Carfilzomib
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Proteasome Inhibitor
Dosing in kidney impairment
Recommended Dosage for End Stage Renal Disease For patients with end stage renal disease who are on hemodialysis, administer Kyprolis after the hemodialysis procedure.
| ANC = absolute neutrophil count | |
| Hematologic Toxicity [see Warnings and Precautions (5.11), Adverse Reactions (6.1)] | Recommended Action |
| ANC less than 0.5 × 109/L | Withhold doseIf recovered to greater than or equal to 0.5 × 109/L, continue at the same dose levelFor 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 doseIf 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 doseIf recovered to greater than or equal to 10 × 109/L and/or bleeding is controlled, continue at the same dose levelFor 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, orCreatinine 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 reductionIf not attributable to Kyprolis, dosing may be resumed at the discretion of the healthcare providerFor 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-threateningGrade 3 and 4. non-hematological toxicities | Withhold until resolved or returned to baselineConsider restarting the next scheduled treatment at 1 dose level reduction |
Dosing in liver impairment
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 , Clinical Pharmacology ] .
Preparation and administration
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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 ] . 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 ] .
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 ] . 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 ] . Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation [see Adverse Reactions ] . Dose Calculation For patients with body surface area (BSA) of 2.2 m 2 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 m 2 , calculate the Kyprolis dose using a BSA of 2.2 m 2 .
Recommended Dosage Once Weekly 20/70 mg/m 2 (30-minute infusion) Kyprolis once weekly 20/70 mg/m 2 administered in combination with dexamethasone (Kd), daratumumab plus dexamethasone (DKd), or daratumumab and hyaluronidase-fihj plus dexamethasone (DKd). The recommended starting dosage of Kyprolis is 20 mg/m 2 on Cycle 1, Day 1.
If tolerated, escalate the dose to 70 mg/m 2 on Cycle 1, Day 8. Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity as shown in Table 1 [see Clinical Studies ] . Administer dexamethasone 30 minutes to 4 hours before Kyprolis and 1 to 3 hours before daratumumab or daratumumab and hyaluronidase-fihj.
For dosage instructions of combination agents with Kyprolis, see Clinical Studies sections 14.2 (Kd) and 14.3 (DKd) . Refer to the Prescribing Information for dexamethasone, intravenous daratumumab, and subcutaneous daratumumab and hyaluronidase-fihj for additional dosage information. [See table below.] Minute Infusion) 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/m 2 ) 20 - - 70 - - 70 - - - - - 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/m 2 ) 70 - - 70 - - 70 - - - - - Twice Weekly 20/56 mg/m 2 (30-minute infusion) Kyprolis twice weekly 20/56 mg/m 2 administered as monotherapy or in combination with dexamethasone (Kd), daratumumab plus dexamethasone (DKd), daratumumab and hyaluronidase-fihj plus dexamethasone (DKd), or isatuximab plus dexamethasone (Isa-Kd).
The recommended starting dosage of Kyprolis is 20 mg/m 2 on Cycle 1, Days 1 and 2. If tolerated, escalate the dose to 56 mg/m 2 on Cycle 1, Day 8. Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle as shown in Table 2 until disease progression or unacceptable toxicity [see Clinical Studies (Section 14) ] .
If given as monotherapy, administer 8 mg dexamethasone orally or intravenously 30 minutes to 4 hours before Kyprolis then as needed to minimize infusion-related reactions [see Dosage and Administration ] . Kyprolis given as monotherapy may be omitted on Days 8 and 9 of cycle 13 onward. For dosage instructions of combination agents administered with Kyprolis, see Clinical Studies sections 14.2 (Kd) , 14.3 (DKd) , 14.4 (Isa-Kd) , and 14.5 (Monotherapy) .
Refer to the Prescribing Information for dexamethasone, intravenous daratumumab, subcutaneous daratumumab and hyaluronidase-fihj, and isatuximab for additional dosage information. [See table below.] Minute Infusion) 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 As monotherapy, dexamethasone premedication is required for each Kyprolis dose in Cycle 1. (mg/m 2 ) 20 20 - 56 56 - 56 56 - - - - 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/m 2 ) 56 56 - 56 56 - 56 56 - - - - Twice Weekly 20/27 mg/m 2 (10-minute infusion) Kyprolis twice weekly 20/27 mg/m 2 is administered as monotherapy or in combination with lenalidomide and dexamethasone (KRd).
