Merck Announces FDA Acceptance of Resubmission of New Drug Application for Sugammadex Sodium Injection
January 7, 2013 8:00 am ET
Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced that the resubmission of the New Drug Application (NDA)
for sugammadex sodium injection has been accepted for review by the U.S.
Food and Drug Administration (FDA). Merck expects the FDA’s review to be
completed in the first half of 2013.
Sugammadex sodium injection is the company’s investigational agent for
the reversal of neuromuscular blockade (NMB) induced by rocuronium or
vecuronium (neuromuscular blocking agents). NMB is used in
anesthesiology to induce muscle relaxation during surgery. Sugammadex is
designed to work by inactivating rocuronium or vecuronium molecules
directly by encapsulation. If approved, it would be the first in a new
class of medicines in the U.S. known as selective relaxant binding
agents to be used in the surgical setting.
In 2008, the FDA did not approve the original NDA for sugammadex sodium
injection, requesting additional data related to hypersensitivity
(allergic) reactions and coagulation (bleeding) events. Merck submitted
this requested data within the NDA resubmission, which the FDA has now
deemed complete for review.
“We are pleased the FDA has accepted our resubmission of sugammadex
sodium injection for review, as this was a key milestone in our effort
to bring this medicine to the U.S.,” said Darryle D. Schoepp, Ph.D.,
senior vice president and head of Neuroscience and Ophthalmology, Merck
Research Laboratories. “Sugammadex sodium injection is an example of
Merck’s ongoing commitment to developing new medicines for patients in
Indication for ZEMURON® (rocuronium bromide)
ZEMURON Injection, from Merck, is indicated for inpatients and
outpatients as an adjunct to general anesthesia to facilitate both rapid
sequence and routine tracheal intubation, and to provide skeletal muscle
relaxation during surgery or mechanical ventilation.
Important safety information about ZEMURON
ZEMURON is contraindicated in patients known to have hypersensitivity
(e.g., anaphylaxis) to rocuronium bromide or other neuromuscular
ZEMURON should be administered in carefully adjusted dosages by or under
the supervision of experienced clinicians who are familiar with the
drug’s actions and the possible complications of its use. The drug
should not be administered unless facilities for intubation, mechanical
ventilation, oxygen therapy, and an antagonist are immediately
available. It is recommended that clinicians administering neuromuscular
blocking agents, such as ZEMURON, employ a peripheral nerve stimulator
to monitor drug effect, need for additional doses, adequacy of
spontaneous recovery or antagonism, and to decrease the complications of
overdosage if additional doses are administered.
Severe anaphylactic reactions to neuromuscular blocking agents,
including ZEMURON, have been reported. These reactions have, in some
cases (including cases with ZEMURON), been life threatening and fatal.
Due to the potential severity of these reactions, the necessary
precautions, such as the immediate availability of appropriate emergency
treatment, should be taken. Precautions should also be taken in those
patients who have had previous anaphylactic reactions to other
neuromuscular blocking agents, since cross-reactivity between
neuromuscular blocking agents, both depolarizing and non-depolarizing,
has been reported.
ZEMURON has no known effect on consciousness, pain threshold, or
cerebration. Therefore, its administration must be accompanied by
adequate anesthesia or sedation.
In order to prevent complications resulting from residual paralysis, it
is recommended to extubate only after the patient has recovered
sufficiently from neuromuscular block. Other factors, which could cause
residual paralysis after extubation in the post-operative phase, (such
as drug interactions or patient condition) should also be considered. If
not used as part of standard clinical practice, the use of a reversal
agent should be considered, especially in those cases where residual
paralysis is more likely to occur.
ZEMURON has not been studied for long-term use in the intensive care
unit (ICU). As with other non-depolarizing neuromuscular blocking drugs,
apparent tolerance to ZEMURON may develop during chronic administration
in the ICU. While the mechanism for development of this resistance is
not known, receptor up-regulation may be a contributing factor. It is
strongly recommended that neuromuscular transmission be monitored
continuously during administration and recovery with the help of a nerve
stimulator. Additional doses of ZEMURON (rocuronium bromide) or any
other neuromuscular blocking agent should not be given until there is a
definite response (one twitch of the train-of-four) to nerve
stimulation. Prolonged paralysis and/or skeletal muscle weakness may be
noted during initial attempts to wean from the ventilator patients who
have chronically received neuromuscular blocking drugs in the ICU.
Myopathy after long-term administration of other non-depolarizing
neuromuscular blocking agents in the ICU alone or in combination with
corticosteroid therapy has been reported. Therefore, for patients
receiving both neuromuscular blocking agents and corticosteroids, the
period of use of the neuromuscular blocking agent should be limited as
much as possible and only used in the setting where in the opinion of
the prescribing agent, the specific advantages outweigh the risk.
