Collegium Pharmaceutical, Inc. (Nasdaq: COLL), a specialty
pharmaceutical company committed to being the leader in responsible
pain management, today announced that five poster presentations
highlighting data regarding its product portfolio will be presented
at the 14th Annual PAINWeek National Conference taking place
virtually September 11-13th.
Poster Presentations
Poster # 1: |
Nonmedical Use of Xtampza® ER versus Other
Oxycodone-Containing Products |
Authors: |
Jody L. Green, PhD; Rebekkah
Robbins, MPH; Taryn Dailey-Govoni, MPH, Stephen F. Butler, PhD |
|
|
Poster # 2: |
Perception of XTAMPZA® ER
and Other Abuse-deterrent Opioid Formulations on the
Internet |
Authors: |
Joshua C. Black, Zachary R.
Margolin, Janetta L. Iwanicki, Richard C. Dart |
|
|
Poster # 3: |
The Diversion and Street
Price of XTAMPZA® ER Relative to Other Prescription
Opioids |
Authors: |
Stevan Geoffrey Severtson,
Zachary R. Margolin, Kevin May, Janetta L. Iwanicki, Richard C.
Dart |
|
|
Poster # 4: |
Abuse of XTAMPZA® ER
Relative to Other Opioid Analgesics |
Authors: |
Stevan Geoffrey Severtson,
Heather Olsen, Janetta L. Iwanicki, Richard C. Dart |
|
|
Poster # 5: |
Abuse of Tapentadol Among
Individuals Entering Treatment for Opioid Use
Disorder |
Authors: |
Stevan Geoffrey Severtson,
Heather Olsen, Janetta L. Iwanicki, Richard C. Dart |
Xtampza® ER, Nucynta® ER and Nucynta® can be
abused or misused, and carry a risk of addiction. These products
are intended for use only in appropriate pain patients and only
when other treatment alternatives are inadequate. Use of
Xtampza® ER, Nucynta® ER and Nucynta® can result in
serious, life-threatening or fatal respiratory depression, even
when used exactly as prescribed. See Important
Safety Information including Boxed Warning on addiction, abuse, and
misuse and other serious risks regarding each of these three
products at the end of this press release.
For more information on PAINWeek 2020,
visit https://www.painweek.org/.
About Collegium Pharmaceutical, Inc.
Collegium is a specialty pharmaceutical company committed to
being the leader in responsible pain management. Collegium’s
headquarters are located in Stoughton, Massachusetts. For more
information, please visit the company’s website at
www.collegiumpharma.com.
About Xtampza® ER
Xtampza® ER is Collegium’s first product utilizing the
DETERx technology platform. Xtampza ER is an abuse-deterrent,
extended-release, oral formulation of oxycodone approved by
the FDA 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.
INDICATIONS AND USAGEXtampza® ER (oxycodone) 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 Xtampza ER for use in patients for whom
alternative treatment options (eg, non-opioid analgesics or
immediate-release opioids) are ineffective, not tolerated, or would
be otherwise inadequate to provide sufficient management of
pain
- Xtampza ER is not indicated as an as-needed (prn)
analgesic
IMPORTANT SAFETY INFORMATION
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND
MITIGATION STRATEGY (REMS); 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 |
Xtampza 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 Xtampza ER
and monitor all patients regularly for the development of these
behaviors or conditions. |
|
Opioid Analgesic Risk Evaluation and Mitigation Strategy
(REMS) |
To ensure that the benefits of opioid analgesics outweigh
the risks of addiction, abuse, and misuse, the Food and Drug
Administration (FDA) has required a REMS for these products. Under
the requirements of the REMS, drug companies with approved opioid
analgesic products must make REMS-compliant education programs
available to healthcare providers. Healthcare providers are
strongly encouraged to |
- complete a REMS-compliant education
program,
|
- counsel patients and/or their caregivers, with every
prescription, on safe use, serious risks, storage, and disposal of
these products,
|
- emphasize to patients and their caregivers the
importance of reading the Medication Guide every time it is
provided by their pharmacist, and
|
- consider other tools to improve patient, household, and
community safety.
|
Life-Threatening Respiratory Depression |
Serious, life-threatening, or fatal respiratory depression
may occur with use of Xtampza ER. Monitor for respiratory
depression, especially during initiation of Xtampza ER or following
a dose increase. |
|
Accidental Ingestion Accidental ingestion
of even one dose of Xtampza ER, especially by children, can result
in a fatal overdose of oxycodone. |
|
Neonatal Opioid Withdrawal Syndrome |
Prolonged use of Xtampza 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. |
|
Cytochrome P450 3A4 Interaction |
The concomitant use of Xtampza ER with all cytochrome P450
3A4 inhibitors may result in an increase in oxycodone plasma
concentrations, which could increase or prolong adverse drug
effects 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 Xtampza ER 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 Xtampza 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.
