WAYNE, Pa., May 18, 2017 /PRNewswire/ -- Egalet Corporation
(Nasdaq: EGLT) ("Egalet"), a fully integrated specialty
pharmaceutical company focused on developing, manufacturing and
commercializing innovative treatments for pain and other
conditions, presented data from a harm reduction model at the
36th American Pain Society (APS) annual meeting. The
model presents evidence that predicts that replacing
extended-release (ER) morphine products that are not in
abuse-deterrent formulations (ADFs) with ARYMO® ER
(morphine sulfate) extended-release tablets for oral use only –CII,
could lead to reductions in healthcare utilization including
emergency room visits, hospitalizations, substance abuse treatments
programs, treatment for IV injection-related medical complications
and death.
The objective of the model was to investigate the extent of
the potential to reduce opioid abuse/misuse and abuse-related
healthcare utilization by simulating, over five years, different
scenarios representing the replacement of non-ADFs of morphine with
ARYMO ER. Model inputs included: diagnosed opioid abuse prevalence
from claims data; ARYMO ER effectiveness in preventing exposure to
abuse via physical manipulation based on Category 1 data; drug
liking properties from clinical human abuse potential studies of
ARYMO ER; opioid non-medical use from the 2014 National Survey on
Drug Use and Health: Summary of National Findings; and route of
administration abuse data from RADARS® System Poison
Center in 2015. Using these inputs, and refining a related model
previously developed by White et al., researchers assessed the
potential impact of ARYMO ER on abuse-related healthcare
utilization such as emergency room visits, hospitalizations and
stays in substance abuse treatment centers in a privately-insured
patient population.
The analysis showed that introduction of ARYMO ER may be
associated with fewer abuse-related emergency department visits,
outpatient visits, hospitalizations, substance abuse treatments,
injection related diseases and deaths. While the model incorporates
actual medical and drug claims for diagnosed abusers, as well as
information on ARYMO ER's physical and chemical properties based on
its in vitro Category 1 abuse-deterrent data, the true extent of
the potential for harm reduction will not be known until ARYMO ER
has been marketed for a period of time and data are generated on
reduction of misuse and abuse in the real world.
"Model results present evidence that abuse-deterrent
formulations of extended-release morphine, such as ARYMO ER, may be
associated with fewer abuse-related emergency department visits,
outpatient visits, hospitalizations, substance abuse treatments,
injection-related diseases and deaths," said Alan G. White, Ph.D., managing principal of the
Analysis Group and author of the data presented. "Abuse-deterrent
opioids are prescribed by physicians to help manage their
patients' painful conditions and may lower the risk of
misuse/abuse, potentially leading to reductions in abuse-related
healthcare utilization."
The poster titled, "A harm reduction model to quantify potential
misuse/abuse reduction and misuse/abuse-related events avoided from
extended-release abuse deterrent opioids," was presented by
Dr. White today. Egalet also presented four other posters
today.
About The American Pain Society
Based in Chicago, the American Pain Society (APS) is a
multidisciplinary community that brings together a diverse group of
scientists, clinicians and other professionals to increase the
knowledge of pain and transform public policy and clinical practice
to reduce pain-related suffering. APS is the professional
home for investigators involved in all aspects of pain research
including basic, translational, clinical and health services
research to obtain the support and inspiration they need to
flourish professionally. APS strongly advocates expansion of
high quality pain research to help advance science to achieve
effective and responsible pain relief. For more information
on APS, visit www.americanpainsociety.org.
About Egalet
Egalet, a fully integrated
specialty pharmaceutical company, is focused on developing,
manufacturing and commercializing innovative treatments for pain
and other conditions. Egalet has three approved products:
ARYMO® ER (morphine sulfate) extended-release tablets
for oral use only –CII, developed using Egalet's proprietary
Guardian™ Technology, OXAYDO® (oxycodone HCI, USP)
tablets for oral use only –CII and SPRIX® (ketorolac
tromethamine) Nasal Spray. Using Guardian Technology Egalet is
developing a pipeline of clinical-stage, product candidates
including Egalet-002, an abuse-deterrent, extended-release, oral
oxycodone formulation for the management of pain severe enough to
require daily, around-the-clock, long-term opioid treatment and for
which alternative treatment options are inadequate. Guardian
Technology can be applied broadly across different classes of
pharmaceutical products and can be used to develop combination
products that include multiple active pharmaceutical ingredients
with similar or different release profiles. For full prescribing
information on ARYMO ER, including the boxed warning and medication
guide, please visit arymoer.com. For full prescribing information
on SPRIX, including the boxed warning and medication guide, please
visit sprix.com. For full prescribing information on OXAYDO,
including the boxed warning and medication guide, please visit
oxaydo.com. For additional information on Egalet, please visit
egalet.com.
