Kyprolis
Carfilzomib · Injection, Powder, Lyophilized, For Solution · Intravenous
Uses
Kyprolis is a proteasome inhibitor that is indicated: for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with Lenalidomide and dexamethasone; or Dexamethasone; or Daratumumab and dexamethasone; or Daratumumab and hyaluronidase-fihj and dexamethasone; or Isatuximab and dexamethasone. ( 1 , 14 ) as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. ( 1 , 14 ) 1.1 Relapsed or Refractory Multiple Myeloma Kyprolis is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with: Lenalidomide and dexamethasone; or Dexamethasone; or Daratumumab and dexamethasone; or Daratumumab and hyaluronidase-fihj and dexamethasone; or Isatuximab and dexamethasone. Kyprolis is indicated as a single agent for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
Dosage and administration
Hydrate prior to and following Kyprolis as needed. ( 2.1 ) Premedicate prior to all Cycle 1 doses and if infusion-related reactions develop or reappear. ( 2.1 ) The recommended dosing regimens are as follows. See Full Prescribing Information for additional dosage information. ( 2.2 ) Regimen Dosage Infusion Time Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) 20/70 mg/m 2 once weekly 30 minutes Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) or Kyprolis, Isatuximab and Dexamethasone (Isa-Kd) or Kyprolis Monotherapy 20/56 mg/m 2 twice weekly 30 minutes Kyprolis, Lenalidomide and Dexamethasone (KRd) or Kyprolis Monotherapy 20/27 mg/m 2 twice weekly 10 minutes 2.1 Administration Precautions Hydration Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high-risk of tumor lysis syndrome (TLS) or renal toxicity. Consider hydration with 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 [see Warnings and Precautions (5.1 , 5.3) ] . Electrolyte Monitoring Monitor serum potassium levels regularly during treatment with Kyprolis [see Adverse Reactions (6.1) ] . Premedications and Concomitant Medications Premedicate with the recommended dose of dexamethasone for monotherapy or dexamethasone administered as part of the combination therapy [see Dosage and Administration (2.2) ] . 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-related reactions [see Warnings and Precautions (5.9) ] . Reinstate dexamethasone premedication if these symptoms occur during subsequent cycles. Provide thromboprophylaxis for patients being treated with Kyprolis in combination with other therapies [see Warnings and Precautions (5.8) ] . Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation [see Adverse Reactions (6.1) ] . Dose Calculation For patients with body surface area (BSA) of 2.2 m 2 or less, calculate the Kyprolis dose using actual BSA. Dose adjustments do not need to be made for weight changes of 20% or less. For patients with a BSA greater than 2.2 m 2 , calculate the Kyprolis dose using a BSA of 2.2 m 2 . 2.2 Recommended Dosage Once Weekly 20/70 mg/m 2 (30-minute infusion) Kyprolis once weekly 20/70 mg/m 2 administered in combination with dexamethasone (Kd), daratumumab plus dexamethasone (DKd), or daratumumab and hyaluronidase-fihj plus dexamethasone (DKd). The recommended starting dosage of Kyprolis is 20 mg/m 2 on Cycle 1, Day 1. If tolerated, escalate the dose to 70 mg/m 2 on Cycle 1, Day 8. Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity as shown in Table 1 [see Clinical Studies (14.2) ] . Administer dexamethasone 30 minutes to 4 hours before Kyprolis and 1 to 3 hours before daratumumab or daratumumab and hyaluronidase-fihj. For dosage instructions of combination agents with Kyprolis, see Clinical Studies sections 14.2 (Kd) and 14.3 (DKd) . Refer to the Prescribing Information for dexamethasone, intravenous daratumumab, and subcutaneous daratumumab and hyaluronidase-fihj for additional dosage information. Table 1: Kyprolis 20/70 mg/m 2 Once Weekly (30-Minute Infusion) Cycle 1 Week 1 Week 2 Week 3 Week 4 Day 1 Day 2 Days 