`
`
`
`
`
`
`
`
`
`is
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`• Use a gradual downward
`
` titration when NUCYNTA® ER
`
` discontinued in a physically dependent patient. (2.3, 5.12)
`
` Reduce the dose of NUCYNTA® ER in patients with moderate hepatic
`
`
`
`
`
`
`
` impairment. (2.4)
`
`
`
`• NUCYNTA® ER use in patients with severe renal impairment is not
`
`
`
`
`
`
` recommended. (2.5)
`
`
`
` Conservative initial dosing of NUCYNTA® ER in elderly patients is
`
`
`
`
` recommended due to possible decreased renal and hepatic function.
`
`
` (2.6)
`
`•
`
` Instruct patients to swallow NUCYNTA® ER tablets whole. (2.7)
`
`
`
`
` ——————— 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 (MAOI) or use within
` the last 14 days. (4)
`
`
`
` ——————— WARNINGS AND PRECAUTIONS———————
`
` See Boxed WARNINGS
`
`
`
`•
`
`
`
` Interaction with CNS depressants: Concomitant use may cause profound
`
`
` sedation, respiratory depression, and death. If co-administration is
`
` required, consider dose reduction of one or both drugs because of
`
`
`
` additive pharmacological effects. (5.4, 7.3)
`
`
`
`
` Elderly, cachectic, debilitated patients, and
`
` those with chronic
` pulmonary disease: Monitor closely because of increased risk for life-
`
`
`
`
` threatening respiratory depression. (5.5, 5.6)
`
`
`
`• Hypotensive effect: Monitor during dose initiation and titration. (5.7)
`
`
`
`
`
`
`•
` Patients with head injury or increased intracranial pressure: Monitor for
`
`sedation and respiratory depression. Avoid use of NUCYNTA® ER in
`
`
`
`
`
`
`
`
`
`
`
`patients with impaired consciousness or coma susceptible to intracranial
`effects of CO2 retention. (5.8)
`
`
`
`
` Seizures: Use with caution in patients with a history of seizures. (5.9)
`
`
`
` Serotonin Syndrome: Potentially life-threatening condition could result
`
` from concomitant administration of drugs with serotonergic activity.
`
`
`
`
`
`
`
` (5.10)
`
`
`
` —————————— ADVERSE REACTIONS—————————
` The most common (≥10%) adverse reactions were nausea, constipation,
`
`
`
`
`
`
`
`
` dizziness, headache, and somnolence. (6)
`
`
`
`
`
` To report SUSPECTED ADVERSE REACTIONS, contact Janssen
`
` Pharmaceuticals, Inc. at 1–800–526–7736 (1-800-JANSSEN) or FDA at 1–
`
`
`
` 800–FDA–1088 or www.fda.gov/medwatch.
`
`
`
` —————————— DRUG INTERACTIONS—————————
`
`
`
`• Monitor for signs of serotonin syndrome when NUCYNTA® ER is used
`
`
`
`
`
`
`
`
`
`
`
` concurrently with SSRIs, SNRIs, tricyclic antidepressants, or triptans.
`
`
`
` (7.4)
`
`• Mixed agonist/antagonist opioids (i.e., pentazocine, nalbuphine, and
`
`
` butorphanol): May reduce analgesic effect and/or precipitate withdrawal
`
` symptoms. (7.6)
`
` ——————— USE IN SPECIFIC POPULATIONS———————
`
`
`•
` Pregnancy: Based on animal data, may cause fetal harm. (8.1)
`
`
`
`• Nursing mothers: Closely monitor infants of nursing women
`
`
`receiving NUCYNTA® ER. (8.3)
`
`
`
`
` Renal or hepatic impairment: Not recommended in patients with severe
`
`
`
`
` renal or hepatic impairment. Reduce dose in patients with moderate
`
`
`
` hepatic impairment. (8.6, 8.7)
`
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`•
`
`
`•
`
` 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 oral tablets C-II
`
`
`Initial U.S. Approval: 2008
`
`
`
`WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE­
`
`
`
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`
`
`
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
`
`
`and INTERACTION WITH ALCOHOL
`
`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)
`
` 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. (5.2)
`
`
`Accidental ingestion of NUCYNTA® ER, especially in children, can
`
`
`
`
`
`
`
`result in fatal overdose of tapentadol. (5.2)
`
`
`
` Prolonged use of NUCYNTA ER during pregnancy can result in
`life-
` neonatal opioid withdrawal syndrome, which may be
`
` 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 (5.3).
`
`
`
` 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. (5.4)
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
` —————————RECENT MAJOR CHANGES————————
`
`
`
`
`
`
` Boxed Warning
` 04/2014
`
` Indications and Usage (1)
`
`
`
`
` 04/2014
`
`
` Dosage and Administration (2)
`
`
` 04/2014
`
`
`
`
`
` 04/2014
`
`
` Warnings and Precautions (5)
` —————————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———————
`
`
`
`
`•
`
` Individualize dosing based on patient’s prior analgesic treatment
`
`
` experience and risk factors for addiction, abuse, and misuse; titrate as
`
`
`
`needed to provide adequate analgesia and minimize adverse reactions.
`(2.1, 2.2)
`
`
`
` For use as the first opioid and in opioid non-tolerant patients, initiate
`
` with 50 mg tablet orally twice daily (approximately every 12 hours).
`
`
`
`
`
`
` (2.1)
`
`
` To convert to NUCYNTA® ER from another opioid, use available
` conversion factors to obtain estimated dose. (2.1)
`
`
` Titrate patients with dose increases of 50 mg no more than twice daily
` every three days. (2.2)
`
`
`
`• Maximum daily dose is 500 mg per day. (2.1)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`
`Reference ID: 3490214
`
`
`
`
`for PATIENT COUNSELING
`See 17
`
`MEDICATION GUIDE.
`
`INFORMATION AND
`
`
`
`Revised: 04/2014
`
`
`
` 1
`
`

