Carfilzomib Dosage

Medically reviewed by Drugs.com. Last updated on Oct 31, 2023.

Usual Adult Dose for Multiple Myeloma

BEFORE INITIATING THIS DRUG:

• Hydrate patients with both oral fluids (30 mL/kg at least 48 hours before Cycle 1, Day 1) and IV fluids (250 to 500 mL prior to each dose in Cycle 1). If needed, give an additional 250 to 500 mL of IV fluids following drug administration.
• Continue oral and/or IV hydration, as needed, in subsequent cycles.
• Monitor for volume overload and adjust hydration to individual need (especially in patients with or at risk for cardiac failure).
• Monitor serum potassium levels regularly.
• Premedicate with dexamethasone at the recommended dose for either monotherapy or combination therapy.
• Administer dexamethasone orally or IV at least 30 minutes but no more than 4 hours prior to all doses during Cycle 1 to reduce infusion reactions.
• Reinstate dexamethasone if symptoms occur during subsequent cycles.
• Provide thromboprophylaxis for patients being treated with this drug in combination with other therapies.
• Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation.

DOSE CALCULATION:

• Calculate the dose based on the actual BSA of the patient at baseline.
• Patients with a BSA greater than 2.2 m2 should receive a dose based upon a BSA of 2.2 m2.
• Dose adjustments do not need to be made for weight changes of 20% or less.

CARFILZOMIB IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE:
CARFILZOMIB:

• Cycle 1: 20 mg/m2 IV over 10 minutes on Days 1 and 2; if tolerated, increase to 27 mg/m2 IV over 10 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
• Cycles 2 through 12: 27 mg/m2 IV over 10 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle
• Cycle 13 and later: 27 mg/m2 IV over 10 minutes on Days 1, 2, 15, and 16 of each 28-day cycle (omit the Day 8 and 9 doses)
• Discontinue carfilzomib after Cycle 18.

LENALIDOMIDE/DEXAMETHASONE:

• All cycles: Lenalidomide 25 mg orally on Days 1 through 21 and dexamethasone 40 mg orally or IV on Days 1, 8, 15, and 22 of the 28-day cycles
• Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
• Continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity.
• Refer to the lenalidomide and dexamethasone prescribing information.

CARFILZOMIB IN COMBINATION WITH DEXAMETHASONE:
TWICE WEEKLY 20/56 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

• Cycle 1: 20 mg/m2 IV over 30 minutes on Days 1 and 2; if tolerated, increase to 56 mg/m2 IV over 30 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
• Cycles 2 and later: 56 mg/m2 IV over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle

DEXAMETHASONE:

• Cycle 1: 20 mg orally or IV Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle
• Cycle 2 and later: 20 mg orally or IV Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle
• Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
• Continue until disease progression or unacceptable toxicity.
• Refer to the dexamethasone prescribing information.

CARFILZOMIB IN COMBINATION WITH DEXAMETHASONE:
ONCE WEEKLY 20/70 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

• Cycle 1: 20 mg/m2 IV over 30 minutes on Day 1; if tolerated, increase to 70 mg/m2 IV over 30 minutes on Days 8 and 15 of the 28-day cycle
• Cycles 2 through 9: 70 mg/m2 IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

DEXAMETHASONE:

• Cycles 1 through 9: 40 mg orally or IV Days 1, 8, 15, and 22 of each 28-day cycle
• Cycles 10 and later: 40 mg orally or IV Days 1, 8, and 15 of each 28-day cycle
• Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
• Continue until disease progression or unacceptable toxicity.
• Refer to the dexamethasone prescribing information.

CARFILZOMIB IN COMBINATION WITH DARATUMUMAB AND DEXAMETHASONE:
TWICE WEEKLY 20/56 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

• Cycle 1: 20 mg/m2 IV over 30 minutes on Days 1 and 2; if tolerated, increase to 56 mg/m2 IV over 30 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
• Cycles 2 and later: 56 mg/m2 IV over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle

DEXAMETHASONE (NOTE: For patients 75 years or older, administer 20 mg of dexamethasone orally or IV weekly after the first week):

• All Cycles: 20 mg orally or IV on Days 1, 2, 8, 9, 15, and 16 and 40 mg orally or IV on Day 22 of each 28-day cycle

DARATUMUMAB:

• Cycle 1: 8 mg/kg on Days 1 and 2 and 16 mg/kg on Days 8, 15, and 22 of the 28-day cycle
• Cycle 2: 16 mg/kg IV on Days 1, 8, 15, and 22 of the 28-day cycle
• Cycles 3 through 6: 16 mg/kg IV on Days 1 and 15 of each 28-day cycle
• Cycles 7 and later: 16 mg/kg on Day 1 of each 28-day cycle
• Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
• Continue until disease progression or unacceptable toxicity.
• Refer to the dexamethasone and daratumumab prescribing information.

