Approved Drug Label (PDF)
Boxed Warning
Additions and/or
revisions underlined:
WARNING: SERIOUS AND
LIFE-THREATENING RISKS FROM USE OF NUCYNTA ER
Addiction,
Abuse, and Misuse
Because
the use of 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 and reassess all patients regularly for the
development of these behaviors and conditions [see Warnings and Precautions (5.1)].
…
5
Warnings and Precautions
5.6 Opioid-Induced Hyperalgesia and Allodynia
New
subsection added:
Opioid-Induced
Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an
increase in pain, or an increase in sensitivity to pain. This condition differs
from tolerance, which is the need for increasing doses of opioids to maintain a
defined effect [see Dependence (9.3)].
Symptoms
of OIH include (but may not be limited to) increased levels of pain upon opioid
dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from
ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only
if there is no evidence of underlying disease progression, opioid tolerance,
opioid withdrawal, or addictive behavior.
Cases
of OIH have been reported, both with short-term and longer-term use of opioid
analgesics. Though the mechanism of OIH is not fully understood, multiple
biochemical pathways have been implicated. Medical literature suggests a strong
biologic plausibility between opioid analgesics and OIH and allodynia. If a
patient is suspected to be experiencing OIH, carefully consider appropriately decreasing
the dose of the current opioid analgesic or opioid rotation (safely switching
the patient to a different opioid moiety) [see
Dosage and Administration (2.6), Warnings and Precautions (5.14)].
5.1 Addiction, Abuse, and Misuse
Additions and/or
revisions underlined:
…
Opioids are sought for nonmedical use and
are subject to diversion from legitimate prescribed use. 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 careful storage of the drug during the course of
treatment and the proper disposal of unused drug
…
5.3
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
Additions and/or revisions underlined:
…
Inform patients and
caregivers of this potential interaction and educate them on the signs and
symptoms of respiratory depression (including sedation).
![]()
…
Subsection
revised; additions and revisions underlined:
5.8
Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary
Disease or in Elderly, Cachectic, or Debilitated Patients
The
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 [see Warnings and Precautions (5.2)].
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 [see Warnings
and Precautions (5.2)].
Regularly
evaluate patients, particularly when initiating and titrating NUCYNTA ER and
when NUCYNTA ER is given concomitantly with other drugs that depress
respiration [see Warnings and Precautions
(5.2), Drug Interactions (7)]. Alternatively, consider the use of non-opioid
analgesics in these patients.
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
6.2 Postmarketing
Experience
Additions and/or revisions underlined:
…
Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an
extended period of time [see Clinical Pharmacology (12.2)].
Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid
therapy of any duration [see Warnings and
Precautions (5.6)]
Hypoglycemia: Cases of hypoglycemia have been reported
in patients taking opioids. Most reports were in patients with at least one
predisposing risk factor (e.g., diabetes).
8
Use in Specific Populations
8.3 Females and Males of Reproductive Potential
Additions
and/or revisions underlined:
Infertility
Use
of opioids for an extended period of time may cause reduced fertility in
females and males of reproductive potential. It is not known whether these effects
on fertility are reversible [see Adverse Reactions
(6.2), Nonclinical Toxicology (13.1)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
…
Hyperalgesia
and Allodynia
Inform
patients and caregivers not to increase opioid dosage without first consulting
a clinician. Advise patients to seek medical attention if they experience symptoms
of hyperalgesia, including worsening pain, increased sensitivity to pain, or
new pain [see Warnings and Precautions (5.6);
Adverse Reactions (6.2)].
…
Infertility
Inform
patients that use of opioids for an extended period of time may cause reduced
fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3)].
MEDICATION GUIDE
Additions
and/or revisions underlined:
…
Tell your healthcare
provider if you are:
noticing your pain getting worse. If your pain gets
worse after you take NUCYNTA ER, do not take more of NUCYNTA ER without first talking
to your healthcare provider. Talk to your healthcare provider if the pain that you
have increases, if you feel more sensitive to pain, or if you have new pain
after taking NUCYNTA ER.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1
Addiction, Abuse, and Misuse
Additions
and/or revisions underlined:
… 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. Consider prescribing
naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3)].