|
CONTRAINDICATIONS:
- Xtampza 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,
known or suspected gastrointestinal obstruction, including
paralytic ileus, and hypersensitivity (eg, anaphylaxis) to
oxycodone
WARNINGS AND PRECAUTIONS: Addiction, Abuse, and
Misuse Xtampza ER contains oxycodone, a Schedule II
controlled substance. As an opioid, Xtampza ER exposes users to the
risks of addiction, abuse, and misuse. As extended-release products
such as Xtampza 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 oxycodone present. Opioid Analgesic Risk
Evaluation and Mitigation Strategy (REMS) To ensure that
the benefits of opioid analgesics outweigh the risks of addiction,
abuse, and misuse, the Food and Drug Administration (FDA) has
required a Risk Evaluation and Mitigation Strategy (REMS) for these
products. Under the requirements of the REMS, drug companies with
approved opioid analgesic products must make REMS-compliant
education programs available to healthcare providers. Healthcare
providers are strongly encouraged to do all of the following:
- Complete a REMS-compliant education program offered by an
accredited provider of continuing education (CE) or another
education program that includes all the elements of the FDA
Education Blueprint for Health Care Providers Involved in the
Management or Support of Patients with Pain
- Discuss with patients and/or their caregivers, with every
prescription, the safe use, serious risks, and proper storage and
disposal of these products. The Patient Counseling Guide (PCG) can
be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG
- Emphasize to patients and their caregivers the importance of
reading the Medication Guide every time it is provided by their
pharmacist
- Consider other tools to improve patient, household, and
community safety such as patient-prescriber agreements that
reinforce patient-prescriber responsibilities
For further information on the REMS and a list of accredited
REMS CME/CE, call 1-800-503-0784, or visit
www.opioidanalgesicrems.com. The FDA Blueprint can be found at
www.fda.gov/OpioidAnalgesicREMSBlueprint.
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
- Opioids can cause sleep-related breathing disorders, including
central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use
increases the risk of CSA in a dose-dependent fashion. In patients
who present with CSA, consider decreasing the opioid dosage using
best practices for opioid taper
Neonatal Opioid Withdrawal Syndrome
- Prolonged use of Xtampza 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 of Concomitant Use or Discontinuation of
Cytochrome P450 3A4 Inhibitors and Inducers
- Concomitant use of Xtampza ER with a CYP3A4 inhibitor, such as
macrolide antibiotics (eg, erythromycin), azole-antifungal agents
(eg, ketoconazole), and protease inhibitors (eg, 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 Xtampza ER is achieved. Similarly, discontinuation of a
CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in
Xtampza ER-treated patients may increase oxycodone plasma
concentrations and prolong opioid adverse reactions. When using
Xtampza ER with CYP3A4 inhibitors or discontinuing CYP3A4 inducers
in Xtampza ER-treated patients, monitor patients closely at
frequent intervals and consider dosage reduction of Xtampza ER
until stable drug effects are achieved
- Concomitant use of Xtampza ER 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. When using Xtampza ER with CYP3A4 inducers
or discontinuing CYP3A4 inhibitors, monitor patients closely at
frequent intervals and consider increasing the opioid dosage if
needed to maintain adequate analgesia or if symptoms of opioid
withdrawal occur
Risks From Concomitant Use With Benzodiazepines or Other
CNS Depressants
- Profound sedation, respiratory depression, coma, and death may
result from the concomitant use of Xtampza ER with benzodiazepines
or other CNS depressants (eg, 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 PatientsThe use of Xtampza 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:
Xtampza 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 Xtampza ER.
Elderly, Cachectic, or Debilitated Patients:
Life-threatening respiratory depression is more likely to occur in
elderly, cachectic, or debilitated patients as they may have
altered pharmacokinetics or altered clearance compared to younger,
healthier patients.
Monitor such patients closely, particularly when initiating and
titrating Xtampza ER and when Xtampza ER is given concomitantly
with other drugs that depress respiration. Alternatively, consider
the use of non-opioid analgesics in these patients. Use an
alternative analgesic for patients who require a dose of Xtampza ER
less than 9 mg.