IMPORTANT SAFETY INFORMATION ABOUT ARYMO ER
WARNING: ADDICTION,
ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION;
ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS
DEPRESSANTS
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Addiction, Abuse,
and Misuse ARYMO™ ER exposes patients and other
users to the risks of opioid addiction, abuse, and misuse, which
can lead to overdose and death. Assess each patient's risk prior to
prescribing ARYMO ER, and monitor all patients regularly for the
development of these behaviors or conditions
Life-Threatening
Respiratory Depression Serious, life-threatening, or fatal respiratory
depression may occur with use of ARYMO ER. Monitor for
respiratory depression, especially during initiation of ARYMO ER or
following a dose increase. Instruct patients to swallow ARYMO ER
tablets whole; crushing, chewing, or dissolving ARYMO ER tablets
can cause rapid release and absorption of a potentially fatal dose
of morphine
Accidental
Ingestion Accidental
ingestion of even one dose of ARYMO ER, especially by children, can
result in a fatal overdose of morphine.
Neonatal Opioid
Withdrawal Syndrome Prolonged use of ARYMO ER during pregnancy can
result in neonatal opioid withdrawal syndrome, which may be
life-threatening if not recognized and treated, and requires
management according to protocols developed by neonatology experts.
If opioid use is required for a prolonged period in a pregnant
woman, advise the patient of the risk of neonatal opioid withdrawal
syndrome and ensure that appropriate treatment will be
available.
Risks From
Concomitant Use With Benzodiazepines Or Other CNS
Depressants Concomitant use of opioids with
benzodiazepines or other central nervous system (CNS) depressants,
including alcohol, may result in profound sedation, respiratory
depression, coma, and death.
- Reserve
concomitant prescribing of ARYMO ER and benzodiazepines or
other CNS depressants for use in patients for whom alternative
treatment options are inadequate.
- Limit dosages
and durations to the minimum required.
- Follow patients
for signs and symptoms of respiratory depression and
sedation.
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Indications
ARYMO ER is indicated for the management of pain severe enough
to require daily, around-the-clock, long-term opioid treatment and
for which alternative treatment options are inadequate.
Limitations of Use
- Because of the risks of addiction, abuse, and misuse with
opioids, even at recommended doses, and because of the greater
risks of overdose and death with extended-release opioid
formulations, reserve ARYMO ER for use in patients for whom
alternative treatment options (e.g., non-opioid analgesics or
immediate-release opioids) are ineffective, not tolerated, or would
be otherwise inadequate to provide sufficient management of
pain.
- ARYMO ER is not indicated as an as-needed (prn) analgesic.
Contraindications
ARYMO ER is contraindicated in patients with: significant
respiratory depression; acute or severe bronchial asthma in an
unmonitored setting or in the absence of resuscitative equipment;
concurrent use of monoamine oxidase inhibitors (MAOIs) or use
within the last 14 days, known or suspected gastrointestinal
obstruction, including paralytic ileus; hypersensitivity (e.g.,
anaphylaxis) to morphine.
Warnings and Precautions
Addiction, Abuse, and Misuse: ARYMO ER contains morphine, a
Schedule II controlled substance. As an opioid, ARYMO ER exposes
its users to the risks of addiction, abuse, and misuse. As
extended-release products such as ARYMO ER deliver the opioid over
an extended period of time, there is a greater risk for overdose
and death due to the larger amount of morphine present.
Life-Threatening Respiratory Depression: Serious,
life-threatening, or fatal respiratory depression has been reported
with the use of opioids, even when used as recommended. Respiratory
depression, if not immediately recognized and treated, may lead to
respiratory arrest and death. Management of respiratory depression
may include close observation, supportive measures, and use of
opioid antagonists, depending on the patient's clinical status.
