`
`
`
`
`
` HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`
`
`
` These highlights do not include all the information needed to use
` NUCYNTA® ORAL SOLUTION safely and effectively. See full
`
`
`
`
`prescribing information for NUCYNTA® ORALSOLUTION.
`NUCYNTA® (tapentadol) oral solution C-II
`
`Initial U.S. Approval: 2008
`
`
`
`
`
`
`
`WARNING: RISK OF MEDICATION ERRORS, ADDICTION,
`
`ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION
`
`STRATEGY (REMS); LIFE-THREATENING RESPIRATORY
`
`DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID
`
`
`
`
`
`WITHDRAWAL SYNDROME; and RISKS FROM
`
`
`
`CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER
`
`
`
`
`CNS DEPRESSANTS
`
`See full prescribing information for complete boxed warning.
`
`Ensure accuracy when prescribing, dispensing, and
`
`
`administering NUCYNTA oral solution. Dosing errors due to
`
`
`
`confusion between mg and mL, and other tapentadol oral
`
`
`solution of different concentrations can result in accidental
`overdose and death. (2.1, 5.1)
`
`
`NUCYNTA oral solution exposes users to risks of addiction,
`abuse, and misuse, which can lead to overdose and death. Assess
`
`
`
`
`patient’s risk before prescribing and monitor regularly for these
`
`
`behaviors and conditions. (5.2)
`
`
`
`
`
`
`
`
`
`
`
`•
`
`
`
`
`
`
`
`
`
`
`
`
`
`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. (5.3)
`
`Serious, life-threatening, or fatal respiratory depression may
`
`occur. Monitor closely, especially upon initiation or following a
`
`
`
`dose increase. (5.4)
`
`Accidental ingestion of NUCYNTA oral solution, especially by
`
`children, can result in a fatal overdose of tapentadol. (5.4)
`
`
`
`Prolonged use of NUCYNTA oral solution during pregnancy can
`result in neonatal opioid withdrawal syndrome, which may be
`
`life-threatening if not recognized and treated. If prolonged
`
`opioid use is required in a pregnant woman, advise the patient of
`
`the risk of neonatal opioid withdrawal syndrome and ensure
`
`
`that appropriate treatment will be available. (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 (5.6, 7).
`
`
`
`
`----------------------------RECENT MAJOR CHANGES--------------------------
`
`
`Dosage and Administration (2.2)
`03/2021
`
`
`Warnings and Precautions (5.2, 5.4, 5.6)
`03/2021
`
`
`----------------------------INDICATIONS AND USAGE----------------------------
`
`NUCYNTA oral solution is an opioid analgesic indicated for the management
`
`
`of acute pain severe enough to require an opioid analgesic and for which
`
`
`
`alternative treatments are inadequate. (1)
`
`
`Limitations of Use (1)
`
`Because of the risks of addiction, abuse, and misuse with opioids, even at
`
`
`recommended doses, reserve NUCYNTA oral solution for use in patients for
`
`
`
`whom alternative treatment options [e.g., non-opioid analgesics or opioid
`
`
`
`
`combination products]:
`
`
` Have not been tolerated, or are not expected to be tolerated,
`
`
`
` Have not provided adequate analgesia, or are not expected to provide
`
`
`
`
`adequate analgesia
`
`-----------------------DOSAGE AND ADMINISTRATION-----------------------
`
`
`
` Use the lowest effective dosage for the shortest duration consistent with
`
`
`individual patient treatment goals. (2.1)
`
`
`
`
`
`
`
`
` Individualize dosing according to the severity of pain, patient response,
`
`
`
`prior analgesic experience, and risk factors for addiction, abuse, and misuse.
`
`(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 Oral Solution. Consider prescribing
`
`
`
`
`naloxone based on the patient’s risk factors for overdose [2.2, 5.2, 5.4, 5.6].
