HAYWARD, Calif., Aug. 7, 2017 /PRNewswire/ -- Impax
Laboratories, Inc. (NASDAQ: IPXL), today announced a
Settlement Agreement (the "Contract Settlement Agreement") to
resolve a contract dispute relating to an agreement entered into in
June 2010 among Endo International
plc ("Endo"), Penwest Pharmaceuticals and Impax regarding the
Abbreviated New Drug Application litigation related to the original
formulation of Opana® ER (oxymorphone hydrochloride) CII
Extended-Release ("ER") tablets (the "2010 ANDA Settlement"). In
the 2010 ANDA Settlement, Impax obtained a non-exclusive license to
certain then-existing and future Endo patents. Orange Book listed
patents for Opana ER extend until November
2029.
The Contract Settlement Agreement includes an amendment to the
2010 ANDA Settlement, whereby Impax agrees to pay Endo a royalty
rate that splits Impax's gross profits for its sales of oxymorphone
hydrochloride CII ER products, commencing January 1, 2018. The royalty will be
eliminated based on certain commercial conditions. Further terms of
the settlement were not disclosed.
"We are pleased to have reached an agreement to settle this
outstanding contractual litigation," said Paul Bisaro, President and Chief Executive
Officer of Impax. "We will continue to make available our generic
version of original Opana ER (oxymorphone hydrochloride) CII ER
tablets for prescribing physicians that prefer this product to
treat patients."
Combined reported net sales of Endo's new formulation of Opana
ER and Impax's generic oxymorphone hydrochloride ER tablets
(AB-rated to original formulation of Opana ER) were $229 million for the last twelve months ended
March 31, 2017.
INDICATIONS AND USAGE
Oxymorphone Hydrochloride
Extended-Release Tablets are 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 Usage
- 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 Oxymorphone Hydrochloride Extended-Release
tablets 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.
- Oxymorphone Hydrochloride Extended-Release Tablets are not
indicated as an as-needed (prn) analgesic.
(OXYMORPHONE HYDROCHLORIDE) CII ER tablets IMPORTANT
SAFETY INFORMATION
BOXED WARNING
WARNING: ADDICTION, ABUSE, AND MISUSE;
LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;
NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL; and
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS
DEPRESSANTS
Addiction, Abuse, and Misuse
Oxymorphone Hydrochloride Extended-Release Tablets expose 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 Oxymorphone Hydrochloride
Extended-Release Tablets, 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 Oxymorphone Hydrochloride Extended-Release
Tablets. Monitor for respiratory depression, especially during
initiation of Oxymorphone Hydrochloride Extended-Release Tablets or
following a dose increase. Instruct patients to swallow Oxymorphone
Hydrochloride Extended-Release Tablets whole; crushing, chewing, or
dissolving Oxymorphone Hydrochloride Extended-Release Tablets can
cause rapid release and absorption of a potentially fatal dose of
oxymorphone.
Accidental Ingestion
Accidental ingestion of even one dose of Oxymorphone Hydrochloride
Extended-Release Tablets, especially by children, can result in
fatal overdose of oxymorphone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of Oxymorphone Hydrochloride Extended-Release Tablets
during pregnancy can result in neonatal opioid withdrawal syndrome,
which may be life-threatening if not recognized 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.
Interaction with Alcohol
Instruct patients not to consume alcoholic beverages or use
prescription or non-prescription products that contain alcohol
while taking Oxymorphone Hydrochloride Extended-Release Tablets.
The co-ingestion of alcohol with Oxymorphone Hydrochloride may
result in increased plasma levels and a potentially fatal overdose
of oxymorphone.
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 Oxymorphone Hydrochloride
Extended-Release Tablets 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.
CONTRAINDICATIONS
Oxymorphone Hydrochloride
Extended-Release Tablets are contraindicated in patients with:
- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting or
in the absence of resuscitative equipment
- Hypersensitivity (e.g., anaphylaxis) to oxymorphone, any other
ingredients in Oxymorphone Hydrochloride Extended-Release
Tablets
- Moderate and severe hepatic impairment
- Known or suspected gastrointestinal obstruction, including
paralytic ileus
WARNINGS AND PRECAUTIONS
Addiction, Abuse, and
Misuse
Oxymorphone Hydrochloride Extended-Release Tablets
contain oxymorphone, a Schedule II controlled substance. As an
opioid, Oxymorphone Hydrochloride Extended-Release Tablets expose
users to the risks of addiction, abuse, and misuse. Because
extended-release products such as Oxymorphone Hydrochloride
Extended-Release Tablets deliver the opioid over an extended period
of time, there is a greater risk for overdose and death due to the
larger amount of oxymorphone present.
