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AJN  April 2021  Vol. 121, No. 4
ajnonline.com
DRUG Watch

Information on drugs, including new approvals and indications, warnings, and other regulatory updates.
MONOCLONAL ANTIBODY APPROVED TO
TREAT EBOLA
-  Ansuvimab-zykl (Ebanga), a hu
man monoclonal antibody, has
been approved to treat Zaire
ebolavirus (Ebolavirus) infection.
-  The most common adverse
effects of the drug are fever,
tachycardia, diarrhea, vomiting,
hypotension, tachypnea, and
chills; these are also common
symptoms of Ebolavirus infection.
T
he Food and Drug Adminis
tration (FDA) has approved
ansuvimab-zykl (Ebanga), a hu
man monoclonal antibody, to
treat Zaire ebolavirus (Ebolavirus)
infection. Zaire ebolavirus is one
of four ebolavirus species that can
cause the potentially lethal Ebola
disease in humans. Ebola can be
transmitted through the blood or
other body fluids of infected peo
ple and animals, as well as from
contaminated surfaces (such as
sheets or clothing). Ansuvimab
zykl prevents the virus from
binding to the cell receptor and
entering the cell.
Ansuvimab-zykl was evalu
ated in a clinical trial during the
2018-2019 Ebola outbreak in
the Democratic Republic of the
Congo. In the multicenter, open-
label, randomized controlled
trial, participants received one
of four investigational drugs:
ansuvimab-zykl, ZMapp (a triple
monoclonal antibody), remdesi
vir (a nucleotide analogue RNA
polymerase inhibitor), or a cofor
mulated combination of three
human IgG1 monoclonal anti
bodies.1 The primary efficacy
endpoint was 28-day mortality.
A total of 681 patients with
confirmed Ebolavirus infection
were enrolled in the trial. Of
these, 174 received ansuvimab
zykl, 169 received ZMapp, 175
received remdesivir, and 155 re
ceived the three-drug combina
tion-all drugs were administered
intravenously. After 28 days,
fewer patients who received
ansuvimab-zykl had died (35.1%)
compared with those who received
ZMapp (49.7%) or remdesivir
(53.1). Even fewer patients receiv
ing the three-drug combination
died (33.5%). Based on these find
ings, ZMapp and remdesivir are
now not used to treat Ebola.1 The
three-drug combination (atoltiv
imab, maftivimab, and odesiv
imab) was approved as an Ebola
treatment in October 2020 and is
sold under the trade name Inmazeb.
Nurses working with patients
receiving ansuvimab-zykl should
monitor them for the drug's most
common adverse effects: fever,
tachycardia, diarrhea, vomiting,
hypotension, tachypnea, and
chills, which are also common
symptoms of Ebolavirus infection.
Patients should also be monitored
for hypersensitivity, including
infusion-related events. Because
ansuvimab-zykl may interact with
the Ebola live virus vaccine and
reduce its efficacy, this combina
tion should be avoided.
To read the FDA news release
regarding the approval of ansuvimab
zykl, go to www.fda.gov/drugs/
drug-safety-and-availability/fda
approves-treatment-ebola-virus.
REFERENCE
1. Mulangu S, et al. A randomized,
controlled trial of Ebola virus disease
therapeutics. N Engl J Med 2019;
381(24):2293-303.
FIRST ORAL HORMONE FOR TREATING
PROSTATE CANCER
-  Relugolix (Orgovyx) has been ap
proved for the treatment of ad
vanced prostate cancer. It is the
first oral gonadotropin-releasing
hormone receptor antagonist.
-  As with other androgen depriva
tion therapy, there is a risk of
prolonging the QT or QTc inter
val with relugolix. The drug may
also cause embryo-fetal toxicity.
A
dvanced prostate cancer can
now be treated with relugolix
(Orgovyx), the first oral gonado
tropin-releasing hormone (GnRH)
receptor antagonist. The drug works
by binding to pituitary GnRH re
ceptors, decreasing the release of
luteinizing hormone and follicle-
stimulating hormone, and conse
quently decreasing testosterone.
The therapeutic effect of relugolix
should be monitored by periodi
cally measuring serum concentra
tions of prostate specific antigen.
The safety and efficacy of relu
golix was evaluated in a random
ized, open-label study in men
with advanced prostate cancer.
In a 2:1 ratio, patients were as
signed to receive relugolix or a
standard therapy, leuprolide ace
tate, by injection. The efficacy
outcome measure was a testo
sterone level low enough to be
considered medical castration
(less than 50 ng/dL) by day 29
through week 48 of treatment.
Those treated with relugolix were
more likely than those treated
with leuprolide acetate to achieve
low testosterone levels by day 29
(99% versus 82%).
Like other androgen depriva
tion therapy, relugolix carries the
risk of prolonging the QT or
QTc interval. The drug may also
cause embryo-fetal toxicity. The
most common adverse effects are
hot flushes, musculoskeletal pain,
fatigue, constipation, and diar
rhea; the most common labora
tory abnormalities are decreases
in hemoglobin and elevations in
glucose, triglycerides, alanine
aminotransferase, and aspartate
aminotransferase.
Nurses should teach men with
female partners of reproductive
age to use effective contraception
during treatment and for two
weeks after the last relugolix
dose. Patients should be told to
swallow the drug whole, not to
crush or chew it. The drug should
be taken at the same time every
day. Nurses should use a drug
database to confirm that the
patient is not also taking a P-gly

