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KYPROLIS is indicated for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate [see Clinical Studies]. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
DOSAGE AND ADMINISTRATION
KYPROLIS is administered intravenously over 2 to 10 minutes, on two consecutive days, each week for three weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17 to 28). Each 28-day period is considered one treatment cycle (Table 1).
In Cycle 1, KYPROLIS is administered at a dose of 20 mg/m². If tolerated in Cycle 1, the dose should be escalated to 27 mg/m² beginning in Cycle 2 and continued at 27 mg/m² in subsequent cycles. Treatment may be continued until disease progression or until unacceptable toxicity occurs.
The dose is calculated using the patient's actual body surface area at baseline. Patients with a body surface area greater than 2.2 m² should receive a dose based upon a body surface area of 2.2 m². Dose adjustments do not need to be made for weight changes of less than or equal to 20%.
Table 1: KYPROLIS Dosage Regimen for Patients with
|Week 1||Week 2||Week 3||Week 4|
|KYPROLIS (20 mg/m²):||Day 1||Day 2||Days 3–7||Day 8||Day 9||Days 10–14||Day 15||Day 16||Days 17–21||Days 22–28|
|20||20||No Dosing||20||20||No Dosing||20||20||No Dosing||No Dosing|
|Cycles 2 and Beyonda|
|Week 1||Week 2||Week 3||Week 4|
|KYPROLIS (27 mg/m²):||Day 1||Day 2||Days 3–7||Day 8||Day 9||Days 10–14||Day 15||Day 16||Days 17–21||Days 22–28|
|27||27||No Dosing||27||27||No Dosing||27||27||No Dosing||No Dosing|
|aIf previous cycle dosage is tolerated.|
Hydration and Fluid Monitoring
Hydrate patients to reduce the risk of renal toxicity and of tumor lysis syndrome (TLS) with KYPROLIS treatment [see WARNINGS AND PRECAUTIONS]. Maintain adequate fluid volume status throughout treatment and monitor blood chemistries closely. Prior to each dose in Cycle 1, give 250 mL to 500 mL of intravenous normal saline or other appropriate intravenous fluid. Give an additional 250 mL to 500 mL of intravenous fluids as needed following KYPROLIS administration. Continue intravenous hydration, as needed, in subsequent cycles. Also monitor patients during this period for fluid overload [see WARNINGS AND PRECAUTIONS].
Pre-medicate with dexamethasone 4 mg orally or intravenously prior to all doses of KYPROLIS during Cycle 1 and prior to all KYPROLIS doses during the first cycle of dose escalation to 27 mg/m² to reduce the incidence and severity of infusion reactions [see WARNINGS AND PRECAUTIONS]. Reinstate dexamethasone premedication (4 mg orally or intravenously) if these symptoms develop or reappear during subsequent cycles.
Dose Modifications based on Toxicities
Recommended actions and dose modifications are presented in Table 2.
Table 2: Dose Modifications for Toxicitya during
|Hematologic Toxicity||Recommended Action|
|Non-Hematologic Toxicity||Recommended Action|
Grade 3 or 4, new onset or worsening of:
|Pulmonary Hypertension [see WARNINGS AND PRECAUTIONS]||
|aNational Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0|
The quantity of KYPROLIS contained in one single-use vial (60 mg carfilzomib) may exceed the required dose. Caution should be used in calculating the quantity delivered to prevent overdosing.
Do not mix KYPROLIS with or administer as an infusion with other medicinal products.
The intravenous administration line should be flushed with normal saline or 5% Dextrose Injection, USP immediately before and after KYPROLIS administration. KYPROLIS should not be administered as a bolus. KYPROLIS should be administered over 2 to 10 minutes.
Reconstitution and Preparation for Intravenous Administration
KYPROLIS vials contain no antimicrobial preservatives and are intended only for single use. 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). The reconstituted solution contains carfilzomib at a concentration of 2 mg/mL. Read the complete preparation instructions prior to reconstitution.
- Remove vial from refrigerator just prior to use.
- Aseptically reconstitute each vial by slowly injecting 29 mL Sterile Water for Injection, USP, directing the solution onto the INSIDE WALL OF THE VIAL to minimize foaming.
- Gently swirl and/or invert the vial slowly for about 1 minute, or until complete dissolution of any cake or powder occurs. DO NOT SHAKE to avoid foam generation. If foaming occurs, allow solution to rest in vial for about 2 to 5 minutes, until foaming subsides.
- After reconstitution, KYPROLIS is ready for intravenous administration. The reconstituted product should be a clear, colorless solution. If any discoloration or particulate matter is observed, do not use the reconstituted product.
- When administering in an intravenous bag, withdraw the calculated dose from the vial and dilute into 50 mL 5% Dextrose Injection, USP intravenous bag.
- Immediately discard the vial containing the unused portion.
The stabilities of reconstituted KYPROLIS under various temperature and container conditions are shown in Table 3.
Table 3: Stability of Reconstituted KYPROLIS
|Storage Conditions of Reconstituted KYPROLIS||Stabilitya per Container|
|Vial||Syringe||IV Bag (D5Wb)|
|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|
|aTotal time from reconstitution to administration should not
exceed 24 hours.
b5% Dextrose Injection, USP.
Dosage Forms And Strengths
KYPROLIS single-use vial contains 60 mg of carfilzomib as a sterile, white to off-white lyophilized cake or powder.
KYPROLIS (carfilzomib) for Injection is supplied as an individually cartoned single-use vial containing a dose of 60 mg of carfilzomib as a white to off-white lyophilized cake or powder.
NDC 76075-101-01, 60 mg carfilzomib per vial
Storage and Handling
Unopened vials should be stored refrigerated (2°C to 8°C; 36°F to 46°F). Retain in original package to protect from light.
Manufactured for: Onyx Pharmaceuticals, Inc. 249 East Grand Avenue South San Francisco, CA 94080. Revised: July 2012
Last reviewed on RxList: 7/25/2012
This monograph has been modified to include the generic and brand name in many instances.
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