`
`
` 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).
`
`
`
`
`
`
`
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`—————————RECENT MAJOR CHANGES————————
`
`03/2021
`Dosage and Administration (2.2)
`
`
`
`
`Warnings and Precautions (5.1, 5.3, 5.5)
`03/2021
`
`
`
`
`
`—————————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
`
`
`
`
`
`
`
`•
`
`Reference ID: 4756514
`
`
`
`
`
`•
`
`
`•
`
` 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)
`
`
`
`
`
` • Do not exceed a total daily dose of NUCYNTA ER of 500 mg. (2.1)
`
`
`
` • Discuss availability of naloxone with the patient and caregiver and
`
`
`
`
`
`
` assess each patient’s need for access to naloxone, both when initiating
`
` and renewing treatment with NUCYNTA ER. Consider prescribing
`
`
` naloxone based on the patient’s risk factors for overdose (2.2, 5.1, 5.3,
`
`
`
` 5.5).
`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 (2.3, 2.4)
`
`•
` Titrate patients with dose increases of 50 mg no more than twice daily
`
`
`
`
` every three days. (2.4)
`
` • 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 (2.5)
`
`
` • 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, andsuicide. (2.6)
` ———————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: 03/2021
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`ADVERSE REACTIONS
`6
`
`
`
`
`
`Clinical Trial Experience
`
`6.1
`
`
`
`Postmarketing Experience
`
`6.2
`
`DRUG INTERACTIONS
`7
`
`
`USE IN SPECIFIC POPULATIONS
`8
`
`
`
`
`Pregnancy
`
`8.1
`
`
`Lactation
`
`8.2
`
`
`
`Females and Males of Reproductive Potential
`
`8.3
`
`
`
`Pediatric Use
`
`8.4
`
`
`
`Geriatric Use
`
`8.5
`
`
`
`Hepatic Impairment
`
`8.6
`
`
`
`Renal Impairment
`
`8.7
`
`DRUG ABUSE AND DEPENDENCE
`9
`
`
`
`
`Controlled Substance
`
`9.1
`
`
`Abuse
`
`9.2
`
`
`Dependence
`
`9.3
`10 OVERDOSAGE
`
`
`11
`DESCRIPTION
`
`
`
`12
`CLINICAL PHARMACOLOGY
`
`
`
`
`12.1
`Mechanism of Action
`
`
`
`12.2
`Pharmacodynamics
`
`
`
`12.3
`Pharmacokinetics
`
`
`NONCLINICAL TOXICOLOGY
`13
`
`
`
`
`13.1
`Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`
`
`
`13.2
`Animal Toxicology and/or Pharmacology
`
`
`14
`CLINICAL STUDIES
`
`
`
`
`14.1
`Clinical Trials Summary
`
`
`
`
`14.2
`Moderate to Severe Chronic Low Back Pain
`
`
`
`
`
`14.3
`Neuropathic Pain Associated with Diabetic PeripheralNeuropathy
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`
`17
`PATIENT COUNSELING INFORMATION
`
`
`
`
`*Sections or subsections omitted from the full prescribing information are not
`
`listed
`
`
`
`
`2.3
`
`2.4
`
`2.5
`
`2.6
`3
`
`4
`
`5
`
`
`5.1
`
`5.2
`
`5.3
`
`5.4
`
`5.5
`
`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
`
`
`INDICATIONS AND USAGE
`1
`
`
`
`2
`DOSAGE AND ADMINISTRATION
`
`
`
`
`
`
`2.1
`Important Dosage and Administration Instructions
`
`
`
`
`2.2
`Patient Access to Naloxone for the Emergency Treatment of Opioid
`
`
`Overdose
`
`
`
`Initial Dosage
`
`
`
`
`Titration and Maintenance ofTherapy
`
`
`
`Dosage Modification in Patients with HepaticImpairment
`
`
`
`Safe Reduction or Discontinuation of NUCYNTA ER
`
`
`
`DOSAGE FORMS AND STRENGTHS
`
`CONTRAINDICATIONS
`
`
`WARNINGS AND PRECAUTIONS
`
`
`Addiction, Abuse, and Misuse
`
`
`
`Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
`
`
`
`Life-Threatening Respiratory Depression
`
`
`
`Neonatal Opioid Withdrawal Syndrome
`
`
`Risk from Concomitant Use with Benzodiazepines or Other CNS
`
`
`Depressants
`
`
`
`
`
`
`
`
`
`
`RiskofLife-ThreateningRespiratoryDepressioninPatientswithChronic
`
`
`
`
`
`
`PulmonaryDisease or in Elderly, Cachectic, or Debilitated Patients
`
`
`
`
`
`Serotonin Syndrome with Concomitant Use of SerotonergicDrugs
`
`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 HepaticImpairment
`
`
`
`
`5.16
`Risk of Toxicity in Patients with Renal Impairment
`
`
`
`5.6
`
`Reference ID: 4756514
`
`
`
`
`
` 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 communitysafety.