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. If adrenal
insufficiency is suspected, confirm the diagnosis with diagnostic
testing as soon as possible. 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. Other opioids may be tried as some cases reported use of
a different opioid without recurrence of adrenal insufficiency. The
information available does not identify any particular opioids as
being more likely to be associated with adrenal insufficiency
Severe Hypotension
- Xtampza 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 (eg,
phenothiazines or general anesthetics). Monitor these patients for
signs of hypotension after initiating or titrating the dosage of
Xtampza ER. In patients with circulatory shock, Xtampza ER may
cause vasodilation that can further reduce cardiac output and blood
pressure. Avoid the use of Xtampza 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 (eg, those with evidence of increased intracranial
pressure or brain tumors), Xtampza 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
Xtampza ER
- Opioids may also obscure the clinical course in a patient with
a head injury. Avoid the use of Xtampza ER in patients with
impaired consciousness or coma
Risks of Use in Patients With Gastrointestinal
Conditions
- Xtampza ER is contraindicated in patients with gastrointestinal
obstruction, including paralytic ileus
- The oxycodone in Xtampza 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
Risk of Use in Patients With Seizure
Disorders
- The oxycodone in Xtampza ER may increase the frequency of
seizures in patients with seizure disorders and may increase the
risk of seizures in other clinical settings associated with
seizures. Monitor patients with a history of seizure disorders for
worsened seizure control during Xtampza ER therapy
Withdrawal
- Do not abruptly discontinue Xtampza ER in a patient physically
dependent on opioids. When discontinuing Xtampza ER in a physically
dependent patient, gradually taper the dosage. Rapid tapering of
oxycodone in a patient physically dependent on opioids may lead to
a withdrawal syndrome and return of pain
- Additionally, avoid the use of mixed agonist/antagonist (eg,
pentazocine, nalbuphine, and butorphanol) or partial agonist (eg,
buprenorphine) analgesics in patients who have received or are
receiving a course of therapy with a full opioid agonist analgesic,
including Xtampza ER. In these patients, mixed
agonist/antagonist and partial agonist analgesics may reduce the
analgesic effect and/or may precipitate withdrawal symptoms
Risks of Driving and Operating Machinery
- Xtampza 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
Xtampza ER and know how they will react to the medication
Laboratory Monitoring
- Not every urine drug test for “opioids” or “opiates” detects
oxycodone reliably, especially those designed for in-office use.
Further, many laboratories will report urine drug concentrations
below a specified “cut-off” value as “negative.” Therefore, if
urine testing for oxycodone is considered in the clinical
management of an individual patient, ensure that the sensitivity
and specificity of the assay is appropriate, and consider the
limitations of the testing used when interpreting results
ADMINISTRATION WITH FOOD:
- Instruct patients to always take Xtampza ER capsules with food
and with approximately the same amount of food in order to ensure
consistent plasma levels are achieved. For patients who have
difficulty swallowing, Xtampza ER can also be taken as a sprinkle
on soft foods or sprinkled into a cup and administered directly
into the mouth, or through a nasogastric or gastric feeding tube
ADVERSE REACTIONS:
- The most common adverse reactions (>5%) reported by patients
in the Phase 3 clinical trial comparing Xtampza ER with placebo
were nausea, headache, constipation, somnolence, pruritus,
vomiting, and dizziness
Please see full Prescribing
Information, including Boxed Warning at
xtampzaer.com.
NUCYNTA® ER (tapentadol) INDICATIONS AND
USAGENUCYNTA ER (tapentadol) 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
- Neuropathic pain associated with diabetic peripheral neuropathy
(DPN) 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 NUCYNTA ER for use in patients for whom
alternative treatment options (eg, non-opioid analgesics or
immediate-release opioids) are ineffective, not tolerated, or would
be otherwise inadequate to provide sufficient management of
pain
- NUCYNTA ER is not indicated as an as-needed (prn)
analgesic
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND
MITIGATION STRATEGY (REMS); 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 |
NUCYNTA 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 NUCYNTA ER,
and monitor all patients regularly for the development of these
behaviors and conditions. |
|
Opioid Analgesic Risk Evaluation and Mitigation Strategy
(REMS) |
To ensure that the benefits of opioid analgesics outweigh
the risks of addiction, abuse, and misuse, the Food and Drug
Administration (FDA) has required a REMS for these products. Under
the requirements of the REMS, drug companies with approved opioid
analgesic products must make REMS-compliant education programs
available to healthcare providers. Healthcare providers are
strongly encouraged to |
- complete a REMS-compliant education
program,
|
- counsel patients and/or their caregivers, with every
prescription, on safe use, serious risks, storage, and disposal of
these products,
|
- emphasize to patients and their caregivers the
importance of reading the Medication Guide every time it is
provided by their pharmacist, and
|
- consider other tools to improve patient, household, and
community safety.
|
Life-Threatening Respiratory Depression |
Serious, life-threatening, or fatal respiratory depression
may occur with use of NUCYNTA ER. Monitor for respiratory
depression, especially during initiation of NUCYNTA ER or following
a dose increase. Instruct patients to swallow NUCYNTA ER tablets
whole; crushing, chewing, or dissolving NUCYNTA ER tablets can
cause rapid release and absorption of a potentially fatal dose of
tapentadol. |
|
Accidental Ingestion |
Accidental ingestion of even one dose of NUCYNTA ER,
especially by children, can result in a fatal overdose of
tapentadol. |
|
Neonatal Opioid Withdrawal Syndrome |
Prolonged use of NUCYNTA 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. |
|
Interaction With Alcohol |
Instruct patients not to consume alcoholic beverages or use
prescription or non-prescription products that contain alcohol
while taking NUCYNTA ER. The co-ingestion of alcohol with NUCYNTA
ER may result in increased plasma tapentadol levels and a
potentially fatal overdose of tapentadol. |
|
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 NUCYNTA 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
|
CONTRAINDICATIONS:NUCYNTA ER is contraindicated
in patients with:
- Significant respiratory depression
- Acute or severe bronchial asthma or hypercarbia in an
unmonitored setting or in the absence of resuscitative
equipment
- Known or suspected gastrointestinal obstruction, including
paralytic ileus
- Hypersensitivity (eg, anaphylaxis, angioedema) to tapentadol or
to any other ingredients of the product
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or use
of MAOIs within the last 14 days
WARNINGS AND PRECAUTIONS:Addiction,
Abuse, and MisuseNUCYNTA ER contains tapentadol, a
Schedule II controlled substance. As an opioid, NUCYNTA ER exposes
users to the risks of addiction, abuse, and misuse. Because
extended-release products such as NUCYNTA 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 tapentadol
present.
