Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 15 June 2018

Indication(s)

1 INDICATIONS AND USAGE Kyprolis is a proteasome inhibitor that is indicated: in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. (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 in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy [see Clinical Studies ( 14.1 )]. Kyprolis is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy [see Clinical Studies ( 14.2 , 14.3 )].

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Advisory information

contraindications
4 CONTRAINDICATIONS None. None (4)
Adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of 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 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 )] Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Patients [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, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia. (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 medical practice. Safety Experience with Kyprolis in Combination with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma The safety of Kyprolis in combination with lenalidomide and dexamethasone (KRd) was evaluated in an open-label randomized study in patients with relapsed multiple myeloma. Details of the study treatment are described in Section 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 27/392 (7%) patients compared with 27/389 (7%) patients who died due to adverse events within 30 days of the last dose of any Rd therapy. The most common cause of deaths occurring in patients (%) in the two arms (KRd versus Rd) included cardiac 10 (3%) versus 7 (2%), infection 9 (2%) versu s 10 (3%), renal 0 (0%) versus 1 (< 1%), and other adverse reactions 9 (2%) versus 10 (3%). Serious adverse reactions were reported in 60% of the patients in the KRd arm and 54% of the patients in the Rd arm. The most common serious adverse reactions reported in the KRd arm as compared with the Rd arm were pneumonia (14% versus 11%), respiratory tract infection (4% versus 1.5%), pyrexia (4% versus 2%), and pulmonary embolism (3% versus 2%). Discontinuation due to any adverse reaction occurred in 26% in the KRd arm versus 25% 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%). Common Adverse Reactions ( ≥ 10%) The adverse reactions in the first 12 cycles of therapy that occurred at a rate of 10% or greater in the KRd arm are presented in Table 8. Table 8: Most Common Adverse Reactions (≥ 10% in the KRd Arm) Occurring in Cycles 1–12 (20/27 mg/m2 Regimen In Combination with Lenalidomide and Dexamethasone) KRd Arm (N = 392) n (%) Rd Arm (N = 389) n (%) Adverse Reactions by Body System Any Grade ≥ Grade 3 Any Grade ≥ Grade 3 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 115 (29) 7 (2) 105 (27) 12 (3) Constipation 68 (17) 0 53 (14) 1 (0) Nausea 60 (15) 1 (0) 39 (10) 3 (1) General Disorders and Administration Site Conditions Fatigue 109 (28) 21 (5) 104 (27) 20 (5) Pyrexia 93 (24) 5 (1) 64 (17) 1 (0) Edema peripheral 63 (16) 2 (1) 57 (15) 2 (1) Asthenia 53 (14) 11 (3) 46 (12) 7 (2) Infections and Infestations Upper respiratory tract infection 85 (22) 7 (2) 52 (13) 3 (1) Nasopharyngitis 63 (16) 0 43 (11) 0 Bronchitis 54 (14) 5 (1) 39 (10) 2 (1) Pneumoniaa 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 88 (22) 3 (1) 73 (19) 3 (1) Nervous System Disorders Peripheral neuropathiesb 43 (11) 7 (2) 37 (10) 4 (1) Psychiatric Disorders Insomnia 63 (16) 6 (2) 50 (13) 8 (2) Respiratory, Thoracic, and Mediastinal Disorders Coughc 91 (23) 2 (1) 52 (13) 0 Dyspnead 70 (18) 9 (2) 58 (15) 6 (2) Skin and Subcutaneous Tissue Disorders Rash 45 (12) 5 (1) 53 (14) 5 (1) Vascular Disorders Embolic and thrombotic events venouse 49 (13) 16 (4) 22 (6) 9 (2) Hypertensionf 41 (11) 12 (3) 15 (4) 4 (1) KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone a Pneumonia includes pneumonia and bronchopneumonia. b Peripheral neuropathies includes peripheral neuropathy, peripheral sensory neuropathy, and peripheral motor neuropathy. c Cough includes cough and productive cough. d Dyspnea includes dyspnea and dyspnea exertional. e Embolic and thrombotic events, venous include deep vein thrombosis, pulmonary embolism, thrombophlebitis superficial, thrombophlebitis, venous thrombosis limb, post thrombotic syndrome, venous thrombosis. f Hypertension includes hypertension, hypertensive crisis. There were 274 (70%) patients in the KRd arm who received treatment beyond Cycle 12. There were no new clinically relevant adverse reactions that