HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`NUCYNTA® ER safely and effectively. See full prescribing information
`for NUCYNTA® ER
`
`NUCYNTA® ER (tapentadol) extended-release tablets for oral use C-II
`Initial U.S. Approval: 2008
`WARNING: ADDICTION, ABUSE, AND MISUSE; RISK
`EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
`INTERACTION WITH ALCOHOL and RISKS FROM
`CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER
`CNS DEPRESSANTS
`See full prescribing information for complete boxed warning.
`NUCYNTA ER exposes users to risks of addiction, abuse, and
`misuse, which can lead to overdose and death. Assess each patient’s
`risk before prescribing, and monitor regularly for development of
`these behaviors or conditions. (5.1)
`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. (5.2)
`Serious, life-threatening, or fatal respiratory depression may occur.
`Monitor closely, especially upon initiation or following a dose
`increase. Instruct patients to swallow NUCYNTA ER tablets whole
`to avoid exposure to a potentially fatal dose of tapentadol. (5. 3)
`Accidental ingestion of NUCYNTA ER, especially in children, can
`result in fatal overdose of tapentadol. (5.3)
`Prolonged use of NUCYNTA ER during pregnancy can result in
`neonatal opioid withdrawal syndrome, which may be life-
`threatening if not recognized and treated. 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 (5.4).
`Instruct patients not to consume alcohol or any products containing
`alcohol while taking NUCYNTA ER because co-ingestion can result
`in fatal plasma tapentadol levels. (5.5)
`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 for use in patients for whom
`alternative treatment options are inadequate; limit dosages and
`durations to the minimum required; and follow patients for signs
`and symptoms of respiratory depression and sedation. (5.5), (7).
`
`•
`
`•
`
`•
`
`•
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`•
`
`•
`
`•
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`
`
`
`—————————RECENT MAJOR CHANGES————————
`Dosage and Administration (2.5)
`
`
`10/2019
`Warnings and Precautions (5.3, 5.13)
`
`
`10/2019
`—————————INDICATIONS AND USAGE————————
`NUCYNTA ER is an opioid agonist 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 (1)
`neuropathic pain associated with diabetic peripheral neuropathy (DPN)
`in adults severe enough to require daily, around-the-clock, long-term
`opioid treatment and for which alternative treatment options are
`inadequate. (1)
`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. (1)
`
`———————DOSAGE AND ADMINISTRATION———————
`•
`To be prescribed only by healthcare providers knowledgeable in use of
`potent opioids for management of chronic pain. (2.1)
`• Use the lowest effective dosage for the shortest duration consistent with
`individual patient treatment goals (2.1).
`Individualize dosing based on the severity of pain, patient response,
`prior analgesic experience, and risk factors for addiction, abuse, and
`
`•
`
`•
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`
`
`Reference ID: 4501042
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`
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`•
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`•
`
`•
`
`•
`
`misuse. (2.1)
`Instruct patients to swallow NUCYNTA ER tablets intact, and not to