Although the risk of addiction in any individual is unknown, it
can occur in patients appropriately prescribed NUCYNTA ER.
Addiction can occur at recommended doses and if the drug is misused
or abused.
Assess each patient’s risk for opioid addiction, abuse, or
misuse prior to prescribing NUCYNTA ER, and monitor all patients
receiving NUCYNTA ER for the development of these behaviors and
conditions. Risks are increased in patients with a personal or
family history of substance abuse (including drug or alcohol abuse
or addiction) or mental illness (eg, major depression). The
potential for these risks should not, however, prevent the
prescribing of NUCYNTA ER for the proper management of pain in any
given patient. Patients at increased risk may be prescribed opioids
such as NUCYNTA ER, but use in such patients necessitates intensive
counseling about the risks and proper use of NUCYNTA ER along with
intensive monitoring for signs of addiction, abuse, and misuse.
Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or
injecting the dissolved product will result in the uncontrolled
delivery of tapentadol 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 NUCYNTA ER. 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 the local state professional
licensing board or state controlled substances authority for
information on how to prevent and detect abuse or diversion of this
product.
Opioid Analgesic Risk Evaluation and Mitigation Strategy
(REMS)To ensure that the benefits of opioid analgesics
outweigh the risks of addiction, abuse, and misuse, the Food and
Drug Administration (FDA) has required a Risk Evaluation and
Mitigation Strategy (REMS) for these products. Under the
requirements of the REMS, drug companies with approved opioid
analgesic products must make REMS-compliant education programs
available to healthcare providers. Healthcare providers are
strongly encouraged to do all of the following:
- Complete a REMS-compliant education program offered by an
accredited provider of continuing education (CE) or another
education program that includes all the elements of the FDA
Education Blueprint for Health Care Providers Involved in the
Management or Support of Patients with Pain
- Discuss the safe use, serious risks, and proper storage and
disposal of opioid analgesics with patients and/or their caregivers
every time these medicines are prescribed. The Patient Counseling
Guide (PCG) can be obtained at this link:
www.fda.gov/OpioidAnalgesicREMSPCG
- Emphasize to patients and their caregivers the importance of
reading the Medication Guide that they will receive from their
pharmacist every time an opioid analgesic is dispensed to them
- Consider using other tools to improve patient, household, and
community safety, such as patient-prescriber agreements that
reinforce patient-prescriber responsibilities
To obtain further information on the opioid analgesic REMS and
for a list of accredited REMS CME/CE, call 1-800-503-0784, or log
on to www.opioidanalgesicrems.com. The FDA Blueprint can be found
at www.fda.gov/OpioidAnalgesicREMSBlueprint.
Life-Threatening Respiratory DepressionSerious,
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 NUCYNTA 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 of NUCYNTA ER.
To reduce the risk of respiratory depression, proper dosing and
titration of NUCYNTA ER are essential. Overestimating the NUCYNTA
ER dosage when converting patients from another opioid product can
result in fatal overdose with the first dose.
Accidental ingestion of even one dose of NUCYNTA ER, especially
by children, can result in respiratory depression and death due to
an overdose of tapentadol.
Opioids can cause sleep-related breathing disorders, including
central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use
increases the risk of CSA in a dose-dependent fashion. In patients
who present with CSA, consider decreasing the opioid dosage using
best practices for opioid taper.
Neonatal Opioid Withdrawal SyndromeProlonged
use of NUCYNTA 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.
Risk From Concomitant Use With Benzodiazepines or Other
CNS DepressantsPatients must not consume alcoholic
beverages or prescription or non-prescription products containing
alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol
with NUCYNTA ER may result in increased plasma tapentadol levels
and a potentially fatal overdose of tapentadol.Profound sedation,
respiratory depression, coma, and death may result from the
concomitant use of NUCYNTA ER with benzodiazepines or other CNS
depressants (eg, 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.
If the decision is made to prescribe a benzodiazepine or other
CNS depressant concomitantly with an opioid analgesic, prescribe
the lowest effective dosages and minimum durations of concomitant
use. In patients already receiving an opioid analgesic, prescribe a
lower initial dose of the benzodiazepine or other CNS depressant
than indicated in the absence of an opioid, and titrate based on
clinical response. If an opioid analgesic is initiated in a patient
already taking a benzodiazepine or other CNS depressant, prescribe
a lower initial dose of the opioid analgesic, and titrate based on
clinical response. Follow patients closely for signs and symptoms
of respiratory depression and sedation.