Abuse, or misuse of Oxymorphone Hydrochloride Extended-Release
Tablets by crushing, chewing, snorting, or injecting the dissolved
product will result in the uncontrolled delivery of the oxymorphone
and can result in overdose and death.
Opioids are sought by drug abusers and people with addiction
disorders and are subject to criminal diversion. Consider these
risks when prescribing or dispensing Oxymorphone Hydrochloride
Extended-Release Tablets. Strategies to reduce these risks include
prescribing the drug in the smallest appropriate quantity and
advising the patient on the proper disposal of unused drug. Contact
local state professional licensing board or state controlled
substances authority for information on how to prevent and detect
abuse or diversion of this product.
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 from opioid use, if not immediately recognized and
treated, may lead to respiratory arrest and death.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of
Oxymorphone Hydrochloride Extended-Release Tablets during pregnancy
can result in withdrawal signs 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.
Risks from Concomitant Use with Benzodiazepines or Other CNS
Depressants
Patients must not consume alcoholic beverages or
prescription or non-prescription products containing alcohol while
on Oxymorphone Hydrochloride Extended-Release Tablet therapy. The
co-ingestion of alcohol with Oxymorphone Hydrochloride
Extended-Release Tablets may result in increased plasma levels and
a potentially fatal overdose of oxymorphone.
Profound sedation, respiratory depression, coma, and death may
result from the concomitant use of Oxymorphone Hydrochloride
Extended-Release Tablets 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.
Risk of Life-Threatening Respiratory Depression in Patients
with Chronic Pulmonary Disease or in Elderly, Cachectic, or
Debilitated Patients
The use of Oxymorphone Hydrochloride
Extended-Release Tablets in patients with acute or severe bronchial
asthma in unmonitored setting or in the absence of resuscitative
equipment is contraindicated.
Patients with Chronic Pulmonary Disease: Oxymorphone
Hydrochloride Extended-Release Tablets 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 Oxymorphone Hydrochloride
Extended-Release Tablets.
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 Oxymorphone Hydrochloride Extended-Release Tablets and
when Oxymorphone Hydrochloride Extended-Release Tablets are given
concomitantly with other drugs that depress respiration.
Alternatively, consider the use of non-opioid analgesics in these
patients.
Anaphylaxis, Angioedema, and Other Hypersensitivity
Reactions
Potentially life-threatening hypersensitivity
reactions, including anaphylaxis and angioedema, have occurred in
patients treated with Oxymorphone Hydrochloride Extended-Release
Tablets in the postmarket setting. The most commonly described
clinical features in these reports were swelling of the face, eyes,
mouth, lips, tongue, hands, and/or throat; dyspnea; hives,
pruritus, and/or rash; and nausea/vomiting. If anaphylaxis or other
hypersensitivity occurs, stop administration of Oxymorphone
Hydrochloride Extended-Release Tablets immediately, discontinue
Oxymorphone Hydrochloride Extended-Release Tablets permanently, and
do not rechallenge with any formulation of oxymorphone. Advise
patients to seek immediate medical attention if they experience any
symptoms of a hypersensitivity reaction.
Adrenal Insufficiency
If adrenal insufficiency is
diagnosed, treat with physiologic replacement doses of
corticosteroids. Wean the patient off of the opioid to allow
adrenal function to recover and continue corticosteroid treatment
until adrenal function recovers.
Use in Patients with Hepatic Impairment
Oxymorphone
Hydrochloride Extended-Release Tablets are contraindicated in
patients with moderate or severe hepatic impairment. In patients
with mild hepatic impairment reduce the starting dose to the lowest
dose and monitor for signs of respiratory and central nervous
system depression.
Severe Hypotension
Monitor these patients for signs of
hypotension after initiating or titrating the dosage of Oxymorphone
Hydrochloride Extended-Release Tablets. In patients with
circulatory shock, Oxymorphone Hydrochloride Extended-Release
Tablets may cause vasodilation that can further reduce cardiac
output and blood pressure. Avoid the use of Oxymorphone
Hydrochloride Extended-Release Tablets in patients with circulatory
shock.
Risks of Use in Patients with Increased Intracranial
Pressure, Brain Tumors, Head Injury, or Impaired
Consciousness
Monitor such patients for signs of sedation
and respiratory depression, particularly when initiating therapy
with Oxymorphone Hydrochloride Extended-Release Tablets.