`cut, break, chew, crush, or dissolve the tablets (risk of potentially fatal
`overdose). (2.1, 5.1)
`Instruct patients to take tablets one at a time, with enough water to
`ensure complete swallowing immediately after placing in mouth. (2.1)
`For opioid-naïve and opioid non-tolerant patients, initiate treatment
`with 50 mg tablet orally twice daily (approximately every 12 hours).
`See full prescribing information for instructions on conversion, titration,
`and maintenance of therapy. (2.2, 2.3)
`Titrate patients with dose increases of 50 mg no more than twice daily
`every three days. (2.3)
`• Maximum daily dose is 500 mg per day. (2.1)
`• Moderate Hepatic Impairment: Initiate treatment with 50 mg
`NUCYNTA ER no more than every 24 hours. Do not exceed 100 mg
`per day. Monitor closely for respiratory and central nervous system
`depression (2.4)
`• Do not abruptly discontinue NUCYNTA ER in a physically-dependent
`patient because rapid discontinuation of opioid analgesics has resulted
`in serious withdrawal symptoms, uncontrolled pain, and suicide.(2.5)
`
`———————DOSAGE FORMS AND STRENGTHS——————
`Extended-release tablets: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg (3)
`
`•
`
`•
`
`
`——————————CONTRAINDICATIONS—————————
`•
`Significant respiratory depression (4)
`• Acute or severe bronchial asthma (4)
`• Known or suspected paralytic ileus (4)
`• Hypersensitivity to tapentadol or to any other ingredients of the product
`(4)
`• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of
`MAOIs within the last 14 days. (4)
`
`———————WARNINGS AND PRECAUTIONS———————
`• Risk of Life-Threatening Respiratory Depression in Patients with
`Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated
`Patients: Monitor closely, particularly during initiation and titration.
`(5.1)
`Serotonin Syndrome: Potentially life-threatening condition could result
`from concomitant serotonergic drug administration. Discontinue
`NUCYNTA ER if serotonin syndrome is suspected. (5.7)
`• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement
`of corticosteroids, and wean patient off of the opioid. (5.8)
`Severe Hypotension: Monitor during dosage initiation and titration.
`Avoid use of NUCYNTA ER in patients with circulatory shock. (5.9)
`• Risks of Use in Patients with Increased Intracranial Pressure, Brain
`Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation
`and respiratory depression. Avoid use of NUCYNTA ER in patients
`with impaired consciousness or coma. (5.10)
`
`—————————— ADVERSE REACTIONS—————————
`The most common (≥10%) adverse reactions were nausea, constipation,
`dizziness, headache, and somnolence. (6)
`To report SUSPECTED ADVERSE REACTIONS, contact
`Collegium Pharmaceutical, Inc. at 1-855-331-5615 or FDA at 1–
`800–FDA–1088 or www.fda.gov/medwatch.
`
`——————————DRUG INTERACTIONS—————————
`• Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics:
`Avoid use with NUCYNTA ER because they may reduce analgesic
`effect of NUCYNTA ER or precipitate withdrawal symptoms. (5.13, 7)
`
`
`——————— USE IN SPECIFIC POPULATIONS———————
`•
`Pregnancy: Based on animal data, may cause fetal harm. (8.1)
`• Nursing mothers: Nursing is not recommended. (8.2)
`•
`Severe Hepatic or Renal Impairment: Use not recommended. (8.6,
`8.7)
`See 17 for PATIENT COUNSELING INFORMATION and
`Medication Guide.
`
`Revised: 10/2019
`
`