emerged in the later treatment cycles. Adverse Reactions Occurring at a Frequency of < 10% Blood and lymphatic system disorders: febrile neutropenia, lymphopenia Cardiac disorders: cardiac arrest, cardiac failure, cardiac failure congestive, myocardial infarction, myocardial ischemia, pericardial effusion Eye disorders: cataract, vision blurred Gastrointestinal disorders: abdominal pain, abdominal pain upper, dyspepsia, gastrointestinal hemorrhage, toothache General disorders and administration site conditions: chills, infusion site reaction, multi-organ failure, pain Infections and infestations: influenza, lung infection, rhinitis, sepsis, urinary tract infection, viral infection Metabolism and nutrition disorders: dehydration, hyperkalemia, hyperuricemia, hypoalbuminemia, hyponatremia, tumor lysis syndrome Musculoskeletal and connective tissue disorders: muscular weakness, myalgia Nervous system disorders: hypoesthesia, intracranial hemorrhage, paresthesia, deafness Psychiatric disorders: anxiety, delirium Renal and urinary disorders: renal failure, renal failure acute, renal impairment Respiratory, thoracic and mediastinal disorders: dysphonia, epistaxis, oropharyngeal pain, pulmonary embolism, pulmonary edema, pulmonary hemorrhage Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus Vascular disorders: deep vein thrombosis, hemorrhage, hypotension Grade 3 and higher adverse reactions that occurred during Cycles 1–12 with a substantial difference (≥ 2%) between the two arms were neutropenia, thrombocytopenia, hypokalemia, and hypophosphatemia. Laboratory Abnormalities Table 9 describes Grade 3–4 laboratory abnormalities reported at a rate of ≥ 10% in the KRd arm for patients who received combination therapy. Table 9 : Grade 3–4 Laboratory Abnormalities (≥ 10% in the KR d A rm ) in Cycles 1 – 12 ( 20/27 mg/m 2 Regimen In Combination with Lenalidomide and Dexamethasone ) Laboratory Abnormality KRd (N = 392) n (%) Rd (N = 389) n (%) Decreased lymphocytes 182 (46) 119 (31) Decreased absolute neutrophil count 152 (39) 140 (36) Decreased phosphorus 122 (31) 106 (27) Decreased platelets 101 (26) 59 (15) Decreased total white blood cell count 97 (25) 71 (18) Decreased hemoglobin 58 (15) 68 (18) Decreased potassium 41 (11) 23 (6) KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone Safety Experience with Kyprolis in Combination with Dexamethasone in Patients with Multiple Myeloma The safety of Kyprolis in combination with dexamethasone was evaluated in an open-label, randomized trial of patients with relapsed multiple myeloma. The study treatment is described in Section 14.2. Patients received treatment for a median duration of 48 weeks in the Kyprolis/dexamethasone (Kd) arm and 27 weeks in the bortezomib/dexamethasone (Vd) arm. Deaths due to adverse reactions within 30 days of last study treatment occurred in 32/463 (7%) patients in the Kd arm and 21/456 (5%) patients in the Vd arm. The causes of death occurring in patients (%) in the two arms (Kd versus Vd) included cardiac 4 (1%) versus 5 (1%), infections 8 (2%) versus 8 (2%), disease progression 7 (2%) versus 4 (1%), pulmonary 3 (1%) versus 2 (< 1%), renal 1 (< 1%) versus 0 (0%), and other adverse events 9 (2%) versus 2 (< 1%). Serious adverse reactions were reported in 59% of the patients in the Kd arm and 40% of the patients in the Vd arm. In both treatment arms, pneumonia was the most commonly reported serious adverse reaction (8% versus 9%). Discontinuation due to any adverse reaction occurred in 29% in the Kd arm versus 26% in the Vd arm. The most common reaction leading to discontinuation was cardiac failure in the Kd arm (n = 8, 2%) and peripheral neuropathy in the Vd arm (n = 22, 5%). Common Adverse Reactions ( ≥ 10%) Adverse reactions in the first 6 months of therapy that occurred at a rate of 10% or greater in the Kd arm are presented in Table 10. Table 10: Most Common Adverse Reactions (≥ 10% in the Kd Arm) Occurring in Months 1–6 (20/56 mg/m2 Regimen In Combination with Dexamethasone) Kd (N = 463) n (%) Vd (N = 456) n (%) Adverse Reaction by Body System Any Grade ≥ Grade 3 Any Grade ≥ Grade 3 Blood and L ymphatic S ystem D isorders Anemia 161 (35) 57 (12) 112 (25) 43 (9) Thrombocytopeniaa 125 (27) 45 (10) 112 (25) 64 (14) Gastrointestinal D isorders Diarrhea 117 (25) 14 (3) 149 (33) 27 (6) Nausea 70 (15) 4 (1) 68 (15) 3 (1) Constipation 60 (13) 1 (0) 113 (25) 6 (1) Vomiting 45 (10) 5 (1) 33 (7) 3 (1) General D isorders and A dministration S ite C onditions Fatigue 116 (25) 14 (3) 126 (28) 25 (6) Pyrexia 102 (22) 