3-7 Day 8 Day 9 Days 10-14 Day 15 Day 16 Days 17-21 Day 22 Day 23 Days 24-28 Kyprolis (mg/m 2 ) 20 - - 70 - - 70 - - - - - Cycles 2 and later Week 1 Week 2 Week 3 Week 4 Day 1 Day 2 Days 3-7 Day 8 Day 9 Days 10-14 Day 15 Day 16 Days 17-21 Day 22 Day 23 Days 24-28 Kyprolis (mg/m 2 ) 70 - - 70 - - 70 - - - - - Twice Weekly 20/56 mg/m 2 (30-minute infusion) Kyprolis twice weekly 20/56 mg/m 2 administered as monotherapy or in combination with dexamethasone (Kd), daratumumab plus dexamethasone (DKd), daratumumab and hyaluronidase-fihj plus dexamethasone (DKd), or isatuximab plus dexamethasone (Isa-Kd). The recommended starting dosage of Kyprolis is 20 mg/m 2 on Cycle 1, Days 1 and 2. If tolerated, escalate the dose to 56 mg/m 2 on Cycle 1, Day 8. Administer Kyprolis intravenously as a 30-minute infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle as shown in Table 2 until disease progression or unacceptable toxicity [see Clinical Studies (Section 14) ] . If given as monotherapy, administer 8 mg dexamethasone orally or intravenously 30 minutes to 4 hours before Kyprolis then as needed to minimize infusion-related reactions [see Dosage and Administration (2.1) ] . Kyprolis given as monotherapy may be omitted on Days 8 and 9 of cycle 13 onward. For dosage instructions of combination agents administered with Kyprolis, see Clinical Studies sections 14.2 (Kd) , 14.3 (DKd) , 14.4 (Isa-Kd) , and 14.5 (Monotherapy) . Refer to the Prescribing Information for dexamethasone, intravenous daratumumab, subcutaneous daratumumab and hyaluronidase-fihj, and isatuximab for additional dosage information. Table 2: Kyprolis 20/56 mg/m 2 Twice Weekly (30-Minute Infusion) Cycle 1 Week 1 Week 2 Week 3 Week 4 Day 1 Day 2 Days 3-7 Day 8 Day 9 Days 10-14 Day 15 Day 16 Days 17-21 Day 22 Day 23 Days 24-28 Kyprolis As monotherapy, dexamethasone premedication is required for each Kyprolis dose in Cycle 1.
Dosage forms and strengths
For injection: 10 mg, 30 mg and 60 mg as a white to off-white lyophilized cake or powder in single-dose vial for reconstitution. For injection: 10 mg, 30 mg or 60 mg lyophilized powder in single-dose vial for reconstitution. ( 3 )
Contraindications
None. None. ( 4 )
Warnings and precautions
Cardiac Toxicities : Monitor for signs and symptoms of cardiac failure or ischemia. Withhold Kyprolis and evaluate promptly. ( 5.1 ) Acute Renal Failure : Monitor serum creatinine regularly. ( 5.2 ) Tumor Lysis Syndrome (TLS) : Administer pre-treatment hydration. (2.1 ) Monitor for TLS, including uric acid levels and treat promptly. ( 5.3 ) Pulmonary Toxicity, including Acute Respiratory Distress Syndrome, Acute Respiratory Failure, and Acute Diffuse Infiltrative Pulmonary Disease : Withhold Kyprolis and evaluate promptly. ( 5.4 ) Pulmonary Hypertension : Withhold Kyprolis and evaluate. ( 5.5 ) Dyspnea : For severe or life-threatening dyspnea, withhold Kyprolis and evaluate. ( 5.6 ) Hypertension, including Hypertensive Crisis : Monitor blood pressure regularly. If hypertension cannot be controlled, interrupt treatment with Kyprolis. ( 5.7 ) Venous Thrombosis : Thromboprophylaxis is recommended. ( 5.8 ) Infusion-related Reactions : Premedicate with dexamethasone. ( 2.1 , 5.9 ) Hemorrhage : Fatal or serious cases of hemorrhage may occur, including gastrointestinal, pulmonary, and intracranial hemorrhage. Promptly evaluate signs and symptoms of blood loss. ( 5.10 ) Thrombocytopenia : Monitor platelet counts; interrupt or reduce Kyprolis dosing as clinically indicated. ( 2.3 , 5.11 ) Hepatic Toxicity and Hepatic Failure : Monitor liver enzymes regularly. Withhold Kyprolis if suspected. ( 5.12 ) Thrombotic Microangiopathy : Monitor for signs and symptoms. Discontinue Kyprolis if suspected. ( 5.13 ) Posterior Reversible Encephalopathy Syndrome (PRES) : Consider neuro-radiological imaging (MRI) for onset of visual or neurological symptoms; discontinue Kyprolis if suspected. ( 5.14 ) Progressive Multifocal