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AJN  March 2020  Vol. 120, No. 3
ajnonline.com
DRUG Watch

Information on drugs, including new approvals and indications, warnings, and other regulatory updates.
TWO NEW DRUGS FOR SICKLE CELL DISEASE
-  Two drugs, voxelotor (Oxbryta)
and crizanlizumab-tmca (Adak
veo), have been approved to
treat sickle cell disease.
-  The most common adverse ef
fects of voxelotor are diarrhea,
headache, abdominal pain,
nausea, fatigue, rash, and fever.
Hypersensitivity reactions are
also possible.
-  The most common adverse ef
fects of crizanlizumab-tmca are
back pain, nausea, fever, and
arthralgia. Serious adverse ef
fects include infusion-related
reactions and interference with
automated platelet counts.
T
wo drugs, voxelotor (Oxbryta)
and crizanlizumab-tmca (Adak
veo), have been approved by the Food
and Drug Administration (FDA) for
the treatment of sickle cell disease.
Voxelotor, approved in patients
12 years of age and older, was
granted accelerated approval, which
allows the FDA to approve drugs
before clinical trials have been com
pleted in instances when the drugs
are likely to provide a clinical bene
fit over current therapy. Further
clinical trials are required by the
FDA to prove the clinical benefit.
Sickle cell disease alters the shape
of the hemoglobin molecule, which
causes red blood cells to have a
curved (or sickled) shape. Sickle
cells are not as flexible as normal
red blood cells and stick to vessel
walls, blocking blood flow and lim
iting oxygen delivery to the tissues,
which cause severe pain. Sickle cells
also break apart more easily, lead
ing to anemia. Voxelotor prevents
red blood cells from forming the
sickle shape.
In a randomized, double-blind,
placebo-controlled, multicenter clin
ical trial of 274 patients with sickle
cell disease, 51.2% of patients who
received voxelotor 1,500 mg had
an increased hemoglobin response
of more than 1 g/dL from baseline
compared with 6.5% of those who
received placebo.
The most common adverse ef
fects of voxelotor (in more than
10% of patients) are diarrhea,
headache, abdominal pain, nausea,
fatigue, rash, and fever. Hypersen
sitivity reactions are possible (in
less than 1% of patients). Adverse
effects in clinical trials were similar
for pediatric and adult patients.
Nurses should check to see if
any coprescribed drugs are strong
cytochrome P-450 (CYP) 3A4 inhib
itors or strong or moderate CYP3A4
inducers. CYP3A4 inhibitors will
increase circulating levels of voxelo
tor, necessitating a smaller voxelotor
dose, and CYP3A4 inducers will de
crease circulating levels of voxelotor,
necessitating a larger voxelotor dose.
Fluconazole, a moderate CYP3A4
inhibitor, should be avoided as it
increases voxelotor's circulation
between 40% and 116%. Adminis
tration of voxelotor with CYP3A4
sensitive substrates will significantly
increase the substrates' circulating
levels; coadministration with sensi
tive substrates that have a narrow
therapeutic index should be avoided.
Voxelotor should be taken dailywith
or without food, the tablets swal
lowed whole. Patients should be told
to seek emergency medical help if
they experience rash, hives, short
ness of breath, or facial swelling.
To read the complete prescribing
information for voxelotor, go to
www.accessdata.fda.gov/drugsatfda_
docs/label/2019/213137s000lbl.pdf.
Crizanlizumab-tmca, a selectin
blocker, reduces the frequency of
vasoocclusive crisis from obstructed
blood flow. Selectin contributes to
red blood cells sticking together.
Approval for crizanlizumab
tmca was based on results of a
randomized clinical trial of 198 pa
tients with sickle cell disease and a
history of vasoocclusive crisis. Pa
tients receiving crizanlizumab-tmca
had fewer health care visits a year
for vasoocclusive crisis than patients
who received placebo (a median an
nual rate of 1.63 versus 2.98 visits).
The most common adverse effects
of crizanlizumab-tmca (in more than
10% of patients) are back pain,
nausea, fever, and arthralgia. Seri
ous adverse effects include infusion-
related reactions and interference
with automated platelet counts (the
reported count may be much lower
than actual platelet levels).
Crizanlizumab-tmca is adminis
tered as an iv infusion over a
30-minute period at week 0, week
2, and then every four weeks. The
dose is weight based. Nurses should
be aware that crizanlizumab-tmca
must be administered as soon after
dilution as possible; once the vials
are at room temperature, the drug
should be completely infused within
4.5 hours after piercing the first vial.
If the drug is refrigerated, it must
be infused within 24 hours of piercing
the vials, including the time needed
for the drug to return to room temper
ature. Patients should be monitored
for up to 24 hours after infusion for
signs and symptoms of infusion-
related reactions, including fever,
chills, nausea, vomiting, fatigue, diz
ziness, pruritus, urticaria, sweating,
shortness of breath, or wheezing.
To read complete prescribing
information for crizanlizumab
tmca, see www.accessdata.fda.
gov/drugsatfda_docs/label/2019/
761128s000lbl.pdf.
NEW TREATMENT FOR PARTIAL-ONSET
SEIZURES IN ADULTS
-  Cenobamate (Xcopri) is now
approved to treat partial-onset
seizures in adults.
-  Serious adverse effects include
drug reaction with eosinophilia
and systemic symptoms (also
called multiorgan hypersensitivity)
and a shortened QT interval.
C
enobamate (Xcopri), a new
treatment option for adults
with partial-onset seizures, has been
approved by the Food and Drug
Administration. It will be classified
in the controlled substance schedule
after review by the Drug Enforce
ment Administration, as it may be
abused or lead to dependency.

