Bronchitis
54 (14%)
5 (1%)
39 (10%)
2 (1%)
Pneumoniaa
54 (14%)
35 (9%)
43 (11%)
27 (7%)
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%)
88 (22%)
3 (1%)
73 (19%)
3 (1%)
43 (11%)
7 (2%)
37 (10%)
4 (1%)
63 (16%)
6 (2%)
50 (13%)
8 (2%)
Metabolism and Nutrition Disorders
Musculoskeletal and Connective Tissue Disorders
Muscle Spasms
Psychiatric Disorders
Insomnia
Respiratory, Thoracic, and Mediastinal Disorders
Cough
85 (22%)
1 (0%)
46 (12%)
0
Dyspneac
70 (18%)
9 (2%)
58 (15%)
6 (2%)
45 (12%)
5 (1%)
53 (14%)
5 (1%)
Embolic and Thrombotic Events,
Venousd
49 (13%)
16 (4%)
22 (6%)
9 (2%)
Hypertensione
41 (11%)
12 (3%)
15 (4%)
4 (1%)
Skin and Subcutaneous Tissue
Disorders
Rash
Vascular Disorders
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
No new clinically relevant ARs emerged in the later treatment cycles in the 274 (70%)
patients in the KRd arm who received treatment beyond Cycle 12.
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
Decreased Lymphocytes
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.
Kyprolis can cause fetal harm when administered to pregnant women Advise females
of reproductive potential to use effective contraception measures to prevent pregnancy
during treatment with Kyprolis and for at least 2 weeks following completion of therapy.
Pediatric Use
The safety and effectiveness of Kyprolis in pediatric patients have not been established.
Geriatric Use
Of 392 patients treated with Kyprolis in combination with lenalidomide and
dexamethasone, 185 patients (47%) were ≥ 65 years of age and 43 patients (11%) were
≥75 years of age. No overall differences in effectiveness were observed between these
and younger patients. 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.
Renal Impairment
No starting dose adjustment is required in patients with baseline mild, moderate, or severe
renal impairment or patients on chronic dialysis based on a phase 2 pharmacokinetic and
safety trial of Kyprolis. The pharmacokinetics of Kyprolis was not influenced by the
degree of baseline renal impairment, including when patients were receiving dialysis.
Administer KYPROLIS after the dialysis procedure.
Hepatic Impairment
The safety, efficacy and pharmacokinetics of Kyprolis have not been evaluated in patients
with baseline hepatic impairment. Patients with the following laboratory values were
excluded from the Kyprolis clinical trials: ALT/AST ≥ 3 × upper limit of normal (ULN)
and bilirubin ≥ 2 × ULN.
Cardiac Impairment
Safety of patients with New York Heart Association Class III and IV heart failure or
recent myocardial infarction (within 3 to 6 months) has not been evaluated.
OVERDOSE
Acute onset of chills, hypotension, renal insufficiency, thrombocytopenia and lymphopenia
has been reported following a dose of 200 mg of Kyprolis administed in error.
There is no specific antidote for Kyprolis overdosage. In the event of overdose, the patient
should be monitored, specifically for the adverse reactions in the adverse reaction section.
Grade 3–4 Laboratory Abnormalities ( ≥ 10%) in Cycles 1-12
(Combination Therapy)
Laboratory Abnormality
Lactation
Contraception
Nervous System Disorders
Peripheral Neuropathies NECb
during pregnancy, or if the patient becomes pregnant while taking Kyprolis, advise the
patient of the potential hazard to the fetus.
KRd
(N = 392)
Rd
(N = 389)
182 (46%)
119 (31%)
Decreased Abso