`
`
`
` Initiate treatment with NUCYNTA oral solution with or without food at
`
`
`
`
`
`
`a dose of 2.5 mL (50 mg), 3.75 mL (75 mg), or 5 mL (100 mg) every 4 to
`
`
`
`6 hours depending upon pain intensity. On the first day of dosing, the
`
`
`
`
`
`second dose may be administered as soon as one hour after the first dose, if
`
`adequate pain relief is not attained with the first dose. Subsequent dosing is
`
`
`
`
`
`
`
`
`2.5 mL (50 mg), 3.75 mL (75 mg), or 5 mL (100 mg) every 4 to 6 hours
`and should be adjusted to maintain adequate analgesia with acceptable
`
`
`tolerability. Daily doses greater than 700 mg on the first day of therapy
`
`
`and 600 mg on subsequent days have not been studied and are, therefore,
`
`not recommended. (2.3)
`
` Moderate Hepatic Impairment: Initiate treatment with 50 mg no more than
`once every 8 hours (maximum of three doses in 24 hours). Monitor closely for
`
`
`
`
`respiratory and central nervous systemdepression. (2.4)
`
`
`
`
`
` Do not abruptly discontinue NUCYNTA oral solution in a physically
`
`
`
`
`dependent patient because rapid discontinuation of opioid analgesics has
`resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. (2.6)
`
`
`
`
`
`--------------------DOSAGE FORMS AND STRENGTHS----------------------
`
`Oral Solution: 20 mg/mL (3)
`
`-------------------------------CONTRAINDICATIONS-------------------------------
`
` Significant respiratorydepression (4)
`
`
`
` Acute or severe bronchial asthma in an unmonitored setting or in absence of
`
`
`
`
`
`resuscitative equipment.(4)
`
`
` Known or gastrointestinal obstruction, including suspected paralytic ileus. (4)
`
`
`
` Hypersensitivity to tapentadol.(4)
`
`
` Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs
`
`
`
`
`within the last 14 days. (4)
`
`---------------------------WARNINGS AND PRECAUTIONS--------------------
`
` Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary
`
`Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely,
`
`
`particularly during initiation and titration. (5.7)
`
`
` Serotonin Syndrome: Potentially life-threatening condition could result from
`
`concomitant serotonergic drug administration. Discontinue NUCYNTA oral
`
`
`solution if serotonin syndrome is suspected. (5.8)
`
`
`
`
` Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of
`
`
`
`corticosteroids, and wean patient off of the opioid. (5.9)
`
`
`
`
` Severe Hypotension: Monitor during dosage initiation and titration. Avoid use
`
`of NUCYNTA oral solution in patients with circulatory shock. (5.10)
`
`
`
`
` 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 oral solution in patients with impaired
`
`
`consciousness or coma. (5.11)
`
`
`
`------------------------------ADVERSE REACTIONS------------------------------
`
`The most common adverse reactions (incidence ≥10%) were nausea, dizziness,
`
`
`
`vomiting and somnolence. (6.1)
`
`
`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 Opioids Analgesics: Avoid
`
`
`
`
`use with NUCYNTA oral solution because they reduce analgesic effect of
`
`
`
`NUCYNTA oral solution or precipitate withdrawal symptoms. (7)
`
`
`
`-----------------------USE IN SPECIFIC POPULATIONS-----------------------
`
` Pregnancy: Based on animal data, may cause fetal harm. (8.1)
`
`
`
`
`
` Lactation: Closely monitor infants of nursing women receiving.
`
`NUCYNTA oral solution. (8.2)
`
`
`
` Severe Hepatic or Renal Impairment: Use not recommended. Reduce
`
`
`
`
`dose in patients with moderate hepatic impairment. (8.6, 8.7)
`
`
`
`
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`
`Guide
`
`Revised: 03/2021
`
`
`
`Reference ID: 4756538
`
`
`

`

`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`WARNING: ADDICTION, ABUSE, AND MISUSE;
`
`
`LIFE-THREATENING RESPIRATORY DEPRESSION;
`ACCIDENTAL INGESTION; NEONATAL OPIOID
`
`WITHDRAWAL SYNDROME; and RISKS FROM
`
`
`CONCOMITANT USE WITH BENZODIAZEPINES OR
`
`OTHER CNS DEPRESSANTS
`
`
`
`INDICATIONS AND USAGE
`1
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`Important Dosage and Administration Instructions
`2.1
`
`
`2.2 Patient Access to Naloxone for the Emergency
`
`
`Treatment of Opioid Overdose
`
`Initial Dosage
`2.3
`
`
`2.4 Dosage Modifications in Patients with Hepatic