9 (2) 52 (11) 3 (1) Asthenia 73 (16) 9 (2) 65 (14) 13 (3) Peripheral edema 62 (13) 3 (1) 62 (14) 3 (1) Infections and I nfestations Upper respiratory tract infection 67 (15) 4 (1) 55 (12) 3 (1) Bronchitis 54 (12) 5 (1) 25 (6) 2 (0) Musculoskeletal and C onnective T issue D isorders Muscle spasms 70 (15) 1 (0) 23 (5) 3 (1) Back pain 64 (14) 8 (2) 61 (13) 10 (2) Nervous S ystem D isorders Headache 67 (15) 4 (1) 39 (9) 2 (0) Peripheral neuropathiesb ,c 56 (12) 7 (2) 170 (37) 23 (5) Psychiatric D isorders Insomnia 105 (23) 5 (1) 116 (25) 10 (2) Respiratory, T horacic and M ediastinal D isorders Dyspnead 128 (28) 23 (5) 69 (15) 8 (2) Coughe 97 (21) 0 (0) 61 (13) 2 (0) Vascular Disorders Hypertensionf 83 (18) 30 (7) 33 (7) 12 (3) Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone a Thrombocytopenia includes platelet count decreased and thrombocytopenia. b Peripheral neuropathies include peripheral neuropathy, peripheral sensory neuropathy, and peripheral motor neuropathy. c See Clinical Studies (14.2). d Dyspnea includes dyspnea and dyspnea exertional. e Cough includes cough and productive cough. f Hypertension includes hypertension, hypertensive crisis, and hypertensive emergency. The event rate of ≥ Grade 2 peripheral neuropathy in the Kd arm was 7% (95% CI: 5, 9) versus 35% (95% CI: 31, 39) in the Vd arm. Adverse Reactions Occurring at a Frequency of < 10% Blood and lymphatic system disorders: febrile neutropenia, leukopenia, lymphopenia, neutropenia, thrombotic microangiopathy, thrombotic thrombocytopenic purpura Cardiac disorders: atrial fibrillation, cardiac arrest, cardiac failure, cardiac failure congestive, myocardial infarction, myocardial ischemia, palpitations, tachycardia Eye disorders: cataract, vision blurred Gastrointestinal disorders: abdominal pain, abdominal pain upper, dyspepsia, gastrointestinal hemorrhage, toothache General disorders and administration site conditions: chest pain, chills, influenza like illness, infusion site reactions (including inflammation, pain, and erythema), malaise, pain Hepatobiliary disorders: cholestasis, hepatic failure, hyperbilirubinemia Immune system disorders: drug hypersensitivity Infections and infestations: bronchopneumonia, gastroenteritis, influenza, lung infection, nasopharyngitis, pneumonia, rhinitis, sepsis, urinary tract infection, viral infection Metabolism and nutrition disorders: decreased appetite, dehydration, hypercalcemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, tumor lysis syndrome Musculoskeletal and connective tissue disorders: muscular weakness, musculoskeletal chest pain, musculoskeletal pain, myalgia Nervous system disorders: cerebrovascular accident, dizziness, hypoesthesia, paresthesia, posterior reversible encephalopathy syndrome Psychiatric disorders: anxiety Renal and urinary disorders: renal failure, renal failure acute, renal impairment Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome, dysphonia, epistaxis, interstitial lung disease, oropharyngeal pain, pneumonitis pulmonary embolism, pulmonary edema, pulmonary hypertension, wheezing Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, rash Vascular disorders: deep vein thrombosis, flushing, hypotension Laboratory Abnormalities Table 11 describes Grades 3–4 laboratory abnormalities reported at a rate of ≥ 10% in the Kd arm. Table 11: Grades 3–4 Laboratory Abnormalities (≥ 10%) in Months 1–6 (20/56 mg/m2 Regimen In Combination with Dexamethasone) Laboratory Abnormality Kd (N = 463) n (%) Vd (N = 456) n (%) Decreased lymphocytes 249 (54) 180 (40) Increase uric acid 244 (53) 198 (43) Decreased hemoglobin 79 (17) 68 (15) Decreased platelets 85 (18) 77 (17) Decreased phosphorus 74 (16) 61 (13) Decreased creatinine clearancea 65 (14) 49 (11) Increased potassium 55 (12) 21 (5) Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone a Calculated using the Cockcroft-Gault formula. Safety Experience with Kyprolis in Patients with Multiple Myeloma who Received Monotherapy The safety of Kyprolis, dosed at 20/27 mg/m2 by up to 10-minute infusion, was evaluated in clinical trials in which 598 patients with relapsed and/or refractory myeloma received Kyprolis monotherapy starting with the 20 mg/m2 dose in Cycle 1, Day 1 and escalating to 27 mg/m2 on Cycle 1, Day 8 or Cycle 2, Day 1. Premedication with dexamethasone 4 mg was required before each dose in Cycle 1 and was optional for subsequent cycles. The median age was 64 years (range 32–87), and approximately 57% were male. The patients received a median of 5 (range 1–20) prior regimens. The