Carbon dioxide (CO2)
retention from opioid-induced respiratory depression can exacerbate
the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression
can occur at any time during the use of ARYMO ER, the risk is
greatest during the initiation of therapy or following a dosage
increase. Monitor patients closely for respiratory depression,
especially within the first 24-72 hours of initiating therapy with
and following dosage increases with ARYMO ER.
To reduce the risk of respiratory depression, proper dosing and
titration of ARYMO ER are essential. Overestimating the ARYMO ER
dose when converting patients from another opioid product can
result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of ARYMO ER, especially by
children, can result in respiratory depression and death due to an
overdose of morphine.
Neonatal Opioid Withdrawal Syndrome: Prolonged use of ARYMO ER
during pregnancy can result in withdrawal in the neonate. Neonatal
opioid withdrawal syndrome, unlike opioid withdrawal syndrome in
adults, may be life-threatening if not recognized and treated, and
requires management according to protocols developed by neonatology
experts. Observe newborns for signs of neonatal opioid withdrawal
syndrome and manage accordingly. Advise pregnant women using
opioids for a prolonged period of the risk of neonatal opioid
withdrawal syndrome and ensure that appropriate treatment will be
available.
Risks from Concomitant Use with Benzodiazepines or Other CNS
Depressants: Profound sedation, respiratory depression, coma, and
death may result from the concomitant use of ARYMO ER with
benzodiazepines or other CNS depressants (e.g., non-benzodiazepine
sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants,
general anesthetics, antipsychotics, other opioids, alcohol).
Because of these risks, reserve concomitant prescribing of these
drugs for use in patients for whom alternative treatment options
are inadequate.
Observational studies have demonstrated that concomitant use of
opioid analgesics and benzodiazepines increases the risk of
drug-related mortality compared to use of opioid analgesics alone.
Because of similar pharmacological properties, it is reasonable to
expect similar risk with the concomitant use of other CNS
depressant drugs with opioid analgesics.
Life-Threatening Respiratory Depression in Patients with Chronic
Pulmonary Disease or in Elderly, Cachectic, or Debilitated
Patients: The use of ARYMO ER in patients with acute or severe
bronchial asthma in an unmonitored setting or in the absence of
resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease: ARYMO ER-treated
patients with significant chronic obstructive pulmonary disease or
cor pulmonale, and those with a substantially decreased respiratory
reserve, hypoxia, hypercapnia, or pre-existing respiratory
depression are at increased risk of decreased respiratory drive
including apnea, even at recommended dosages of ARYMO ER.
Elderly, Cachectic, or Debilitated Patients:
Life-threatening respiratory depression is more likely to occur in
elderly, cachectic, or debilitated patients because they may have
altered pharmacokinetics or altered clearance compared to younger,
healthier patients.
Monitor such patients closely, particularly when initiating and
titrating ARYMO ER and when ARYMO ER is given concomitantly with
other drugs that depress respiration. Alternatively, consider the
use of non-opioid analgesics in these patients.
Interaction with Monoamine Oxidase Inhibitors: Monoamine oxidase
inhibitors (MAOIs) may potentiate the effects of morphine,
including respiratory depression, coma, and confusion. ARYMO ER
should not be used in patients taking MAOIs or within 14 days of
stopping such treatment.
Adrenal Insufficiency: Cases of adrenal insufficiency have been
reported with opioid use, more often following greater than one
month of use. Presentation of adrenal insufficiency may include
non-specific symptoms and signs including nausea, vomiting,
anorexia, fatigue, weakness, dizziness, and low blood pressure.
Severe Hypotension: ARYMO ER may cause severe hypotension
including orthostatic hypotension and syncope in ambulatory
patients. There is an increased risk in patients whose ability to
maintain blood pressure has already been compromised by a reduced
blood volume or concurrent administration of certain CNS depressant
drugs (e.g., phenothiazines or general anesthetics). Monitor these
patients for signs of hypotension after initiating or titrating the
dose of ARYMO ER. In patients with circulatory shock, ARYMO ER may
cause vasodilation that can further reduce cardiac output and blood
pressure. Avoid the use ARYMO ER in patients with circulatory
shock.
