- Large reductions in the incidence of simulated cardiac
arrest caused by potentially lethal doses of fentanyl or
carfentanil were observed following a single IN dose of OPVEE
compared to a single dose of IN naloxone.
- Across scenarios of fentanyl or carfentanil overdoses,
simultaneous administration of four doses of IN naloxone (4×4 mg)
was needed to reduce the incidence of simulated cardiac arrest to
values approaching those obtained with a single dose of OPVEE
(3mg). Modeling predictions in chronic opioid users indicate that
the incidence of cardiac arrest following an intravenous (IV)
fentanyl overdose (2.97 mg) decreased from 78% in the absence of
intervention to 12% with OPVEE and 47% with a 4 mg IN dose of
naloxone.
RICHMOND, Va., June 18,
2024 /PRNewswire/ -- Indivior PLC (LSE/Nasdaq:
INDV) today announced the publication of a modeling study in
Frontiers in Psychiatry that predicts OPVEE (nalmefene) nasal
spray (2.7 mg nalmefene, equivalent to 3 mg of nalmefene
hydrochloride) resulted in larger reductions in the incidence of
simulated cardiac arrest following overdose from high doses of
potent synthetic opioids, compared to a 4 mg dose of IN
naloxone.
Model simulations were performed using a validated translational
model1 developed by the Division of Applied
Regulatory Science in the US Food and Drug Administration's Center
for Drug Evaluation and Research. In the present study, this
translational model was further expanded with data from
pharmacokinetic and pharmacodynamic studies with
OPVEE2,3 and IN naloxone pharmacokinetic
data.2 Simulations were conducted in 2000 virtual
patients. Following an IV dose of 2.97 mg fentanyl that resulted in
a 78% incidence of cardiac arrest in chronic opioid users, a single
administration of 4 mg IN naloxone reduced this rate to 47% while a
single dose of IN OPVEE reduced this rate to 12%. Four simultaneous
doses of 4 mg IN naloxone were needed to lower the incidence
of cardiac arrest to 17% which was comparable to that
observed following a single dose of OPVEE (12%).
Simulations in opioid naïve individuals illustrated the same
trend, although a higher incidence of cardiac arrest was predicted
in this population given the lack of tolerance to the respiratory
effects of opioids. Simulation of an IV fentanyl overdose
(2.97 mg) in opioid naïve individuals led to an incidence of
cardiac arrest of 90%, which was reduced to 26% with IN OPVEE and
to 68% after 4 mg IN naloxone, respectively.
More than 78,200 fatal opioid overdoses in the US were reported
in the one year ending December 2023,
with almost 92% (71,821) linked to synthetic
opioids.4 According to The State Unintentional
Drug Overdose Reporting System (SUDORS), the percentage of overdose
deaths in which naloxone was administered (22% in the US in
2022)5, suggests that naloxone might not have been
administered fast enough or at sufficient dosage.
"These modeling data are relevant considering today's overdose
epidemic with increasing prevalence of overdoses from illicitly
manufactured synthetic opioids, which can be extremely difficult to
reverse6," said Christian
Heidbreder, PhD, Chief Scientific Officer, Indivior, Inc.
"These simulated data serve two purposes. First, they quantify the
challenge of effectively reversing a synthetic opioid overdose.
Second, these data inform the approach for first responders (e.g.,
police, fire and rescue personnel, friends and family of the
overdose victim) in a community setting that does not benefit from
the ventilatory support available in an Emergency Department.
Without adequate ventilatory support, there is a limited time
window before hypoxic injury is irreversible and cardiac arrest
occurs; this can happen extremely rapidly with fentanyl and other
synthetic opioids7."
Similar effects were observed following opioid overdose
simulations using carfentanil, which is 100-times more potent than
fentanyl.8 These trends remain consistent for both
chronic and opioid naïve individuals overdosing on
carfentanil.
About OPVEE®
OPVEE (nalmefene) nasal spray
INDICATION
OPVEE nasal spray is an opioid antagonist indicated for the
emergency treatment of known or suspected overdose induced by
natural or synthetic opioids in adults and pediatric patients aged
12 years and older, as manifested by respiratory and/or central
nervous system depression.
OPVEE nasal spray is intended for immediate administration as
emergency therapy in settings where opioids may be present.
OPVEE nasal spray is not a substitute for emergency medical
care.
HIGHLIGHTED SAFETY INFORMATION
CONTRAINDICATIONS
Hypersensitivity to nalmefene or to any of the other
ingredients.
WARNINGS AND PRECAUTIONS
Risk of Recurrent Respiratory and Central Nervous System
Depression: While the duration of action of nalmefene is as long as
most opioids, a recurrence of respiratory depression is possible,
therefore, keep patient under continued surveillance and administer
repeat doses of OPVEE using a new nasal spray with each dose, as
necessary, while awaiting emergency medical assistance.
Limited Efficacy with Partial Agonists or Mixed
Agonist/Antagonists: Reversal of respiratory depression caused by
partial agonists or mixed agonists/antagonists, such as
buprenorphine and pentazocine, may be incomplete. Larger or repeat
doses may be required.
Precipitation of Severe Opioid Withdrawal: Use in patients who
are opioid dependent may precipitate opioid withdrawal. In
neonates, opioid withdrawal may be life-threatening if not
recognized and properly treated. Monitor for the development of
opioid withdrawal.
Risk of Cardiovascular (CV) Effects: Abrupt postoperative
reversal of opioid depression may result in adverse CV effects.
These events have primarily occurred in patients who had
preexisting CV disorders or received other drugs that may have
similar adverse CV effects. Monitor these patients closely in an
appropriate healthcare setting after use of nalmefene
hydrochloride.
Risk of Opioid Overdose from Attempts to Overcome the Blockade:
Attempts to overcome opioid withdrawal symptoms caused by opioid
antagonists with high or repeated doses of exogenous opioids may
lead to opioid intoxication and death.
ADVERSE REACTIONS
Most common adverse reactions (incidence at least 2%) are nasal
discomfort, headache, nausea, dizziness, hot flush, vomiting,
anxiety, fatigue, nasal congestion, throat irritation, rhinalgia,
decreased appetite, dysgeusia, erythema, and hyperhidrosis.
For more information about OPVEE and the full Prescribing
Information visit www.opvee.com.
About Indivior
Indivior is a global pharmaceutical company working to help
change patients' lives by developing medicines to treat substance
use disorders (SUD), opioid overdose and serious mental illnesses.
Our vision is that all patients around the world will have access
to evidence-based treatment for the chronic conditions and
co-occurring disorders of SUD. Indivior is dedicated to
transforming SUD from a global human crisis to a recognized and
treated chronic disease. Building on its global portfolio of opioid
use disorder treatments, Indivior has a pipeline of product
candidates designed to both expand on its heritage in this category
and potentially address other chronic conditions and co-occurring
disorders of SUD. Headquartered in the
United States in Richmond,
VA, Indivior employs more than 1,100 individuals globally
and its portfolio of products is available in 37 countries
worldwide. Visit www.indivior.com to learn more. Connect with
Indivior on LinkedIn by visiting
www.linkedin.com/company/indivior.
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Strauss DG, Li Z. Development of a Translational Model to Assess
the Impact of Opioid Overdose and Naloxone Dosing on Respiratory
Depression and Cardiac Arrest. Clin Pharmacol Ther. 2022
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Crisis. https://www.justice.gov/usao-edky/file/898991/dl.
Accessed May 3, 2024
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