KYPROLIS (carfilzomib) for Injection Menu

Adding KYPROLIS® to dexamethasone or Rd (Kd or KRd)

Kd dosing regimen1,2 Kd dosing regimen1,2

KYPROLIS® consecutive-day dosing1

Target the therapeutic dose from the Kd vs Vd study

PRIMING DOSE — CYCLE 1, DAYS 1 and 21

  • Administer a priming dose of KYPROLIS® (20 mg/m2) as a 30-minute IV infusion to evaluate tolerability to treatment with KYPROLIS®

ALL SUBSEQUENT DOSES:

  • *Target the Therapeutic Dose (56 mg/m2) of KYPROLIS® starting on Day 8 of Cycle 1 if the Priming Dose is tolerated on Days 1 and 2 of Cycle 11
  • Administer KYPROLIS® (56 mg/m2) as a 30-minute IV infusion on two consecutive days each week for three weeks, followed by a 12-day rest period, as part of a 28-day treatment cycle1
  • Treatment may be continued until disease progression or unacceptable toxicity occurs1

Modify dosing based on toxicity. Refer to Dose Modifications for toxicity during KYPROLIS® treatment1

Consecutive-day dosing schedule for KYPROLIS®1
See the consecutive-day dosing schedule for the Kd vs Vd study
  • Rationale for the dosing regimen was based on preclinical studies that demonstrated that consecutive-day dosing of KYPROLIS® suppressed recovery of proteasome activity between doses. Proteasome inhibition was maintained for ≥ 48 hours following the first dose of KYPROLIS® for each week of dosing.1,2
    • The clinical significance of preclinical studies is unknown.
KRd dosing regimen1,2 KRd dosing regimen1,2

KYPROLIS® consecutive-day dosing1

Target the therapeutic dose from the KRd vs Rd study

PRIMING DOSE — CYCLE 1, DAYS 1 and 21

  • Administer a priming dose of KYPROLIS® (20 mg/m2) as a 10-minute IV infusion to evaluate tolerability to treatment with KYPROLIS®

ALL SUBSEQUENT DOSES:

  • Target the Therapeutic Dose (27 mg/m2) of KYPROLIS® starting on Day 8 of Cycle 1 if the Priming Dose is tolerated on Days 1 and 2 of Cycle 11
  • Administer KYPROLIS® (27 mg/m2) as a 10-minute IV infusion on two consecutive days each week for three weeks, followed by a 12-day rest period, as part of a 28-day treatment cycle1
  • Starting in Cycle 13, omit Days 8 and 91
  • Treatment may be continued until disease progression or unacceptable toxicity occurs1
  • KYPROLIS® should be discontinued after Cycle 18 when given in combination with lenalidomide and dexamethasone1

Modify dosing based on toxicity. Refer to Dose Modifications for toxicity during KYPROLIS® treatment1

Consecutive-day dosing schedule for KYPROLIS®1
See the consecutive-day dosing schedule for the KRd vs Rd study
  • Rationale for the dosing regimen was based on preclinical studies that demonstrated that consecutive-day dosing of KYPROLIS® suppressed recovery of proteasome activity between doses. Proteasome inhibition was maintained for ≥48 hours following the first dose of KYPROLIS® for each week of dosing.1,2
    • The clinical significance of preclinical studies is unknown.
Dose modifications1

Dose modifications for hematologic and non-hematologic toxicities during KYPROLIS® treatment

Hematologic toxicity Recommended action
    Absolute neutrophil count (ANC) < 0.5 x 109/L
  • Withhold dose
    • If recovered to ≥ 0.5 x 109/L, continue at the same dose level
  • For subsequent drops to < 0.5 x 109/L, follow the same recommendations as above and consider 1 dose level reduction when restarting KYPROLIS®
  • Febrile neutropenia (ANC < 0.5 x 109/L and an oral temperature > 38.5°C or two consecutive readings of > 38.0°C for 2 hours)
  • Withhold dose
    • If ANC returns to baseline grade and fever resolves, resume at the same dose level
  • Platelets < 10 x 109/L or evidence of bleeding with thrombocytopenia
  • Withhold dose
    • If recovered to ≥ 10 x 109/L and/or bleeding is controlled, continue at the same dose level
  • For subsequent drops to < 10 x 109 /L, follow the same recommendations as above and consider 1 dose level reduction when restarting KYPROLIS®
Renal toxicity Recommended action
  • Serum creatinine ≥ 2 × baseline, or
  • Creatinine clearance < 15 mL/min, or creatinine clearance decreases 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 reduction
    • If not attributable to KYPROLIS®, dosing may be resumed at the discretion of the physician
  • For patients on hemodialysis receiving KYPROLIS®, the dose is to be administered after the hemodialysis procedure
Other non-hematologic toxicity Recommended action
  • All other severe or life-threatening§ non-hematological toxicities
  • Withhold until resolved or returned to baseline
  • Consider restarting the next scheduled treatment at 1 dose level reduction