`Impairment
`
`
`2.5 Titration and Maintenance of Therapy
`
`
`2.6 Safe Reduction or Discontinuation of NUCYNTA
`
`
`
`oral solution
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`
`4 CONTRAINDICATIONS
`
`
`5 WARNINGS AND PRECAUTIONS
`
`
`
`
`5.1 Risk of Accidental Overdose and Death due to
`Medication Errors
`
`
`5.2 Addiction, Abuse, and Misuse
`
`
`
`
`5.3 Opioid Analgesic Risk Evaluation and Mitigation
`Strategy (REMS)
`
`
`5.4 Life Threatening-Respiratory Depression
`
`
`
`5.5 Neonatal Opioid Withdrawal Syndrome
`
`
`5.6 Risks from Concomitant Use with
`
`
`Benzodiazepines or Other CNS Depressants
`
`
`
`
`5.7 Life-Threatening Respiratory Depression in
`
`Patients with Chronic Pulmonary Disease or in
`
`
`Elderly, Cachectic, or Debilitated Patients
`
`
`
`5.8 Serotonin Syndrome with Concomitant Use of
`Serotonergic Drugs
`
`
`5.9 Adrenal Insufficiency
`
`
`5.10 Severe Hypotension
`
`
`
`5.11 Risks of Use in Patients with Increased Intracranial
`
`
`Pressure, Brain Tumors, Head Injury, or Impaired
`
`Consciousness
`
`
`5.12 Risks of Use in Patients with Gastrointestinal
`
`Conditions
`
`
`
`5.13 Increased Risk of Seizures in Patients with Seizure Disorders
`
`
`
`
`5.14 Withdrawal
`
`
`5.15 Risks of Driving and Operating Machinery
`
`
`5.16 Interactions with Alcohol, Other Opioids, and Drugs of Abuse
`
`
`
`
`
`5.17 Risk of Toxicity in Patients with Hepatic Impairment
`
`
`
`5.18 Risk of Toxicity in Patients with Renal Impairment
`
`
`
`6 ADVERSE REACTIONS
`
`
`6.1 Clinical Trials Experience
`
`
`6.2 Post-marketing Experience
`
`
`7 DRUG INTERACTIONS
`
`
`8 USE IN SPECIFIC POPULATIONS
`
`
`
`8.1 Pregnancy
`
`
`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
`
`
`9 DRUG ABUSE AND DEPENDENCE
`
`
`
`9.1 Controlled Substance
`
`
`9.2 Abuse
`
`
`9.3 Dependence
`
`
`10 OVERDOSAGE
`
`
`11 DESCRIPTION
`
`
`12 CLINICAL PHARMACOLOGY
`
`
`
`12.1 Mechanism of Action
`
`
`
`
`12.2 Pharmacodynamics
`
`
`12.3 Pharmacokinetics
`
`
`13 NON-CLINICAL TOXICOLOGY
`
`
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`
`13.2 Animal Toxicology and/or Pharmacology
`
`
`
`
`14 CLINICAL STUDIES
`
`
`
`14.1 Orthopedic Surgery – Bunionectomy
`
`
`
`14.2 End-Stage Degenerative Joint Disease
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`
`17 PATIENT COUNSELING INFORMATION
`
`
`
`*Sections or subsections omitted from the full prescribing information are
`
`not listed
`
`
`
`
`Reference ID: 4756538
`
`
`

`

`FULL PRESCRIBING INFORMATION
`
`WARNING: RISK OF MEDICATION ERRORS, ADDICTION, ABUSE, AND MISUSE;
`RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;
`NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM
`CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
`
`
`Risk of Medication Errors
`Ensure accuracy when prescribing, dispensing, and administering NUCYNTA oral
`solution. Dosing errors due to confusion between mg and mL can result in accidental
`overdose and death [see Dosage and Administration (2.1), Warnings and Precautions (5.1)].
`
`
`Addiction, Abuse, and Misuse
`NUCYNTA oral solution 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 oral solution, and monitor all patients regularly for the
`development of these behaviors and conditions [see Warnings and Precautions (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 REMS for these
`products [see Warnings and Precautions (5.3)]. 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
`oral solution. Monitor for respiratory depression, especially during initiation of
`
`
`NUCYNTA oral solution or following a dose increase [see Warnings and Precautions (5.4)].
`
`
`Accidental Ingestion
`
` Accidental ingestion of even one dose of NUCYNTA oral solution, especially by children,
`
`
`
`
` can result in a fatal overdose of tapentadol [see Warnings and Precautions (5.4)].
`
`
`Neonatal Opioid Withdrawal Syndrome
`Prolonged use of NUCYNTA oral solution 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
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4756538
`
`
`

`

`
`
`
`
` of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be
`available [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 (5.6), Drug Interactions (7)].