Leukoencephalopathy : Consider PML if new or worsening neurologic manifestations. Discontinue Kyprolis in patients who develop PML. ( 5.15 ) Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Patients ( 5.16 ) Embryo-Fetal Toxicity : Kyprolis can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.17 , 8.1 ) 5.1 Cardiac Toxicities New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), 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 randomized, open-label, multicenter trials for combination therapies, the incidence of cardiac failure events was 8% and that of arrythmias was 8% (majority of which were atrial fibrillation and sinus tachycardia) [see Adverse Reactions (6.1) ]. 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 reactions until recovery and consider whether to restart Kyprolis at 1 dose level reduction based on a benefit/risk assessment [see Dosage and Administration (2.3) ] . 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 [see Dosage and Administration (2.1) ] . In patients ≥ 75 years of age, the risk of cardiac failure is increased compared to younger patients. 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; for these patients, complete a comprehensive medical assessment (including blood pressure control and fluid management) prior to starting treatment with Kyprolis and remain under close follow-up [see Use in Specific Populations (8.5) ] . 5.2 Acute Renal Failure Cases of acute renal failure have occurred in patients receiving Kyprolis. Some of these events have been fatal. Renal insufficiency (including renal failure) has occurred in approximately 9% of patients who received Kyprolis. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received Kyprolis monotherapy. The risk of fatal renal failure was greater in patients with a baseline reduced estimated creatinine clearance (calculated using Cockcroft-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 (2.3) ] . 5.3 Tumor Lysis Syndrome Cases of 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. Administer oral and intravenous fluids before administration of Kyprolis in Cycle 1 and in subsequent cycles as needed. Consider uric acid-lowering drugs in patients at risk for TLS. Monitor for TLS during treatment and manage promptly, including interruption of Kyprolis until TLS is resolved [see Dosage and Administration (2.1) ] . 5.4 Pulmonary Toxicity Acute Respiratory Distress Syndrome (ARDS) and acute respiratory failure have occurred in approximately 2% of patients who received Kyprolis.
Side effects
The following clinically significant adverse reactions are described elsewhere in the labeling: Cardiac Toxicities [see Warnings and Precautions (5.1) ] Acute Renal Failure [see Warnings and Precautions (5.2) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.3) ] Pulmonary Toxicity [see Warnings and Precautions (5.4) ] Pulmonary Hypertension [see Warnings and Precautions (5.5) ] Dyspnea [see Warnings and Precautions (5.6) ] Hypertension [see Warnings and Precautions (5.7) ] Venous Thrombosis [see Warnings and Precautions (5.8) ] Infusion-Related Reactions [see Warnings and Precautions (5.9) ] Hemorrhage [see Warnings and Precautions (5.10) ] Thrombocytopenia [see Warnings and Precautions (5.11) ] Hepatic Toxicity and Hepatic Failure [see Warnings and Precautions (5.12) ] Thrombotic Microangiopathy [see Warnings and Precautions (5.13) ] Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.14) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.15) ] The most common adverse reactions occurring in at least 20% of patients treated with Kyprolis in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral. ( 6 ) The most common adverse reactions occurring in at least 20% of patients treated with Kyprolis in the combination therapy trials: anemia, diarrhea, hypertension, fatigue, upper respiratory tract infection, thrombocytopenia, pyrexia, cough, dyspnea, and