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Kyprolis

Last reviewed on RxList: 9/1/2020
Kyprolis Side Effects Center

What Is Kyprolis?

Kyprolis (carfilzomib) is an antineoplastic agent indicated to treat patients with multiple myeloma who have received at least two prior therapies, including treatment with Velcade (bortezomib) and an immunomodulatory therapy.

What Are Side Effects of Kyprolis?

Common side effects of Kyprolis are:

Serious side effects of Kyprolis include:

Patients should be monitored closely and treatment withheld if these serious side effects of Kyprolis occur.

Dosage for Kyprolis

Kyprolis is administered intravenously over 2 to 10 minutes, on two consecutive days each week for three weeks, followed by a 12-day rest period. The recommended cycle 1 dose is 20 mg/m2/day and if tolerated increase cycle 2 dose and subsequent cycles doses to 27 mg/m2/day.

What Drugs, Substances, or Supplements Interact with Kyprolis?

Other drugs may interact with Kyprolis. Tell your doctor all medications you use. Kyprolis can cause fetal harm. Women should avoid becoming pregnant while being treated.

Kyprolis During Pregnancy and Breastfeeding

Female patients should be advised that if she becomes pregnant during treatment, to contact her physician immediately. Advise patients not to take Kyprolis treatment while pregnant or breastfeeding. If a patient wishes to restart breastfeeding after treatment, advise her to discuss the appropriate timing with her physician.

Additional Information

Our Kyprolis Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Kyprolis Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

  • Cardiac Toxicities [see WARNINGS AND PRECAUTIONS]
  • Acute Renal Failure [see WARNINGS AND PRECAUTIONS]
  • Tumor Lysis Syndrome [see WARNINGS AND PRECAUTIONS]
  • Pulmonary Toxicity [see WARNINGS AND PRECAUTIONS]
  • Pulmonary Hypertension [see WARNINGS AND PRECAUTIONS]
  • Dyspnea [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]
  • Venous Thrombosis [see WARNINGS AND PRECAUTIONS]
  • Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]
  • Hemorrhage [see WARNINGS AND PRECAUTIONS]
  • Thrombocytopenia [see WARNINGS AND PRECAUTIONS]
  • Hepatic Toxicity and Hepatic Failure [see WARNINGS AND PRECAUTIONS]
  • Thrombotic Microangiopathy [see WARNINGS AND PRECAUTIONS]
  • Posterior Reversible Encephalopathy Syndrome [see WARNINGS AND PRECAUTIONS]
  • Progressive Multifocal Leukoencephalopathy [see WARNINGS AND PRECAUTIONS]
  • Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Patients [see WARNINGS AND PRECAUTIONS]

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 [see Clinical Studies]. 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 common 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 common 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%). In patients treated with Kyprolis, 47% were 65 and over and 11% were 75 years and over. The incidence of serious adverse reactions was 57% in patients < 65 years of age, 73% in patients 65 to 74 years of age, and 81% in patients ≥ 75 years of age [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. 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.

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 10.

Table 10: 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)