5.3 Life-Threatening Respiratory Depression
Additions and/or revisions underlined:
… 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.
Educate patients
and caregivers on how to recognize respiratory depression and emphasize the
importance of calling 911 or getting emergency medical help right away in the
event of a known or suspected overdose [see
Patient Counseling Information (17)].
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 [see Dosage and Administration (2.6)].
Newly added information:
Patient Access to
Naloxone for the Emergency Treatment of Opioid Overdose
Discuss the
availability of naloxone for the emergency treatment of opioid overdose with
the patient and caregiver and assess the potential need for access to naloxone,
both when initiating and renewing treatment with NUCYNTA ER. Inform patients
and caregivers about the various ways to obtain naloxone as permitted by
individual state naloxone dispensing and prescribing requirements or guidelines
(e.g., by prescription, directly from a pharmacist, or as part of a
community-based program). Educate patients and caregivers on how to recognize
respiratory depression and emphasize the importance of calling 911 or getting
emergency medical help, even if naloxone is administered [see Patient Counseling Information (17)].
Consider
prescribing naloxone, based on the patient’s risk factors for overdose, such as
concomitant use of CNS depressants, a history of opioid use disorder, or prior
opioid overdose. The presence of risk factors for overdose should not prevent
the proper management of pain in any given patient. Also consider prescribing
naloxone if the patient has household members (including children) or other
close contacts at risk for accidental ingestion or overdose. If naloxone is
prescribed, educate patients and caregivers on how to treat with naloxone. [see Warnings and Precautions (5.1, 5.5),
Patient Counseling Information (17)].
5.5 Risks from Concomitant Use with Benzodiazepines or
Other CNS Depressants
Additions and/or revisions underlined:
… 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.
If concomitant use
is warranted, consider prescribing naloxone for the emergency treatment of
opioid overdose [see Dosage and
Administration (2.2), Warnings and Precautions (5.3)].
7
Drug Interactions
Table 3:
Clinically Significant Drug Interactions with NUCYNTA ER
Benzodiazepines
and Other Central Nervous System (CNS) Depressants
Under Intervention, the
following language is added:
If concomitant use is warranted, consider prescribing naloxone for the
emergency treatment of opioid overdose [see Dosage and Administration (2.2),
Warnings and Precautions (5.1, 5.3, 5.5)].
Muscle Relaxants
Under Intervention, the
following language is added:
Due to the risk of
respiratory depression with concomitant use of skeletal muscle relaxants and
opioids, consider prescribing naloxone for the emergency treatment of opioid
overdose
[see Dosage and Administration (2.2), Warnings and Precautions (5.3,
5.5)]
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Life-Threatening
Respiratory Depression
Newly added information:
Educate patients
and caregivers on how to recognize respiratory depression and emphasize the
importance of calling 911 or getting emergency medical help right away in the
event of a known or suspected overdose [see
Warnings and Precautions (5.3)].
Newly added information:
Patient Access to
Naloxone for the Emergency Treatment of Opioid Overdose
Discuss with the
patient and caregiver the availability of naloxone for the emergency treatment
of opioid overdose, both when initiating and renewing treatment with NUCYNTA
ER. Inform patients and caregivers about the various ways to obtain naloxone as
permitted by individual state naloxone dispensing and prescribing requirements
or guidelines (e.g., by prescription, directly from a pharmacist, or as part of
a community-based program) [see Dosage
and Administrations (2.2), Warnings and Precautions (5.3)].
Educate patients
and caregivers on how to recognize the signs and symptoms of an overdose.
Explain to
patients and caregivers that naloxone’s effects are temporary, and that they
must call 911 or get emergency medical help right away in all cases of known or
suspected opioid overdose, even if naloxone is administered [see Overdosage (10)].
If naloxone is
prescribed, also advise patients and caregivers:
How
to treat with naloxone in the event of an opioid overdose
To
tell family and friends about their naloxone and to keep it in a place where
family and friends can access it in an emergency
To
read the Patient Information (or other educational material) that will come
with their naloxone. Emphasize the importance of doing this before an opioid
emergency happens, so the patient and caregiver will know what to do.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.3
Life-Threatening Respiratory Depression
Newly added
information to end of subsection:
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.