See table below for dose level reductions.
§CTCAE Grades 3 and 4.

Dose level reductions for KYPROLIS®
Regimen Dose First dose reduction Second dose reduction Third dose reduction
Kd or monotherapy 56 mg/m2 45 mg/m2 36 mg/m2 27 mg/m**
KRd or monotherapy 27 mg/m2 20 mg/m2 15 mg/m**
  • Reduce the dose of KYPROLIS® by 25% for patients with mild or moderate hepatic impairment

Note: Infusion times remain unchanged during dose reduction(s).
**If toxicity persists, discontinue KYPROLIS® treatment.

Administration precautions1

    Hydration1

  • Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high risk of tumor lysis syndrome or renal toxicity. The recommended hydration includes 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.
  • Electrolyte Monitoring1

  • Monitor serum potassium levels regularly during treatment with KYPROLIS®.
  • Premedications1

  • 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.
  • Administration1

  • Infuse over 10 or 30 minutes depending on the KYPROLIS® dose regimen. Do not administer as a bolus. 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.
  • Dose Calculation1

  • Calculate the KYPROLIS® dose using the patient's actual body surface area at baseline. In patients with a body surface area greater than 2.2 m2, calculate the dose based upon a body surface area of 2.2 m2.
  • Thromboprophylaxis1

  • 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.
  • Infection Prophylaxis1

  • Consider antiviral prophylaxis in patients being treated with KYPROLIS® to decrease the risk of herpes zoster reactivation.
  • Patients on Hemodialysis1

  • Administer KYPROLIS® after the hemodialysis procedure.
Preparation and administration1

Reconstitution and preparation for intravenous administration

  • KYPROLIS® vials contain no antimicrobial preservatives and are intended for single use 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). 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:

  1. Remove vial from refrigerator just prior to use.
  2. 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%.
  3. Use a 21-gauge or larger gauge needle (0.8 mm or smaller external diameter needle) to aseptically reconstitute each vial by slowly injecting 29 mL (for 60 mg vial) or 15 mL (for 30 mg vial) Sterile Water for Injection, USP, through the stopper and directing the solution onto the INSIDE WALL OF THE VIAL to minimize foaming. Illustration of injection onto the inside wall of the vial
  4. 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.
  5. 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.
  6. 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.
  7. Optionally, KYPROLIS® can be administered in an intravenous bag.
  8. 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 5% Dextrose Injection, USP (based on the calculated total dose and infusion time).
  • The stabilities of reconstituted KYPROLIS® under various temperature and container conditions are shown in the table below.

Stability of reconstituted KYPROLIS®

Stability†† per container
Storage conditions of reconstituted KYPROLIS® 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

††Total time from reconstitution to administration should not exceed 24 hours.

‡‡5% Dextrose Injection, USP.

References

1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 2. Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67:6383-6391.

Important Safety Information

Cardiac Toxicities

  • New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration.
  • Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment.
  • While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure.
  • Patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.

Acute Renal Failure

Tumor Lysis Syndrome

Pulmonary Toxicity

Pulmonary Hypertension

Dyspnea

Hypertension

Venous Thrombosis

Infusion Reactions

Hemorrhage

Thrombocytopenia

Hepatic Toxicity and Hepatic Failure

Thrombotic Microangiopathy

Posterior Reversible Encephalopathy Syndrome (PRES)

Embryo-fetal Toxicity

Adverse reactions

Please see full Prescribing Information.

Indications