`

`FULL PRESCRIBING INFORMATION: CONTENTS*
` WARNING: ADDICTION, ABUSE, AND MISUSE; RISK
`EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
`INTERACTION WITH ALCOHOL and RISKS FROM
`CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS
`DEPRESSANTS
`1
`INDICATIONS AND USAGE
`DOSAGE AND ADMINISTRATION
`2
`Important Dosage and Administration Instructions
`2.1
`2.2
`Initial Dosage
`2.3
`Titration and Maintenance of Therapy
`2.4
`Dosage Modification in Patients with Hepatic Impairment
`2.5
`Safe Reduction or Discontinuation of NUCYNTA ER
`DOSAGE FORMS AND STRENGTHS
`3
`CONTRAINDICATIONS
`4
`5 WARNINGS AND PRECAUTIONS
`Addiction, Abuse, and Misuse
`5.1
`5.2
`Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
`5.3
`Life-Threatening Respiratory Depression
`5.4
`Neonatal Opioid Withdrawal Syndrome
`5.5
`Risk from Concomitant Use with Benzodiazepines or Other CNS
`Depressants
`Risk of Life-Threatening Respiratory Depression in Patients with
`Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated
`Patients
`Serotonin Syndrome with Concomitant Use of Serotonergic Drugs
`5.7
`Adrenal Insufficiency
`5.8
`Severe Hypotension
`5.9
`5.10 Risks of Use in Patients with Increased Intracranial Pressure, Brain
`Tumors, Head Injury, or Impaired Consciousness
`5.11 Risks of Use in Patients with Gastrointestinal Conditions
`Increased Risk of Seizures in Patients with Seizure Disorders
`5.12
`5.13 Withdrawal
`5.14 Risks of Driving and Operating Machinery
`5.15 Risk of Toxicity in Patients with Hepatic Impairment
`5.16 Risk of Toxicity in Patients with Renal Impairment
`
`
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`
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`ADVERSE REACTIONS
`Clinical Trial Experience
`6.1
`6.2
`Postmarketing Experience
`DRUG INTERACTIONS
`
`USE IN SPECIFIC POPULATIONS
`Pregnancy
`8.1
`8.2
`Lactation
`8.3
`Females and Males of Reproductive Potential
`8.4
`Pediatric Use
`8.5
`Geriatric Use
`8.6
`Hepatic Impairment
`8.7
`Renal Impairment
`DRUG ABUSE AND DEPENDENCE
`Controlled Substance
`9.1
`9.2
`Abuse
`9.3
`Dependence
`OVERDOSAGE
`10.1 Clinical Presentation
`Treatment of Overdose
`10.2
`DESCRIPTION
`
`12
`
`13
`
`14
`
`CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`Pharmacodynamics
`12.2
`12.3
`Pharmacokinetics
`NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`13.2 Animal Toxicology and/or Pharmacology
`CLINICAL STUDIES
`14.1 Clinical Trials Summary
`14.2 Moderate to Severe Chronic Low Back Pain
`14.3 Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
`HOW SUPPLIED/STORAGE AND HANDLING
`16
`17 PATIENT COUNSELING INFORMATION
`
`
`*Sections or subsections omitted from the full prescribing information
`are not listed
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`5.6
`
`Reference ID: 4501042
`
`

`

`
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`
`
`FULL PRESCRIBING 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 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 [see
`Warnings and Precautions (5.1)].
`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 [see Warnings and
`Precautions (5.2)]. Under the requirements of the REMS, drug companies with approved opioid
`analgesic products must make REMS-compliant education programs available to healthcare providers.
`Healthcare providers are strongly encouraged to
`• complete a REMS-compliant education program,
`• counsel patients and/or their caregivers, with every prescription, on safe use, serious risks,
`storage, and disposal of these products,
`• emphasize to patients and their caregivers the importance of reading the Medication Guide
`every time it is provided by their pharmacist, and
`• consider other tools to improve patient, household, and community safety.
`
`
`Life-threatening Respiratory Depression
`Serious, life-threatening, or fatal respiratory depression may occur with use of NUCYNTA ER.
`Monitor for respiratory depression, especially during initiation of NUCYNTA ER or following a
`dose increase. Instruct patients to swallow NUCYNTA ER tablets whole; crushing, chewing, or
`dissolving NUCYNTA ER tablets can cause rapid release and absorption of a potentially fatal dose
`of tapentadol [see Warnings and Precautions (5.3)].
`
`Accidental Ingestion
`Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in a
`fatal overdose of tapentadol [see Warnings and Precautions (5.3)].
`
`Neonatal Opioid Withdrawal Syndrome
`Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal
`syndrome, which may be life-threatening if not recognized and treated, and requires management
`according to protocols developed by neonatology experts. If opioid use is required for a prolonged
`period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome
`and ensure that appropriate treatment will be available [see Warnings and Precautions (5.4)].
`Interaction with Alcohol
`Instruct patients not to consume alcoholic beverages or use prescription or non-prescription
`products that contain alcohol while taking NUCYNTA ER. The co-ingestion of alcohol with
`
`Reference ID: 4501042
`
`