`
`Reserve concomitant prescribing of NUCYNTA oral solution 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 (tapentadol) oral solution is indicated for the management of acute pain severe enough
`
` to require an opioid analgesic and for which alternative treatments are inadequate in adults.
`
` Limitations of Use
`
`Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see
`
`Warnings and Precautions (5.2)], reserve NUCYNTA oral solution for use in patients for whom
`alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:
`
`
` Have not been tolerated, or are not expected to be tolerated,
`
` Have not provided adequate analgesia, or are not expected to provide adequate analgesia
`
`
`2 DOSAGE AND ADMINISTRATION
`
`2.1
`
`
`
` Important Dosage and Administration Instructions
`
`Ensure accuracy when prescribing, dispensing, and administering NUCYNTA oral solution to avoid
`dosing errors due to confusion between mg and mL, which could result in accidental overdose and
`
`death. Ensure the proper dose is communicated and dispensed. The oral solution contains 20 mg
`tapentadol per milliliter (mL), when writing prescriptions, include both the total dose in mg and the
`total dose in volume.
`
`Always use the enclosed calibrated measuring syringe when administering NUCYNTA oral solution
`to ensure the dose is measured and administered accurately. An oral syringe is supplied with dose
`marks corresponding directly to 2.5 mL (equals 50 mg) oral solution, 3.75 mL (equals 75 mg) oral
`solution, and 5 mL (equals 100 mg) oral solution.
`
`Do not use household teaspoons or tablespoons to measure NUCYNTA oral solution, as using a
`
`tablespoon instead of a teaspoon could lead to overdosage.
`
`Inform patients of the availability of FDA-approved patient labeling, Instructions for Use, for
`
`step-by-step instructions for patients on how to use the medicine bottle and the oral syringe.
`
`
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`
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`
`
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`
`
`
`
`Reference ID: 4756538
`
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`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 (5.2)].
`
`Monitor patients closely for respiratory depression, especially within the first 24-72 hours of
`
`initiating therapy and following dosage increases with NUCYNTA and adjust the dosage
`accordingly [see Warnings and Precautions (5.4)]
`
`
`2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose
`
`Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient
`and caregiver and assess the potential need for access to naloxone, both when initiating and
`renewing treatment with NUCYNTA Oral Solution [see Warnings and Precautions (5.4), Patient
`Counseling Information (17)].
`
`
`Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual
`state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly
`from a pharmacist, or as part of a community-based program).
`
`Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant
`use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of
`risk factors for overdose should not prevent the proper management of pain in any given patient [see
`
`Warnings and Precautions (5.2, 5.4, 5.6)].
`
`
`Consider prescribing naloxone if the patient has household members (including children) or other
`close contacts at risk for accidental ingestion or overdose.
`
`
`
`2.3
`
`Initial Dosage
`
`
`
`
`
`Initiate treatment with NUCYNTA oral solution in a dosing range of 50 mg (2.5 mL) to 100 mg (5
`mL) every 4 to 6 hours as needed for pain.
`
`On the first day of dosing, the second dose may be administered as soon as one hour after the
`first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 2.5 mL
`
`
`(equivalent to 50 mg), 3.75 mL (equivalent to 75 mg), or 5 mL (equivalent to 100 mg) every 4 to 6
`hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.
`
`Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not
`been studied and are not recommended.
`
`NUCYNTA oral solution may be given with or without food [see Clinical Pharmacology (12.3)].
`
`
`Conversion from NUCYNTA oral solution to NUCYNTA ER
`
`
`Patients can be converted from NUCYNTA oral solution to NUCYNTA ER using the equivalent
`total daily dose of NUCYNTA oral solution 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 oral solution four times per day (200 mg/day) may be converted to 100 mg NUCYNTA
`
`Reference ID: 4756538
`
`
`

`

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` ER twice a day.
`
`
`2.4 Dosage Modifications in Patients with Hepatic Impairment
`
`The safety and efficacy of NUCYNTA oral solution has not been studied in patients with severe
`hepatic impairment (Child-Pugh Score 10-15) and use in this population is not recommended [see
`
`
`
`Warnings and Precautions (5.17)].
`
`Initiate treatment of patients with moderate hepatic impairment (Child-Pugh Score 7 to 9) with 50
`mg no more frequently than once every 8 hours (maximum of three doses in 24 hours).