insomnia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 practice. The pooled safety population described in the Warnings and Precautions reflect exposure to Kyprolis in 2,239 patients administered in combination with other drugs in ASPIRE, ENDEAVOR, A.R.R.O.W., CANDOR, IKEMA, EQUULEUS, and PLEIADES. The most common adverse reactions occurring in at least 20% of patients who received Kyprolis in combination were anemia, diarrhea, hypertension, fatigue, upper respiratory tract infection, thrombocytopenia, pyrexia, cough, dyspnea, and insomnia. Kyprolis in Combination with Lenalidomide and Dexamethasone The safety of Kyprolis 20/27 mg/m 2 twice weekly in combination with lenalidomide and dexamethasone (KRd) was evaluated in ASPIRE [see Clinical Studies (14.1) ] . The median number of cycles initiated was 22 cycles for the KRd arm and 14 cycles for the Rd arm. Deaths due to adverse reactions within 30 days of the last dose of any therapy in the KRd arm occurred in 45/392 (12%) patients compared with 42/389 (11%) patients who died due to adverse reactions within 30 days of the last dose of any Rd therapy. The most frequent cause of deaths occurring in patients (%) in the two arms (KRd versus Rd) included infection 12 (3%) versus 11 (3%), cardiac 10 (3%) versus 9 (2%), and other adverse reactions 23 (6%) versus 22 (6%). Serious adverse reactions were reported in 65% of the patients in the KRd arm and 57% of the patients in the Rd arm. The most frequent serious adverse reactions reported in the KRd arm as compared with the Rd arm were pneumonia (17% versus 13%), respiratory tract infection (4% versus 2%), pyrexia (4% versus 3%), and pulmonary embolism (3% versus 2%). Discontinuation due to any adverse reaction occurred in 33% in the KRd arm versus 30% in the Rd arm. Adverse reactions leading to discontinuation of Kyprolis occurred in 12% of patients and the most common reactions included pneumonia (1%), myocardial infarction (0.8%), and upper respiratory tract infection (0.8%). The incidence of cardiac failure events was 7% in the KRd arm versus 4% in the Rd arm. Table 8 summarizes the adverse reactions in the first 12 cycles in ASPIRE. Table 8: Adverse Reactions (≥ 10%) Occurring in Cycles 1–12 in Patients Who Received KRd (20/27 mg/m 2 Regimen) in ASPIRE Adverse Reactions KRd (N = 392) n (%) Rd (N = 389) n (%) Any Grade ≥ Grade 3 Any Grade ≥ Grade 3 KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone Blood and Lymphatic System Disorders Anemia 138 (35) 53 (14) 127 (33) 47 (12) Neutropenia 124 (32) 104 (27) 115 (30) 89 (23) Thrombocytopenia 100 (26) 58 (15) 75 (19) 39 (10) Gastrointestinal Disorders Diarrhea 119 (30) 8 (2) 106 (27) 12 (3) Constipation 68 (17) 0 (0) 55 (14) 1 (0) Nausea 63 (16) 1 (0) 43 (11) 3 (1) General Disorders and Administration Site Conditions Fatigue 113 (29) 23 (6) 107 (28) 20 (5) Pyrexia 93 (24) 5 (1) 64 (17) 1 (0) Edema peripheral 59 (15) 3 (1) 48 (12) 2 (1) Asthenia 54 (14) 11 (3) 49 (13) 7 (2) Infections Upper respiratory tract infection 87 (22) 7 (2) 54 (14) 4 (1) Bronchitis 55 (14) 5 (1) 40 (10) 2 (1) Viral upper respiratory tract infection 55 (14) 0 (0) 44 (11) 0 (0) Pneumonia Pneumonia includes pneumonia and bronchopneumonia. 54 (14) 35 (9) 43 (11) 27 (7) Metabolism and Nutrition Disorders Hypokalemia 78 (20) 22 (6) 35 (9) 12 (3) Hypocalcemia 55 (14) 10 (3) 39 (10) 5 (1) Hyperglycemia 43 (11) 18 (5) 33 (9) 15 (4) Musculoskeletal and Connective Tissue Disorders Muscle spasms 92 (24) 3 (1) 75 (19) 3 (1) Back pain 41 (11) 4 (1) 54 (14) 6 (2) Nervous System Disorders Peripheral neuropathies Peripheral neuropathies includes peripheral neuropathy, peripheral sensory neuropathy, and peripheral motor neuropathy. 43 (11) 7 (2) 39 (10) 4 (1) Psychiatric Disorders Insomnia 64 (16) 6 (2) 51 (13) 8 (2) Respiratory, Thoracic and Mediastinal Disorders Cough Cough includes cough and productive cough. 93 (24) 2 (1) 54 (14) 0 (0) Dyspnea Dyspnea includes dyspnea and dyspnea exertional.