median number of cycles initiated was 4 (range 1–35). Serious adverse reactions, regardless of causality, were reported in 50% of patients in the pooled Kyprolis monotherapy studies (N = 598). The most common serious adverse reactions were: pneumonia (8%), acute renal failure (5%), disease progression (4%), pyrexia (3%), hypercalcemia (3%), congestive heart failure (3%), multiple myeloma (3%), anemia (2%), and dyspnea (2%). In patients treated with Kyprolis, the incidence of serious adverse reactions was higher in those ≥ 65 years old and those ≥ 75 years old [see Geriatric Use ( 8.5 )]. Deaths due to adverse reactions within 30 days of the last dose of Kyprolis occurred in 30/598 (5%) patients receiving Kyprolis monotherapy. These adverse reactions were related to cardiac disorders in 10 (2%) patients, infections in 8 (1%) patients, renal disorders in 4 (< 1%) patients, and other adverse reactions in 8 (1%) patients. In a randomized trial comparing Kyprolis as a single agent versus corticosteroids with optional oral cyclophosphamide for patients with relapsed and refractory multiple myeloma, mortality was higher in the patients treated with Kyprolis in comparison to the control arm in the subgroup of 48 patients ≥ 75 years of age. The most common cause of discontinuation due to an adverse reaction was acute renal failure (2%). Safety of Kyprolis monotherapy dosed at 20/56 mg/m2 by 30-minute infusion was evaluated in a multicenter, open-label study in patients with relapsed and/or refractory multiple myeloma. The study treatment is described in Section 14.3. The patients received a median of 4 (range 1–10) prior regimens. The common adverse reactions occurring at a rate of 20% or greater with Kyprolis monotherapy are presented in Table 12. Table 12: Most Common Adverse Reactions (≥ 20%) with Kyprolis Monotherapy 20/56 mg/m 2 by 30-minute infusion (N = 24) 20/27 mg/m 2 by 2- to 10-minute infusion (N = 598) Adverse Reaction Any Grade n (%) Grades 3 - 5 n (%) Any Grade n (%) Grades 3 - 5 n (%) Fatigue 14 (58) 2 (8) 238 (40) 25 (4) Dyspneaa 14 (58) 2 (8) 202 (34) 21 (4) Pyrexia 14 (58) 0 177 (30) 11 (2) Thrombocytopenia 13 (54) 13 (54) 220 (37) 152 (25) Nausea 13 (54) 0 211 (35) 7 (1) Anemia 10 (42) 7 (29) 291 (49) 141 (24) Hypertensionb 10 (42) 3 (13) 90 (15) 22 (4) Chills 9 (38) 0 73 (12) 1 (< 1) Headache 8 (33) 0 141 (24) 7 (1) Coughc 8 (33) 0 134 (22) 2 (< 1) Vomiting 8 (33) 0 104 (17) 4 (1) Lymphopenia 8 (33) 8 (33) 85 (14) 73 (12) Insomnia 7 (29) 0 75 (13) 0 Dizziness 7 (29) 0 64 (11) 5 (1) Diarrhea 6 (25) 1 (4) 160 (27) 8 (1) Blood creatinine increased 6 (25) 1 (4) 103 (17) 15 (3) Peripheral edema 5 (21) 0 118 (20) 1 (< 1) Back pain 5 (21) 1 (4) 115 (19) 19 (3) Upper respiratory tract infection 5 (21) 1 (4) 112 (19) 15 (3) Decreased appetite 5 (21) 0 89 (15) 2 (< 1) Muscle spasms 5 (21) 0 62 (10) 2 (< 1) Chest pain 5 (21) 0 20 (3) 1 (< 1) a Dyspnea includes preferred terms of dyspnea and dyspnea exertional. b Hypertension includes hypertension, hypertensive crisis, and hypertensive emergency. c Cough includes cough and productive cough. Adverse Reactions Occurring at a Frequency of < 20 % Blood and lymphatic system disorders: febrile neutropenia, leukopenia, neutropenia Cardiac disorders: cardiac arrest, cardiac failure, cardiac failure congestive, myocardial infarction, myocardial ischemia Eye disorders: cataract, blurred vision Gastrointestinal disorders: abdominal pain, abdominal pain upper, constipation, dyspepsia, gastrointestinal hemorrhage, toothache General disorders and administration site conditions: asthenia, infusion site reaction, multi-organ failure, pain Hepatobiliary disorders: hepatic failure Infections and infestations: bronchitis, bronchopneumonia, influenza, lung infection, pneumonia, nasopharyngitis, respiratory tract infection, rhinitis, sepsis, urinary tract infection Metabolism and nutrition disorders: hypercalcemia, hyperglycemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, tumor lysis syndrome Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal pain, musculoskeletal chest pain, myalgia, pain in extremity Nervous system disorders: hypoesthesia, intracranial hemorrhage, paresthesia, peripheral motor neuropathy, peripheral neuropathy, peripheral sensory neuropathy Psychiatric disorders : anxiety Renal and urinary disorders: acute renal failure, renal failure, renal impairment Respiratory, thoracic and mediastinal disorders: dysphonia, epistaxis, oropharyngeal pain, pulmonary edema, pulmonary hemorrhage Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, rash