Adverse Reactions by Body SystemKRd Arm
(N = 392)
n (%)
Rd Arm
(N = 389)
n (%)
Any Grade≥ Grade 3Any Grade≥ Grade 3
Blood and Lymphatic System Disorders
Anemia138 (35)53 (14)127 (33)47 (12)
Neutropenia124 (32)104 (27)115 (30)89 (23)
Thrombocytopenia100 (26)58 (15)75 (19)39 (10)
Gastrointestinal Disorders
Diarrhea119 (30)8 (2)106 (27)12 (3)
Constipation68 (17)0 (0)55 (14)1 (0)
Nausea63 (16)1 (0)43 (11)3 (1)
General Disorders and Administration Site Conditions
Fatigue113 (29)23 (6)107 (28)20 (5)
Pyrexia93 (24)5 (1)64 (17)1 (0)
Edema peripheral59 (15)3 (1)48 (12)2 (1)
Asthenia54 (14)11 (3)49 (13)7 (2)
Infections and Infestations
Upper respiratory tract infection87 (22)7 (2)54 (14)4 (1)
Bronchitis55 (14)5 (1)40 (10)2 (1)
Viral upper respiratory tract infection55 (14)0 (0)44 (11)0 (0)
Pneumoniaa54 (14)35 (9)43 (11)27 (7)
Metabolism and Nutrition Disorders
Hypokalemia78 (20)22 (6)35 (9)12 (3)
Hypocalcemia55 (14)10 (3)39 (10)5 (1)
Hyperglycemia43 (11)18 (5)33 (9)15 (4)
Musculoskeletal and Connective Tissue Disorders
Muscle spasms92 (24)3 (1)75 (19)3 (1)
Back pain41 (11)4 (1)54 (14)6 (2)
Nervous System Disorders
Peripheral neuropathiesb43 (11)7 (2)39 (10)4 (1)
Psychiatric Disorders
Insomnia64 (16)6 (2)51 (13)8 (2)
Respiratory, Thoracic and Mediastinal Disorders
Coughc93 (24)2 (1)54 (14)0 (0)
Dyspnead71 (18)8 (2)61 (16)6 (2)
Skin and Subcutaneous Tissue Disorders
Rash45 (12)5 (1)54 (14)5 (1)
Vascular Disorders
Embolic and thrombotic eventse49 (13)16 (4)23 (6)9 (2)
Hypertensionf41 (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 includes 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
  • Ear and labyrinth disorders: deafness, tinnitus
  • 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: clostridium difficile colitis, 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
  • 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 11 describes Grade 3-4 laboratory abnormalities reported at a rate of ≥ 10% in the KRd arm for patients who received combination therapy.

Table 11: Grade 3-4 Laboratory Abnormalities (≥ 10% in the KRd Arm) in Cycles 1-12 (20/27 mg/m² Regimen in Combination with Lenalidomide and Dexamethasone)

Laboratory AbnormalityKRd
(N = 392)
n (%)
Rd
(N = 389)
n (%)
Decreased lymphocytes182 (46)119 (31)
Decreased absolute neutrophil count152 (39)141 (36)
Decreased phosphorus122 (31)106 (27)
Decreased platelets101 (26)59 (15)
Decreased total white blood cell count97 (25)71 (18)
Decreased hemoglobin58 (15)68 (18)
Increased glucose53 (14)30 (8)
Decreased potassium41 (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 two open-label, randomized trials (ENDEAVOR and A.R.R.O.W.).

ENDEAVOR evaluated patients with relapsed or refractory multiple myeloma [see Clinical Studies]. Patients received treatment for a median duration of 48 weeks in the twice weekly Kyprolis/dexamethasone (Kd) 20/56 mg/m² 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 reactions 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%). In patients treated with Kyprolis, 52% were 65 and over and 17% were 75 and over. The incidence of serious adverse reactions was 54% in patients < 65 years of age, 60% in patients 65 to 74 years of age, and 69% in patients ≥ 75 years of age [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. 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%). The incidence of cardiac failure events was 11% in the Kd arm versus 3% in the Vd arm.

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 12.

Table 12: Most Common Adverse Reactions (≥ 10% in the Kd Arm) Occurring in Months 1-6 (20/56 mg/m² Regimen in Combination with Dexamethasone)