Use in specific populations
Geriatric Use : In the Kyprolis clinical trials, the incidence of adverse reactions was greater in patients ≥ 75 years of age. ( 8.5 ) Hepatic Impairment : Reduce the dose of Kyprolis by 25% in patients with mild or moderate hepatic impairment. ( 2.4 ) Patients on Hemodialysis : Administer Kyprolis after the hemodialysis procedure. ( 2.1 ) Lactation : Advise women not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Kyprolis can cause fetal harm based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] . There are no available data on Kyprolis use in pregnant women to evaluate for drug-associated risks. Kyprolis caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Data ) . Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Data Animal Data Carfilzomib administered intravenously to pregnant rats and rabbits during the period of organogenesis was not teratogenic at doses up to 2 mg/kg/day in rats and 0.8 mg/kg/day in rabbits. In rabbits, there was an increase in pre-implantation loss at ≥ 0.4 mg/kg/day and an increase in early resorptions and post-implantation loss and a decrease in fetal weight at the maternally toxic dose of 0.8 mg/kg/day. The doses of 0.4 and 0.8 mg/kg/day in rabbits are approximately 20% and 40%, respectively, of the recommended dose in humans of 27 mg/m 2 based on BSA. 8.2 Lactation Risk Summary There are no data on the presence of Kyprolis in human milk, the effects on the breastfed child, or the effects of the drug on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with Kyprolis and for 2 weeks after treatment. 8.3 Females and Males of Reproductive Potential Based on its mechanism of action and findings in animals, Kyprolis can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Conduct pregnancy testing on females of reproductive potential prior to initiating Kyprolis treatment. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Kyprolis and for 6 months following the last dose. Males Advise males with female sexual partners of reproductive potential to use effective contraception during treatment with Kyprolis and for 3 months following the last dose. Infertility Based on the mechanism of action, Kyprolis may have an effect on either male or female fertility [see Clinical Pharmacology (12.1) , Nonclinical Toxicology (13.1) ] . There are no data on the effect of Kyprolis on human fertility. 8.4 Pediatric Use The safety and effectiveness of Kyprolis in pediatric patients have not been established. The safety and effectiveness of Kyprolis in combination with chemotherapy was evaluated, but not established in an open label trial (Study 20140106; NCT02303821) in 124 patients aged 1 to younger than 17 years with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) who have received prior targeted B-cell immune therapy or relapsed or refractory T-cell ALL. No new safety signals were observed in these pediatric patients. The systemic exposure of carfilzomib in these pediatric patients was within range of that observed in adults given the same dose based on body surface area. 8.5 Geriatric Use Of the 2,837 patients with relapsed or refractory multiple myeloma exposed to Kyprolis in monotherapy and combination therapy studies [see Clinical Studies (14.1 , 14.2 , 14.3 , 14.4 , 14.5) ] , 50% were 65 years and older, while 13% were 75 years and older. The incidence of serious adverse reactions was 50% in patients < 65 years of age, 60% in patients 65 to 74 years of age, and 63% in patients ≥ 75 years of age. Of the 308 patients in CANDOR who received DKd, 47% of patients were 65 years and older, while 9% were 75 years and older. Fatal adverse reactions in the DKd arm of CANDOR occurred in 6% of patients < 65 years of age, 14% of patients between 65 to 74 years of age, and 14% of patients ≥ 75 years of age [see Adverse Reactions (6.1) ] . No overall differences in effectiveness were observed between older and younger patients. 8.6 Hepatic Impairment Reduce the dose of Kyprolis by 25% in patients with mild (total bilirubin 1 to 1.5 × ULN and any AST or total bilirubin ≤ ULN and AST > ULN) or moderate (total bilirubin > 1.5 to 3 × ULN and any AST) hepatic impairment. A recommended dosage of Kyprolis has not been established for patients with severe hepatic impairment (total bilirubin > 3 × ULN and any AST) [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ] . The incidence of serious adverse reactions was higher in patients with mild, moderate, and severe hepatic impairment combined (22/35 or 63%) than in patients with normal hepatic function (3/11 or 27%) [see Warnings and Precautions (5.12) , Clinical Pharmacology (12.3) ] .
Pregnancy
8.1 Pregnancy Risk Summary Kyprolis can cause fetal harm based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] . There are no available data on Kyprolis use in pregnant women to evaluate for drug-associated risks. Kyprolis caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Data ) . Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Data Animal Data Carfilzomib administered intravenously to pregnant rats and rabbits during the period of organogenesis was not teratogenic at doses up to 2 mg/kg/day in rats and 0.8 mg/kg/day in rabbits. In rabbits, there was an increase in pre-implantation loss at ≥ 0.4 mg/kg/day and an increase in early resorptions and post-implantation loss and a decrease in fetal weight at the maternally toxic dose of 0.8 mg/kg/day. The doses of 0.4 and 0.8 mg/kg/day in rabbits are approximately 20% and 40%, respectively, of the recommended dose in humans of 27 mg/m 2 based on BSA.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Kyprolis in pediatric patients have not been established. The safety and effectiveness of Kyprolis in combination with chemotherapy was evaluated, but not established in an open label trial (Study 20140106; NCT02303821) in 124 patients aged 1 to younger than 17 years with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) who have received prior targeted B-cell immune therapy or relapsed or refractory T-cell ALL. No new safety signals were observed in these pediatric patients. The systemic exposure of carfilzomib in these pediatric patients was within range of that observed in adults given the same dose based on body surface area.