`

`
`
`
`
` FULL PRESCRIBING INFORMATION: CONTENTS*
`
` WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE­
`
`
`
`
` THREATENING RESPIRATORY DEPRESSION;
` ACCIDENTAL INGESTION; NEONATAL OPIOID
`
`
`
`
`
` WITHDRAWAL SYNDROME; and INTERACTION
`
`
` WITH ALCOHOL
`
`
`1
` INDICATIONS AND USAGE
`
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`
`Initial Dosing
`
`2.1
`
`
`Titration and Maintenance of Therapy
`
`2.2
`
`
`
`2.3 Discontinuation of NUCYNTA® ER
`
`
`
`
`2.4 Patients with Hepatic Impairment
`
`
`
`2.5 Patients with Renal Impairment
`
`
`
`
`2.6 Elderly Patients
`
`
`
`2.7 Administration of NUCYNTA® ER
`
`
`
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`
`4 CONTRAINDICATIONS
`
`
`5 WARNINGS AND PRECAUTIONS
`
`
`
`5.1 Addiction, Abuse, and Misuse
`
`
`
`Life-Threatening Respiratory Depression
`
`5.2
`
`
`5.3 Neonatal Opioid Withdrawal Syndrome
`
`
`5.4
`Interactions with Central Nervous System
`
`
`
`
`Depressants
`
`
`5.5 Use in Elderly, Cachectic, and Debilitated
`
`
`
`Patients
`
`
`
`5.6 Use in Patients with Chronic Pulmonary Disease
`
`
`
`5.7 Hypotensive Effect
`
`
`5.8 Use in Patients with Head Injury or Increased
`
`
`Intracranial Pressure
`
`
`
`5.9 Seizures
`
`
`
`5.10 Serotonin Syndrome
`
`
`
`5.11 Use in Patients with Gastrointestinal Conditions
`
`
`
`5.12 Avoidance of Withdrawal
`
`
`
`5.13 Driving and Operating Heavy Machinery
`
`
`
`5.14 Hepatic Impairment
`
`
`
`5.15 Renal Impairment
`
`
`
`6 ADVERSE REACTIONS
`
`
`6.1 Clinical Trial Experience
`
`
`
`
`6.2 Postmarketing Experience
`
`
`
`7 DRUG INTERACTIONS
`
`
`
`
`
`
`Reference ID: 3490214
`
`
`
`7.1 Alcohol
`
`
`
`7.2 Monoamine Oxidase Inhibitors
`
`
`
`7.3 CNS Depressants
`
`
`
`7.4 Serotonergic Drugs
`
`
`
`7.5 Muscle Relaxants
`
`
`
`7.6 Mixed Agonist/Antagonist Opioid Analgesics
`
`
`
`
`7.7 Anticholinergics
`
`
`
`8 USE IN SPECIFIC POPULATIONS
`
`
`8.1 Pregnancy
`
`
`
`8.2
`Labor and Delivery
`
`
`
`8.3 Nursing Mothers
`
`
`
`8.4 Pediatric Use
`
`
`
`8.5 Geriatric Use
`
`
`
`8.6 Renal Impairment
`
`
`
`8.7 Hepatic Impairment
`
`
`
`9 DRUG ABUSE AND DEPENDENCE
`
`
`
`9.1 Controlled Substance
`
`
`
`9.2 Abuse
`
`
`
`9.3 Dependence
`
`
`
`10 OVERDOSAGE
`
`
`10.1 Clinical Presentation
`
`
`
`10.2 Treatment of Overdose
`
`
`
`11 DESCRIPTION
`
`
`12 CLINICAL PHARMACOLOGY
`
`
`12.1 Mechanism of Action
`
`
`
`
`12.2 Pharmacodynamics
`
`
`
`12.3 Pharmacokinetics
`
`
`
`13 NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of
`
`
`
`
`Fertility
`
`
`
`13.2 Animal Toxicology and/or Pharmacology
`
`
`
`14 CLINICAL STUDIES
`
`
`14.1 Moderate to Severe Chronic Low Back Pain
`
`
`
`14.2 Neuropathic Pain Associated with Diabetic
`
`
`
`Peripheral Neuropathy
`
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`
`17 PATIENT COUNSELING INFORMATION
`
`
`
`*Sections or subsections omitted from the full prescribing information are not
`
`
`listed
`
`
`
`
`
`
` 2
`
`