Vascular disorders: embolic and thrombotic events, venous (including deep vein thrombosis and pulmonary embolism), hemorrhage, hypotension Grade 3 and higher adverse reactions occurring at an incidence of > 1% include febrile neutropenia, cardiac arrest, cardiac failure congestive, pain, sepsis, urinary tract infection, hyperglycemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hyponatremia, hypophosphatemia, renal failure, renal failure acute, renal impairment, pulmonary edema, and hypotension. Laboratory Abnormalities Table 13 describes Grade 3–4 laboratory abnormalities reported at a rate of > 10% for patients who received Kyprolis monotherapy. Table 13: Grade 3–4 Laboratory Abnormalities (> 10%) with Kyprolis Monotherapy Laboratory Abnormality Kyprolis 20/56 mg/m 2 (N = 24) Kyprolis 20/27 mg/m 2 (N = 598) Decreased lymphocytes 15 (63) 151 (25) Decreased platelets 11 (46) 184 (31) Decreased hemoglobin 7 (29) 132 (22) Decreased total white blood cell count 3 (13) 71 (12) Decreased sodium 2 (8) 69 (12) Decreased absolute neutrophil count 2 (8) 67 (11) 6.2 Postmarketing Experience The following additional adverse reactions were reported in the postmarketing experience with Kyprolis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: hemolytic uremic syndrome (HUS), gastrointestinal perforation, pericarditis.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for dosing. (2.2) Hydrate prior to and following Kyprolis administration as needed. (2.1) Premedicate Kyprolis infusions with dexamethasone prior to all Cycle 1 doses and if infusion reaction symptoms develop or reappear. (2.1) Administer the 20/56 mg/m2 regimen by 30-minute infusion and the 20/27 mg/m2 regimen by 10-minute infusion. (2.2) 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. 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 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 [see Warnings and Precautions ( 5.1 , 5.3 )]. • Electrolyte Monitoring - Monitor serum potassium levels regularly during treatment with Kyprolis. • Premedications - Premedicate with the recommended dose of dexamethasone for monotherapy or the recommended dexamethasone dose if on 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 reactions [see Warnings and Precautions ( 5.9 )]. Reinstate dexamethasone premedication if these symptoms occur during subsequent cycles. • Administration - Kyprolis can be administered in a 50 mL or 100 mL intravenous bag of 5% Dextrose Injection, USP. Infuse over 10 or 30 minutes depending on the Kyprolis dose regimen [see Dosage and Administration ( 2.2 )]. 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 Calculation - Calculate the Kyprolis dose [see Dosage and Administration ( 2.2 )] 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. • Thromboprophylaxis - 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 [see Warnings and Precautions ( 5.8 )]. • Infection Prophylaxis - Consider antiviral prophylaxis for patients being treated with Kyprolis to decrease the risk of herpes zoster reactivation. • Patients on Hemodialysis - Administer Kyprolis after the hemodialysis procedure. 2.2 Recommended Dosing Kyprolis in Combination with Lenalidomide and Dexamethasone For the combination regimen with lenalidomide and dexamethasone, administer Kyprolis intravenously as a 10-minute infusion on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 1. Each 28-day period is considered one treatment cycle. The recommended starting dose of Kyprolis is 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m2 on Day 8 of Cycle 1. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis. Discontinue Kyprolis after Cycle 18. Lenalidomide 25 mg is taken orally on Days 1–21 and dexamethasone 40 mg by mouth or intravenously on Days 1, 8, 15, and 22 of the 28-day cycles. Table 1: Kyprolis (10-Minute Infusion) in Combination with Lenalidomide and Dexamethasone 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 Days 23-28 Kyprolis (mg/m 2 ) 20 20 - 27 27 - 27 27 - - - Dexamethasone (mg) 40 - - 40 - - 40 - - 40 - Lenalidomide 25 mg daily on Days 1-21 - - Cycles 2 to 12 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 Days 23-28 Kyprolis (mg/m 2 ) 27 27 - 27 27 - 27 27 - - - Dexamethasone (mg) 40 - - 40 - - 40 - - 40 - Lenalidomide 25 mg daily on Days 1-21 - - Cycles 13 and later a 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 Days 23-28 Kyprolis (mg/m 2 ) 27 27 - - - - 27 27 - - - Dexamethasone (mg) 40 - - 40 - - 40 - - 40 - Lenalidomide 25 mg daily on Days 1-21 - - a