WAYNE, Pa.,
June 20, 2017 /PRNewswire/
-- Egalet Corporation (Nasdaq: EGLT) ("Egalet"), a fully
integrated specialty pharmaceutical company focused on developing,
manufacturing and marketing innovative treatments for pain and
other conditions, today announced that it received a complete
response letter (CRL) from the U.S. Food and Drug Administration
(FDA) regarding the prior approval supplement (PAS) of
OXAYDO® (oxycodone HCl, USP) tablets C-II in 10 mg and
15 mg dosage strengths.
The FDA has requested more information
regarding the effect of food on OXAYDO 15 mg and the intranasal
abuse-deterrent properties of OXAYDO 10 mg and 15 mg. Egalet will
work with the FDA to determine the path forward.
OXAYDO is an immediate-release oral formulation of
oxycodone HCl indicated for the management of acute and chronic,
moderate to severe pain where the use of an opioid analgesic is
appropriate. OXAYDO, initially approved in
December 2015 in 5 mg
and 7.5 mg dosage strengths, is designed
to discourage intranasal abuse. Through its novel, patent protected
formulation, OXAYDO contains inactive ingredients that may cause
nasal burning if manipulated and snorted. There is no evidence that
OXAYDO has reduced abuse liability compared to immediate-release
oxycodone.
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 –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
OXAYDO
WARNING: ADDICTION, ABUSE, AND MISUSE;
LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;
NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4
INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR
OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
OXAYDO 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 OXAYDO,
and monitor all patients regularly for the development of these
behaviors and conditions.
Life-Threatening Respiratory
Depression
Serious, life-threatening, or fatal respiratory
depression may occur with use of OXAYDO. Monitor for respiratory
depression, especially during initiation of OXAYDO or following a
dose increase.
Accidental Ingestion
Accidental ingestion of even one dose of OXAYDO,
especially by children, can result in a fatal overdose of
oxycodone.
Neonatal Opioid Withdrawal
Syndrome
Prolonged use of OXAYDO 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.
Cytochrome P450 3A4 Interaction
The concomitant use of OXAYDO with all cytochrome
P450 3A4 inhibitors may result in an increase in oxycodone plasma
concentrations, which could increase or prolong adverse reactions
and may cause potentially fatal respiratory depression. In
addition, discontinuation of a concomitantly used cytochrome P450
3A4 inducer may result in an increase in oxycodone plasma
concentration. Monitor patients receiving OXAYDO
and any CYP3A4 inhibitor or
inducer.
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 OXAYDO 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.
|
Indications and Usage
OXAYDO is indicated for the management of acute and
chronic pain severe enough to require an opioid analgesic and for
which alternative treatments are inadequate.
Limitations of Use
Because of the risks of addiction, abuse, and misuse with
opioids, even at recommended doses, reserve OXAYDO for use in
patients for whom alternative treatment options (e.g., non-opioid
analgesics or opioid combination products):
- Have not been tolerated, or are not expected to be
tolerated,
- Have not provided adequate analgesia, or are not expected
to provide adequate analgesia.
Contraindications
OXAYDO is contraindicated in patients with significant
respiratory depression; acute or severe bronchial asthma in an
unmonitored setting or in the absence of resuscitative equipment;
known or suspected gastrointestinal obstruction, including
paralytic ileus; hypersensitivity to oxycodone, oxycodone salts, or
any components of the product (e.g., anaphylaxis).
Warnings and Precautions
Addiction, Abuse, and Misuse
OXAYDO contains oxycodone, a Schedule II controlled
substance. As an opioid, OXAYDO exposes users to the risks of
addiction, abuse, and misuse.
Although the risk of addiction in any individual is
unknown, it can occur in patients appropriately prescribed OXAYDO.
Addiction can occur at recommended dosages and if the drug is
misused or abused.
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.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of OXAYDO 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.
