dose
    • If ANC returns to baseline grade and fever resolves, resume at the same dose level
  • Platelets less than 10 × 109/L or evidence of bleeding with thrombocytopenia
  • Withhold dose
    • If recovered to greater than or equal to 10 × 109/L 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 Kyprolis*
Renal Toxicity
[see Warnings and Precautions (5.2)]
Recommended Action
  • Serum creatinine greater than or equal to 2 × baseline, or
  • Creatinine clearance less than 15 mL/min, or creatinine clearance decreases to less than or equal to 50% of baseline, or need for hemodialysis
  • Withhold dose and continue monitoring renal function (serum creatinine or creatinine clearance)
    • If attributable to Kyprolis, resume when renal function has recovered to within 25% of baseline; start at 1 dose level reduction*
    • If not attributable to Kyprolis, dosing may be resumed at 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
[see Adverse Reactions (6.1)].
Recommended Action
  • All other severe or life-threatening non-hematological toxicities
  • Withhold until resolved or returned to baseline
  • Consider restarting the next scheduled treatment at 1 dose level reduction*
Table 9: Dose Level Reductions for Adverse Reactions
Regimen Dose First Dose Reduction Second Dose Reduction Third Dose Reduction
Note: Infusion times remain unchanged during dose reduction(s).
*
If toxicity persists, discontinue Kyprolis treatment.
Kyprolis and Dexamethasone
OR
Kyprolis, Daratumumab and Dexamethasone (once weekly)
70 mg/m2 56 mg/m2 45 mg/m2 36 mg/m2*
Kyprolis and Dexamethasone
OR
Kyprolis, Daratumumab, and Dexamethasone
OR
Kyprolis Monotherapy (twice weekly)
56 mg/m2 45 mg/m2 36 mg/m2 27 mg/m2*
Kyprolis, Lenalidomide, and Dexamethasone
OR
Kyprolis Monotherapy (twice weekly)
27 mg/m2 20 mg/m2 15 mg/m2*

Dosage Modifications for Hepatic Impairment

For patients with mild (total bilirubin 1 to 1.5 × ULN and any AST or total bilirubin ≤ ULN and AST > ULN) or moderate (total bilirubin > 1.5 to 3 × ULN and any AST) hepatic impairment, reduce the dose of Kyprolis by 25% [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Recommended Dosage for End Stage Renal Disease

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

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 10. 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.

    Image

    Table 10: 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 11.

Table 11: Stability of Reconstituted Kyprolis
Storage Conditions of Reconstituted Kyprolis Stability* per Container
Vial Syringe Intravenous Bag
(D5W)
*
Total time from reconstitution to administration should not exceed 24 hours.
5% Dextrose Injection, USP.
Refrigerated 2°C to 8°C (36°F to 46°F) 24 hours 24 hours 24 hours
Room Temperature 15°C to 30°C (59°F to 86°F) 4 hours 4 hours 4 hours

Frequently asked questions

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.