Advise both patients and caregivers about the risks of
respiratory depression and sedation when NUCYNTA ER 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 depressants 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.
Risk of Life-Threatening Respiratory Depression in
Patients With Chronic Pulmonary Disease or in Elderly, Cachectic,
or Debilitated PatientsThe use of NUCYNTA 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:
NUCYNTA 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 NUCYNTA 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. Alternatively, consider the use of non-opioid
analgesics in these patients.
Monitor such patients closely, particularly when initiating and
titrating NUCYNTA ER and when NUCYNTA ER is given concomitantly
with other drugs that depress respiration.
Serotonin Syndrome With Concomitant Use of Serotonergic
DrugsCases of serotonin syndrome, a potentially
life-threatening condition, have been reported during concomitant
use of tapentadol with serotonergic drugs. Serotonergic drugs
include selective serotonin reuptake inhibitors (SSRIs), serotonin
and norepinephrine reuptake inhibitors (SNRIs), tricyclic
antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs
that affect the serotonergic neurotransmitter system (eg,
mirtazapine, trazodone, tramadol), certain muscle relaxants (ie,
cyclobenzaprine, metaxalone), and drugs that impair metabolism of
serotonin (including MAO inhibitors, both those intended to treat
psychiatric disorders and also others, such as linezolid and
intravenous methylene blue). This may occur within the recommended
dosage range.
Serotonin syndrome symptoms may include mental status changes
(eg, agitation, hallucinations, coma), autonomic instability (eg,
tachycardia, labile blood pressure, hyperthermia), neuromuscular
aberrations (eg, hyperreflexia, incoordination, rigidity), and/or
gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). The
onset of symptoms generally occurs within several hours to a few
days of concomitant use, but may occur later than that. Discontinue
NUCYNTA ER if serotonin syndrome is suspected.
Adrenal InsufficiencyCases 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. If adrenal insufficiency is suspected, confirm the
diagnosis with diagnostic testing as soon as possible. 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. Other opioids may be
tried as some cases reported use of a different opioid without
recurrence of adrenal insufficiency. The information available does
not identify any particular opioids as being more likely to be
associated with adrenal insufficiency.
Severe HypotensionNUCYNTA 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 (eg, phenothiazines or general anesthetics).
Monitor these patients for signs of hypotension after initiating or
titrating the dosage of NUCYNTA ER. In patients with circulatory
shock, NUCYNTA ER may cause vasodilation that can further reduce
cardiac output and blood pressure. Avoid the use of NUCYNTA ER in
patients with circulatory shock.
Risks of Use in Patients With Increased Intracranial
Pressure, Brain Tumors, Head Injury, or Impaired
ConsciousnessIn patients who may be susceptible to the
intracranial effects of CO2 retention (eg, those with evidence of
increased intracranial pressure or brain tumors), NUCYNTA 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 NUCYNTA ER.Opioids may also obscure the
clinical course in a patient with a head injury. Avoid the use of
NUCYNTA ER in patients with impaired consciousness or coma.
Risks of Use in Patients With Gastrointestinal
ConditionsNUCYNTA ER is contraindicated in patients with
known or suspected gastrointestinal obstruction, including
paralytic ileus.
The tapentadol in NUCYNTA ER 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
DisordersThe tapentadol in NUCYNTA ER may increase the
frequency of seizures in patients with seizure disorders and may
increase the risk of seizures in other clinical settings associated
with seizures. Monitor patients with a history of seizure disorders
for worsened seizure control during NUCYNTA ER therapy.
WithdrawalDo not abruptly discontinue NUCYNTA
ER in a patient physically dependent on opioids. When discontinuing
NUCYNTA ER in a physically dependent patient, gradually taper the
dosage. Rapid tapering of tapentadol in a patient physically
dependent on opioids may lead to a withdrawal syndrome and return
of pain.
Additionally, avoid the use of mixed agonist/antagonist (eg,
pentazocine, nalbuphine, and butorphanol) or partial agonist (eg,
buprenorphine) analgesics in patients who have received or are
receiving a course of therapy with a full opioid agonist analgesic,
including NUCYNTA ER. In these patients, mixed
agonists/antagonists and partial agonist analgesics may reduce the
analgesic effect and/or may precipitate withdrawal symptoms.
Risks of Driving and Operating MachineryNUCYNTA
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 NUCYNTA ER and
know how they will react to the medication.
Risk of Toxicity in Patients With Hepatic
ImpairmentA study with an immediate-release formulation of
tapentadol in subjects with hepatic impairment showed higher serum
concentrations of tapentadol than in those with normal hepatic
function. Avoid use of NUCYNTA ER in patients with severe hepatic
impairment. Reduce the dose of NUCYNTA ER in patients with moderate
hepatic impairment. Closely monitor patients with moderate hepatic
impairment for respiratory and central nervous system depression
when initiating and titrating NUCYNTA ER.