`
`
`
`
`
`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)].
`
`
`
`
`Reference ID: 4756514
`
`
`
` 3
`
`
`
`
`
` Interaction with Alcohol
`
`
`Instruct patients not to consume alcoholic beverages or use prescription or non
`
`prescription products that contain alcohol while taking NUCYNTA ER. The co-
`
`
`
`
`ingestion of alcohol with NUCYNTA ER may result in increased plasma
`
`tapentadol levels and a potentially fatal overdose of tapentadol [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
`
`
`
`
`
`
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`•
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`Reference ID: 4756514
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` 4
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` addiction, abuse, and misuse [see Warnings and Precautions (5.1)]
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` • Monitor patients closely for respiratory depression, especially within the first 24-72 hours
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` of initiating therapy and following dosage increases with NUCYNTA ER and adjust the
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` dosage accordingly [see Warnings and Precautions (5.3)].
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` Instruct patients to swallow NUCYNTA ER tablets whole, one tablet at a time, with enough water to
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` ensure complete swallowing immediately after placing in the mouth [see Patient Counseling
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` Information (17)].
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` Crushing, chewing, or dissolving NUCYNTA ER tablets will result in uncontrolled delivery of
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` tapentadol and can lead to overdose or death [see Warnings and Precautions (5.1)].
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` Discontinue all other tapentadol and tramadol products when beginning and while taking
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` NUCYNTA ER [see Warnings and Precautions (5.7)]. Although the maximum approved
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` total daily dose of NUCYNTA immediate-release formulation is 600 mg per day, the
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` maximum total daily dose of NUCYNTA ER is 500 mg. Do not exceed a total daily dose of
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` NUCYNTA ER of 500 mg.
` Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose
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` 2.2
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` Discuss the availability of naloxone for the emergency treatment of opioid overdose with
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`the patient and caregiver and assess the potential need for access to naloxone, both when
` initiating and renewing treatment with NUCYNTA ER [see Warnings and Precautions
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`(5.3), Patient Counseling Information (17)].
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`Inform patients and caregivers about the various ways to obtain naloxone as permitted by
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`individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by
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`prescription, directly from a pharmacist, or as part of a community-based program).
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`Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as
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`concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid
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`overdose. The presence of risk factors for overdose should not prevent the proper
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`management of pain in any given patient [see Warnings and Precautions (5.1, 5.3, 5.5)].
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`Consider prescribing naloxone if the patient has household members (including children) or
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`other close contacts at risk for accidental ingestion or overdose.
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` Initial Dosage
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` 2.3
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` Use of NUCYNTA ER as the First Opioid Analgesic (opioid-naïve patients)
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`Initiate treatment with NUCYNTA ER with the 50 mg tablet orally twice daily (approximately
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`every 12 hours).
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`Use of NUCYNTA ER in Patients who are not Opioid Tolerant
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` The starting dose for patients who are not opioid tolerant is NUCYNTA ER 50 mg orally twice
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` daily (approximately every 12 hours). Use of higher starting doses in patients who are not opioid
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` tolerant may cause fatal respiratorydepression.
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` Conversion from NUCYNTA to NUCYNTA ER
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`Patients can be converted from NUCYNTA to NUCYNTA ER using the equivalent total daily
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`dose of NUCYNTA and dividing it into two equal doses of NUCYNTA ER separated by
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`approximately 12-hour intervals. As an example, a patient receiving 50 mg of NUCYNTA four
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`times per day (200 mg/day) may be converted to 100 mg NUCYNTA ER twice a day.
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`Reference ID: 4756514
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` 5
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` Conversion from Other Opioids to NUCYNTA ER
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` 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
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` hours.
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` It is safer to underestimate a patient’s 24-hour oral tapentadol dosage and provide rescue medication
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` (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
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` readily available, there is inter-patient variability in the potency of opioid drugs and opioid
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` formulations.
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` Close observation and frequent titration are warranted until pain management is stable on the
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` new opioid. Monitor patients for signs and symptoms of opioid withdrawal and for signs of
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` oversedation/toxicity after converting patients to NUCYNTA ER.
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` Conversion from Methadone to NUCYNTA ER
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`Close monitoring is of particular importance when converting from methadone to other opioid
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`agonists. The ratio between methadone and other opioid agonists may vary widely as a function of
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`previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.
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` Titration and Maintenance of Therapy
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` 2.4
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` Individually titrate NUCYNTA ER to a dose that provides adequate analgesia and minimizes
` adverse reactions. Continually reevaluate patients receiving NUCYNTA ER to assess the
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` maintenance of pain control and the relative incidence of adverse reactions, as well as
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` monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions
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` (5.1)]. Frequent communication is important among the prescriber, other members of the
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` healthcare team, the patient, and the caregiver/family during periods of changing analgesic
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` requirements, including initial titration. During chronic therapy, periodically reassess the
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` continued need for opioid analgesics.
