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CLINICAL NEWS
factors that were later associated with mortality included
higher alkaline phosphatase (p<0.0001), white blood cells
(p=0.048), creatinine (p=0.043), and tricuspid regurgitation velocity (p=0.0082).
The patients who died were significantly older at the
time of study enrollment (41.8 vs. 32.5 years, respectively; p=0.0067) and had lower HbF (p=0.0044). A lower
proportion of these patients were prescribed hydroxyurea in the recommended dose range (15-35 mg/kg/
day) compared with patients who survived (29% vs. 46%;
p=0.0039).
survival (HR=0.58; 95% CI = 0.34-0.97; p=0.040). This
benefit was even more pronounced in those taking 15
mg/kg to 35 mg/kg per day (HR=0.36; 95% CI 0.17-0.73;
p=0.0050) or >35 mg/kg per day (HR=0.72; 95% CI
0.20-2.55; p=0.61) compared to those taking <15 mg/
kg per day. “To our knowledge, this is the first study to
demonstrate that doses below the recommended starting
dose may not confer a survival benefit,” Dr. Fitzhugh and
colleagues wrote.
Among patients who experienced hydroxyureainduced HbF, the only marker of organ damage that was
6.2 Post-marketing
Experience
6.2 Post-marketing
Experience
The following
adverse
reactions
were reported
the post-marketing
experience
The following
adverse
reactions
were reported
in the in
post-marketing
experience
with with
109 (28%)
104 (27%)
109 (28%)
21 (5%)21 (5%)
104 (27%)
20 (5%)20 (5%)Kyprolis.
Kyprolis.
Because
these reactions
are reported
voluntarily
a population
of uncertain
Because
these reactions
are reported
voluntarily
from afrom
population
of uncertain
is not always
possible
to reliably
estimate
their frequency
or establish
a causal
is notit always
possible
to reliably
estimate
their frequency
or establish
a causal
93 (24%)5 (1%) 5 (1%)64 (17%)
64 (17%)1 (0%) 1 (0%) size, itsize,
93 (24%)
relationship
drug exposure:
dehydration,
TTP/HUS,
TLS including
fatal outcomes,
relationship
to drugtoexposure:
dehydration,
TTP/HUS,
TLS including
fatal outcomes,
63 (16%)2 (1%) 2 (1%)57 (15%)
57 (15%)2 (1%) 2 (1%) and PRES.
63 (16%)
and PRES.
Disorders
and Administration
Site Conditions
GeneralGeneral
Disorders
and Administration
Site Conditions
FatigueFatigue
PyrexiaPyrexia
Peripheral
Edema Edema
Peripheral
Asthenia
Asthenia
ent Infections
Infections
and Infestations
and Infestations
es
S)
d
op
ed.
s
Deceased patients also had more hepatic dysfunction,
kidney dysfunction, and cardiopulmonary dysfunction.
Among the 66 percent of patients who were taking
hydroxyurea, just 66 percent were on the recommended
dose, with 18 percent treated below the recommended
dose range. Among hydroxyurea-treated patients, the
maximum HbF and mean corpuscular volume were
greater among those who survived and those who died
following treatment: 14.3±9.5 vs. 11.3±11.4 (p=0.0044)
and 102.7±15.2 vs. 104.2±16.5 (p=0.57), respectively.
Patients treated with hydroxyurea also had improved
53 (14%)
46 (12%)7 (2%) 7 (2%)
53 (14%)
11 (3%)11 (3%)
46 (12%)
7. DRUG
INTERACTIONS
7. DRUG
INTERACTIONS
Kyprolis
is primarily
metabolized
via peptidase
and epoxide
hydrolase
activities,
Kyprolis
is primarily
metabolized
via peptidase
and epoxide
hydrolase
activities,
and asand as
a result, the pharmacokinetic profile of Kyprolis is unlikely to be affected by concomitant
administration
of cytochrome
P450 inhibitors
and inducers.
Kyprolis
is not expected
administration
of cytochrome
P450 inhibitors
and inducers.
Kyprolis
is not expected
to to
0 influence
influence
exposure
of drugs.
other drugs.
exposure
of other
Upper Respiratory
Tract Infection
Upper Respiratory
Tract Infection
85 (22%)7 (2%) 7 (2%)52 (13%)
52 (13%)3 (1%) 3 (1%) a result, the pharmacokinetic profile of Kyprolis is unlikely to be affected by concomitant
85 (22%)
Nasopharyngitis
Nasopharyngitis
63 (16%) 0
63 (16%)
Bronchitis
Bronchitis
54 (14%)5 (1%) 5 (1%)39 (10%)
39 (10%)2 (1%) 2 (1%) 8. USE8.INUSE
54 (14%)
IN SPECIFIC
POPULATIONS
SPECIFIC
POPULATIONS
a
a
Pneumonia
Pneumonia
8.1 Pregnancy
54 (14%)
43 (11%)
54 (14%)
35 (9%)35 (9%)
43 (11%)
27 (7%)27 (7%)8.1 Pregnancy
0 43 (11%)
43 (11%) 0
Kyprolis
may cause
fetal harm.
no adequate
and well-controlled
in
Kyprolis
may cause
fetal harm.
There There
are noare
adequate
and well-controlled
studiesstudies
in
pregnant
using Kyprolis.
pregnant
womenwomen
using Kyprolis.
Hypokalemia
78 (20%)
Hypokalemia
78 (20%)
22 (6%)22 (6%)35 (9%)35 (9%)12 (3%)12 (3%)Females
Females
of reproductive
potential
be advised
to becoming
avoid becoming
pregnant
of reproductive
potential
shouldshould
be advised
to avoid
p &Vv