Risks of Use in Patients with Increased Intracranial Pressure,
Brain Tumors, Head Injury, or Impaired Consciousness: In patients
who may be susceptible to the intracranial effects of
CO2 retention (e.g., those with evidence of increased
intracranial pressure or brain tumors), ARYMO ER may reduce
respiratory drive, and the resultant CO2 retention can
further increase intracranial pressure. Monitor such patients for
signs of sedation and respiratory depression, particularly when
initiating therapy with ARYMO ER.
Opioids may also obscure the clinical course in a patient with a
head injury. Avoid the use of ARYMO ER in patients with
impaired consciousness or coma.
Difficulty in Swallowing and Risk for Obstruction in Patients at
Risk for a Small Gastrointestinal Lumen: Moistened ARYMO ER tablets
may become sticky leading to difficulty in swallowing the tablets.
Patients could experience choking, gagging, regurgitation and
tablets stuck in the throat. Instruct patients not to pre-soak,
lick, or otherwise wet ARYMO ER tablets prior to placing in the
mouth, and to take one tablet at a time with enough water to ensure
complete swallowing immediately after placing in the mouth.
Tablet stickiness and swelling may also predispose patients to
intestinal obstruction and exacerbation of diverticulitis. Patients
with underlying GI disorders such as esophageal cancer or colon
cancer with a small gastrointestinal lumen are at greater risk of
developing these complications. Consider use of an alternative
analgesic in patients who have difficulty swallowing and patients
at risk for underlying GI disorders resulting in a small
gastrointestinal lumen.
Risks of Use in Patients with Gastrointestinal Conditions: ARYMO
ER is contraindicated in patients with gastrointestinal
obstruction, including paralytic ileus. The morphine in ARYMO ER
may cause spasm of the sphincter of Oddi. Opioids may cause
increases in the serum amylase. Monitor patients with biliary tract
disease, including acute pancreatitis, for worsening symptoms.
Increased Risk of Seizures in Patients with Seizure Disorders:
The morphine in ARYMO ER may increase the frequency of seizures in
patients with seizure disorders, and may increase the risk of
seizures occurring in other clinical settings associated with
seizures. Monitor patients with a history of seizure disorders for
worsened seizure control during ARYMO ER therapy.
Withdrawal: Avoid the use of mixed agonist/antagonist (i.e.,
pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g.,
buprenorphine) analgesics in patients who have received or are
receiving a course of therapy with a full opioid agonist analgesic,
including ARYMO ER. In these patients, mixed agonists/antagonist
and partial agonist analgesics may reduce the analgesic effect
and/or may precipitate withdrawal symptoms.
When discontinuing ARYMO ER, gradually taper the dose. Do not
abruptly discontinue ARYMO ER.
Risks of Driving and Operating Machinery: ARYMO ER may impair
the mental or physical abilities needed to perform potentially
hazardous activities such as driving a car or operating machinery.
Warn patients not to drive or operate dangerous machinery unless
they are tolerant to the effects of ARYMO ER and know how they
will react to the medication.
Adverse Reactions
In clinical trials, the most common adverse reactions with
morphine sulfate extended-release formulations were constipation,
dizziness, sedation, nausea, vomiting, sweating, dysphoria, and
euphoric mood.
Additional Drug Interactions
Serotonergic Drugs: The concomitant use of opioids with other
drugs that affect the serotonergic neurotransmitter system has
resulted in serotonin syndrome.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics:
May reduce the analgesic effect of ARYMO ER and/or precipitate
withdrawal symptoms; avoid concomitant use.
Muscle Relaxants: Morphine may enhance the neuromuscular
blocking action of skeletal muscle relaxants and produce an
increased degree of respiratory depression.
Cimetidine: The concomitant use of cimetidine can potentiate
morphine effects and increase risk of hypotension, respiratory
depression, profound sedation, coma, and death.
Diuretics: Opioids can reduce the efficacy of diuretics by
inducing the release of antidiuretic hormone.
