May 26, 2016
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Kyprolis

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Kyprolis




Kyprolis Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Kyprolis (carfilzomib) is indicated to treat patients with multiple myeloma who have received at least two prior therapies, including treatment with Velcade (bortezomib) and an immunomodulatory therapy. The most common side effects are fatigue, low blood cell count and blood platelet levels, shortness of breath, diarrhea, and fever. Serious side effects included heart failure and shortness of breath. Patients should be monitored closely and treatment withheld if these serious side effects occur.

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. 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. 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.

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.

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Kyprolis FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

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

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 events 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%) versus 10 (3%), renal 0 (0%) versus 1 ( < 1%), and other adverse events 9 (2%) versus 10 (3%). Serious adverse events 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 events 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 event occurred in 26% in the KRd arm versus 25% in the Rd arm. Adverse events leading to discontinuation of Kyprolis occurred in 12% of patients and the most common events included pneumonia (1%), myocardial infarction (0.8%), and upper respiratory tract infection (0.8%).

Common Adverse Events ( ≥ 10%)

The adverse events in the first 12 cycles of therapy that occurred at a rate of 10% or greater in the KRd arm are presented in Table 5.

Table 5: Common Adverse Events ( ≥ 10% in the KRd Arm) Occurring in Cycles 1-12 (Combination Therapy)

System Organ Class Preferred Term KRd Arm
(N = 392)
Rd Arm
(N = 389)
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 Neuropathies NECb 43 (11%) 7 (2%) 37 (10%) 4 (1%)
Psychiatric Disorders
  Insomnia 63 (16%) 6 (2%) 50 (13%) 8 (2%)
Respiratory, Thoracic, and Mediastinal Disorders
  Cough 85 (22%) 1 (0%) 46 (12%) 0
  Dyspneac 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, Venous 49 (13%) 16 (4%) 22 (6%) 9 (2%)
  Hypertensione 41 (11%) 12 (3%) 15 (4%) 4 (1%)
KRd = Kyprolis, lenalidomide, and low-dose dexamethasone; Rd = lenalidomide and low-dose dexamethasone
a Pneumonia includes preferred terms of pneumonia, bronchopneumonia
b Peripheral neuropathies NEC includes preferred terms under HLT peripheral neuropathies NEC
c Dyspnea includes preferred terms of dyspnea, dyspnea exertional
d Embolic and thrombotic events, venous include preferred terms in MedDRA SMQ narrow scope search of embolic and thrombotic events, venous.
e Hypertension includes preferred terms of hypertension, hypertensive crisis, hypertensive emergency

There were 274 (70%) patients in the KRd arm who received treatment beyond Cycle 12. There were no new clinically relevant AEs that emerged in the later treatment cycles.

Adverse Reactions Occurring at a Frequency of < 10%

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 6 describes Grade 3-4 laboratory abnormalities reported at a rate of ≥ 10% in the KRd arm for patients who received combination therapy.

Table 6: Grade 3-4 Laboratory Abnormalities ( ≥ 10%) in Cycles 1-12 (Combination Therapy)

Laboratory Abnormality KRd
(N = 392)
Rd
(N = 389)
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 low-dose dexamethasone; Rd = lenalidomide and low-dose dexamethasone

Safety Experience with Kyprolis in Patients with Multiple Myeloma who Received Monotherapy

The safety of Kyprolis 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. The median age of these patients was 64 years (range 32-87) . The patients received a median of 5 (range 1-20) prior regimens. Approximately 57% of the patients were male. The median number of cycles initiated was 4 (range 1-35).

Serious adverse events were reported, regardless of causality, in 50% of patients in the pooled Kyprolis monotherapy studies (n = 598). The most common serious adverse events 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 events was higher in those > 65 years old and in those > 75 years old [see Geriatric Use].

Deaths due to adverse events within 30 days of the last dose of Kyprolis occurred in 30/598 (5%) patients receiving Kyprolis monotherapy. These adverse events were related to cardiac disorders in 10 (2%) patients, infections in 8 (1%) patients, renal disorders in 4 ( < 1%) patients, and other adverse events 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 event was acute renal failure (2%). The common adverse events occurring at a rate of 10% or greater with Kyprolis monotherapy are presented in Table 7.

