For patients with a body surface area (BSA) of 2.2 m2 or less, calculate the dose using actual BSA:
To calculate the priming and therapeutic doses, multiply the patient’s BSA by the KYPROLIS® dose for the specific treatment regimen:
Priming dose: 1.8 m2 x 20 mg/m2 = 36 mg
Therapeutic dose: 1.8 m2 x 70 mg/m2 = 126 mg
Using the patient’s total dose calculated, refer to the full Prescribing Information to determine the appropriate number of vials required for administration. KYPROLIS® is supplied in 60-mg, 30-mg, and 10-mg single-dose vials for reconstitution.
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.
Remove vial from refrigerator just prior to use.1
Calculate the dose (mg/m2) and number of vials of KYPROLIS® required using the patient’s body surface area (BSA) 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 less than or equal to 20%.1
Aseptically reconstitute each KYPROLIS® vial only with Sterile Water for Injection, USP using the volumes described in the Reconstitution Table below. 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®.1
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.1
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.1
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.1
Administer KYPROLIS® directly by intravenous infusion or optionally, administer in a 50 mL to 100 mL intravenous bag containing 5% Dextrose Injection, USP. Do not administer as an intravenous push or bolus.1
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).1
Flush the intravenous administration line with normal saline or 5% Dextrose Injection, USP immediately before and after KYPROLIS® administration.1
Do not mix KYPROLIS® with or administer as an infusion with other medicinal products.1
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.1
The quantity of KYPROLIS® (carfilzomib) contained in one single-dose vial (30 mg or 60 mg) may exceed the recommended dose. Caution should be used in calculating the quantity delivered to prevent overdosing.
Administer as an intravenous infusion.
KYPROLIS® vials contain no antimicrobial preservatives and are intended for single dose only. Unopened vials of KYPROLIS® are stable until the date indicated on the package when stored in the original package at 2°C to 8°C (36°F to 46°F). Retain in original package to protect from light. The reconstituted solution contains carfilzomib at a concentration of 2 mg/mL.
Adequate hydration is required prior to KYPROLIS® dosing in Cycle 1—especially in patients at high risk of tumor lysis syndrome or renal toxicity.1
During cycle 1
If needed, give an additional 250-500 mL of IV fluids following KYPROLIS® administration
In subsequent cycles
Continue oral and/or IV hydration, as needed
Monitor patients for evidence of volume overload and adjust hydration to individual patient needs, especially in patients with, or at risk for, cardiac failure
Consider hydration with both oral and IV fluids
at least 48 hours before Cycle 1, Day 1
prior to each dose in Cycle 1
mL = milliliter; IV = intravenous; mL/kg = milliliters per kilogram.
BEFORE Identify & Plan2
Identify and assess patients at risk for cardiac ARs
Control hypertension and active heart failure and optimize blood pressure prior to initiating treatment
Consider cardiology consult before initiating treatment
Plan for fluid management during treatment
Measure blood pressure regularly in all patients
Check for signs and symptoms of cardiac ARs
Monitor volume status in all patients and adjust fluids
AFTER Stop & Assess2
Withhold for Grade 3 or 4 cardiac ARs until recovery
Consider reinitiating with one dose-level reduction based on a benefit-risk assessment†
*KYPROLIS® is approved in combination with both daratumumab for intravenous infusion and daratumumab and hyaluronidase-fihj for subcutaneous injection.
†Consultation with a cardiologist is warranted at the time of AR and upon reinitiation of treatment.
AR = adverse reaction.
Premedicate with the recommended dose of dexamethasone for monotherapy or dexamethasone administered as part of the combination therapy. 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 reactions. Reinstate dexamethasone premedication if these symptoms occur during subsequent cycles
Provide thromboprophylaxis for patients being treated with KYPROLIS® in combination with other therapies
Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation
Advise patients to discuss with their healthcare provider any medication they are currently taking prior to starting treatment with KYPROLIS® or prior to starting any new medication(s) during treatment with KYPROLIS®
Refer to the dexamethasone Prescribing Information for other concomitant medications. If treating with lenalidomide, refer to that Prescribing Information for other concomitant medications. If treating with Darzalex® (daratumumab), refer to that Prescribing Information for other concomitant medications
Absolute neutrophil count (ANC) less than 0.5 x 109/L
For subsequent drops to less than 0.5 x 109/L, follow the same recommendations as above and consider one dose level reduction when restarting KYPROLIS®*
Febrile neutropenia (ANC less than 0.5 x 109/L and an oral temperature more than 38.5°C or two consecutive readings of more than 38.0°C for 2 hours)
Platelets less than 10 x 109/L or evidence of bleeding with thrombocytopenia
For subsequent drops to less than 10 x 109/L, follow the same recommendations as above and consider one dose level reduction when restarting KYPROLIS®*
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 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
All other severe or life-threatening (Grade 3 or 4) non-hematological toxicities
Withhold until resolved or returned to baseline
Consider restarting the next scheduled treatment at one dose level reduction (see table below for dose level reductions)*
Dose modifications for use in hepatic impairment1
Dosing in patients with end stage renal disease1
Note: Infusion times remain unchanged during dose reduction(s).
*If toxicity persists, discontinue KYPROLIS® treatment.
mL/min = milliliter per minute; mg/m2 = milligrams per meter squared body surface area; ANC = absolute neutrophil count; L = liter; mg/min = milligrams per minute.
References: 1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Jakubowiak AJ, DeCara JM, Mezzi K. Cardiovascular events during carfilzomib therapy for relapsed myeloma: practical management aspects from two case studies. Hematology. 2017;22(10):585-591.