Geriatric use
8.5 Geriatric Use Of the 2,837 patients with relapsed or refractory multiple myeloma exposed to Kyprolis in monotherapy and combination therapy studies [see Clinical Studies (14.1 , 14.2 , 14.3 , 14.4 , 14.5) ] , 50% were 65 years and older, while 13% were 75 years and older. The incidence of serious adverse reactions was 50% in patients < 65 years of age, 60% in patients 65 to 74 years of age, and 63% in patients ≥ 75 years of age. Of the 308 patients in CANDOR who received DKd, 47% of patients were 65 years and older, while 9% were 75 years and older. Fatal adverse reactions in the DKd arm of CANDOR occurred in 6% of patients < 65 years of age, 14% of patients between 65 to 74 years of age, and 14% of patients ≥ 75 years of age [see Adverse Reactions (6.1) ] . No overall differences in effectiveness were observed between older and younger patients.
Overdosage
Acute onset of chills, hypotension, renal insufficiency, thrombocytopenia, and lymphopenia has been reported following a dose of 200 mg of Kyprolis administered in error. There is no known specific antidote for Kyprolis overdosage. In the event of overdose, monitor patients for adverse reactions and provide supportive care as appropriate.
Description
Carfilzomib is a proteasome inhibitor. The chemical name for carfilzomib is (2S)-N-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide. Carfilzomib has the following structure: Carfilzomib is a crystalline substance with a molecular weight of 719.9. The molecular formula is C 40 H 57 N 5 O 7 . Carfilzomib is practically insoluble in water and very slightly soluble in acidic conditions. Kyprolis for injection, for intravenous use is a sterile, white to off-white lyophilized powder in a single-dose vial. Each 10 mg vial contains 10 mg of carfilzomib, 500 mg sulfobutylether beta-cyclodextrin, and 9.6 mg anhydrous citric acid and sodium hydroxide for pH adjustment (target pH 3.5). Each 30 mg vial contains 30 mg of carfilzomib, 1500 mg sulfobutylether beta-cyclodextrin, and 28.8 mg anhydrous citric acid and sodium hydroxide for pH adjustment (target pH 3.5). Each 60 mg vial contains 60 mg of carfilzomib, 3000 mg sulfobutylether beta-cyclodextrin, 57.7 mg citric acid, and sodium hydroxide for pH adjustment (target pH 3.5). Chemical Structure
Mechanism of action
12.1 Mechanism of Action Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. Carfilzomib had antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells. In animals, carfilzomib inhibited proteasome activity in blood and tissue and delayed tumor growth in models of multiple myeloma, hematologic, and solid tumors.
How supplied
How Supplied Kyprolis (carfilzomib) for Injection is supplied as: An individually packaged single-dose vial containing 10 mg of carfilzomib as a white to off-white lyophilized cake or powder: NDC 76075-103-01, NDC 76075-103-21. An individually packaged single-dose vial containing 30 mg of carfilzomib as a white to off-white lyophilized cake or powder: NDC 76075-102-01, NDC 76075-102-21. An individually packaged single-dose vial containing 60 mg of carfilzomib as a white to off-white lyophilized cake or powder: NDC 76075-101-01, NDC 76075-101-21. 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.
Storage
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.