`

`NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose
`of tapentadol [see Warnings and Precautions (5.5)].
`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 [see
`Warnings and Precautions (5.5), Drug Interactions (7)].
`• 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
`
`1
`
`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 [see
`Warnings and Precautions (5.1)], 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.
`
`2
`2.1
`
`DOSAGE AND ADMINISTRATION
`Important Dosage and Administration Instructions
`
`
`
`
`
`
`
`
`•
`
`NUCYNTA ER should be prescribed only by healthcare professionals who are knowledgeable in the use of
`potent opioids for the management of chronic pain.
`• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment
`goals [see Warnings and Precautions (5)].
`Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain,
`patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse
`[see Warnings and Precautions (5.1)]
`• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating
`therapy and following dosage increases with NUCYNTA ER and adjust the dosage accordingly [see
`Warnings and Precautions (5.3)].
`Instruct patients to swallow NUCYNTA ER tablets whole, one tablet at a time, with enough water to ensure
`complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].
`Crushing, chewing, or dissolving NUCYNTA ER tablets will result in uncontrolled delivery of tapentadol and
`can lead to overdose or death [see Warnings and Precautions (5.1)].
`
`
`Reference ID: 4501042
`
`

`

`Discontinue all other tapentadol and tramadol products when beginning and while taking NUCYNTA ER
`[see Warnings and Precautions (5.7)]. Although the maximum approved total daily dose of NUCYNTA
`immediate-release formulation is 600 mg per day, the maximum total daily dose of NUCYNTA ER is 500
`mg. Do not exceed a total daily dose of NUCYNTA ER of 500 mg.
`Initial Dosage
`2.2
`
`Use of NUCYNTA ER as the First Opioid Analgesic (opioid-naïve patients)
`
`Initiate treatment with NUCYNTA ER with the 50 mg tablet orally twice daily (approximately every 12
`hours).
`
`Use of NUCYNTA ER in Patients who are not Opioid Tolerant
`
`The starting dose for patients who are not opioid tolerant is NUCYNTA ER 50 mg orally twice daily
`(approximately every 12 hours). Use of higher starting doses in patients who are not opioid tolerant may cause
`fatal respiratory depression.
`
`Conversion from NUCYNTA to NUCYNTA ER
`
`Patients can be converted from NUCYNTA to NUCYNTA ER using the equivalent total daily dose of
`NUCYNTA and dividing it into two equal doses of NUCYNTA ER separated by approximately 12-hour
`intervals. As an example, a patient receiving 50 mg of NUCYNTA four times per day (200 mg/day) may be
`converted to 100 mg NUCYNTA ER twice a day.
`
`Conversion from Other Opioids to NUCYNTA ER
`
`There are no established conversion ratios for conversion from other opioids to NUCYNTA ER defined by
`clinical trials. Initiate dosing using NUCYNTA ER 50 mg orally every 12 hours.
`
`It is safer to underestimate a patient’s 24-hour oral tapentadol dosage and provide rescue medication (e.g.,
`immediate-release opioid) than to overestimate the 24-hour oral tapentadol requirements which could result in an
`adverse reaction due to an overdose. While useful tables of opioid equivalents are readily available, there is
`inter-patient variability in the potency of opioid drugs and opioid formulations.
`
`Close observation and frequent titration are warranted until pain management is stable on the new opioid.
`Monitor patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after
`converting patients to NUCYNTA ER.
`
`Conversion from Methadone to NUCYNTA ER
`
`Close monitoring is of particular importance when converting from methadone to other opioid agonists. The
`ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure.
`Methadone has a long half-life and can accumulate in the plasma.
`Titration and Maintenance of Therapy
`2.3
`
`Individually titrate NUCYNTA ER to a dose that provides adequate analgesia and minimizes adverse
`reactions. Continually reevaluate patients receiving NUCYNTA ER to assess the maintenance of pain
`control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction,
`abuse, or misuse [see Warnings and Precautions (5.1)]. Frequent communication is important among the
`Reference ID: 4501042
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`prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of
`changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the
`continued need for opioid analgesics.
`
`Patients who experience breakthrough pain may require a dosage adjustment of NUCYNTA ER, or may need
`rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases
`after dose stabilization, attempt to identify the source of increased pain before increasing the NUCYNTA ER
`dosage. Titrate patients to adequate analgesia with dose increases of 50 mg no more than twice daily every three
`days. In clinical studies, efficacy with NUCYNTA ER was demonstrated relative to placebo in the dosage range
`of 100 mg to 250 mg twice daily [see Clinical Studies (14)].
`
`If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage
`to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
`Dosage Modification in Patients with Hepatic Impairment
`2.4
`
`The use of NUCYNTA ER in patients with severe hepatic impairment (Child-Pugh Score 10-15) is not
`recommended [see Warnings and Precautions (5.15)].
`
`In patients with moderate hepatic impairment (Child-Pugh Score 7 to 9), initiate treatment using 50 mg
`NUCYNTA ER, administer no more frequently than once every 24 hours, and monitor closely for respiratory and
`central nervous system depression, particularly during initiation and titration of NUCYNTA ER. The maximum
`recommended dose for patients with moderate hepatic impairment is 100 mg of NUCYNTA ER per day. Monitor
`closely for respiratory and central nervous system depression [see Clinical Pharmacology (12.2)].
`
`No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5 to 6)
`[see Warnings and Precautions (5.15), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
`Safe Reduction or Discontinuation of NUCYNTA ER
`2.5
`
`Do not abruptly discontinue NUCYNTA ER in patients who may be physically dependent on opioids. Rapid
`discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious
`withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with
`attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.
`Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and
`other substances.
`
`When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient
`taking NUCYNTA ER, there are a variety of factors that should be considered, including the dose of
`NUCYNTA ER the patient has been taking, the duration of treatment, the type of pain being treated, and the
`physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to
`agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and
`expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected
`substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use
`disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid
`use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a
`specialist.
`
`There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates
`a patient-specific plan to taper the dose of the opioid gradually. For patients on NUCYNTA ER who are
`physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25%
`Reference ID: 4501042
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`

