ber 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.Aseptically reconstitute each vial by slowly injecting 29 mL Sterile Water for Injection, USP, through the stopper and directing the solution onto the INSIDE WALL OF THE VIAL to minimize foaming.
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.
7.Optionally, Kyprolis can be administered in an intravenous bag.
8.When administering in an intravenous bag, withdraw the calculated dose [see Dosage
and Administration (2)] 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 Table 7.
Table 7: Stability of Reconstituted Kyprolis
Total time from reconstitution to administration should not exceed 24 hours.
5% Dextrose Injection, USP.
3 DOSAGE FORMS AND STRENGTHS
For injection: 60 mg lyophilized cake or powder in single-dose vial for reconstitution
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 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. In clinical studies with Kyprolis, these events occurred throughout the course of Kyprolis therapy. Death due to cardiac arrest has occurred within one day of Kyprolis administration. In a randomized, open-label, multicenter trial eva luating Kyprolis in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide/dexamethasone (Rd), the incidence of cardiac failure events was 6% in the KRd arm versus 4% in the Rd arm. In a randomized, open-label, multicenter trial of Kyprolis plus dexamethasone (Kd) versus bortezomib plus dexamethasone (Vd), the incidence of cardiac failure events was 8% in the Kd arm versus 3% in the Vd arm.
Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. eva luate 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 [see Dosage and Administration (2)].
While adequate hydration is required prior to each dose in Cycle 1, all patients should also be monitored for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline c |