Adverse Reactions by Body SystemKd
(N = 463)
n (%)
Vd
(N = 456)
n (%)
Any Grade≥ Grade 3Any Grade≥ Grade 3
Blood and Lymphatic System Disorders
Anemia161 (35)57 (12)112 (25)43 (9)
Thrombocytopeniaa125 (27)45 (10)112 (25)64 (14)
Gastrointestinal Disorders
Diarrhea117 (25)14 (3)149 (33)27 (6)
Nausea70 (15)4 (1)68 (15)3 (1)
Constipation60 (13)1 (0)113 (25)6 (1)
Vomiting45 (10)5 (1)33 (7)3 (1)
General Disorders and Administration Site Conditions
Fatigue116 (25)14 (3)126 (28)25 (6)
Pyrexia102 (22)9 (2)52 (11)3 (1)
Asthenia73 (16)9 (2)65 (14)13 (3)
Peripheral edema62 (13)3 (1)62 (14)3 (1)
Infections and Infestations
Upper respiratory tract infection67 (15)4 (1)55 (12)3 (1)
Bronchitis54 (12)5 (1)25 (6)2 (0)
Musculoskeletal and Connective Tissue Disorders
Muscle spasms70 (15)1 (0)23 (5)3 (1)
Back pain64 (14)8 (2)61 (13)10 (2)
Nervous System Disorders
Headache67 (15)4 (1)39 (9)2 (0)
Peripheral neuropathiesb,c56 (12)7 (2)170 (37)23 (5)
Psychiatric Disorders
Insomnia105 (23)5 (1)116 (25)10 (2)
Respiratory, Thoracic and Mediastinal Disorders
Dyspnead128 (28)23 (5)69 (15)8 (2)
Coughe97 (21)0 (0)61 (13)2 (0)
Vascular Disorders
Hypertensionf83 (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 includes peripheral neuropathy, peripheral sensory neuropathy, and peripheral motor neuropathy.
c See Clinical Studies.
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
  • Ear and labyrinth disorders: tinnitus
  • 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 13 describes Grade 3-4 laboratory abnormalities reported at a rate of ≥ 10% in the Kd arm.

Table 13: Grade 3-4 Laboratory Abnormalities (≥ 10%) in Months 1-6 (20/56 mg/m² Regimen in Combination with Dexamethasone)

Laboratory AbnormalityKd
(N = 463)
n (%)
Vd
(N = 456)
n (%)
Decreased lymphocytes249 (54)180 (40)
Increased uric acid244 (53)198 (43)
Decreased hemoglobin79 (17)68 (15)
Decreased platelets85 (18)77 (17)
Decreased phosphorus74 (16)61 (13)
Decreased creatinine clearancea65 (14)49 (11)
Increased potassium55 (12)21 (5)
Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone
a Calculated using the Cockcroft-Gault formula.

A.R.R.O.W. evaluated patients with relapsed and refractory multiple myeloma [see Clinical Studies]. Patients received treatment for a median duration of 38 weeks in the once weekly Kd 20/70 mg/m² arm and 29.1 weeks in the twice weekly Kd 20/27 mg/m² arm of A.R.R.O.W. The safety profile for the once weekly Kd 20/70 mg/m² regimen was similar to the twice weekly Kd 20/27 mg/m² regimen.

Deaths due to adverse reactions within 30 days of last study treatment occurred in 22/238 (9%) patients in the Kd 20/70 mg/m² arm and 18/235 (8%) patients in the Kd 20/27 mg/m² arm. The most frequent fatal adverse reactions occurring in patients (%) in the two arms (once weekly Kd 20/70 mg/m² versus twice weekly Kd 20/27 mg/m²) were sepsis 2 (< 1%) versus 2 (< 1%), septic shock 2 (< 1%) versus 1 (< 1%), and infection 2 (< 1%) versus 0 (0%). Serious adverse reactions were reported in 43% of the patients in the Kd 20/70 mg/m² arm and 41% of the patients in the Kd 20/27 mg/m² arm. In both treatment arms, pneumonia was the most commonly reported serious adverse reaction (8% versus 7%). In patients treated with once weekly Kd 20/70 mg/m², 57% were 65 and over and 19% were 75 and over. The incidence of serious adverse reactions was 37% in patients < 65 years of age, 50% in patients 65 to 74 years of age, and 44% in patients ≥ 75 years of age [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. Discontinuation due to any adverse reaction occurred in 13% in the Kd 20/70 mg/m² arm versus 12% in the Kd 20/27 mg/m² arm. The most common reaction leading to discontinuation was acute kidney injury (2% versus 2%). The incidence of cardiac failure events was 3.8% in the once weekly Kd 20/70 mg/m² arm versus 5.1% in the twice weekly Kd 20/27 mg/m² arm.