The recommended starting dosage of Kyprolis is 20 mg/m 2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m 2 on Day 8 of Cycle 1 and thereafter. Administer Kyprolis intravenously as a 10-minute infusion [see Clinical Studies ] . 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 3.
From Cycle 13, administer Kyprolis on Days 1, 2, 15 and 16 of each 28-day cycle. If given as monotherapy, 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 ] . Continue Kyprolis with the regimens shown in Table 3 until disease progression or unacceptable toxicity occurs.
When combined with lenalidomide and dexamethasone, discontinue Kyprolis after Cycle 18 and continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity occurs. For dosage instructions of combination agents with Kyprolis, see Clinical Studies sections 14.1 (KRd) and 14.5 (Monotherapy) . Refer to the Prescribing Information for dexamethasone and lenalidomide for additional dosage information. [See table below.] Minute Infusion) 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/m 2 ) Dexamethasone premedication is required for each Kyprolis dose in Cycle 1. 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/m 2 ) 27 27 - 27 27 - 27 27 - - Cycles 13 and later When administered in combination with lenalidomide and dexamethasone, discontinue Kyprolis after Cycle 18.
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/m 2 ) 27 27 - - - - 27 27 - -
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 : Remove vial from refrigerator just prior to use. Calculate the dose (mg/m 2 ) and number of vials of Kyprolis required using the patient's BSA at baseline. Aseptically reconstitute each Kyprolis vial only with Sterile Water for Injection, USP using the volumes described in Table 6. 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 through the stopper and directing the Sterile Water for Injection 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. [See table below.] 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.
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. 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. Administer Kyprolis directly by intravenous infusion or in a 50 mL to 100 mL intravenous bag containing 5% Dextrose Injection . Do not administer as an intravenous push or bolus. 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 (based on the calculated total dose and infusion time).
Flush the intravenous administration line with 0.9% Sodium Chloride Injection or 5% Dextrose Injection immediately before and after Kyprolis administration. 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 7. [See table below.] . per Container Vial Syringe Intravenous Bag (D5W 5% Dextrose Injection. ) 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 Figure
| Regimen | Dosage | Infusion Time |
|---|---|---|
| Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) | 20/70 mg/m2 once weekly | 30 minutes |
| Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) or Kyprolis, Isatuximab and Dexamethasone (Isa-Kd) or Kyprolis Monotherapy | 20/56 mg/m2 twice weekly | 30 minutes |
| Kyprolis, Lenalidomide and Dexamethasone (KRd) or Kyprolis Monotherapy | 20/27 mg/m2 twice weekly | 10 minutes |
| 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 | - | - | - | - | - |
| 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) | 70 | - | - | 70 | - | - | 70 | - | - | - | - | - |
| 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 | |
| KyprolisAs monotherapy, dexamethasone premedication is required for each Kyprolis dose in Cycle 1. (mg/m2) | 20 | 20 | - | 56 | 56 | - | 56 | 56 | - | - | - | - |
| 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 | - | - | - | - |
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Kyprolis can cause fetal harm based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] . There are no available data on Kyprolis use in pregnant women to evaluate for drug-associated risks. Kyprolis caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Data ) . Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.
Data Animal Data Carfilzomib administered intravenously to pregnant rats and rabbits during the period of organogenesis was not teratogenic at doses up to 2 mg/kg/day in rats and 0.8 mg/kg/day in rabbits. In rabbits, there was an increase in pre-implantation loss at ≥ 0.4 mg/kg/day and an increase in early resorptions and post-implantation loss and a decrease in fetal weight at the maternally toxic dose of 0.8 mg/kg/day. The doses of 0.4 and 0.8 mg/kg/day in rabbits are approximately 20% and 40%, respectively, of the recommended dose in humans of 27 mg/m 2 based on BSA.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.