CARFILZOMIB IN COMBINATION WITH DARATUMUMAB AND DEXAMETHASONE:
ONCE WEEKLY 20/70 MG/M2 REGIMEN BY 30-MINUTE INFUSION:
CARFILZOMIB:

• Cycle 1: 20 mg/m2 IV over 30 minutes on Day 1 and 70 mg/m2 IV over 30 minutes on Days 8 and 15 of the 28-day cycle
• Cycle 2 and later: 70 mg/m2 IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

DEXAMETHASONE (NOTE: For patients 75 years or older, administer 20 mg of dexamethasone orally or IV weekly after the first week):

• Cycles 1 and 2: 20 mg orally or IV on Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle
• Cycles 3 through 6: 20 mg orally or IV on Days 1,2, 15, and 16 and 40 mg orally or IV on Days 8 and 22 of each 28-day cycle
• Cycle 7 and later: 20 mg orally or IV on Days 1 and 2 and 40 mg orally or IV on Days 8, 15, and 22 of each 28-day cycle

DARATUMUMAB:

• Cycle 1: 8 mg/kg on Days 1 and 2 and 16 mg/kg on Days 8, 15, and 22 of the 28-day cycle
• Cycle 2: 16 mg/kg IV on Days 1, 8, 15, and 22 of the 28-day cycle
• Cycles 3 through 6: 16 mg/kg IV on Days 1 and 15 of the 28-day cycle
• Cycles 7 and later: 16 mg/kg on Day 1 of each 28-day cycle
• Administer dexamethasone 30 minutes to 4 hours before carfilzomib.
• Continue until disease progression or unacceptable toxicity.
• Refer to the dexamethasone and daratumumab prescribing information.

MONOTHERAPY BY THE 10-MINUTE INFUSION:
20/27 MG/M2 TWICE WEEKLY REGIMEN BY 10-MINUTE INFUSION:

• Cycle 1: 20 mg/m2 IV over 10 minutes on Days 1 and 2; if tolerated, increase to 27 mg/m2 IV over 10 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
• Cycles 2 through 12: 27 mg/m2 IV over 10 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle
• Cycles 13 and later: 27 mg/m2 IV over 10 minutes on Days 1, 2, 15, and 16 of each 28-day cycle
• Premedicate with dexamethasone 4 mg orally or IV 30 minutes to 4 hours before each dose of this drug in Cycle 1, then as needed to prevent infusion reactions.
• Continue therapy until disease progression or unacceptable toxicity.

MONOTHERAPY BY THE 30-MINUTE INFUSION:
20/56 MG/M2 TWICE WEEKLY REGIMEN BY 30-MINUTE INFUSION:

• Cycle 1: 20 mg/m2 IV over 30 minutes on Days 1 and 2; if tolerated, increase to 56 mg/m2 IV over 30 minutes on Days 8, 9, 15, and 16 of the 28-day cycle
• Cycles 2 through 12: 56 mg/m2 IV over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day treatment cycle
• Cycles 13 and later: 56 mg/m2 IV over 30 minutes on Days 1, 2, 15, and 16 of each 28-day treatment cycle
• Premedicate with dexamethasone 8 mg orally or IV 30 minutes to 4 hours before each dose of this drug in Cycle 1, then as needed to prevent infusion reactions.
• Continue therapy until disease progression or unacceptable toxicity.

Uses:

• For patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of therapy in combination with lenalidomide and dexamethasone, or dexamethasone, or daratumumab and dexamethasone
• As a single agent for the treatment of relapsed or refractory multiple myeloma who have received 1 or more lines of therapy

Renal Dose Adjustments

• Serum creatinine 2 x baseline or greater, OR CrCl less than 15 mL/min, OR CrCl decreased to 50% or less of baseline, OR need for hemodialysis: Withhold dose and monitor renal function (serum creatinine or CrCl).
• If attributable to this drug, resume when renal function has recovered to within 25% of baseline; start at 1 dose level reduction.
• If not attributable to this drug, dosing may be resumed at the discretion of the physician.
• The dose is to be administered after the hemodialysis procedure for patients on hemodialysis.