`

`
` FULL PRESCRIBING INFORMATION
`
`
`
`
` WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY
`
`
`
`
` DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
`
` and INTERACTION WITH ALCOHOL
`
`
`
`
`
`
` 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 or conditions [see Warnings
`
`
`
`
` and Precautions (5.1)].
`
`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 (5.2)].
`
`
`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 (5.2)].
`
`
`
`
`
`
`
`
`
`
`
`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 (5.3)].
`
`
`
`
`
` 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 (5.4)].
`
`
` INDICATIONS AND USAGE
` 1
`
`
`
`
` NUCYNTA® ER (tapentadol) is indicated for the management of:
`
`
`
`
`
`
`
`
`
`Reference ID: 3490214
`
`

`

`
`
`
`• 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) in adults severe enough to
`
` require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options
`
`
` are inadequate.
`
`
`
` Limitations of Usage
`
`
`
`
`• 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.
`
`
`
`
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1
`Initial Dosing
`
`
`NUCYNTA® ER should be prescribed only by healthcare professionals who are knowledgeable in the use of
`
`
`
`potent opioids for the management of chronic pain.
`
`
`
`Initiate the dosing regimen for each patient individually, taking into account the patient's 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
`
`
`with NUCYNTA® ER [see Warnings and Precautions (5.2)].
`
`
`
`
`
`
`
`NUCYNTA® ER tablets must be taken whole. 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
`
`
`
`(5.2)].
`
`NUCYNTA® ER is administered at a frequency of twice daily (every 12 hours).
`
`
`
`
`Discontinue all other tapentadol and tramadol products when beginning and while taking NUCYNTA® ER
`
`
`[see Warnings and Precautions (5.10)]. 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.
`
`
`
`
`Use of NUCYNTA® ER as the First Opioid Analgesic
`
`
` Initiate treatment with NUCYNTA® ER with the 50 mg tablet orally twice daily (approximately every 12
`
`
`
`
`
` hours).
`
`
`
`
`
`
`
`Reference ID: 3490214
`
`

`

`
` 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. Patients who are opioid tolerant are those receiving, for one week or longer, at
`
`
`
`
`
` least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8
`
`
` mg oral hydromorphone per day, 25 mg oral oxymorphone per day or an equianalgesic dose of another opioid.
`
`
`
`
`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 opioid to NUCYNTA® ER defined by
`
`
` clinical trials. Discontinue all other around-the-clock opioid drugs when NUCYNTA® ER therapy is initiated.
`
`
`
`
`
`
`While there are useful tables of opioid equivalents readily available, there is substantial inter-patient
`
`
`
`variability in the relative potency of different opioid drugs and products. As such, it is safer to underestimate a
`
`patient’s 24-hour oral tapentadol requirements and provide rescue medication (e.g., immediate-release opioid)
`
`
`
`
`than to overestimate the 24-hour oral tapentadol requirements which could result in adverse reactions.
`
`
`
`
`
`
`In general, as with other opioid analgesics, begin with half of the estimated daily tapentadol requirement as
`
`
`the initial dose, managing inadequate analgesia by supplementation with immediate-release rescue
`
`medication.
`
`
`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.
`
`
`
`2.2 Titration and Maintenance of Therapy
`
`
`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. Frequent communication is important among the 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.
`
`
`
`
`Reference ID: 3490214
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`