Table 7: Most Commonly Reported Adverse Events ( ≥ 10%) with Kyprolis Monotherapy

System Organ Class Kyprolis Monotherapy 20/27 mg/m² (N = 598)
Any Grade ≥ Grade 3
Blood and Lymphatic System Disorders
  Anemia 291 (49%) 141 (24%)
  Thrombocytopenia 220 (37%) 152 (25%)
  Neutropenia 113 (19%) 63 (11%)
  Lymphopenia 85 (14%) 73 (12%)
  Leukopenia 61 (10%) 26 (4%)
Gastrointestinal Disorders
  Nausea 211 (35%) 7 (1%)
  Diarrhea 160 (27%) 8 (1%)
  Vomiting 104 (17%) 4 (1%)
  Constipation 90 (15%) 1 (0%)
General Disorders and Administration Site Conditions
  Fatigue 238 (40%) 25 (4%)
  Pyrexia 177 (30%) 11 (2%)
  Edema Peripheral 118 (20%) 1 (0%)
  Chills 73 (12%) 1 (0%)
  Asthenia 71 (12%) 9 (2%)
Infections and Infestations
  Upper Respiratory Tract Infection 112 (19%) 15 (3%)
  Pneumoniaa 71 (12%) 54 (9%)
Metabolism and Nutrition Disorders
  Decreased Appetite 89 (15%) 2 (0%)
  Hypercalcemia 68 (11%) 26 (4%)
  Hypokalemia 61 (10%) 17 (3%)
Musculoskeletal and Connective Tissue Disorders
  Back Pain 115 (19%) 19 (3%)
  Arthralgia 83 (14%) 5 (1%)
  Pain in Extremity 69 (12%) 7 (1%)
  Muscle Spasms 62 (10%) 2 (0%)
  Musculoskeletal Pain 60 (10%) 12 (2%)
Nervous System Disorders
  Headache 141 (24%) 7 (1%)
  Dizziness 64 (11%) 5 (1%)
  Peripheral Neuropathies NECb 62 (10%) 5 (1%)
Psychiatric Disorders
  Insomnia 75 (13%) 0
Respiratory, Thoracic, and Mediastinal Disorders
  Dyspneac 202 (34%) 21 (4%)
  Cough 120 (20%) 2 (0%)
  Epistaxis 60 (10%) 5 (1%)
Renal Disorders
  Renal Failure 76 (13%) 49 (8%)
Vascular Disorders
  Hypertensiond 90 (15%) 22 (4%)
a Pneumonia includes the preferred terms of pneumonia, bronchopneumonia.
b Peripheral neuropathies NEC includes the preferred terms under HLT peripheral neuropathies NEC.
c Dyspnea includes the preferred terms of dyspnea, dyspnea exertional.
d Hypertension includes the preferred terms of hypertension, hypertensive crisis, and hypertensive emergency.

Adverse Reactions Occurring at a Frequency of < 10%
  • Blood and lymphatic system disorders: febrile neutropenia
  • Cardiac disorders: cardiac arrest, cardiac failure congestive, myocardial infarction, myocardial ischemia
  • Eye disorders: cataract, blurred vision
  • Gastrointestinal disorders: abdominal pain, abdominal pain upper, dyspepsia, toothache
  • General disorders and administration site conditions: infusion site reaction, multi-organ failure, pain
  • Hepatobiliary disorders: hepatic failure
  • Infections and infestations: bronchitis, influenza, nasopharyngitis, respiratory tract infection, sepsis, urinary tract infection
  • Metabolism and nutrition disorders: hyperglycemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, tumor lysis syndrome
  • Musculoskeletal and connective tissue disorders: musculoskeletal chest pain, myalgia
  • Nervous system disorders: hypoesthesia, paresthesia
  • Psychiatric disorders: anxiety
  • Renal and urinary disorders: renal impairment
  • Respiratory, thoracic and mediastinal disorders: dysphonia, oropharyngeal pain, pulmonary edema
  • Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, rash
  • Vascular disorders: embolic and thrombotic events, venous (including deep vein thrombosis and pulmonary embolism), 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 8 describes Grade 3-4 laboratory abnormalities reported at a rate of > 10% for patients who received Kyprolis monotherapy.

Table 8: Grade 3-4 Laboratory Abnormalities ( > 10%) (Monotherapy)

Adverse Reaction Kyprolis
(N = 598)
Decreased Platelets 184 (31%)
Decreased Lymphocytes 151 (25%)
Decreased Hemoglobin 132 (22%)
Decreased Total White Blood Cell Count 71 (12%)
Decreased Sodium 69 (12%)
Decreased Absolute Neutrophil Count 67 (11%)

Post-marketing Experience

The following adverse reactions were reported in the post-marketing 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: dehydration, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), tumor lysis syndrome including fatal outcomes, and posterior reversible encephalopathy syndrome (PRES).

Read the entire FDA prescribing information for Kyprolis (Carfilzomib)

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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