Liver Dose Adjustments

Mild (total bilirubin 1 to 1.5 x upper limit of normal [ULN] and any AST or total bilirubin less than or equal to ULN and AST greater than ULN) or moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) hepatic impairment: Reduce the dose of by 25%
Severe hepatic impairment: Data not available

Dose Adjustments

HEMATOLOGIC TOXICITY:

• Absolute neutrophil count (ANC) less than 0.5 X 10(9)/L: Withhold dose; if recovered to 0.5 x 10(9)/L or greater, continue at the same dose level. For subsequent drops to less than 0.5 x 10(9) /L, follow the same recommendations as above and consider 1 dose level reduction when restarting therapy.
• Febrile neutropenia (ANC less than 0.5 x 10(9)/L and an oral temperature of more than 38.5C or 2 consecutive readings of more than 38C for 2 hours): Withhold dose; if ANC returns to baseline grade and fever resolves, resume at the same dose level.
• Platelets less than 10 X 10(9)/L or evidence of bleeding with thrombocytopenia: Withhold dose; if recovered to greater than or equal to 10 x 10(9)/L and/or bleeding is controlled, continue at the same dose level. For subsequent drops to less than 10 x 10(9)/L, follow the same recommendations as above and consider 1 dose level reduction when restarting therapy.

OTHER NONHEMATOLOGIC TOXICITY:

• All other severe or life-threatening nonhematologic toxicities (Grades 3 and 4): Withhold therapy until resolved or returned to baseline; consider restarting the next scheduled dose at 1 dose level reduction.

DOSE LEVEL REDUCTION GUIDELINES:
CARFILZOMIB AND DEXAMETHASONE OR CARFILZOMIB, DARATUMUMAB, AND DEXAMETHASONE (ONCE WEEKLY):

• Initial dose: 70 mg/m2
• First dose reduction: 56 mg/m2
• Second dose reduction: 45 mg/m2
• Third dose reduction: 36 mg/m2; if toxicity persists, discontinue therapy

CARFILZOMIB AND DEXAMETHASONE OR KYPROLIS, DARATUMUMAB, AND DEXAMETHASONE OR KYPROLIS MONOTHERAPY (TWICE WEEKLY):

• Initial dose: 56 mg/m2
• First dose reduction: 45 mg/m2
• Second dose reduction: 36 mg/m2
• Third dose reduction: 27 mg/m2; if toxicity persists, discontinue therapy

CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE OR CARFILZOMIB MONOTHERAPY (TWICE WEEKLY):

• Initial dose: 27 mg/m2
• First dose reduction: 20 mg/m2
• Second dose reduction: 15 mg/m2; if toxicity persists, discontinue therapy

Precautions

CONTRAINDICATIONS:

• None

This drug is not recommended for use in children.

Consult WARNINGS section for additional precautions.

Dialysis

Patients with end stage renal disease on dialysis: Administer the dose after the dialysis procedure.

Other Comments

OTHER COMMENTS:
Administration advice:

• The IV administration line should be flushed with normal saline or 5% dextrose injection immediately before and after drug administration.
• This drug is available for IV use only.
• Do not administer this drug as a bolus.
• Do not mix this drug with or administer as an infusion with other medicinal products.
• Infuse over 10 or 30 minutes depending on dosing regimen.

Storage requirements:

• Store unopened vials refrigerated 2C to 8C (36F to 46F).
• Retain in original package to protect from light.

General:

• The quantity of drug contained in one single-use vial may exceed the required dose; caution should be used in calculating dosage to prevent overdosing.
• Clinical benefit, such as improvement in survival or symptoms, has not been verified.
• Approval of this drug is based on response rate.

Monitoring:

• Cardiovascular: Fluid overload, cardiac complications
• Hematologic: Blood chemistries, platelet counts, Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome
• Hepatic: Liver function (transaminases, bilirubin)
• Nervous: Posterior Reversible Encephalopathy Syndrome
• Oncologic: Tumor Lysis Syndrome
• Other: Infusion reactions (immediately following or up to 24 hours after treatment administration)
• Renal: Renal function (serum creatinine)
• Respiratory: Dyspnea, pulmonary arterial hypertension

Frequently asked questions

• Is Kyprolis a chemo drug and how does it work?
• How is Kyprolis (carfilzomib) administered?

Further information

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

Medical Disclaimer