Kyprolis is administered through Cycle 18; lenalidomide and dexamethasone continue thereafter. Continue treatment until disease progression or unacceptable toxicity occurs [see Dosage and Administration ( 2.3 )]. Refer to the lenalidomide and dexamethasone Prescribing Information for other concomitant medications, such as the use of anticoagulant and antacid prophylaxis, that may be required with those agents. Kyprolis in Combination with Dexamethasone For the combination regimen with dexamethasone, administer Kyprolis intravenously as a 30-minute infusion on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 2. Each 28-day period is considered one treatment cycle. Administer Kyprolis by 30-minute infusion at a starting dose of 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 56 mg/m2 on Day 8 of Cycle 1. Dexamethasone 20 mg is taken by mouth or intravenously on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Administer dexamethasone 30 minutes to 4 hours before Kyprolis. Table 2: Kyprolis (30-Minute Infusion) in Combination with Dexamethasone 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 20 - 56 56 - 56 56 - - - - Dexamethasone (mg) 20 20 - 20 20 - 20 20 - 20 20 - 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 ) 56 56 - 56 56 - 56 56 - - - - Dexamethasone (mg) 20 20 - 20 20 - 20 20 - 20 20 - Treatment may be continued until disease progression or unacceptable toxicity occurs [see Dosage and Administration ( 2.3 )]. Refer to the dexamethasone Prescribing Information for other concomitant medications. Kyprolis Monotherapy For monotherapy, administer Kyprolis intravenously as a 10-minute or 30-minute infusion depending on the regimen as described below. 20/27 mg/m 2 regimen by 10-minute infusion For monotherapy using the 20/27 mg/m2 regimen, administer Kyprolis intravenously as a 10-minute infusion [see Clinical Studies ( 14.3 )]. In Cycles 1 through 12, administer Kyprolis on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 3. Each 28-day period is considered one treatment cycle. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis (see Table 3). Premedicate with dexamethasone 4 mg orally or intravenously 30 minutes to 4 hours before each Kyprolis dose in Cycle 1, then as needed to help prevent infusion reactions [see Dosage and Administration ( 2.1 )]. The recommended starting dose of Kyprolis is 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m2 on Day 8 of Cycle 1. Treatment may continue until disease progression or unacceptable toxicity occurs. Table 3: Kyprolis Monotherapy (10-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 Days 22–28 Kyprolis (mg/m 2 ) a 20 20 - 27 27 - 27 27 - - Cycles 2 to 12 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 Days 22–28 Kyprolis (mg/m 2 ) 27 27 - 27 27 - 27 27 - - Cycles 13 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 Days 22–28 Kyprolis (mg/m 2 ) 27 27 - - - - 27 27 - - a Dexamethasone premedication is required for each Kyprolis dose in Cycle 1. 20/56 mg/m 2 regimen by 30-minute infusion For monotherapy using the 20/56 mg/m2 regimen, administer Kyprolis intravenously as a 30-minute infusion [see Clinical Studies ( 14.3 )]. In Cycles 1 through 12, administer Kyprolis on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 4. Each 28-day period is considered one treatment cycle. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis (see Table 4). Premedicate with dexamethasone 8 mg orally or intravenously 30 minutes to 4 hours before each Kyprolis dose in Cycle 1, then as needed to help prevent infusion reactions [see Dosage and Administration ( 2.1 )]. The recommended starting dose of Kyprolis is 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 56 mg/m2 on Day 8 of Cycle 1. Treatment may continue until disease progression or unacceptable toxicity occurs. Table 4: Kyprolis Monotherapy (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 Days 22–28 Kyprolis (mg/m 2 ) a 20 20 - 56 56 - 56 56 - - Cycles 2 to 12 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 Days 22–28 Kyprolis (mg/m 2 ) 56 56 - 56 56 - 56 56 - - Cycles 13 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 Days 22–28 Kyprolis (mg/m 2 ) 56 56 - - - - 56 56 - - a Dexamethasone premedication is required for each Kyprolis dose in Cycle 1. 