`These highlights do not include all the information needed to use
`
`
`NUCYNTA® TABLETS safely and effectively. See full prescribing
`
`information for NUCYNTA® TABLETS.
`NUCYNTA® (tapentadol) 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; and
`
`RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR
`
`
`
`OTHER CNS DEPRESSANTS
`
`
`See full prescribing information for complete boxed warning.
`NUCYNTA tablets expose 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. (5.1)
`
`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. (5.3)
`
`Accidental ingestion of NUCYNTA tablets, especially by children,
`
`can result in a fatal overdose of tapentadol. (5.3)
`
`
`
`
`Prolonged use of NUCYNTA tablets 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. (5.4)
`
`
`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)
`
`03/2021
`Warnings and Precautions (5.1, 5.3, 5.5)
`
`
`
`
`----------------------------INDICATIONS AND USAGE----------------------------
`
`
`NUCYNTA tablets are 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 tablets 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 based on 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 tablets. Consider prescribing
`
`
`naloxone based on the patient’s risk factors for overdose (2.2, 5.1, 5.3, 5.5)
`
`
`
`
`
`
` Initiate treatment with NUCYNTA tablets at a dose of 50 mg, 75 mg, or 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
`
`
`
`
`
`
`
`
`
`Reference ID: 4756498
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`the first dose, if adequate pain relief is not attained with the first dose.
`
`Subsequent dosing is 50 mg, 75 mg, or 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 system depression. (2.4)
`
`
`
`
`
`
`
` Do not abruptly discontinue NUCYNTA tablets 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----------------------
`
`Tablets: 50 mg, 75 mg, 100 mg (3)
`
`-------------------------------CONTRAINDICATIONS-------------------------------
`
` Significant respiratory depression (4)
`
`
` Acute or severe bronchial asthma in an unmonitored setting or in absence of
`
`
`
`resuscitative equipment. (4)
`
` Known or suspected gastrointestinal obstruction, including 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. (5.6)
`
` Serotonin Syndrome: Potentially life-threatening condition could result from
`
`concomitant serotonergic drug administration. Discontinue NUCYNTA
`
`tablets 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 tablets 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 tablets in patients with
`
`
`
`impaired consciousness or coma. (5.10)
`
`
`------------------------------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 Opioid Analgesics: Avoid
`
`
`
`use with NUCYNTA tablets because they reduce analgesic effect of
`
`NUCYNTA tablets 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
`
`tablets. (8.2)
`
`
` Severe Renal or Hepatic Impairment: Not recommended. (8.6, 8.7)
`
`
`
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`
`Guide.
`
`Revised: 03/2021
`
`
`
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`WARNING: ADDICTION, ABUSE, AND MISUSE; RISK
`
`EVALUATION AND MITIGATION STRATEGY (REMS);
`
`LIFE-THREATENTING RESPIRATORY DEPRESSION;
`
`
`ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL
`
`SYNDROME; and RISKS FROM CONCOMITANT USE WITH
`
`BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
`
`
`
`1
`INDICATIONS AND USAGE
`
`
`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
`Tablets
`3 DOSAGE FORMS AND STRENGTHS
`
`
`
`4 CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
`
`
`
`5.1 Addiction, Abuse, and Misuse
`5.2 Opioid Analgesic Risk Evaluation and Mitigation
`
`Strategy (REMS)
`
`
`5.3
`Life-Threatening Respiratory Depression
`
`5.4 Neonatal Opioid Withdrawal Syndrome
`
`5.5 Risks from Concomitant Use with
`
`Benzodiazepines or Other CNS Depressants
`
`Life-Threatening Respiratory Depression in
`
`Patients with Chronic Pulmonary Disease or in
`
`
`Elderly, Cachectic, or Debilitated Patients
`
`
`5.7 Serotonin Syndrome with Concomitant Use of
`
`Serotonergic Drugs
`
`
`
`5.8 Adrenal Insufficiency
`5.9 Severe Hypotension
`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
`
`5.13 Withdrawal
`
`
`5.14 Risks of Driving and Operating Machinery
`
`
`5.12
`
`
`5.6
`
`5.15
`
`
`
`Interactions with Alcohol, Other Opioids, and
`
`Drugs of Abuse
`
`
`5.16 Risk of Toxicity in Patients with Hepatic
`
`
`
`Impairment
`
`
`5.17 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
`Lactation
`8.2
`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: 4756498
`
`
`
`FULL PRESCRIBING INFORMATION
`
`WARNING: 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
`Addiction, Abuse, and Misuse
`NUCYNTA tablets 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 tablets, and monitor all patients regularly for the development of
`these behaviors and conditions [see Warnings and Precautions (5.1)].
`Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
`
`To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse,
`
`
`
`and misuse, the Food and Drug Administration (FDA) has required a REMS for these
`
`
`
`
`products [see Warnings and Precautions (5.2)]. Under the requirements of the REMS,
`drug companies with approved opioid analgesic products must make REMS-compliant
`education programs available to healthcare providers. Healthcare providers are
`strongly encouraged to
` complete a REMS-compliant education program,
`
` counsel patients and/or their caregivers, with every prescription, on safe use,
`
`
`serious risks, storage, and disposal of these products,
`
` emphasize to patients and their caregivers the importance of reading the
`
`
`Medication Guide every time it is provided by their pharmacist, and
`
`
`
` consider other tools to improve patient, household, and community safety.
`
`
`Life-Threatening Respiratory Depression
`
`Serious, life-threatening, or fatal respiratory depression may occur with use of NUCYNTA
`tablets. Monitor for respiratory depression, especially during initiation of NUCYNTA
`tablets or following a dose increase [see Warnings and Precautions (5.3)].
`Accidental Ingestion
`Accidental ingestion of even one dose of NUCYNTA tablets, 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 tablets 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)].
`
`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 tablets 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.
`
`
`
`
`
`Reference ID: 4756498
`
`3
`
`
`
`
`1
`
`
`
` INDICATIONS AND USAGE
`
`NUCYNTA (tapentadol) tablets are 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 (5.1)], reserve NUCYNTA tablets 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
`
`Important Dosage and Administration Instructions
`2.1
`Use the lowest effective dosage for the shortest duration consistent with individual patient
`treatment goals [see Warnings and Precautions (5)].
`
`
`Initiate the dosing regimen for each patient individually, taking into account the patient's severity
`of pain, patient response, prior analgesic treatment experience, and risk factors for addiction,
`abuse, and misuse [see Warnings and Precautions (5.1)].
`
`Monitor patients closely for respiratory depression, especially within the first 24-72 hours of
`initiating therapy and following dosage increases with NUCYNTA and adjust the dosage
`accordingly [see Warnings and Precautions (5.3)]
`
`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 tablets [see Warnings and
`Precautions (5.3), 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 (5.1, 5.3, 5.5)].
`
`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
`Initiating Treatment with NUCYNTA Tablets
`Initiate treatment with NUCYNTA tablets in a dosing range of 50 mg to 100 mg 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
`
`
`
`Reference ID: 4756498
`
`4
`
`
`
`first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg,
`75 mg, or 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 tablets may be given with or without food [see Clinical Pharmacology (12.3)].
`
`
`Conversion from NUCYNTA Tablets to NUCYNTA ER
`Patients can be converted from NUCYNTA tablets to NUCYNTA ER using the equivalent total
`
`daily dose of NUCYNTA tablets 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 tablets four times per day (200 mg/day) may be converted to 100 mg NUCYNTA
`ER twice a day.
`
`2.4 Dosage Modifications in Patients with Hepatic Impairment
`The safety and efficacy of NUCYNTA tablets 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 (5.16)].
`
`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 tablets to assess the maintenance of pain
`control and the relative incidence of adverse reactions, as well as monitoring for the development
`of addiction, abuse, or misuse [see Warnings and Precautions (5.1)]. Frequent communication
`is important among the 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 tablets 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 Tablets
`
`Do not abruptly discontinue NUCYNTA Tablets 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.