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` Patients who experience breakthrough pain may require a dosage adjust ment of NUCYNTA ER, or
` may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level
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`of pain increases after dose stabilization, attempt to identify the source of increased pain before
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` increasing the NUCYNTA ER dosage. Titrate patients to adequate analgesia with dose increases of 50
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` mg no more than twice daily every three days. In clinical studies, efficacy with NUCYNTA ER was
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` demonstrated relative to placebo in the dosage range of 100 mg to 250 mg twice daily [see Clinical
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` Studies(14)].
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` If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage.
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` Adjust the dosage to obtain an appropriate balance between management of pain and opioid-
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` related adverse reactions.
` Dosage Modification in Patients with Hepatic Impairment
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` 2.5
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` The use of NUCYNTA ER in patients with severe hepatic impairment (Child-Pugh Score
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` 10-15) is not recommended [see Warnings and Precautions (5.15)].
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` 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
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` respiratory and central nervous system depression, particularly during initiation and titration of
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`Reference ID: 4756514
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` 6
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`NUCYNTA ER. The maximum recommended dose for patients with moderate hepatic impairment is
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`100 mg of NUCYNTA ER per day. Monitor closely for respiratory and central nervous system
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`depression [see Clinical Pharmacology (12.2)].
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`No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5
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`to 6) [see Warnings and Precautions (5.15), Use in Specific Populations (8.6), Clinical Pharmacology
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`(12.3)].
` Safe Reduction or Discontinuation of NUCYNTA ER
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` 2.6
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` Do not abruptly discontinue NUCYNTA ER in patients who may be physically dependent on
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`opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on
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` 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.
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`Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as
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`heroin, and other substances.
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`When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent
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`patient taking NUCYNTA ER, there are a variety of factors that should be considered, including
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`the dose of NUCYNTA ER the patient has been taking, the duration of treatment, the type of pain
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`being treated, and the physical and psychological attributes of the patient. It is important to ensure
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`ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so
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`that patient and provider goals and expectations are clear and realistic. When opioid analgesics are
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`being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or
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`refer for evaluation and treatment of the substance use disorder. Treatment should include
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`evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex
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`patients with comorbid pain and substance use disorders may benefit from referral to a specialist.
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`There are no standard opioid tapering schedules that are suitable for all patients. Good clinical
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`practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on
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`NUCYNTA ER who are physically opioid-dependent, initiate the taper by a small enough
`increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms,
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`and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking
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`opioids for briefer periods of time may tolerate a more rapid taper.
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`It may be necessary to provide the patient with lower dosage strengths to accomplish a successful
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`taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they
`emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning,
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`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
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`withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the
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`dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition,
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`monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other
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`substances.
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`When managing patients taking opioid analgesics, particularly those who have been treated for a
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`long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain
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`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
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`Reference ID: 4756514
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` 7
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` chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings
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` and Precautions (5.13), Drug Abuse and Dependence (9.3)].
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` 3
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` DOSAGE FORMS AND STRENGTHS
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` NUCYNTA ER 50 mg, 100 mg, 150 mg, 200 mg and 250 mg extended-release tablets are
` available in the following colors and prints:
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` • 50 mg extended-release tablets are white oblong-shaped with a black print “OMJ 50” on one
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` side
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` • 100 mg extended-release tablets are light-blue oblong-shaped with a black print “OMJ
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` 100” on one side
` • 150 mg extended-release tablets are blue-green oblong-shaped with a black print “OMJ
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` 150” on one side
` • 200 mg extended-release tablets are blue oblong-shaped with a depression in the
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` middle running lengthwise on each side and a black print “OMJ 200” on one side
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` • 250 mg extended-release tablets are dark blue oblong-shaped with a depression in the
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` middle running lengthwise on each side and a white print “OMJ 250” on one side.
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` 4
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` CONTRAINDICATIONS
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` NUCYNTA ER is contraindicated in patients with:
` • Significant respiratory depression
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` • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in
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` the absence of resuscitative equipment
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` • Known or suspected gastrointestinal obstruction, including paralyticileus
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` • Hypersensitivity (e.g. anaphylaxis, angioedema) to tapentadol or to any other ingredients of
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` the product
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` see Adverse Reactions (6.2)].
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` • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last
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` 14 days [see Drug Interactions (7)].
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` 5
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` 5.1
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` WARNINGS AND PRECAUTIONS
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` 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
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` NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose
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` 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
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` prescribed NUCYNTA ER. Addiction can occur at recommended doses and if the drug is misused or
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` abused.
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`Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA
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`ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors
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`Reference ID: 4756514
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` 8
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` 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).
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` The potential for these risks should not, however, prevent the prescribing of NUCYNTA ER for
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` the proper management of pain in any given patient. Patients at increased risk may be prescribed
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` opioids such as NUCYNTA ER, but use in such patients necessitates intensive counseling about
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` the risks and proper use of NUCYNTA ER along with intensive monitoring for signs of
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` addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of