2.3 Dose Modifications Based on Toxicities Modify dosing based on toxicity. Recommended actions and dose modifications for Kyprolis are presented in Table 5. Dose level reductions are presented in Table 6. See the lenalidomide and dexamethasone Prescribing Information respectively for dosing recommendations. Table 5: Dose Modifications for Toxicitya during Kyprolis Treatment Hematologic Toxicity Recommended Action ANC less than 0.5 × 109/L Withhold dose • If recovered to greater than or equal to 0.5 × 109/L, continue at the same dose level For subsequent drops to less than 0.5 × 109/L, follow the same recommendations as above and consider 1 dose level reduction when restarting Kyprolisa Febrile neutropenia ANC less than 0.5 × 109/L and an oral temperature more than 38.5ºC or two consecutive readings of more than 38.0ºC for 2 hours Withhold dose • If ANC returns to baseline grade and fever resolves, resume at the same dose level Platelets less than 10 × 109/L or evidence of bleeding with thrombocytopenia [see Warnings and Precautions ( 5 )] Withhold dose • If recovered to greater than or equal to 10 × 109/L and/or bleeding is controlled, continue at the same dose level • For subsequent drops to less than 10 × 109/L, follow the same recommendations as above and consider 1 dose level reduction when restarting Kyprolisa Renal Toxicity Recommended Action Serum creatinine greater than or equal to 2 × baseline, or Creatinine clearance less than 15 mL/min, or creatinine clearance decreases to less than or equal to 50% of baseline, or need for hemodialysis [see Warnings and Precautions ( 5 )] 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 reductiona • 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-threateningb non-hematological toxicities Withhold until resolved or returned to baseline Consider restarting the next scheduled treatment at 1 dose level reductiona ANC = absolute neutrophil count a See Table 6 for dose level reductions. b CTCAE Grades 3 and 4. Table 6: Dose Level Reductions for Kyprolis Regimen Dose First Dose Reduction Second Dose Reduction Third Dose Reduction Kyprolis, Lenalidomide, and Dexamethasone, or Monotherapy (20/27 mg/m2) 27 mg/m2 20 mg/m2 15 mg/m2a — Kyprolis and Dexamethasone, or Monotherapy (20/56 mg/m2) 56 mg/m2 45 mg/m2 36 mg/m2 27 mg/m2a Note: Infusion times remain unchanged during dose reduction(s). a If toxicity persists, discontinue Kyprolis treatment. 2.4 Dose Modifications for Use in Hepatic Impairment For patients with mild or moderate hepatic impairment, reduce the dose of Kyprolis by 25%. Dosing recommendation cannot be made in patients with severe hepatic impairment [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )]. 2.5 Dosing in Patients with End Stage Renal Disease For patients with end stage renal disease who are on dialysis, administer Kyprolis after the hemodialysis procedure. 2.6 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), 15 mL (for 30 mg vial), or 5 mL (for 10 mg vial) Sterile Water for Injection, USP, through the stopper and directing the solution onto the INSIDE WALL OF THE VIAL to minimize foaming. There is no data to support the use of closed system transfer devices with Kyprolis. 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. Kyprolis can be administered directly by intravenous infusion or optionally, administered in a 50 mL to 100 mL intravenous bag containing 5% Dextrose Injection, USP. Do not administer as an intravenous push or bolus. 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 [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 Stability a per Container Storage Conditions of Reconstituted Kyprolis Vial Syringe Intravenous Bag (D5W b ) 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 a Total time from reconstitution to administration should not exceed 24 hours. b 5% Dextrose Injection, USP.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Geriatric use: In the Kyprolis clinical trials, the incidence of adverse events 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) 8.1 Pregnancy Risk Summary Kyprolis can cause fetal harm based on findings from animal studies [see Data] and the drug’s mechanism of action [see Clinical Pharmacology ( 12.1 )]. There are no adequate and well-controlled studies in pregnant women using Kyprolis. Females of reproductive potential should be advised to avoid becoming pregnant while being treated with Kyprolis. Males of reproductive potential should be advised to avoid fathering a child while being treated with Kyprolis. Consider the benefits and risks of Kyprolis and possible risks to the fetus when prescribing Kyprolis to a pregnant woman. If Kyprolis is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard 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. Carfilzomib was not teratogenic at any dose tested. 