- KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone ... Read More
Administration and dose modifications
Dosing reference guide
3 easy steps to determine your patient's KYPROLIS® priming and therapeutic dose amounts1:
This tool provides assistance only. It is not designed or intended to replace the physician’s clinical judgment in determining the appropriate dose for his or her patient.
- At initiation of therapy, the patient’s body surface area (BSA) should always be used when calculating the KYPROLIS® dose.
- 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 calculated for weight changes of less than or equal to 20%
- To calculate the priming and therapeutic dose, multiply the patient’s BSA by the KYPROLIS® dose for the specific treatment regimen:
- Patient’s body surface area (BSA; m2) x dose (mg/m2)
- Example: Calculate the correct Kd once-weekly dose for a patient with a BSA of 1.8 m2
- Priming dose: 1.8 m2 x 20 mg/m2 = 36 mg
- Therapeutic dose: 1.8 m2 x 70 mg/m2 = 126 mg
Reconstitution and preparation
Follow these steps to reconstitute and prepare KYPROLIS®
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
Remove vial from refrigerator just prior to use.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
|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|
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
KYPROLIS® can be administered directly by intravenous infusion or optionally, administered 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
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
Administration and storage
Precautions for administration of KYPROLIS®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.
- KYPROLIS® 56 mg/m2 is infused intravenously over 30 minutes
- KYPROLIS® 27 mg/m2 is infused intravenously for 10 minutes
Administer as an intravenous infusion. Flush the intravenous administration line with normal saline or 5% Dextrose Injection, USP, immediately before and after KYPROLIS® administration. Do not mix KYPROLIS® with or administer as an infusion with other medicinal products.
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.
Stability of reconstituted KYPROLIS®1
|Storage conditions of reconstituted KYPROLIS®||Stability per container*|
|Vial||Syringe||Intravenous bag (D5W†)|
|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|
Additional dosing considerations
Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high risk of tumor lysis syndrome (TLS) or renal toxicity.
- The recommended hydration includes both oral fluids (30 mL per kg at least 48 hours before Cycle 1, Day 1) and IV fluids (250 mL to 500 mL of appropriate IV 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
Hydration requirements for KYPROLIS® prior to Cycle 11
Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high risk of TLS.
- Cases of TLS, including fatal outcomes, have been reported in patients who received KYPROLIS®
- Patients with multiple myeloma and a high tumor burden should be considered to be at greater risk for TLS
- Ensure that patients are well hydrated before administration of KYPROLIS® in Cycle 1, and in subsequent cycles as needed
- Uric acid lowering drugs should be considered in patients at risk for TLS
- Monitor for evidence of TLS during treatment and manage promptly
- Interrupt KYPROLIS® until TLS is resolved
- Infusion reactions, including life‑threatening reactions, have been reported in patients who received KYPROLIS®
- Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina
- These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS®. Administer dexamethasone prior to KYPROLIS® to reduce the incidence and severity of infusion reactions
- Inform patients of the risk and symptoms and to contact a physician immediately if symptoms of an infusion reaction occur
Premedications and concomitant medications1
- Premedicate with the recommended dose of dexamethasone for monotherapy or the recommended dexamethasone dose if on 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
- Consider antiviral prophylaxis for patients being treated with KYPROLIS® to decrease the risk of herpes zoster reactivation
- Advise patients to discuss any medication they are currently taking prior to starting treatment with KYPROLIS®, or prior to starting any new medication(s) during treatment with KYPROLIS®
- Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS® with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks
- Refer to the dexamethasone Prescribing Information for other concomitant medications. If treating with lenalidomide, refer to that Prescribing Information for other concomitant medications
Dose modifications for toxicity during KYPROLIS® treatment1
|Hematologic toxicity||Recommended action|
| || |
| || |
|Renal toxicity||Recommended action|
|Other non-hematologic toxicity||Recommended action|
CTCAE = Common Terminology Criteria for Adverse Events.
Dose modifications for use in hepatic impairment1
For patients with mild or moderate hepatic impairment, reduce the dose of KYPROLIS® by 25%. Dosing recommendation cannot be made in patients with severe hepatic impairment.
Dosing in patients with end stage renal disease1
For patients with end stage renal disease who are on dialysis, administer KYPROLIS® after the hemodialysis procedure.
Dose level reductions for KYPROLIS®1
|Regimen||Dose||First dose reduction||Second dose reduction||Third dose reduction|
omide, and dexa-
methasone, or mono-
therapy (20/27 mg/m2)
|27 mg/m2||20 mg/m2||15 mg/m2||—|
|KYPROLIS® and dexa-|
methasone, or mono-
therapy (20/56 mg/m2)
|56 mg/m2||45 mg/m2||36 mg/m2||27 mg/m2,*|
|KYPROLIS® and dexa-|
methasone (20/70 mg/m2)
|70 mg/m2||56 mg/m2||45 mg/m2||36 mg/m2|
Note: Infusion times remain unchanged during dose reduction(s).