Opioids may also obscure the clinical course in a patient with a
head injury. Avoid the use of Oxymorphone Hydrochloride
Extended-Release Tablets in patients with impaired consciousness or
coma.
Risks of Use in Patients with Gastrointestinal
Conditions
Oxymorphone Hydrochloride Extended-Release
Tablets are contraindicated in patients with known or suspected
gastrointestinal obstruction, including paralytic ileus.
The oxymorphone in Oxymorphone Hydrochloride Extended-Release
Tablets 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
Monitor patients with a history of seizure
disorders for worsened seizure control during Oxymorphone
Hydrochloride Extended-Release Tablets therapy.
ADVERSE REACTIONS
Adverse reactions in ≥2% of patients
in placebo-controlled trials: nausea, constipation, dizziness,
somnolence, vomiting, pruritus, headache, sweating increased, dry
mouth, sedation, diarrhea, insomnia, fatigue, appetite decreased,
and abdominal pain.
DRUG INTERACTIONS
Serotonergic Drugs: Concomitant use
may result in serotonin syndrome. Discontinue Oxymorphone
Hydrochloride Extended-Release Tablets if serotonin syndrome is
suspected.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics:
Avoid use with Oxymorphone Hydrochloride Extended-Release Tablets
because they may reduce analgesic effect of Oxymorphone
Hydrochloride Extended-Release Tablets or precipitate withdrawal
symptoms.
Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects
of oxymorphone. Avoid concomitant use in patients receiving MAOIs
or within 14 days of stopping treatment with an MAOI.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Prolonged use of opioid analgesics during pregnancy may cause
neonatal opioid withdrawal syndrome. Available data with
Oxymorphone Hydrochloride Extended-Release Tablets in pregnant
women are insufficient to inform a drug-associated risk for major
birth defects and miscarriage.
Clinical Considerations
Fetal/Neonatal adverse reactions
Prolonged use of opioid
analgesics during pregnancy for medical or nonmedical purposes may
cause fetal-neonatal physical dependence and neonatal withdrawal
syndrome shortly after birth. Observe newborns for symptoms of
neonatal opioid withdrawal syndrome, and manage accordingly.
Labor or delivery
Opioids cross the placenta and may
produce respiratory depression and pyscho-physiologic effects in
neonates. An opioid antagonist, such as naloxone must be available
for reversal of opioid-induced respiratory depression in the
neonate. Oxymorphone Hydrochloride Extended-Release Tablets are not
recommended for use in women during and immediately prior to labor,
when use of shorter acting analgesics or other analgesic techniques
are more appropriate. Monitor neonates exposed to opioid analgesics
during labor for signs of excess sedation and respiratory
depression.
Lactation
Risk Summary
There is no information regarding the presence of oxymorphone in
human milk, the effects on the breastfed infant, or the effects on
milk production. Because of the potential for serious adverse
reactions, including excess sedation and respiratory depression in
a breastfed infant, advise patients that breastfeeding is not
recommended during treatment with Oxymorphone Hydrochloride
Extended-Release Tablets.
Clinical Considerations
Monitor infants exposed to Oxymorphone Hydrochloride
Extended-Release Tablets through breast milk for excess sedation
and respiratory depression. Withdrawal symptoms can occur in
breastfed infants when maternal administration of an opioid
analgesic is stopped, or when breast-feeding is stopped.
Females and Males Reproductive
Potential
Infertility
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 and effectiveness of
Oxymorphone Hydrochloride Extended-Release Tablets in patients
below the age of 18 years have not been established.
Geriatric Use
Of the total number of subjects in
clinical studies of Oxymorphone Hydrochloride Extended-Release
Tablets, 27% were 65 and over, while 9% were 75 and over. No
overall differences in effectiveness were observed between these
subjects and younger subjects. There were several adverse events
that were more frequently observed in subjects 65 and over compared
to younger subjects. These adverse events included dizziness,
somnolence, confusion, and nausea. On average, age greater than 65
years was associated with a 1.4-fold increase in oxymorphone AUC
and a 1.5-fold increase in Cmax.
Oxymorphone is known to be substantially excreted by the kidney
and the risk of adverse reactions to this drug may be greater in
patients with impaired renal function. Because the elderly patients
are more likely to have decreased renal function, care should be
taken in dose selection, and it may be useful to monitor renal
function.
Hepatic Impairment
Patients with mild hepatic
impairment have an increase in oxymorphone bioavailability of
1.6-fold.
Renal Impairment
Patients with moderate to severe
renal impairment were shown to have an increase in oxymorphone
bioavailability compared to the subjects with normal renal
function.