Anticholinergic Drugs: The concomitant use of anticholinergic
drugs may increase risk of urinary retention and/or severe
constipation, which may lead to paralytic ileus.
P-Glycoprotein (P-gp) Inhibitors: The concomitant use of P-gp
inhibitors can increase the exposure to morphine by about two-fold
and can increase risk of hypotension, respiratory depression,
profound sedation, coma, and death.
Use in Specific Populations
Pediatrics: The safety and effectiveness in pediatric patients
below the age of 18 have not been established.
Geriatrics: The pharmacokinetics of ARYMO ER have not been
studied in elderly patients. Elderly patients (aged 65 years or
older) may have increased sensitivity to morphine.
Hepatic Impairment: Morphine pharmacokinetics have been reported
to be significantly altered in patients with cirrhosis. Start these
patients with a lower than usual dosage of ARYMO ER and titrate
slowly while monitoring for signs of respiratory depression,
sedation, and hypotension.
Renal Impairment: Morphine pharmacokinetics are altered in
patients with renal failure. Start these patients with a lower than
usual dosage of ARYMO ER and titrate slowly while monitoring for
signs of respiratory depression, sedation, and hypotension.
Overdosage
Acute overdosage with morphine can be manifested by respiratory
depression, somnolence progressing to stupor or coma, skeletal
muscle flaccidity, cold and clammy skin, constricted pupils, and,
in some cases, pulmonary edema, bradycardia, hypotension, partial
or complete airway obstruction, atypical snoring, and death. Marked
mydriasis rather than miosis may be seen due to severe hypoxia in
overdose situations.
Safe Harbor
Statements included in this press release that are not historical
in nature and contain the words "anticipate," "believe,"
"estimate," "expect," "intend," "may," "plan," "predict,"
"project," "suggest," "target," "potential," "will," "would,"
"could," "should," "continue," "look forward to" and other similar
expressions are "forward-looking statements" within the meaning of
the Private Securities Litigation Reform Act of 1995. These
forward-looking statements, which include expectations in 2017 of
seeing continued growth with the dedicated SPRIX salesforce, the
potential addition of new OXAYDO dosage strengths and the
introduction of ARYMO ER to healthcare providers, are based on
management's current expectations, and are subject to known and
unknown uncertainties and risks. Actual results could differ
materially from those discussed due to a number of factors,
including, but not limited to: the success of Egalet's clinical
trials, including the timely recruitment of trial subjects and
meeting the timelines therefor; Egalet's ability to obtain
regulatory approval of its product candidates and the labeling
claims that Egalet believes are necessary or desirable for
successful commercialization of its products and product
candidates; Egalet's ability to maintain the intellectual property
position of its products and product candidates; Egalet's ability
to identify and reliance upon qualified third parties to
manufacture its products; Egalet's ability to commercialize its
products; and to do so successfully; the costs of commercialization
activities, including marketing, sales and distribution; the size
and growth potential of the markets for Egalet's products and
product candidates, and Egalet's ability to service those markets;
Egalet's ability to obtain reimbursement and third-party payor
contracts for its products; Egalet's ability to service its debt
obligations; Egalet's ability to raise additional funds to execute
its business plan and growth strategy on terms acceptable to
Egalet, if at all; Egalet's ability to find and hire qualified
sales professionals; the rate and degree of receptivity in the
marketplace and among physicians to Egalet's products; the success
of products which compete with Egalet's that are or become
available; general market conditions; and the Risk Factors set
forth in Egalet's Annual Report on Form 10-K and Quarterly Reports
on Form 10-Q filed with the United States Securities and Exchange
Commission (SEC) and in other filings Egalet makes with the SEC
from time to time. In addition, the forward-looking
statements included in this press release represent Egalet's views
only as of the date hereof. Egalet anticipates that subsequent
events and developments may cause its views to change. While Egalet
may elect to update these forward-looking statements at some point
in the future, it specifically disclaims any obligation to update
or revise any forward-looking-statements contained in this press
release whether as a result of new information or future events,
except as may be required by law.
Investor and Media Contact:
E. Blair Clark-Schoeb
Senior Vice President, Communications
Email: bcs@egalet.com
Tel: 484-259-7370
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SOURCE Egalet Corporation