ASH Clinical News July 2015_updated | Page 5

B:16.75” T:16.25” S:14.625” reatment (continued) ction has recovered to Grade 1 tor renal function. LIS, restart at the next scheduled dose (from 27 mg/m2 to mg/m2 to 15 mg/m2). PROLIS, restart at the dose used d dose may be escalated to the scretion of the physician. or returned to baseline. d prior to the event or reduced o 20 mg/m2, OR from 20 mg/m2 scretion of the physician. d dose may be escalated to the scretion of the physician. or returned to baseline. he next scheduled treatment uction (from 27 mg/m2 to  mg/m2 to 15 mg/m2). d dose may be escalated to the scretion of the physician. CI CTCAE) Version 3.0. ained in one single-use vial (60  mg in calculating the quantity delivered to infusion with other medicinal products. l saline or 5% Dextrose Injection, USP should not be administered as a bolus. constitution and Preparation for crobial preservatives and are intended e date indicated on the package when onstituted solution contains carfilzomib n instructions prior to reconstitution. erator just prior to use. 2. Aseptically ection, USP, directing the solution onto l and/or invert the vial slowly for about ccurs.  DO NOT SHAKE to avoid foam 2 to 5 minutes, until foaming subsides. ation. The reconstituted product should matter is observed, do not use the ag, withdraw the calculated dose [see % Dextrose Injection, USP intravenous rtion. The stabilities of reconstituted shown in Table 3. reported in patients who received KYPROLIS. Monitor for signs and symptoms of TTP/HUS. If the diagnosis is suspected, stop KYPROLIS and evaluate. If the diagnosis of TTP/HUS is excluded, KYPROLIS can be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known. Posterior Reversible Encephalopathy Syndrome (PRES): PRES, formerly termed Reversible Posterior Leukoencephalopathy Syndrome (RPLS), is a neurological disorder, which can present with seizure, headache, lethargy, confusion, blindness, altered consciousness, and other visual and neurological disturbances, along with hypertension, and the diagnosis is confirmed by neuro-radiological imaging (MRI). Cases of PRES have been reported in patients receiving KYPROLIS. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known. Embryo-fetal Toxicity. KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. There are no adequate and wellcontrolled studies in pregnant women using KYPROLIS. Carfilzomib caused embryo-fetal toxicity in pregnant rabbits at doses that were lower than in patients receiving the recommended dose. Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations]. ADVERSE REACTIONS: The following adverse reactions are discussed in greater detail in other sections of the labeling: • Cardiac Arrest, Congestive Heart Failure, Myocardial Ischemia [see Warnings and Precautions] • Pulmonary Hypertension [see Warnings and Precautions] • Pulmonary Complications [see Warnings and Precautions] • Infusion Reactions [see Warnings and Precautions] • Tumor Lysis Syndrome [see Warnings and Precautions] • Thrombocytopenia [see Warnings and Precautions] • Hepatic Toxicity and Hepatic Failure [see Warnings and Precautions] The most common adverse reactions (incidence of 30% or greater) to KYPROLIS observed in clinical trials of patients with multiple myeloma were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. Clinical Trials Safety Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug, and may not reflect the rates observed in medical practice. A total of 526 patients with relapsed and/or refractory multiple myeloma received KYPROLIS as monotherapy or with pre-dose dexamethasone. Patients received a median of four treatment cycles with a median cumulative KYPROLIS dose of 993.4 mg. Deaths due to all causes within 3 ^\