ardiac failure or who are at risk for cardiac failure [see Dosage and Administration (2)].
In patients ≥ 75 years of age, the risk of cardiac failure is increased compared to patients ˂ 75 years of age. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias uncontrolled by medications were not eligible for the clinical trials. These patients 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 [see Use in Specific Populations (8)].
5.2 Acute Renal Failure
Cases of acute renal failure have occurred in patients receiving Kyprolis. Renal insufficiency adverse events (including renal failure) have occurred in approximately 10% of patients treated with Kyprolis. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received Kyprolis monotherapy. This risk was greater in patients with a baseline reduced estimated creatinine clearance (calculated using Cockcroft and Gault equation). Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate [see Dosage and Administration (2)].
5.3 Tumor Lysis Syndrome
Cases of tumor lysis syndrome (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 [see Dosage and Administration (2)]. Consider uric acid-lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, including interruption of Kyprolis until TLS is resolved [see Dosage and Administration (2)].
5.4 Pulmonary Toxicity
Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in less than 1% of patients receiving Kyprolis. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue Kyprolis [see Dosage and Administration (2)].
5.5 Pulmonary Hypertension
Pulmonary arterial hypertension was reported in approximately 1% of patients treated with Kyprolis and was Grade 3 or greater in less than 1% of patients. eva luate with cardiac imaging and/or other tests as indicated. Withhold Kyprolis for pulmonary hypertension until resolved or returned to baseline, and consider whether to restart Kyprolis based on a benefit/risk assessment [see Dosage and Administration (2)].
5.6 Dyspnea
Dyspnea was reported in 28% of patients treated with Kyprolis and was Grade 3 or greater in 4% of patients. eva luate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop Kyprolis for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart Kyprolis based on a benefit/risk assessment [see Dosage and Administration (2.3); Warnings and Precautions (5.1 and 5.4); and Adverse Reactions (6)].
5.7 Hypertension
Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with Ky |