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ajn@wolterskluwer.com
AJN  April 2021  Vol. 121, No. 4
23

By Diane S. Aschenbrenner, MS, RN
coprotein (P-gp) inhibitor such as
amiodarone, carvedilol, erythro
mycin, ritonavir, or verapamil,
because coadministration with
these drugs can increase blood
levels of relugolix and therefore
the risk of adverse effects. If co-
administration with P-gp inhibi
tors cannot be avoided, relugolix
should be taken first followed by
a waiting period of at least six
hours before taking the other
drug. Drugs that are P-gp induc
ers or inducers of the cytochrome
P-450 (CYP) isoenzyme CYP3A
(for example, phenytoin, fosphe
nytoin, and rifampin, which in
duces both) should be avoided, if
possible, as they decrease circu
lating levels of relugolix.
Because of the risk of a pro
longed QT interval, the patient
should be assessed for electro
lyte abnormalities prior to and
throughout therapy, and any ab
normalities should be corrected.
Patients may require electrocardio
gram monitoring during therapy.
For complete prescribing infor
mation for relugolix, go to www.
accessdata.fda.gov/drugsatfda_
docs/label/2020/214621s000lbl.pdf.
NEW ADJUVANT DRUG FOR LUNG CANCER
-  A new adjuvant treatment,
osimertinib (Tagrisso), has been
approved for patients with non-
small cell lung cancer whose tu
mors have certain mutations.
-  The most common adverse ef
fects of treatment are leukopenia,
lymphopenia, thrombocytopenia,
diarrhea, anemia, rash, musculo
skeletal pain, nail toxicity, neutro
penia, dry skin, stomatitis, fatigue,
and cough.
A
new adjuvant therapy,
osimertinib (Tagrisso), has
been approved after tumor resec
tion for adults with non-small
cell lung cancer whose tumors
have epidermal growth factor re
ceptor (EGFR) exon 19 deletions
or exon 21 L858R mutations, as
Table 1. Serious Adverse Effects of Osimertinib
Adverse Effect
Signs or Symptoms
Assessment
Interstitial lung
disease/
pneumonitis
New or worsening respiratory symp-
toms (dyspnea, cough, shortness of
breath, and fever)
Assess for respiratory
changes.
QTc interval
prolongation
Dizziness, lightheadedness, and syn-
cope
Monitor ECG results
and electrolyte levels;
assess for use of other
drugs that also pro-
long the QTc interval.
Cardiomyopathy
Shortness of breath, fatigue, dizziness,
lightheadedness, fainting during physi-
cal activity, arrythmias, chest pain, heart
murmur, swelling in the extremities
Conduct cardiac
monitoring, including
LVEF, in patients with
cardiac risk factors.
Keratitis
Eye inflammation, lacrimation, light
sensitivity, eye pain, red eye, or changes
in vision
Refer to opthalmolo-
gist promptly.
Erythema multiforme
and Stevens-
Johnson syndrome
Target lesions (ring like) or severe blis-
tering or peeling of skin
Assess skin regularly.
Cutaneous vasculitis
Multiple, nonblanching red papules
on forearms, lower legs, or buttocks, or
large hives on the trunk that do not go
away within 24 hours and develop a
bruised appearance
Assess skin regularly.
ECG = electrocardiogram; LVEF = left ventricular ejection fraction.
detected by a test approved by
the Food and Drug Administra
tion. It is also approved as first-
line treatment for those with
non-small cell lung cancer whose
tumors have the same deletion or
mutation. Osimertinib was pre
viously approved as treatment
for metastatic EGFR T790M
mutation-positive non-small
cell lung cancer. Osimertinib is
a kinase inhibitor of the EGFR
and it irreversibly binds to certain
mutant forms of the EGFR.
Osimertinib's efficacy was
demonstrated in a randomized,
double-blind, placebo-controlled
trial (ADAURA) of patients with
non-small cell lung cancer and
EGFR exon 19 deletions or exon
21 L858R mutations who had
complete tumor resection, with
or without prior adjuvant che
motherapy. Patients received
either osimertinib or placebo fol
lowing recovery from surgery
and standard adjuvant chemo
therapy (if given). The major ef
ficacy outcome was disease-free
survival (defined as a reduction
in the risk of disease recurrence
or death). There was a difference
in disease-free survival with
osimertinib use that was both
statistically significant and clini
cally meaningful compared with
placebo.
The efficacy of osimertinib was
also measured in a randomized,
double-blind, active-controlled,
multicenter trial (FLAURA) in
patients with EGFR exon 19
deletions or exon 21 L858R
mutation-positive, metastatic non-
small cell lung cancer, who hadn't
received previous systemic treat
ment for metastatic disease. Those
who received osimertinib had sta
tistically significant improvement
in overall survival compared with