`

`of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every
`2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
`
`It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper.
`Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common
`withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and
`mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain,
`weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure,
`respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period
`of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In
`addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.
`
`When managing patients taking opioid analgesics, particularly those who have been treated for a long duration
`and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including
`mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal
`approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful
`tapering of the opioid analgesic [see Warnings and Precautions (5.13), Drug Abuse and Dependence (9.3)].
`
`3
`
`DOSAGE FORMS AND STRENGTHS
`
`NUCYNTA ER 50 mg, 100 mg, 150 mg, 200 mg and 250 mg extended-release tablets are available in the
`following colors and prints:
`• 50 mg extended-release tablets are white oblong-shaped with a black print “OMJ 50” on one side
`• 100 mg extended-release tablets are light-blue oblong-shaped with a black print “OMJ 100” on one
`side
`• 150 mg extended-release tablets are blue-green oblong-shaped with a black print “OMJ 150” on one
`side
`• 200 mg extended-release tablets are blue oblong-shaped with a depression in the middle running
`lengthwise on each side and a black print “OMJ 200” on one side
`• 250 mg extended-release tablets are dark blue oblong-shaped with a depression in the middle running
`lengthwise on each side and a white print “OMJ 250” on one side.
`
`4
`
`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
`see Adverse Reactions (6.2)].
`• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see
`Drug Interactions (7)].
`
`
`
`
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`Reference ID: 4501042
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`5
`5.1
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`WARNINGS AND PRECAUTIONS
`Addiction, Abuse, and Misuse
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`NUCYNTA 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 [see Drug Abuse and Dependence (9)].
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`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.
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`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.
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`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 [see Overdosage (10)].
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`Opioid 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 [see Patient Counseling Information (17)]. 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.
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`5.2 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.
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`Reference ID: 4501042
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`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 Depression
`5.3
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`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 [see Overdosage (10)].
`Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects
`of opioids.
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`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.
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`To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential [see
`Dosage and Administration (2)]. Overestimating the NUCYNTA ER dosage when converting patients from
`another opioid product can result in fatal overdose with the first dose.
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`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.
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`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
`(2.5)].
`5.4
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`Neonatal Opioid Withdrawal Syndrome
`
`Prolonged 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 man