Patient information
Discuss the following with patients prior to treatment with Kyprolis: Cardiac Toxicities: Advise patients of the risks and symptoms of cardiac failure and ischemia [see Warnings and Precautions (5.1) ] . Dehydration: Counsel patients to avoid dehydration, since patients receiving Kyprolis therapy may experience vomiting and/or diarrhea. Instruct patients to seek medical advice if they experience symptoms of dehydration [see Warnings and Precautions (5.3) ] . Respiratory: Advise patients that they may experience cough or shortness of breath (dyspnea) during treatment with Kyprolis. This most commonly occurs within a day of dosing. Advise patients to contact their healthcare provider if they experience shortness of breath [see Warnings and Precautions (5.6) ] . Venous Thrombosis: Inform patients of the risk of venous thromboembolism and discuss the options for prophylaxis. Advise patients to seek immediate medical attention for symptoms of venous thrombosis or embolism [see Warnings and Precautions (5.8) ] . Infusion-Related Reactions: Advise patients of the risk of infusion-related reactions and discuss the common signs and symptoms of infusion-related reactions with the patients [see Warnings and Precautions (5.9) ] . Bleeding: Inform patients that they may bruise or bleed more easily or that it may take longer to stop bleeding and to report to their healthcare provider any prolonged, unusual or excessive bleeding. Instruct patients on the signs of occult bleeding [see Warnings and Precautions (5.10) ] . Hepatic: Inform patients of the risk of developing hepatic failure. Advise patients to contact their healthcare provider for symptoms of hepatitis including worsening fatigue or yellow discoloration of skin or eyes [see Warnings and Precautions (5.12) ] . Other: Inform patients to contact their healthcare provider if they experience neurologic symptoms such as headaches, confusion, dizziness or loss of balance, difficulty talking or walking, decreased strength or weakness on one side of the body, seizures, or visual loss [see Warnings and Precautions (5) and Adverse Reactions (6) ] . Driving/Operating Machines: Advise patients that Kyprolis may cause fatigue, dizziness, fainting, and/or drop in blood pressure. Advise patients not to drive or operate machinery if they experience any of these symptoms [see Adverse Reactions (6.1) ] . Embryo-Fetal Toxicity: Advise females of the potential risk to the fetus. Advise females of reproductive potential to inform their healthcare provider immediately of a known or suspected pregnancy. Advise female patients to use effective contraceptive during treatment with Kyprolis and for 6 months following the last dose. Advise male patients with female sexual partners of reproductive potential to use effective contraception during treatment with Kyprolis and for 3 months following the last dose [see Warnings and Precautions (5.17) , Use in Specific Populations (8.1 , 8.3) ] . Lactation: Advise patients to avoid breastfeeding while receiving Kyprolis and for 2 weeks after the last dose [see Use in Specific Populations (8.2) ] . Concomitant Medications: Advise patients to discuss with their healthcare provider any medication they are currently taking prior to starting treatment with Kyprolis, or prior to starting any new medication(s) during treatment with Kyprolis.
Label text from the FDA structured product label by Onyx Pharmaceuticals, Inc. (revised Jun 18, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Carfilzomib in 3 products
Kyprolis NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 76075-101 | Carfilzomib 60 mg/30mL Injection, Powder, Lyophilized, For Solution | Onyx Pharmaceuticals, Inc. | NDA |
| 76075-102 | Carfilzomib 30 mg/15mL Injection, Powder, Lyophilized, For Solution | Onyx Pharmaceuticals, Inc. | NDA |
| 76075-103 | Carfilzomib 10 mg/5mL Injection, Powder, Lyophilized, For Solution | Onyx Pharmaceuticals, Inc. | NDA |
Kyprolis recalls
- D-0226-2017 Dec 28, 2016 · Class II · Terminated
Lack of Assurance of Sterility: Potential cracks in glass vials
Frequently asked questions
What is Kyprolis used for?
Kyprolis is a proteasome inhibitor that is indicated: for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with Lenalidomide and dexamethasone; or Dexamethasone; or Daratumumab and dexamethasone; or Daratumumab and hyaluronidase-fihj and dexamethasone; or Isatuximab and dexamethasone. ( 1 , 14 ) as a single…
What are the side effects of Kyprolis?
The following clinically significant adverse reactions are described elsewhere in the labeling: Cardiac Toxicities [see Warnings and Precautions (5.1) ] Acute Renal Failure [see Warnings and Precautions (5.2) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.3) ] Pulmonary Toxicity [see Warnings and Precautions (5.4) ] Pulmonary Hypertension [see Warnings and Precautions (5.5) ] Dyspnea… See the full label for the complete list.
Who makes Kyprolis?
Kyprolis is listed by 1 labeler in the FDA NDC directory, including Onyx Pharmaceuticals, Inc..
Has Kyprolis been recalled?
The FDA enforcement database lists 1 recall for Kyprolis, most recently D-0226-2017 (class ii): Lack of Assurance of Sterility: Potential cracks in glass vials