ZEMURON has not been studied in malignant hyperthermia-susceptible
patients. Because ZEMURON is always used with other agents, and the
occurrence of malignant hyperthermia during anesthesia is possible even
in the absence of known triggering agents, clinicians should be familiar
with early signs, confirmatory diagnosis and treatment of malignant
hyperthermia prior to the start of any anesthetic.
Conditions associated with an increased circulatory delayed time, e.g.,
cardiovascular disease or advanced age, may be associated with a delay
in onset time.
The overall analysis of ECG data in pediatric patients indicates that
the concomitant use of ZEMURON with general anesthetic agents can
prolong the QTc interval.
Non-depolarizing neuromuscular blocking agents have been found to
exhibit profound neuromuscular blocking effects in cachectic or
debilitated patients, patients with neuromuscular diseases and patients
with carcinomatosis. Certain inhalation anesthetics, particularly
enflurane and isoflurane, antibiotics, magnesium salts, lithium, local
anesthetics, procainamide and quinidine, have been shown to increase the
duration of neuromuscular block and decrease infusion requirements of
neuromuscular blocking agents. In these or other patients in whom
potentiation of neuromuscular block or difficulty with reversal may be
anticipated, a decrease from the recommended initial dose of ZEMURON
should be considered.
Resistance to non-depolarizing agents, consistent with up-regulation of
skeletal muscle acetylcholine receptors, is associated with burns,
disuse atrophy, denervation, and direct muscle trauma. Receptor
up-regulation may also contribute to the resistance to non-depolarizing
muscle relaxants, which sometimes develops in patients with cerebral
palsy, patients chronically receiving anticonvulsant agents, such as
carbamazepine or phenytoin, or with chronic exposure to non-depolarizing
agents. When ZEMURON (rocuronium bromide) is administered to these
patients, shorter durations of neuromuscular block may occur, and
infusion rates may be higher due to the development of resistance to
non-depolarizing muscular relaxants.
Severe acid-base and/or electrolyte abnormalities may potentiate or
cause resistance to the neuromuscular blocking action of ZEMURON. No
data are available in such patients, and no dosing recommendations can
ZEMURON, which has an acid pH, should not be mixed with alkaline
solutions (e.g. barbiturate solutions) in the same syringe or
administered simultaneously during intravenous infusion through the same
ZEMURON may be associated with increased pulmonary vascular resistance,
so caution is appropriate in patients with pulmonary hypertension or
valvular heart disease.
In patients with myasthenia gravis or myasthenic (Eaton-Lambert)
syndrome, small doses of non-depolarizing neuromuscular blocking agents
may have profound effects. In such patients, a peripheral nerve
stimulator and use of a small test dose may be of value in monitoring
the response to administration of muscle relaxants.
If extravasation occurs, it may be associated with signs or symptoms of
local irritation. The injection or infusion should be terminated
immediately and restarted in another vein.
In clinical trials, the most common adverse reactions (2 percent) are
transient hypotension and hypertension.
There are no controlled studies documenting the use of ZEMURON before or
after other non-depolarizing muscle relaxants. Interactions have been
observed when other non-depolarizing muscle relaxants have been
administered in succession.
The use of ZEMURON before succinylcholine, for the purpose of
attenuating some of the side effects of succinylcholine, has not been
Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/z/zemuron/zemuron_pi.pdf.
Merck’s Commitment to Hospital-Based Medicine
Merck is committed to scientific excellence, and the discovery and
development of innovative treatments for patient care in hospitals. We
strive to develop new solutions to help our hospital-based customers
deliver quality care to their patients.
Today’s Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside the United States and Canada.
Through our prescription medicines, vaccines, biologic therapies, and
consumer care and animal health products, we work with customers and
operate in more than 140 countries to deliver innovative health
solutions. We also demonstrate our commitment to increasing access to
healthcare through far-reaching policies, programs and partnerships. For
more information, visit www.merck.com
and connect with us on Twitter, Facebook and YouTube.
This news release includes “forward-looking statements” within the
meaning of the safe harbor provisions of the United States Private
Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of Merck’s management and are
subject to significant risks and uncertainties. There can be no
guarantees with respect to pipeline candidates that the candidates will
receive the necessary regulatory approvals or that they will be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and health care legislation in the
United States and internationally; global trends toward health care cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; Merck’s ability to accurately
predict future market conditions; manufacturing difficulties or delays;
financial instability of international economies and sovereign risk;
dependence on the effectiveness of Merck’s patents and other protections
for innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or
otherwise. Additional factors that could cause results to differ
materially from those described in the forward-looking statements can be
found in Merck’s 2011 Annual Report on Form 10-K and the company’s other
filings with the Securities and Exchange Commission (SEC) available at
the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for ZEMURON (rocuronium bromide)
Pam Eisele, 908-423-5042
Lainie Keller, 908-423-4187
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088