Additions and/or
revisions underlined:
5.7 Serotonin
Syndrome with Concomitant Use of Serotonergic Drugs
Cases 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), certain muscle relaxants (i.e.,
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)
5.13 Withdrawal
Do 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 …
7
Drug Interactions
Table 3: Clinically Significant Drug
Interactions with NUCYNTA ER
Serotonergic Drugs
Additions and/or
revisions underlined:
Example: Selective serotonin reuptake inhibitors
(SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants
(TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin
neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e.,
cyclobenzaprine, metaxalone), monoamine oxidase (MAO)
inhibitors (those intended to treat psychiatric disorders and also others, such
as linezolid and intravenous methylene blue).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or
revisions underlined in bulleted information:
Important
information about NUCYNTA ER:
Store NUCYNTA ER securely, out
of sight and reach of children, and in a location not accessible by others,
including visitors to the home.
When taking NUCYNTA ER:
Dispose of expired,
unwanted, or unused NUCYNTA ER by promptly flushing down the toilet, if a drug
take-back option is not readily available. Visit www.fda.gov/drugdisposal for
additional information on disposal of unused medicines.
PATIENT COUNSELING INFORMATION
Storage and Disposal:
Additions and/or
revisions underlined:
Because of the
risks associated with accidental ingestion, misuse, and abuse, advise patients
to store NUCYNTA ER securely, out of sight and reach of children, and in a
location not accessible by others, including visitors to the home. Inform
patients that leaving NUCYNTA ER unsecured can pose a deadly risk to others in
the home.
Advise patients
and caregivers that when medicines are no longer needed, they should be
disposed of promptly. Expired, unwanted, or unused NUCYNTA ER should be
disposed of by flushing the unused medication down the toilet if a drug
take-back option is not readily available. Inform patients that they can visit
www.fda.gov/drugdisposal
for a complete list of medicines recommended for disposal by flushing, as well
as additional information on disposal of unused medicines.
Newly added titled
section:
Important Discontinuation Instructions
In order to
avoid developing withdrawal symptoms, instruct patients not to discontinue NUCYNTA
ER without first discussing a tapering plan with the prescriber.
Approved Drug Label (PDF)
Boxed Warning
(Additions and/or revisions are underlined)
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
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.
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
4
Contraindications
(Additions and/or revisions are underlined)
NUCYNTA ER is contraindicated in:
- Known or suspected gastrointestinal
obstruction, including paralytic ileus
- Concurrent use of
monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the
last 14 days
5
Warnings and Precautions
5.1 Addiction, Abuse, and Misuse
(Additions and/or revisions are underlined)
…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.
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…
5.10 Risks of Use in Patients with Gastrointestinal Conditions
(Revised subsection
title; Additions and/or revisions are
underlined)
NUCYNTA ER is contraindicated in patients with known or
suspected gastrointestinal obstruction, including paralytic ileus.
… Opioids may cause
increases in serum amylase…
5.11 Increased Risk of Seizures in Patients with Seizure Disorders
(Revised subsection
title; Additions and/or revisions are
underlined)
The tapentadol in NUCYNTA ER may increase the frequency
of seizures in patients with seizure disorders, and may increase the risk of
seizures occurring in other clinical settings associated with seizures…
5.12 Withdrawal
(Revised subsection
title; Additions and/or revisions are
underlined)
When discontinuing NUCYNTA
ER, gradually taper the dose.
Do not abruptly discontinue NUCYNTA ER.
5.13 Risks of Driving and Operating Machinery
(Revised subsection
title)
5.14 Risk of Toxicity in Patients with Hepatic Impairment
(Revised subsection title)
5.15 Risk of Toxicity in Patients with Renal Impairment
(Revised subsection title)
5.2 Life-Threatening Respiratory Depression
(Additions and/or revisions are underlined)
…Monitor patients closely for respiratory depression especially
within the first 24-72 hours of initiating therapy with and following dosage
increases of NUCYNTA ER.