Risk of Toxicity in Patients With Renal
ImpairmentUse of NUCYNTA ER in patients with severe renal
impairment is not recommended due to accumulation of a metabolite
formed by glucuronidation of tapentadol. The clinical relevance of
the elevated metabolite is not known.
ADVERSE REACTIONS:In clinical studies, the most
common (≥10%) adverse reactions were nausea, constipation,
dizziness, headache, and somnolence.
Please see full Prescribing
Information, including Boxed Warning.
NUCYNTA® (tapentadol) INDICATIONS AND
USAGENUCYNTA (tapentadol) tablets are indicated for the
management of acute pain severe enough to require an opioid
analgesic and for which alternative treatments are inadequate in
adults.
Limitations of UseBecause of the risks of addiction, abuse, and
misuse with opioids, even at recommended doses, reserve NUCYNTA
tablets for use in patients for whom alternative treatment options
(eg, 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
IMPORTANT SAFETY INFORMATION
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND
MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY
DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL
SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR
OTHER CNS DEPRESSANTS |
|
Addiction, Abuse, and Misuse |
NUCYNTA 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
NUCYNTA tablets, and monitor all patients regularly for the
development of these behaviors and conditions. |
|
Opioid Analgesic Risk Evaluation and Mitigation Strategy
(REMS) |
To ensure that the benefits of opioid analgesics outweigh
the risks of addiction, abuse, and misuse, the Food and Drug
Administration (FDA) has required a REMS for these products. Under
the requirements of the REMS, drug companies with approved opioid
analgesic products must make REMS-compliant education programs
available to healthcare providers. Healthcare providers are
strongly encouraged to |
- complete a REMS-compliant education
program,
|
- counsel patients and/or their caregivers, with every
prescription, on safe use, serious risks, storage, and disposal of
these products,
|
- emphasize to patients and their caregivers the
importance of reading the Medication Guide every time it is
provided by their pharmacist, and
|
- consider other tools to improve patient, household, and
community safety.
|
Life-Threatening Respiratory Depression |
Serious, life-threatening, or fatal respiratory depression
may occur with use of NUCYNTA tablets. Monitor for respiratory
depression, especially during initiation of NUCYNTA tablets or
following a dose increase. |
|
Accidental Ingestion |
Accidental ingestion of even one dose of NUCYNTA tablets,
especially by children, can result in a fatal overdose of
tapentadol. |
|
Neonatal Opioid Withdrawal Syndrome |
Prolonged use of NUCYNTA tablets 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 NUCYNTA 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:NUCYNTA 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
- Known or suspected gastrointestinal obstruction, including
suspected paralytic ileus
- Hypersensitivity to tapentadol (eg, anaphylaxis, angioedema) or
to any other ingredients of the product
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or use
of MAOIs within the last 14 days
WARNINGS AND PRECAUTIONS:Addiction,
Abuse, and MisuseNUCYNTA tablets contain tapentadol, a
Schedule II controlled substance. As an opioid, NUCYNTA tablets
expose 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 NUCYNTA tablets.
Addiction can occur at recommended dosages and if the drug is
misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or
misuse prior to prescribing NUCYNTA tablets and monitor all
patients receiving NUCYNTA tablets for the development of these
behaviors and conditions. Risks are increased in patients with a
personal or family history of substance abuse (including drug or
alcohol abuse or addiction) or mental illness (eg, major
depression). The potential for these risks should not, however,
prevent the proper management of pain in any given patient.
Patients at increased risk may be prescribed opioids such as
NUCYNTA tablets, but use in such patients necessitates intensive
counseling about the risks and proper use of NUCYNTA tablets along
with intensive monitoring for signs of addiction, abuse, and
misuse.
Opioids are sought by drug abusers and people with addiction
disorders and are subject to criminal diversion. Consider these
risks when prescribing or dispensing NUCYNTA 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.
Opioid Analgesic Risk Evaluation and Mitigation Strategy
(REMS)To ensure that the benefits of opioid analgesics
outweigh the risks of addiction, abuse, and misuse, the Food and
Drug Administration (FDA) has required a Risk Evaluation and
Mitigation Strategy (REMS) for these products. Under the
requirements of the REMS, drug companies with approved opioid
analgesic products must make REMS-compliant education programs
available to healthcare providers. Healthcare providers are
strongly encouraged to do all of the following:
- Complete a REMS-compliant education program offered by an
accredited provider of continuing education (CE) or another
education program that includes all the elements of the FDA
Education Blueprint for Health Care Providers Involved in the
Management or Support of Patients with Pain
- Discuss the safe use, serious risks, and proper storage and
disposal of opioid analgesics with patients and/or their caregivers
every time these medicines are prescribed. The Patient Counseling
Guide (PCG) can be obtained at this link:
www.fda.gov/OpioidAnalgesicREMSPCG
- Emphasize to patients and their caregivers the importance of
reading the Medication Guide that they will receive from their
pharmacist every time an opioid analgesic is dispensed to them
- Consider using other tools to improve patient, household, and
community safety, such as patient-prescriber agreements that
reinforce patient- prescriber responsibilities
To obtain further information on the opioid analgesic REMS and
for a list of accredited REMS CME/CE, call 1-800-503-0784, or log
on to www.opioidanalgesicrems.com. The FDA Blueprint can be found
at www.fda.gov/OpioidAnalgesicREMSBlueprint.