Risks of Concomitant Use or Discontinuation of Cytochrome
P450 3A4 Inhibitors and Inducers
Concomitant use of OXAYDO with a CYP3A4 inhibitor, such as
macrolide antibiotics (e.g., erythromycin), azole-antifungal agents
(e.g., ketoconazole), and protease inhibitors (e.g., ritonavir),
may increase plasma concentrations of oxycodone and prolong opioid
adverse reactions, which may cause potentially fatal respiratory
depression, particularly when an inhibitor is added after a stable
dose of OXAYDO is achieved. Similarly, discontinuation of a
CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in
OXAYDO-treated patients may increase oxycodone plasma
concentrations and prolong opioid adverse reactions. When using
OXAYDO with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in
OXAYDO-treated patients, monitor patients closely at frequent
intervals and consider dosage reduction of OXAYDO until stable drug
effects are achieved.
Concomitant use of OXAYDO with CYP3A4 inducers or
discontinuation of a CYP3A4 inhibitor could decrease oxycodone
plasma concentrations, decrease opioid efficacy or, possibly, lead
to a withdrawal syndrome in a patient who had developed physical
dependence to oxycodone.
Risks from Concomitant Use with Benzodiazepines or Other
CNS Depressants
Profound sedation, respiratory depression, coma, and death
may result from the concomitant use of OXAYDO 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.
Advise both patients and caregivers about the risks of
respiratory depression and sedation when OXAYDO is used with
benzodiazepines or other CNS depressants (including alcohol and
illicit drugs). Advise patients not to drive or operate heavy
machinery until the effects of concomitant use of the
benzodiazepine or other CNS depressant have been determined. Screen
patients for risk of substance use disorders, including opioid
abuse and misuse, and warn them of the risk for overdose and death
associated with the use of additional CNS depressants including
alcohol and illicit drugs.
Life-Threatening Respiratory Depression in Patients with
Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated
Patients
The use of OXAYDO 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:
OXAYDO-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 OXAYDO.
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 OXAYDO and when OXAYDO is given
concomitantly with other drugs that depress respiration.
Alternatively, consider the use of non-opioid analgesics in these
patients.
Adrenal Insufficiency
Cases of adrenal insufficiency have been reported with
opioid use, more often following greater than one month of
use.
Severe Hypotension
OXAYDO may cause severe hypotension including orthostatic
hypotension and syncope in ambulatory patients. There is 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 dosage of OXAYDO. In patients with circulatory shock,
OXAYDO may cause vasodilation that can further reduce cardiac
output and blood pressure. Avoid the use of OXAYDO 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), OXAYDO 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 OXAYDO.
Opioids may also obscure the clinical course in a patient
with a head injury. Avoid the use of OXAYDO in patients with
impaired consciousness or coma.
Risks of Use in Patients with Gastrointestinal
Conditions
OXAYDO is contraindicated in patients with known or
suspected gastrointestinal obstruction, including paralytic
ileus.
The oxycodone in OXAYDO may cause spasm of the sphincter
of Oddi. Opioids may cause increases in serum amylase. Monitor
patients with biliary tract disease, including acute pancreatitis,
for worsening symptoms.
Increased Risk of Seizures in Patients with Seizure
Disorders
The oxycodone in OXAYDO 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 OXAYDO therapy.
Withdrawal
Avoid the use of mixed agonist/antagonist (e.g.,
pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g.,
buprenorphine) analgesics in patients who are receiving a full
opioid agonist analgesic, including OXAYDO. In these patients,
mixed agonist/antagonist and partial agonist analgesics may reduce
the analgesic effect and/or precipitate withdrawal
symptoms.
When discontinuing OXAYDO in a physically-dependent
patient, gradually taper the dosage. Do not abruptly discontinue
OXAYDO in these patients.
Risks of Driving and Operating Machinery
OXAYDO 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
OXAYDO and know how they will react to the medication.
Adverse Reactions
Serious adverse reactions that may be associated with
OXAYDO include: respiratory depression, respiratory arrest,
circulatory depression, cardiac arrest, hypotension, and/or
shock.