5.3 Neonatal Opioid Withdrawal Syndrome
(Additions and/or revisions are underlined)
…Observe newborns for signs of neonatal opioid withdrawal
syndrome and manage accordingly…
5.4 Risk from Concomitant Use with Benzodiazepines or Other CNS Depressants
(Revised subsection
title; Additions and/or revisions are
underlined)
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 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.
5.5 Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients
(Revised subsection
title; Additions and/or revisions are
underlined)
The 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.
5.6 Serotonin Syndrome with Concomitant Use of Serotonergic Drugs
(Revised subsection title; Additions and/or
revisions are underlined)
…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)…
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.
5.7 Adrenal Insufficiency
(Newly added subsection)
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.
5.8 Severe Hypotension
(Revised subsection
title; Additions and/or revisions are
underlined)
NUCYNTA ER may cause severe hypotension including
orthostatic hypotension and syncope in ambulatory patients…
5.9 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness
(Revised subsection
title)
6
Adverse Reactions
(Additions and/or revisions are underlined)
The following serious adverse reactions are described, or
described in greater detail, in other sections:
- Interaction with Benzodiazepine
or Other CNS Depressants
- Adrenal Insufficiency
- Severe Hypotension
- Gastrointestinal Adverse
Reactions
- Withdrawal
6.2 Postmarketing Experience
The following adverse reactions have been identified during post
approval use of tapentadol...
Serotonin syndrome: Cases of serotonin syndrome, a
potentially life-threatening condition, have been reported during
concomitant use of opioids with serotonergic drugs.
Adrenal insufficiency: Cases of adrenal insufficiency
have been reported with opioid use, more often following greater than one month
of use.
Anaphylaxis: Anaphylaxis has been reported with
ingredients contained in NUCYNTA ER.
Androgen deficiency: Cases of androgen deficiency have
occurred with chronic use of opioids.
7
Drug Interactions
(Additions and/or revisions are underlined)
Table 3 includes clinically significant drug interactions
with NUCYNTA ER. (Table has been added; please refer to
label)
8
Use in Specific Populations
8.1 Pregnancy
(Additions and/or revisions are underlined;
Pregnancy and Lactation Labeling Rule (PLLR) Conversion)
Risk Summary
Prolonged use of opioid analgesics during pregnancy may
cause neonatal opioid withdrawal syndrome.
Available data with NUCYNTA ER are insufficient to inform a drug-
associated risk for major birth defects and miscarriage. In animal reproduction
studies, embryofetal mortality and structural malformations were observed with
subcutaneous administration of tapentadol during organogenesis to rabbits and
delays in skeletal maturation were observed in rats at exposures equivalent to
and less than the maximum recommended human dose (MRHD), respectively. When administered to pregnant rats during
organogenesis and through lactation, increased pup mortality was noted
following oral tapentadol exposures to doses equivalent to the MRHD. Based on
animal data, advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and
miscarriage for the indicated population is unknown. Adverse outcomes in
pregnancy can occur regardless of the health of the mother or the use of
medications. In the U.S. general population, the estimated background risk of
major birth defects and miscarriage in clinically recognized pregnancies is
2-4% and 15-20%, respectively.
Clinical Considerations
Labor or Delivery
Opioids cross the placenta and may produce respiratory
depression and psychphysiologic effects in neonates. An opioid
antagonist, such as naloxone, must be available for reversal of opioid-induced
respiratory depression in the neonate. NUCYNTA ER is not recommended for
use in pregnant women during and immediately prior to labor, when
use of shorter-acting analgesics or other analgesic techniques are more
appropriate… Monitor
neonates exposed to opioid analgesics during labor for signs of excess sedation
and respiratory depression.
8.2 Lactation
(Additions and/or revisions are underlined;
Pregnancy and Lactation Labeling Rule (PLLR) Conversion)
Risk Summary
…Because of the potential for serious adverse reactions
including excess sedation and respiratory depression in a breastfed
infant, advise patients that breast feeding is not recommended during treatment
with NUCYNTA ER.
Clinical Considerations
Monitor infants exposed to NUCYNTA ER
through breast milk for excess sedation and respiratory depression.
Withdrawal symptoms can occur in breastfed infants when maternal administration
of an opioid analgesic is stopped, or when breast-feeding is stopped.