Life-Threatening Respiratory DepressionSerious,
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 NUCYNTA tablets, 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 of NUCYNTA tablets.
To reduce the risk of respiratory depression, proper dosing and
titration of NUCYNTA tablets are essential. Overestimating the
NUCYNTA tablets dosage when converting patients from another opioid
product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of NUCYNTA tablets,
especially by children, can result in respiratory depression and
death due to an overdose of tapentadol.
Opioids can cause sleep-related breathing disorders, including
central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use
increases the risk of CSA in a dose-dependent fashion. In patients
who present with CSA, consider decreasing the opioid dosage using
best practices for opioid taper.
Neonatal Opioid Withdrawal SyndromeProlonged
use of NUCYNTA tablets 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 DepressantsProfound sedation, respiratory depression,
coma, and death may result from the concomitant use of NUCYNTA
tablets with benzodiazepines or other CNS depressants (eg,
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.
If the decision is made to prescribe a benzodiazepine or other
CNS depressant concomitantly with an opioid analgesic, prescribe
the lowest effective dosages and minimum durations of concomitant
use. In patients already receiving an opioid analgesic, prescribe a
lower
initial dose of the benzodiazepine or other CNS depressant than
indicated in the absence of an opioid, and titrate based on
clinical response. If an opioid analgesic is initiated in a patient
already taking a benzodiazepine or other CNS depressant, prescribe
a lower initial dose of the opioid analgesic, and titrate based on
clinical response. Follow patients closely for signs and symptoms
of respiratory depression and sedation.
Advise both patients and caregivers about the risks of
respiratory depression and sedation when NUCYNTA tablets are 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
PatientsThe use of NUCYNTA tablets 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:
NUCYNTA 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 NUCYNTA 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 NUCYNTA tablets and when NUCYNTA tablets are given
concomitantly with other drugs that depress respiration.
Alternatively, consider the use of non-opioid analgesics in these
patients.
Serotonin Syndrome With Concomitant Use of Serotonergic
DrugsCases of serotonin syndrome, a potentially
life-threatening condition, have been reported during concurrent
use of tapentadol with serotonergic drugs. Serotonergic drugs
include selective serotonin reuptake inhibitors (SSRIs), serotonin
and norepinephrine reuptake inhibitors (SNRIs), tricyclic
antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs
that affect the serotonergic neurotransmitter system (eg,
mirtazapine, trazodone, tramadol), certain muscle relaxants (ie,
cyclobenzaprine, metaxalone), and drugs that impair metabolism of
serotonin (including MAO inhibitors, both those intended to treat
psychiatric disorders and also others, such as linezolid and
intravenous methylene blue). This may occur within the recommended
dosage range.
Serotonin syndrome symptoms may include mental-status changes
(eg, agitation, hallucinations, coma), autonomic instability (eg,
tachycardia, labile blood pressure, hyperthermia), neuromuscular
aberrations (eg, hyperreflexia, incoordination)
and/orgastrointestinal symptoms (eg, nausea, vomiting, diarrhea)
and can be fatal. The onset of symptoms generally occurs within
several hours to a few days of concomitant use, but may occur later
than that. Discontinue NUCYNTA tablets if serotonin syndrome is
suspected.
Adrenal InsufficiencyCases 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. If adrenal insufficiency is suspected, confirm the
diagnosis with diagnostic testing as soon as possible. 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. Other opioids may be
tried as some cases reported use of a different opioid without
recurrence of adrenal insufficiency. The information available does
not identify any particular opioids as being more likely to be
associated with adrenal insufficiency.
Severe HypotensionNUCYNTA tablets 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 (eg, phenothiazines or general anesthetics).
Monitor these patients for signs of hypotension after initiating or
titrating the dosage of NUCYNTA tablets. In patients with
circulatory shock, NUCYNTA tablets may cause vasodilation that can
further reduce cardiac output and blood pressure. Avoid the use of
NUCYNTA tablets in patients with circulatory shock.
Risks of Use in Patients With Increased Intracranial
Pressure, Brain Tumors, Head Injury, or Impaired
ConsciousnessIn patients who may be susceptible to the
intracranial effects of CO2 retention (eg, those with evidence of
increased intracranial pressure or brain tumors), NUCYNTA tablets
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 NUCYNTA tablets.
Opioids may also obscure the clinical course in a patient with a
head injury. Avoid the use of NUCYNTA tablets in patients with
impaired consciousness or coma.
Risks of Use in Patients With Gastrointestinal
ConditionsNUCYNTA tablets are contraindicated in patients
with known or suspected gastrointestinal obstruction, including
paralytic ileus.
The tapentadol in NUCYNTA 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
DisordersThe tapentadol in NUCYNTA tablets 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 NUCYNTA
tablets therapy.
