Collegium Pharmaceutical, Inc. (Nasdaq: COLL), a specialty
pharmaceutical company committed to being the leader in responsible
pain management, today announced that four poster presentations
relating to rates of abuse and diversion of Xtampza® ER
(oxycodone), Nucynta® ER (tapentadol) and Nucynta® (tapentadol)
relative to other opioids will be presented at the 13th annual
PAINWeek National Conference taking place Sept. 3-7, 2019 in Las
Vegas, NV. The posters will be presented on Thursday, Sept. 5th
from 6:30 p.m. to 8:30 p.m. PT.
Three Collegium-supported posters (#113 to #115) were authored
and will be presented by Richard Dart, M.D., Ph.D., Director of
Rocky Mountain Poison & Drug Safety – Denver Health and
Hospital Authority. The posters report analyses of data from
several surveillance programs within the Researched Abuse,
Diversion and Addiction-Related Surveillance (RADARS®) System
related to the abuse and diversion of Xtampza® ER compared to other
categories of opioids. Collegium has been monitoring RADARS
surveillance for the three years since the launch of Xtampza® ER,
and this is the first time these data will be shared
publicly.
A fourth poster (#139) was authored and will be presented by
Steven Passik, Ph.D., Vice President, Scientific Affairs &
Education at Collegium. The poster reports a retrospective study of
urine drug testing records of patients admitted to a regional
outpatient addiction treatment facility and compares the incidence
of urine samples positive for the presence of tapentadol to the
incidence of positive tests for other prescription opioids.
Xtampza® ER, Nucynta® ER and Nucynta® can be abused or misused,
and carry a risk of addiction. Like all opioid medications, these
products are intended for use only in appropriate pain patients and
only when other treatment alternatives are inadequate. Use of any
opioid can result in serious, life-threatening or fatal respiratory
depression, even when used exactly as prescribed. See
Important Safety Information regarding each of these three products
at the end of this press release.
For more information on PAINWeek 2019, visit
http://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
INDICATIONS AND USAGE
Xtampza® 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
DEPRESSANTSAddiction, Abuse, and
MisuseXtampza 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
DepressionSerious, 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
IngestionAccidental ingestion of even one dose of
Xtampza ER, especially by children, can result in a fatal overdose
of oxycodone.Neonatal Opioid Withdrawal
SyndromeProlonged 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
InteractionThe 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
DepressantsConcomitant 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
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 nonspecific
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
- 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
- When discontinuing Xtampza ER, gradually taper the dosage.
Do not abruptly discontinue Xtampza ER
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 III clinical trial comparing Xtampza ER with
placebo were nausea, headache, constipation, somnolence, pruritus,
vomiting, and dizziness
Please see full Prescribing
Information, including Boxed Warning.
About NUCYNTA® ER
INDICATIONS AND USAGE
NUCYNTA 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 (e.g., 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
IMPORTANT SAFETY
INFORMATION
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
DEPRESSANTSAddiction, Abuse, and
MisuseNUCYNTA 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
DepressionSerious, 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
IngestionAccidental ingestion of even one dose of
NUCYNTA ER, especially by children, can result in a fatal overdose
of tapentadol.Neonatal Opioid Withdrawal
SyndromeProlonged 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
AlcoholInstruct 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
DepressantsConcomitant 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 (e.g. 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 (e.g., 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.
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 Depressants Patients 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 (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.
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 (e.g.,
mirtazapine, trazodone, tramadol), 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
(e.g., agitation, hallucinations, coma), autonomic instability
(e.g., tachycardia, labile blood pressure, hyperthermia),
neuromuscular aberrations (e.g., hyperreflexia, incoordination,
rigidity), and/or gastrointestinal symptoms (e.g., 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 (e.g., 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 (e.g., 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.
WithdrawalAvoid the use of mixed
agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol)
or partial agonist (e.g., buprenorphine) analgesics in patients who
have received or are receiving a course of therapy with a full
opioid agonist analgesic, including NUCYNTA ER. In these patients,
mixed agonists/antagonists and partial agonist analgesics may
reduce the analgesic effect and/or may precipitate withdrawal
symptoms.
When discontinuing NUCYNTA ER, gradually taper the dose. Do not
abruptly discontinue NUCYNTA ER.
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.
About NUCYNTA®
INDICATIONS AND USAGE
NUCYNTA (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 (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
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 DEPRESSANTSAddiction, Abuse, and
MisuseNUCYNTA 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
DepressionSerious, 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
IngestionAccidental ingestion of even one dose of
NUCYNTA tablets, especially by children, can result in a fatal
overdose of tapentadol.Neonatal Opioid Withdrawal
SyndromeProlonged 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
DepressantsConcomitant 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 (e.g. 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 (e.g., 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.
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 (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.
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 (e.g.
mirtazapine, trazodone, tramadol), 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
(e.g., agitation, hallucinations, coma), autonomic instability
(e.g., tachycardia, labile blood pressure, hyperthermia),
neuromuscular aberrations (e.g., hyperreflexia, incoordination)
and/or gastrointestinal symptoms (e.g., 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 (e.g., 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 (e.g., 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.
WithdrawalAvoid 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 NUCYNTA
tablets. In these patients, mixed agonist/antagonist and partial
agonist analgesics may reduce the analgesic effect and/or
precipitate withdrawal symptoms.
When discontinuing NUCYNTA tablets in a physically-dependent
patient, gradually taper the dosage. Do not abruptly discontinue
NUCYNTA tablets in these patients.
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. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or
results 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 our ability to obtain and maintain regulatory
approval of our products and product candidates; our ability to
effectively commercialize in-licensed products and manage our
relationships with licensors; the success of competing products
that are or become available; 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 outcome of any patent infringement 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 product candidates and manufacture adequate supplies
of 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; 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, 2019, and in other reports which we file 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 Dasalla adasalla@collegiumpharma.com
Collegium Pharmaceutical (NASDAQ:COLL)
Historical Stock Chart
From Aug 2024 to Sep 2024
Collegium Pharmaceutical (NASDAQ:COLL)
Historical Stock Chart
From Sep 2023 to Sep 2024