Common Adverse Reactions (≥ 10%)

Adverse reactions that occurred at a rate of 10% or greater in either Kd arm is presented in Table 14.

Table 14: Most Common Adverse Reactions (≥ 10% in either Kd Arm)

Adverse Reactions by Body SystemOnce weekly Kd 20/70 mg/m²
(N = 238)
n (%)
Twice weekly Kd 20/27 mg/m²
(N = 235)
n (%)
Any Grade≥ Grade 3Any Grade≥ Grade 3
Blood and Lymphatic System Disorders
Anemiaa64 (27)42 (18)76 (32)42 (18)
Thrombocytopeniab53 (22)26 (11)41 (17)27 (12)
Neutropeniac30 (13)21 (9)27 (12)17 (7)
Gastrointestinal Disorders
Diarrhea44 (19)2 (1)47 (20)3 (1)
Nausea34 (14)1 (< 1)26 (11)2 (1)
General Disorders and Administration Site Conditions
Pyrexia55 (23)2 (1)38 (16)4 (2)
Fatigue48 (20)11 (5)47 (20)5 (2)
Asthenia24 (10)3 (1)25 (11)2 (1)
Peripheral edema18 (8)0 (0)25 (11)2 (1)
Infections and Infestations
Respiratory tract infectiond70 (29)7 (3)79 (34)7 (3)
Pneumonia28 (12)24 (10)20 (9)16 (7)
Bronchitis27 (11)2 (1)25 (11)5 (2)
Musculoskeletal and Connective Tissue Disorders
Back pain28 (12)2 (1)28 (12)4 (2)
Nervous System Disorders
Headache25 (11)1 (< 1)23 (10)1 (< 1)
Psychiatric Disorders
Insomnia35 (15)2 (1)47 (20)0 (0)
Respiratory, Thoracic and Mediastinal Disorders
Coughe37 (16)2 (1)31 (13)0 (0)
Dyspneaf28 (12)1 (< 1)26 (11)2 (1)
Vascular Disorders
Hypertensiong51 (21)13 (6)48 (20)12 (5)
Kd = Kyprolis and dexamethasone
a Anemia includes anemia, hematocrit decreased, and hemoglobin decreased.
b Thrombocytopenia includes platelet count decreased and thrombocytopenia.
c Neutropenia includes neutrophil count decreased and neutropenia.
d Respiratory tract infection includes respiratory tract infection, lower respiratory tract infection, upper respiratory tract infection, and viral upper respiratory tract infection.
e Cough includes cough and productive cough.
f Dyspnea includes dyspnea and dyspnea exertional.
g Hypertension includes hypertension and hypertensive crisis.

Adverse Reactions Occurring At A Frequency Of < 10%
  • Blood and lymphatic system disorders: febrile neutropenia, leukopenia, lymphopenia, neutropenia, thrombotic microangiopathy
  • Cardiac disorders: atrial fibrillation, cardiac arrest, cardiac failure, cardiac failure congestive, myocardial infarction, myocardial ischemia, palpitations, pericardial effusion, tachycardia
  • Ear and labyrinth disorders: tinnitus
  • Eye disorders: cataract, vision blurred
  • Gastrointestinal disorders: abdominal pain, abdominal pain upper, constipation, dyspepsia, toothache, vomiting
  • 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
  • Infections and infestations: clostridium difficile colitis, gastroenteritis, influenza, lung infection, nasopharyngitis, rhinitis, sepsis, septic shock, urinary tract infection, viral infection
  • Metabolism and nutrition disorders: decreased appetite, dehydration, hypercalcemia, hyperglycemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, tumor lysis syndrome
  • Musculoskeletal and connective tissue disorders: muscle spasms, muscular weakness, musculoskeletal chest pain, musculoskeletal pain, myalgia
  • Nervous system disorders: cerebrovascular accident, dizziness, paresthesia, peripheral neuropathy
  • Psychiatric disorders: anxiety, delirium
  • Renal and urinary disorders: acute kidney injury, renal failure, renal impairment
  • Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome, dysphonia, epistaxis, interstitial lung disease, oropharyngeal pain, pneumonitis, pulmonary hemorrhage, pulmonary embolism, pulmonary hypertension, pulmonary  edema, wheezing
  • Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, rash
  • Vascular disorders: deep vein thrombosis, flushing, hypotension