`Further treatment should reflect maintenance of analgesia with acceptable tolerability, to be
`
`achieved by either shortening or lengthening the dosing interval. Monitor closely for respiratory
`and central nervous system depression [see Clinical Pharmacology (12.3)].
`
`No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh
`Score 5 to 6) [see Clinical Pharmacology (12.3)].
`
`2.5 Titration and Maintenance of Therapy
`
` Continually reevaluate patients receiving NUCYNTA oral solution 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 (5.2)]. 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.
`
`
`If the level of pain increases after dosage stabilization, attempt to identify the source of increased
`pain before increasing the NUCYNTA oral solution dosage. 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.
`
`
`2.6 Safe Reduction or Discontinuation of NUCYNTA oral solution
`
`Do not abruptly discontinue NUCYNTA Oral Solution 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.
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`When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent
`patient taking NUCYNTA Oral Solution, there are a variety of factors that should be considered,
`including the dose of NUCYNTA Oral Solution the patient has been taking, the duration of
`treatment, the type of pain being treated, and the physical and psychological attributes of the
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`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 co-morbid pain and substance use
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`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 Oral Solution 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, 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.
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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,
`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
`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
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`analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic
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`pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and
`Precautions (5.14), Drug Abuse and Dependence (9.3)].
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`3 DOSAGE FORMS AND STRENGTHS
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`Oral solution: 20 mg/mL in 100 mL and 200 mL fill bottles with child-resistant closure [see
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` Description (11) and How Supplied/Storage and Handling (16)].
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` 4 CONTRAINDICATIONS
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`NUCYNTA oral solution is contraindicated in patients with:
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` Significant respiratory depression [see Warnings and Precautions (5.4)]
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` Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative
`equipment [see Warnings and Precautions (5.7)]
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` Known or suspected gastrointestinal obstruction, including suspected paralytic ileus [see
`Warnings and Precautions (5.12)]
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` Hypersensitivity to tapentadol (e.g. anaphylaxis, angioedema) or to any other ingredients of
`the product [see Adverse Reactions (6.2)].
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` Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last
`14 days [see Drug Interactions (7)].
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` 5 WARNINGS AND PRECAUTIONS
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`5.1 Risk of Accidental Overdose and Death due to Medication Errors
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`Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from
`confusion between mg and mL when prescribing, dispensing, and administering NUCYNTA oral
`solution. Ensure that the dose is communicated clearly and dispensed accurately. Always use the
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`enclosed calibrated syringe when administering NUCYNTA to ensure the dose is measured and
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` administered accurately. Do not use a teaspoon or a tablespoon to measure a dose. A household
`teaspoon or tablespoon is not an adequate measuring device. Given the inexactitude of the
`household spoon measure and the possibility of using a tablespoon instead of a teaspoon, which
`could lead to overdosage, it is strongly recommended that caregivers obtain and use a calibrated
`measuring device. Health care providers should recommend a calibrated device that can measure
`and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in
`measuring the dosage.
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`5.2 Addiction, Abuse, and Misuse
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`NUCYNTA oral solution contains tapentadol, a Schedule II controlled substance.
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`As an opioid, NUCYNTA oral solution exposes users to the risks of addiction, abuse, and misuse
`[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 oral solution. Addiction can occur at recommended dosages 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
`oral solution and monitor all patients receiving NUCYNTA oral solution for the development of
`these behaviors and conditions. Risks are increased in patients with a personal or family history of
`substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major
`depression). The potential for these risks should not, however, prevent the proper management of
`pain in any given patient. Patients at increased risk may be prescribed opioids such as NUCYNTA
`oral solution, but use in such patients necessitates intensive counseling about the risks and proper
`use of NUCYNTA oral solution along with intensive monitoring for signs of addiction, abuse, and
`misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage
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`and Administration (2.2), Warnings and Precautions (5.4)].
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`Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal
`diversion. Consider these risks when prescribing or dispensing NUCYNTA oral solution. 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 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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`5.3
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` Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
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`To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse,
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` 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. Prescribers are strongly encouraged to do all of the following:
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`• 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.
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`• Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with
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` patients and/or their caregivers every time these medicines are prescribed. The Patient
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` Counseling Guide (PCG) can be obtained at this link:
`www.fda.gov/OpioidAnalgesicREMSPCD.
` Emphasize to patients and their caregivers the importance of reading the Medication Guide that
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` they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
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`• 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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`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.
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` 5.4 Life Threatening-Respiratory Depression
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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
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` 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 oral solution, 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
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`o