See Full Prescribing Information , for complete drug information
including additional important risk information about oxymorphone
hydrochloride extended-release tablets.
About Impax Laboratories, Inc.
Impax Laboratories,
Inc. (Impax) is a specialty pharmaceutical company applying its
formulation expertise and drug delivery technology to the
development of controlled-release and specialty generics in
addition to the development of central nervous system disorder
branded products. Impax markets its generic products through its
Impax Generics division and markets its branded products through
the Impax Specialty Pharma division. Additionally, where
strategically appropriate, Impax develops marketing partnerships to
fully leverage its technology platform and pursues partnership
opportunities that offer alternative dosage form technologies, such
as injectables, nasal sprays, inhalers, patches, creams, and
ointments. For more information, please visit the Company's Web
site at: www.impaxlabs.com.
"Safe Harbor" statement under the Private Securities
Litigation Reform Act of 1995:
To the extent any statements
made in this news release contain information that is not
historical; these statements are forward-looking in nature and
express the beliefs and expectations of management. Such statements
are based on current expectations and involve a number of known and
unknown risks and uncertainties that could cause the Company's
future results, performance, or achievements to differ
significantly from the results, performance, or achievements
expressed or implied by such forward-looking statements. Such risks
and uncertainties include, but are not limited to: fluctuations in
the Company's operating results and financial condition; the
volatility of the market price of the Company's common stock; the
Company's ability to successfully develop and commercialize
pharmaceutical products in a timely manner; the impact of
competition; the effect of any manufacturing or quality control
problems; the Company's ability to manage its growth; risks
related to acquisitions of or investments in technologies, products
or businesses; risks relating to goodwill and intangibles; the
reduction or loss of business with any significant customer; the
substantial portion of the Company's total revenues derived from
sales of a limited number of products; the impact of consolidation
of the Company's customer base; the Company's ability to sustain
profitability and positive cash flows; the impact of any valuation
allowance on the Company's deferred tax assets; the restrictions
imposed by the Company's credit facility and indenture; the
Company's level of indebtedness and liabilities and the potential
impact on cash flow available for operations; the availability of
additional funds in the future; any delays or unanticipated
expenses in connection with the operation of the Company's
manufacturing facilities; the effect of foreign economic,
political, legal and other risks on the Company's operations
abroad; the uncertainty of patent litigation and other legal
proceedings; the increased government scrutiny on the Company's
agreements to settle patent litigations, product development risks
and the difficulty of predicting FDA filings and approvals;
consumer acceptance and demand for new pharmaceutical products; the
impact of market perceptions of the Company and the safety and
quality of the Company's products; the Company's determinations to
discontinue the manufacture and distribution of certain products;
the Company's ability to achieve returns on its investments in
research and development activities; changes to FDA approval
requirements; the Company's ability to successfully conduct
clinical trials; the Company's reliance on third parties to conduct
clinical trials and testing; the Company's lack of a license
partner for commercialization of Numient® (IPX066) outside of
the United States; impact of
illegal distribution and sale by third parties of counterfeits or
stolen products; the availability of raw materials and impact of
interruptions in the Company's supply chain; the Company's policies
regarding returns, rebates, allowances and chargebacks; the use of
controlled substances in the Company's products; the effect of
current economic conditions on the Company's industry, business,
results of operations and financial condition; disruptions or
failures in the Company's information technology systems and
network infrastructure caused by third party breaches or other
events; the Company's reliance on alliance and collaboration
agreements; the Company's reliance on licenses to proprietary
technologies; the Company's dependence on certain employees; the
Company's ability to comply with legal and regulatory requirements
governing the healthcare industry; the regulatory environment; the
effect of certain provisions in the Company's government contracts;
the Company's ability to protect its intellectual property;
exposure to product liability claims; changes in tax regulations;
uncertainties involved in the preparation of the Company's
financial statements; the Company's ability to maintain an
effective system of internal control over financial reporting; the
effect of terrorist attacks on the Company's business; the location
of the Company's manufacturing and research and development
facilities near earthquake fault lines; expansion of social media
platforms and other risks described in the Company's periodic
reports filed with the Securities and Exchange Commission.
Forward-looking statements speak only as to the date on which they
are made, and the Company undertakes no obligation to update
publicly or revise any forward-looking statement, regardless of
whether new information becomes available, future developments
occur or otherwise.
Contact:
Mark
Donohue
Investor Relations and Corporate Communications
(215) 558-4526
www.impaxlabs.com
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SOURCE Impax Laboratories, Inc.