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 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, 49% were 65 and over, while 16% were 75 and over. The incidence of serious adverse reactions 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 and Use In Specific Populations].

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 [see Clinical Studies]. 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 15.

Table 15: Most Common Adverse Reactions (≥ 20%) with Kyprolis Monotherapy

Adverse Reactions20/56 mg/m² by 30-minute infusion
(N = 24)
20/27 mg/m² by 2- to 10-minute infusion
(N = 598)
Any Grade n (%)Grade 3-5 n (%)Any Grade n (%)Grade 3-5 n (%)
Fatigue14 (58)2 (8)238 (40)25 (4)
Dyspneaa14 (58)2 (8)202 (34)21 (4)
Pyrexia14 (58)0177 (30)11 (2)
Thrombocytopenia13 (54)13 (54)220 (37)152 (25)
Nausea13 (54)0211 (35)7 (1)
Anemia10 (42)7 (29)291 (49)141 (24)
Hypertensionb10 (42)3 (13)90 (15)22 (4)
Chills9 (38)073 (12)1 (< 1)
Headache8 (33)0141 (24)7 (1)
Coughc8 (33)0134 (22)2 (< 1)
Vomiting8 (33)0104 (17)4 (1)
Lymphopenia8 (33)8 (33)85 (14)73 (12)
Insomnia7 (29)075 (13)0
Dizziness7 (29)064 (11)5 (1)
Diarrhea6 (25)1 (4)160 (27)8 (1)
Blood creatinine increased6 (25)1 (4)103 (17)15 (3)
Peripheral edema5 (21)0118 (20)1 (< 1)
Back pain5 (21)1 (4)115 (19)19 (3)
Upper respiratory tract infection5 (21)1 (4)112 (19)15 (3)
Decreased appetite5 (21)089 (15)2 (< 1)
Muscle spasms5 (21)062 (10)2 (< 1)
Chest pain5 (21)020 (3)1 (< 1)
a Dyspnea includes 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
  • Ear and labyrinth disorders: tinnitus
  • 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 16 describes Grade 3-4 laboratory abnormalities reported at a rate of > 10% for patients who received Kyprolis monotherapy.

Table 16: Grade 3-4 Laboratory Abnormalities (> 10%) with Kyprolis Monotherapy

Laboratory AbnormalityKyprolis 20/56 mg/m²
(N = 24)
Kyprolis 20/27 mg/m²
(N = 598)
Decreased lymphocytes15 (63)151 (25)
Decreased platelets11 (46)184 (31)
Decreased hemoglobin7 (29)132 (22)
Decreased total white blood cell count3 (13)71 (12)
Decreased sodium2 (8)69 (12)
Decreased absolute neutrophil count2 (8)67 (11)

Postmarketing Experience

The following adverse reactions have been identified during post approval use of 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), hepatitis B virus reactivation, gastrointestinal perforation, pericarditis, and cytomegalovirus infection, including chorioretinitis, pneumonitis, enterocolitis, and viremia.

Read the entire FDA prescribing information for Kyprolis (Carfilzomib)

Related Resources for Kyprolis

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© Kyprolis Patient Information is supplied by Cerner Multum, Inc. and Kyprolis Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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