The most frequent of the adverse reactions include nausea,
constipation, vomiting, headache, and pruritus.
Additional Drug Interactions
Serotonergic Drugs
The concomitant use of opioids with other drugs that
affect the serotonergic neurotransmitter system has resulted in
serotonin syndrome.
Monoamine Oxidase Inhibitors (MAOIs)
MAOI interactions with opioids may manifest as serotonin
syndrome or opioid toxicity (e.g., respiratory depression,
coma).
Mixed Agonist/Antagonist and Partial Agonist Opioid
Analgesics
May reduce the analgesic effect of OXAYDO and/or
precipitate withdrawal symptoms.
Muscle Relaxants
Oxycodone may enhance the neuromuscular blocking action of
skeletal muscle relaxants and produce an increased degree of
respiratory depression.
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.
Use in Specific Populations
Pregnancy
Prolonged use of opioid analgesics during pregnancy may
cause neonatal opioid withdrawal syndrome. There are no available
data with OXAYDO in pregnant women to inform a drug-associated risk
for major birth defects and miscarriage.
Labor or Delivery
Opioids cross the placenta and may produce respiratory
depression and psycho-physiologic effects in neonates. An opioid
antagonist, such as naloxone, must be available for reversal of
opioid-induced respiratory depression in the neonate. OXAYDO is not
recommended for use in pregnant women during or immediately prior
to labor, when other analgesic techniques are more appropriate.
Opioid analgesics, including OXAYDO, can prolong labor through
actions which temporarily reduce the strength, duration, and
frequency of uterine contractions. However, this effect is not
consistent and may be offset by an increased rate of cervical
dilation, which tends to shorten labor. Monitor neonates exposed to
opioid analgesics during labor for signs of excess sedation and
respiratory depression.
Lactation
Oxycodone is present in breast milk. Because of the
potential for serious adverse reactions, including excess sedation
and respiratory depression in a breastfed infant, breastfeeding is
not recommended during treatment with OXAYDO.
Females and Males of Reproductive Potential
Chronic use of opioids may cause reduced fertility in
females and males of reproductive potential. It is not known
whether these effects on fertility are
reversible.
Pediatric Use
The safety, effectiveness, and pharmacokinetics of OXAYDO
in pediatric patients below the age of 18 have not been
established.
Geriatric Use
Elderly patients (aged 65 years or older) may have
increased sensitivity to oxycodone. In general, use caution when
selecting a dosage for an elderly patient, usually starting at the
low end of the dosing range, reflecting the greater frequency of
decreased hepatic, renal, or cardiac function and of concomitant
disease or other drug therapy.
Respiratory depression is the chief risk for elderly
patients treated with opioids, and has occurred after large initial
doses were administered to patients who were not opioid-tolerant or
when opioids were co-administered with other agents that depress
respiration. Titrate the dosage of OXAYDO slowly in geriatric
patients and monitor closely for signs of central nervous system
and respiratory depression.
Hepatic Impairment
Since oxycodone is extensively metabolized in the liver,
its clearance may decrease in patients with hepatic impairment.
Follow a conservative approach to initiate dosing in patients with
hepatic impairment. Monitor patients closely and adjust the dose
based on clinical response.
Renal Impairment
Information from oxycodone HCl indicates that patients
with renal impairment had higher plasma concentrations of oxycodone
than subjects with normal renal function. Use a conservative
approach to initiate dosing in patients with renal impairment.
Monitor patients closely and adjust the dose based on clinical
response.
Safe Harbor
Statements included in this press release (including but not
limited to upcoming milestones) 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 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 Egalet's 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 Egalet's 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 that compete with Egalet's that are or become
available; general market conditions; and other 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. 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
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/egalet-receives-complete-response-letter-from-us-food-and-drug-administration-for-prior-approval-supplement-for-10-mg-and-15-mg-dosage-strengths-of-oxaydo-300476520.html
SOURCE Egalet Corporation