WithdrawalDo not abruptly discontinue NUCYNTA
tablets in a patient physically dependent on opioids. When
discontinuing NUCYNTA tablets in a physically dependent patient,
gradually taper the dosage. Rapid tapering of tapentadol in a
patient physically dependent on opioids may lead to a withdrawal
syndrome and return of pain.
Additionally, avoid the use of mixed agonist/antagonist (eg,
pentazocine, nalbuphine, and butorphanol) or partial agonist (eg,
buprenorphine) analgesics in patients who are receiving a full
opioid agonist analgesic, including NUCYNTA tablets. In these
patients, mixed agonist/antagonist and partial agonist analgesics
may reduce the analgesic effect and/or precipitate withdrawal
symptoms.
Risks of Driving and Operating MachineryNUCYNTA
tablets 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
NUCYNTA tablets and know how they will react to the medication.
Interactions With Alcohol, Other Opioids, and Drugs of
AbuseDue to its mu-opioid agonist activity, NUCYNTA
tablets may be expected to have additive effects when used in
conjunction with alcohol, other opioids, or illicit drugs that
cause central nervous system depression, respiratory depression,
hypotension, and profound sedation, coma or death. Instruct
patients not to consume alcoholic beverages or use prescription or
non-prescription products containing alcohol, other opioids, or
drugs of abuse while on NUCYNTA tablets therapy.
Risk of Toxicity in Patients With Hepatic
ImpairmentA study with NUCYNTA tablets in subjects with
hepatic impairment showed higher serum concentrations of tapentadol
than in those with normal hepatic function. Avoid use of NUCYNTA
tablets in patients with severe hepatic impairment. Reduce the dose
of NUCYNTA tablets in patients with moderate hepatic impairment.
Closely monitor patients with moderate hepatic impairment for
respiratory and central nervous system depression when receiving
NUCYNTA tablets.
Risk of Toxicity in Patients With Renal
ImpairmentUse of NUCYNTA tablets in patients with severe
renal impairment is not recommended due to accumulation of a
metabolite formed by glucuronidation of tapentadol. The clinical
relevance of the elevated metabolite is not known.
ADVERSE REACTIONS:In clinical studies, the most
common (≥10%) adverse reactions were nausea, dizziness, vomiting,
and somnolence.
Please see full Prescribing
Information, including Boxed Warning.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. We may, in some cases, use terms such as "predicts,"
"forecasts," "believes," "potential," "proposed," "continue,"
"estimates," "anticipates," "expects," "plans," "intends," "may,"
"could," "might," "should" or other words that convey uncertainty
of future events or outcomes to identify these forward-looking
statements. Examples of forward-looking statements contained in
this press release include, among others, statements regarding
financial guidance for Xtampza ER and Nucynta Franchise revenues,
total operating expenses, current and future market opportunities
for our products and our assumptions related thereto. Such
statements are subject to numerous important factors, risks and
uncertainties that may cause actual events or results, performance,
or achievements to differ materially from the company's current
expectations. Management's expectations and, therefore, any
forward-looking statements in this press release could also be
affected by risks and uncertainties relating to a number of other
factors, including the impact of the COVID-19 pandemic on our
ability to conduct our business, reach our customers, and supply
the market with our products; our ability to commercialize and grow
sales of our products; our ability to manage our relationships with
licensors; the success of competing products that are or become
available; our ability to obtain and maintain regulatory approval
of our products and any product candidates, and any related
restrictions, limitations, and/or warnings in the label of an
approved product; the size of the markets for our products and
product candidates, and our ability to service those markets; our
ability to obtain reimbursement and third-party payor contracts for
our products; the rate and degree of market acceptance of our
products and product candidates; the costs of commercialization
activities, including marketing, sales and distribution; changing
market conditions for our products; the outcome of any patent
infringement, opioid-related or other litigation that may be
brought by or against us, including litigation with Purdue Pharma,
L.P. and Teva Pharmaceuticals USA, Inc.; the outcome of any
governmental investigation related to the manufacture, marketing
and sale of opioid medications; our ability to secure adequate
supplies of active pharmaceutical ingredient for each of our
products and manufacture adequate supplies of commercially saleable
inventory; our ability to obtain funding for our operations and
business development; regulatory developments in the U.S.; our
expectations regarding our ability to obtain and maintain
sufficient intellectual property protection for our products; our
ability to comply with stringent U.S. and foreign government
regulation in the manufacture of pharmaceutical products, including
U.S. Drug Enforcement Agency, or DEA, compliance; our customer
concentration; and the accuracy of our estimates regarding
expenses, revenue, capital requirements and need for additional
financing. These and other risks are described under the heading
"Risk Factors" in our Quarterly Report on Form 10-Q for the quarter
ended June 30, 2020 and other filings with the SEC. Any
forward-looking statements that we make in this press release speak
only as of the date of this press release. We assume no obligation
to update our forward-looking statements whether as a result of new
information, future events or otherwise, after the date of this
press release.
Contact:Alex Dasallaadasalla@collegiumpharma.com
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