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` 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
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` 100 mg to 250 mg twice daily [see Clinical Studies (14)].
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` Patients who experience breakthrough pain may require a dose increase of NUCYNTA® ER, or may need
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` rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases
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`after dose stabilization, attempt to identify the source of increased pain before increasing the NUCYNTA® ER
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`dose.
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`If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust
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`the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
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` 2.3 Discontinuation of NUCYNTA® ER
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`When the patient no longer requires therapy with NUCYNTA® ER tablets, use a gradual downward titration
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`of the dose to prevent signs and symptoms of withdrawal in the physically-dependent patient.
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`2.4 Patients with Hepatic Impairment
`The use of NUCYNTA® ER in patients with severe hepatic impairment (Child-Pugh Score 10-15) is not
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`recommended.
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`In patients with moderate hepatic impairment (Child-Pugh Score 7 to 9), initiate treatment using 50 mg
` NUCYNTA® ER and administer no more frequently than once every 24 hours. The maximum recommended
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`dose for patients with moderate hepatic impairment is 100 mg of NUCYNTA® ER per day [see Clinical
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` Pharmacology (12.3)].
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` No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5 to 6)
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` [see Warnings and Precautions (5.14) and Clinical Pharmacology (12.3)].
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` 2.5 Patients with Renal Impairment
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` No dosage adjustment is recommended in patients with mild or moderate renal impairment. Use of
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`NUCYNTA® ER in patients with severe renal impairment is not recommended [see Warnings and
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`Precautions (5.15) and Clinical Pharmacology (12.3)].
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`2.6 Elderly Patients
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`In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for
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`younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to
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`have decreased renal and hepatic function, consideration should be given to starting elderly patients with the
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`lower range of recommended doses [see Clinical Pharmacology (12.3)].
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`Reference ID: 3490214
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`

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` 2.7 Administration of NUCYNTA® ER
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` Instruct patients to swallow NUCYNTA® ER tablets whole. The tablets are not to be cut, crushed, dissolved,
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` or chewed due to the risk of rapid release and absorption of a potentially fatal dose of tapentadol [see
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` Warnings and Precautions (5.1, 5.2)].
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`Instruct patients to take NUCYNTA® ER one tablet at a time and with enough water to ensure complete
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`swallowing immediately after placing in the mouth [see Warnings and Precautions (5.2), and Patient
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`Counseling Information (17)].
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` 3 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
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` 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 side
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` • 100 mg extended-release tablets are light-blue oblong-shaped with a black print “OMJ 100” on one
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` side
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` • 150 mg extended-release tablets are blue-green oblong-shaped with a black print “OMJ 150” on one
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` side
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` • 200 mg extended-release tablets are blue oblong-shaped with a depression in the middle running
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` 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 middle running
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` lengthwise on each side and a white print “OMJ 250” on one side.
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` 4 CONTRAINDICATIONS
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`NUCYNTA® ER is contraindicated in:
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`• Patients with significant respiratory depression
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`• Patients with acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the
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`absence of resuscitative equipment
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`• Patients with known or suspected paralytic ileus
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`• Patients with hypersensitivity (e.g. anaphylaxis, angioedema) to tapentadol or to any other ingredients
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`of the product [see Adverse Reactions (6.2)].
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`• Patients who are receiving monoamine oxidase inhibitors (MAOI) or who have taken them within the
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`last 14 days due to potential additive effects on norepinephrine levels which may result in adverse
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`cardiovascular events [see Drug Interactions (7.2)].
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`Reference ID: 3490214
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`

`

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`5 WARNINGS AND PRECAUTIONS
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` 5.1 Addiction, Abuse, and Misuse
`
`
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` NUCYNTA® ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA® ER
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` exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)]. As
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`modified-release products such as NUCYNTA® ER deliver the opioid over an extended period of time, there
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`is a greater risk for overdose and death due to the larger amount of tapentadol present.
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`Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed
`NUCYNTA® ER and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if
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`the drug is misused or abused.
`
`Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA® ER, and
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`monitor all patients receiving NUCYNTA® ER for the development of these behaviors or conditions. Risks
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`are increased in patients with a personal or family history of substance abuse (including drug or alcohol
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`addiction or abuse) or mental illness (e.g., major depression). The potential for these risks should not,
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`however, prevent the prescribing of NUCYNTA® ER for the proper management of pain in any given patient.
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`Patients at increased risk may be prescribed modified-release opioid formulations such as NUCYNTA® ER,
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`but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA® ER
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`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
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`result in the uncontrolled delivery of tapentadol and can result in overdose and death [see Overdosage (10)].
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`Opioid agonists such as NUCYNTA® ER are sought by drug abusers and people with addiction disorders and
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`are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA® ER.
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`Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising
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`the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local
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`state professional licensing board or state controlled substances authority for information on how to prevent
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`and detect abuse or diversion of this product.
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`5.2 Life-Threatening Respiratory Depression
`
`Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified-release
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`opioids, even when used as recommended. Respiratory depression from opioid use, if not immediately
`
`recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may
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`include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s
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`clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory
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`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 dose increase. Closely
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`Reference ID: 3490214
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`