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/m2 based on body surface area. 8.2 Lactation Risk Summary There is no information regarding the presence of Kyprolis in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Kyprolis and any potential adverse effects on the breastfed infant from Kyprolis or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Contraception Kyprolis can cause fetal harm [see Use in Specific Populations ( 8.1 )]. Advise female patients of reproductive potential to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with Kyprolis and for at least 30 days following completion of therapy. Advise male patients of reproductive potential to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with Kyprolis and for at least 90 days following completion of therapy. 8.4 Pediatric Use The safety and effectiveness of Kyprolis in pediatric patients have not been established. 8.5 Geriatric Use Of 598 patients in clinical studies of Kyprolis monotherapy dosed at 20/27 mg/m2 by up to 10-minute infusion, 49% were 65 and over, while 16% were 75 and over. The incidence of serious adverse events was 44% in patients < 65 years of age, 55% in patients 65 to 74 years of age, and 56% in patients ≥ 75 years of age [see Warnings and Precautions ( 5.1 )]. In a single-arm, multicenter clinical trial of Kyprolis monotherapy dosed at 20/27 mg/m2 (N = 266), no overall differences in effectiveness were observed between older and younger patients. Of 392 patients treated with Kyprolis in combination with lenalidomide and dexamethasone, 47% were 65 and over and 11% were 75 years and over. The incidence of serious adverse events was 50% in patients < 65 years of age, 70% in patients 65 to 74 years of age, and 74% in patients ≥ 75 years of age [see Warnings and Precautions ( 5.1 )]. No overall differences in effectiveness were observed between older and younger patients. Of 463 patients treated with Kyprolis dosed at 20/56 mg/m2 by 30-minute infusion in combination with dexamethasone, 52% were 65 and over and 17% were 75 and over. The incidence of serious adverse events was 54% in patients < 65 years of age, 60% in patients 65 to 74 years of age, and 70% in patients ≥ 75 years of age [ see Warnings and Precautions ( 5.1 ) ]. 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 or moderate hepatic impairment. Dosing recommendation cannot be made for patients with severe hepatic function [see Dosage and Administration ( 2.4 ), Clinical Pharmacology ( 12.3 )]. The pharmacokinetics and safety of Kyprolis were evaluated in patients with advanced malignancies who had either normal hepatic function, or mild (bilirubin > 1 to 1.5 × ULN or AST > ULN), moderate (bilirubin > 1.5 to 3 × ULN), or severe (bilirubin > 3 × ULN) hepatic impairment. The AUC of carfilzomib increased by approximately 50% in patients with mild and moderate hepatic impairment compared to patients with normal hepatic function. PK data were not collected in patients with severe hepatic impairment. The incidence of serious adverse events 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 ), Clinic al Phar m a cology ( 12.3 )]. Monitor liver enzymes regularly, regardless of baseline values, and modify dose based on toxicity [see Dosage and Administration ( 2.3 )]. 8.7 Renal Impairment No starting dose adjustment is required in patients with baseline mild, moderate, or severe renal impairment or patients on chronic hemodialysis. The pharmacokinetics and safety of Kyprolis were evaluated in a Phase 2 trial in patients with normal renal function and those with mild, moderate, and severe renal impairment and patients on chronic hemodialysis. In addition, a pharmacokinetic study was conducted in patients with normal renal function and end-stage renal disease (ESRD) [see Clinical Pharmacology ( 12.3 )]. In these studies, the pharmacokinetics of Kyprolis was not influenced by the degree of baseline renal impairment, including the patients on hemodialysis. Since dialysis clearance of Kyprolis concentrations has not been studied, the drug should be administered after the hemodialysis procedure [see Clinical Pharmacology ( 12.3 )].

More information

Category Value
Authorisation number NDA202714
Agency product number 72X6E3J5AR
Orphan designation No
Product NDC 76075-102,76075-103,76075-101
Date Last Revised 30-05-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 1806934
Storage and handling 16.2 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.
Marketing authorisation holder Onyx Pharmaceuticals, Inc.