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• 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
A.R.R.O.W. evaluated patients with relapsed and refractory multiple myeloma. Patients received treatment for
a median duration of 38 weeks in the once weekly Kd 20/70 mg/m 2 arm and 29.1 weeks in the twice weekly
Kd 20/27 mg/m 2 arm of A.R.R.O.W.. The safety profile for the once weekly Kd 20/70 mg/m 2 regimen was
similar to the twice weekly Kd 20/27 mg/m 2 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/m 2 arm and 18/235 (8%) patients in the Kd 20/27 mg/m 2 arm. The most frequent fatal
adverse reactions occurring in patients (%) in the two arms (once weekly Kd 20/70 mg/m 2 versus twice
weekly Kd 20/27 mg/m 2 ) 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/m 2 arm and 41% of the patients in the Kd 20/27 mg/m 2 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/m 2 , 57% were 65 and over and 19% were 75 and over. The incidence of
serious adverse events 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. Discontinuation due to any adverse reaction occurred in 13% in
the Kd 20/70 mg/m 2 arm versus 12% in the Kd 20/27 mg/m 2 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/m 2 arm versus 5.1% in the twice weekly Kd 20/27 mg/m 2 arm.
Most Common Adverse Reactions (≥ 10% in either Kd Arm)
Once weekly Kd
20/70 mg/m 2
(N = 238), n (%)
Adverse Reactions by Body System
Twice weekly Kd
20/27 mg/m 2
(N = 235), n (%)
Any Grade ≥ Grade 3 Any Grade ≥ Grade 3
Anemia a 64 (26.9) 42 (17.6) 76 (32.3) 42 (17.9)
Thrombocytopenia b 53 (22.3) 26 (10.9) 41 (17.4) 27 (11.5)
Neutropenia c 30 (12.6) 21 (8.8) 27 (11.5) 17 (7.2)
Diarrhea 44 (18.5) 2 (0.8) 47 (20.0) 3 (1.3)
Nausea 34 (14.3) 1 (0.4) 26 (11.1) 2 (0.9)
Blood and Lymphatic System Disorders
Gastrointestinal Disorders
General Disorders and Administration Site Conditions
Pyrexia 55 (23.1) 2 (0.8) 38 (16.2) 4 (1.7)
Fatigue 48 (20.2) 11 (4.6) 47 (20.0) 5 (2.1)
Asthenia 24 (10.1) 3 (1.3) 25 (10.6) 2 (0.9)
Peripheral edema 18 (7.6) 0 (0.0) 25 (10.6) 2 (0.9)
Infections and Infestations
K
• 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
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.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Kyprolis can cause fetal harm based on findings from animal studies and the drug’s mechanism of action.
There are no studies with the use of Kyprolis in pregnant women to inform drug-associated risks of adverse
developmental outcomes. Kyprolis caused embryo-fetal lethality in rabbits at doses lower than the clinical
dose. Advise pregnant women of the potential risk to the fetus. The estimated background risk of major birth
defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk
of birth defect, loss, or other adverse outcomes. 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.
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 many drugs are excreted in human milk and because the potential
for serious adverse reactions in a breastfed child from Kyprolis is unknown, advise nursing women not to
breastfeed during treatment with Kyprolis and for 2 weeks after treatment.
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.
Pregnancy Testing
Conduct pregnancy testing on females of reproductive potential prior to initiating Kyprolis treatment.
Contraception
Females
Advise females of reproductive potential to avoid pregnancy and use effective contraception during treatment
with Kyprolis and for at least 6 months following the final dose.
Males
Advise males with female sexual partners of reproductive potential to use effective contraception during
treatment with Kyprolis and for at least 3 months following the final dose.
Infertility
Based on the mechanism of action, Kyprolis may have an effect on either male or female fertility. There are
no data on the effect of Kyprolis on human fertility.
Respiratory tract infection d 70 (29.4) 7 (2.9) 79 (33.6) 7 (3.0) Pneumonia 28 (11.8) 24 (10.1) 20 (8.5) 16 (6.8) Bronchitis 27 (11.3) 2 (0.8) 25 (10.6) 5 (2.1) 28 (11.8) 2 (0.8) 28 (11.9) 4 (1.7) Pediatric Use
The safety and effectiveness of Kyprolis in pediatric patients have not been established.
25 (10.5) 1 (0.4) 23 (9.8) 1 (0.4) 35 (14.7) 2 (0.8) 47 (20.0) 0 (0.0) Geriatric Use
Of 1691 patients in clinical studies of Kyprolis, 50.4% were 65 and over, while 15.4% were 75 and over.
The incidence of serious adverse events in patients 65 and over was higher than the incidence in younger
patients. No overall differences in effectiveness were observed between older and younger patients.
Musculoskeletal and Connective Tissue Disorders
Back pain
Nervous System Disorders
Headache
Psychiatric Disorders
Insomnia
Respiratory, Thoracic and Mediastinal Disorders
Cough e 37 (15.5) 2 (0.8) 31 (13.2) 0 (0.0)
Dyspnea f 28 (11.8) 1 (0.4) 26 (11.1) 2 (0.9)
51 (21.4) 13 (5.5) 48 (20.4) 12 (5.1)
Vascular Disorders
Hypertension g
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
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. Dosing recommendation cannot be made for patients with severe hepatic function.
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%).
Overdosage
Acute onset of chills, hypotension, renal insufficiency, thrombocytopenia, and lymphopenia has been reported
following a dose of 200 mg of Kyprolis administrated in error.
There is no known specific antidote for Kyprolis overdosage. In the event of overdose, the patient should be
monitored, specifically for the side effects and/or adverse reactions listed.
The risk information provided here is not comprehensive. The FDA‑approved product labeling can be
found at www.kyprolis.com or contact Amgen Medical Information at 1‑800‑772‑6436.
This Brief Summary is based on the Kyprolis Prescribing Information v19, 09/18.
U.S. Patent Numbers: http://pat.amgen.com/kyprolis
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