8.3 Females and Males of Reproductive Potential
(Additions and/or revisions are underlined;
Pregnancy and Lactation Labeling Rule (PLLR) Conversion)
Infertility
Chronic use of opioids may cause reduced fertility in
females and males of reproductive potential. It is not known whether these
effects on fertility are reversible.
8.5 Geriatric Use
(Additions and/or revisions are underlined)
Elderly patients (aged 65 or older) may have increased
sensitivity to tapentadol. In general, use caution when selecting a
dosage for an elderly patient, usually starting at the low end of
the dosing range, reflecting the greater frequency of decreased hepatic, renal,
or cardiac function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly
patients treated with opioids, and has occurred after large initial doses were
administered to patients who were not opioid-tolerant or when opioids were
co-administered with other agents that depress respiration. Titrate the
dosage of NUCYNTA ER slowly in geriatric patients and monitor closely for signs
of central nervous system and respiratory depression.
Tapentadol is known to be substantially excreted by the kidney,
and the risk of adverse reactions to this drug may be greater in patients with
impaired renal function. Because
elderly patients are more likely to have decreased renal function, care
should be taken in dose selection,
and it may be useful to monitor renal function.
8.6 Hepatic Impairment
(Additions and/or revisions are underlined)
Use of NUCYNTA ER in patients with severe hepatic
impairment (Child-Pugh Score 10-15) is not recommended. In patients with
moderate hepatic impairment (Child-Pugh Score 7 to 9), dosage reduction of
NUCYNTA ER is recommended. No
dosage adjustment is recommended in patients with mild hepatic
impairment (Child-Pugh Score 5 to 6).
8.7 Renal Impairment
(Additions and/or revisions are underlined)
Use of NUCYNTA ER in patients with severe renal
impairment (creatinine clearance less than 30 mL/minute) is not
recommended. No dosage adjustment is recommended in patients with mild or
moderate renal impairment (creatinine clearance 30-90 mL/minute).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions are underlined)
Interactions with Benzodiazepines and other CNS
Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if
NUCYNTA ER is used with benzodiazepines or other CNS depressants,
including and not to use these concomitantly unless supervised by a
health care provider
Serotonin Syndrome
…Instruct patients to inform their healthcare providers
if they are taking, or plan to take serotonergic medications.
MAOI Interaction
Inform patients not to take NUCYNTA ER while using any
drugs that inhibit monoamine oxidase. Patients should not start MAOIs while
taking NUCYNTA ER.
Adrenal Insufficiency
Inform patients that opioids could cause adrenal
insufficiency, a potentially life- threatening condition. Adrenal insufficiency
may present with non-specific symptoms and signs such as nausea, vomiting,
anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients
to seek medical attention if they experience a constellation of these symptoms.
Pregnancy
Neonatal Opioid
Withdrawal Syndrome
Inform female patients of reproductive potential that
prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid
withdrawal syndrome, which may be life-threatening if not recognized and
treated.
Lactation
Advise patients that breastfeeding is not recommended
during treatment with NUCYNTA ER.
Infertility
Inform patients that chronic use of opioids may cause
reduced fertility. It is not known whether these effects on fertility are
reversible.
Medication Guide
(Additions and/or revisions are underlined)
Important information
about NUCYNTA ER:
- Taking NUCYNTA ER with
other opioid medicines, benzodiazepines, alcohol, or other central nervous
system depressants (including street drugs) can cause severe drowsiness,
decreased awareness, breathing problems, coma, and death.
Tell your healthcare
provider if you are:
- breastfeeding. Not recommended during treatment with NUCYNTA
ER…
When taking NUCYNTA
ER:
- Do not change your dose.
Take NUCYNTA ER exactly as prescribed by your healthcare provider. Use
the lowest effective dose for the shortest time needed.
Get emergency medical
help if you have:
- trouble breathing,
shortness of breath, fast heartbeat, chest pain, swelling of your face,
tongue, or throat, extreme drowsiness, light- headedness when changing
positions, feeling faint, agitation, high body temperature, trouble
walking, stiff muscles, or mental changes such as confusion.
Marketed by: Depomed, Inc (of which Depo NF Sub, LLC is a
subsidiary) Newark, CA 94560
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