`

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` monitor patients for respiratory depression when initiating therapy with NUCYNTA® ER and following dose
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` increases.
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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 dose when converting patients from
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`
` 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
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` depression and death due to an overdose of tapentadol.
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` 5.3 Neonatal Opioid Withdrawal Syndrome
`Prolonged use of NUCYNTA® ER during pregnancy can result in withdrawal signs in the neonate. Neonatal
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`opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not
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`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
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`opioid withdrawal syndrome and ensure that appropriate treatment will be available.
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`Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high
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`pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of
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`neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and
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`amount of last maternal use, and rate of elimination of the drug by the newborn.
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`Interactions with Central Nervous System Depressants
`5.4
`Patients must not consume alcoholic beverages or prescription or non-prescription products containing
`alcohol while on NUCYNTA® ER therapy. The co-ingestion of alcohol with NUCYNTA® ER may result in
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`increased plasma tapentadol levels and a potentially fatal overdose of tapentadol [see Clinical Pharmacology
`
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`(12.3)].
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`Hypotension, profound sedation, coma, respiratory depression, and death may result if NUCYNTA® ER is
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`used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives,
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`anxiolytics, hypnotics, neuroleptics, other opioids).
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`When considering the use of NUCYNTA® ER in a patient taking a CNS depressant, assess the duration of use
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`of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS
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`depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that cause CNS depression. If the
`decision to begin NUCYNTA® ER is made, start with NUCYNTA® ER 50 mg every 12 hours, monitor
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`patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant
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`CNS depressant [see Drug Interactions (7.3)].
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`Reference ID: 3490214
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`

`

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`5.5 Use in Elderly, Cachectic, and Debilitated Patients
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`Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as
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`they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
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`Therefore, closely monitor such patients, particularly when initiating and titrating NUCYNTA® ER and when
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`NUCYNTA® ER is given concomitantly with other drugs that depress respiration [see Warnings and
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`Precautions (5.2)].
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` 5.6 Use in Patients with Chronic Pulmonary Disease
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`Monitor for respiratory depression those patients with significant chronic obstructive pulmonary disease or
`
`cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre­
`existing respiratory depression, particularly when initiating therapy and titrating with NUCYNTA® ER, as in
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`these patients, even usual therapeutic doses of NUCYNTA® ER may decrease respiratory drive to the point of
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`apnea [see Warnings and Precautions (5.2)]. Consider the use of alternative non-opioid analgesics in these
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`patients if possible.
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`5.7 Hypotensive Effect
`NUCYNTA® ER may cause severe hypotension. There is an increased risk in patients whose ability to
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`maintain blood pressure has already been compromised by a reduced blood volume or concurrent
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`administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug
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`Interactions (7.3)]. Monitor these patients for signs of hypotension after initiating or titrating the dose of
`NUCYNTA® ER. In patients with circulatory shock, NUCYNTA® ER may cause vasodilation that can further
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`reduce cardiac output and blood pressure. Avoid the use of NUCYNTA® ER in patients with circulatory
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`shock.
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`5.8 Use in Patients with Head Injury or Increased Intracranial Pressure
`Monitor patients taking NUCYNTA® ER who may be susceptible to the intracranial effects of CO2 retention
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`(e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and
`respiratory depression, particularly when initiating therapy with NUCYNTA® ER. NUCYNTA® ER may
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`reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids
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`may also obscure the clinical course in a patient with a head injury.
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`Avoid the use of NUCYNTA® ER in patients with impaired consciousness or coma.
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`5.9 Seizures
`NUCYNTA® ER has not been evaluated in patients with a predisposition to a seizure disorder, and such
`
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`patients were excluded from clinical studies. The active ingredient tapentadol in NUCYNTA® ER may
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`aggravate convulsions in