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ajn@wolterskluwer.com
AJN  March 2020  Vol. 120, No. 3
25
By Diane S. Aschenbrenner, MS, RN

Serious adverse effects occurred
in a small percentage of patients
during clinical trials of cenobamate.
Cases of drug reaction with eosino
philia and systemic symptoms
(DRESS; also called multiorgan
hypersensitivity) and one death
occurred with rapid dose titration
(within a week or less). Symptoms
of DRESS include fever, rash,
lymphadenopathy, and/or facial
swelling, in association with signs of
other organ system involvement (for
example, lymphadenopathy, hepati
tis, nephritis, hematologic abnormal
ities, myocarditis, or myositis). An
elevated eosinophil count may occur.
In the clinical trials, patients
randomized to cenobamate had
a higher incidence of shortened
QT interval than those receiving
placebo. Cenobamate is contra
indicated in patients with familial
short QT syndrome. Like all anti
convulsants, cenobamate carries a
warning that suicidal behavior or
ideation can occur. The most com
mon adverse effects of cenobamate
(in 10% or more of patients) include
somnolence, dizziness, fatigue,
double vision, and headache.
Because of potential neurologic
adverse effects, patients should not
drive or operate machinery until
they know how cenobamate affects
them. Concomitant use of other
central nervous system depres
sants or alcohol may have additive
effects.
Drug interactions with other
anticonvulsants may require dose
adjustments: a decrease in the cen
obamate dose with phenytoin,
phenobarbital, or clobazam, and
an increase with lamotrigine or
carbamazepine. Cenobamate can
also interact with drugs through
the cytochrome P-450 (CYP) iso
enzyme system. Patients receiving
CYP2B6 or CYP3A substrates
will need to increase the cenobam
ate dose, whereas those receiving
CYP2C19 substrates will need to
decrease it. Oral contraceptives
may be less effective if taken con
comitantly with cenobamate.
Nurses should evaluate pa
tients at the first sign of hyper
sensitivity reactions, even if a
rash is not present. If an alterna
tive cause of the hypersensitivity
reaction cannot be determined,
cenobamate should be discontin
ued. Female patients who use
oral contraceptives should use
additional nonhormonal birth
control. Nurses should instruct
patients to swallow cenobamate
tablets whole with liquid once daily.
For complete prescribing in
formation for cenobamate, go to
www.accessdata.fda.gov/drug
satfda_docs/label/2019/212839s
000lbl.pdf.
NEW ANTIBIOTIC FOR COMPLICATED UTIs
-  Cefiderocol (Fetroja) is a newly
approved cephalosporin antibi
otic for adults with complicated
urinary tract infections, including
pyelonephritis, caused by sus
ceptible gram-negative microor
ganisms when there are limited
or no alternative treatments.
-  A higher rate of all-cause mortal
ity was seen in cefiderocol-treated
patients compared with patients
given other antibiotics in a clinical
trial of critically ill patients with
carbapenem-resistant gram-
negative infections.
C
efiderocol (Fetroja) is a newly
approved cephalosporin anti
biotic for adults with complicated
urinary tract infections (cUTI), in
cluding pyelonephritis, caused by
susceptible gram-negative micro
organisms when there are limited
or no alternative treatments.
The safety and effectiveness of
cefiderocol were demonstrated in
a multinational, double-blind
clinical trial of 448 patients with
cUTI that compared cefiderocol
2g iv every eight hours (infused
over one hour) with imipenem-
cilastatin (Primaxin) 1g iv every
eight hours (infused over one
hour) for seven to 14 days. Of
the patients taking cefiderocol,
72.6% experienced a resolution
of symptoms and eradication of
bacteria within seven days of
completing treatment compared
with 54.6% of those who re
ceived imipenem-cilastatin.
Cefiderocol's labeling carries a
warning that an increase in all-
cause mortality was seen in pa
tients treated with cefiderocol,
compared with those treated
with other antibiotics, in a clinical
trial of critically ill patients with
carbapenem-resistant gram-negative
infections. The reason for this has
not been determined. Cefiderocol
also carries warnings that hyper
sensitivity reactions, including
anaphylaxis, may occur and can be
fatal, and that seizures and other
central nervous system adverse ef
fects are also possible. Like almost all
antibiotics, cefiderocol may induce
Clostridioides difficile-associated
diarrhea.
The most common adverse ef
fects of cefiderocol include diarrhea,
constipation, nausea, vomiting, ele
vations in liver function tests, rash,
infusion site reactions, candidiasis,
cough, headache, and hypokalemia.
Cefiderocol is contraindicated when
there is a known history of severe
hypersensitivity to -lactam anti
bacterial drugs.
Nurses should confirm the
patient's creatinine clearance, as
patients with low creatinine clear
ance will need a lower cefiderocol
dose. After reconstitution and
further dilution, the drug is stable
for four hours at room tempera
ture. Nurses should administer iv
cefiderocol slowly (over three
hours) every eight hours. The
duration of treatment is seven to
14 days.
For complete prescribing in
formation for cefiderocol, see
www.accessdata.fda.gov/drug
satfda_docs/label/2019/209445s
000lbl.pdf. 
Diane S. Aschenbrenner is an assistant pro
fessor at Notre Dame of Maryland Univer
sity in Baltimore. She also coordinates
Drug Watch: daschenbrenner@ndm.edu.