`
`
`
`
`Reference ID: 4756498
`
`5
`
`
`
`When a decision has been made to decrease the dose or discontinue therapy in an opioid-
`dependent patient taking NUCYNTA Tablets, there are a variety of factors that should be
`considered, including the dose of NUCYNTA Tablets the patient has been taking, the duration of
`treatment, the type of pain being treated, and the physical and psychological attributes of the
`patient. It is important to ensure ongoing care of the patient and to agree on an appropriate
`
`tapering schedule and follow-up plan so that patient and provider goals and expectations are
`clear and realistic. When opioid analgesics are being discontinued due to a suspected substance
`use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance
`use disorder. Treatment should include evidence-based approaches, such as medication assisted
`treatment of opioid use disorder. Complex patients with co-morbid pain and substance use
`disorders may benefit from referral to a specialist.
`
`
`There are no standard opioid tapering schedules that are suitable for all patients. Good clinical
`practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on
`NUCYNTA Tablets 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.
`
`It may be necessary to provide the patient with lower dosage strengths to accomplish a
`successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms,
`should they emerge. Common withdrawal symptoms include restlessness, lacrimation,
`rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms
`also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal
`cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory
`rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a
`period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed
`with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal
`thoughts, or use of other substances.
`
`When managing patients taking opioid analgesics, particularly those who have been treated for a
`long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain
`management, including mental health support (if needed), is in place prior to initiating an opioid
`
`analgesic taper. A multimodal approach to pain management may optimize the treatment of
`
`
`chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings
`and Precautions (5.13), Drug Abuse and Dependence (9.3)].
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`Tablets: 50 mg, 75 mg, 100 mg.
`
`50 mg: round, biconvex and film-coated yellow tablets with “O-M” on one side and “50” on the
`other side.
`
`75 mg: round, biconvex and film-coated yellow-orange tablets with “O-M” on one side and “75”
`on the other side.
`
`100 mg: round, biconvex and film-coated orange tablets with “O-M” on one side and “100” on
`the other side.
`
` 4 CONTRAINDICATIONS
`
`
`
`
`
`Reference ID: 4756498
`
`6
`
`
`
`NUCYNTA tablets are contraindicated in patients with:
`
`
` Significant respiratory depression [see Warnings and Precautions (5.3)]
`
`
`
` Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative
`
` equipment [see Warnings and Precautions (5.6)]
`
` Known or suspected gastrointestinal obstruction, including suspected paralytic ileus [see
`
` Warnings and Precautions (5.11)]
`
` Hypersensitivity to tapentadol (e.g. anaphylaxis, angioedema) or to any other ingredients of
`the product [see Adverse Reactions (6.2)].
`
` Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last
`14 days [see Drug Interactions (7)].
`
`
`
`
` 5 WARNINGS AND PRECAUTIONS
`
`5.1 Addiction, Abuse, and Misuse
`NUCYNTA tablets contain tapentadol, a Schedule II controlled substance. As an opioid,
`NUCYNTA tablets exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse
`and Dependence (9)].
`
`Although the risk of addiction in any individual is unknown, it can occur in patients
`appropriately prescribed NUCYNTA tablets. Addiction can occur at recommended dosages and
`if the drug is misused or abused.
`
`Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA
`tablets and monitor all patients receiving NUCYNTA tablets 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 tablets, but use in such patients necessitates intensive counseling about the risks and
`proper use of NUCYNTA tablets along with intensive monitoring for signs of addiction, abuse,
`and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see
`
`Dosage and Administration (2.2), Warnings and Precautions (5.3)].
`
`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 tablets.
`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.
`
` 5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
`
`To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and
`misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation
`Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with
`approved opioid analgesic products must make REMS-compliant education programs available
`to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:
`
` Complete a REMS-compliant education program offered by an accredited provider of
`continuing education (CE) or another education program that includes all the elements of
`the FDA Education Blueprint for Health Care Providers Involved in the Management or
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`Support of Patients with Pain.
`
` Discuss the safe use, serious risks, and proper storage and disposal of opioid
`
`analgesics with patients and/or their caregivers every time these medicines are
`
`prescribed. The Patient Counseling Guide (PCG) can be obtained at this link:
`
`
`www.fda.gov/OpioidAnalgesicREMSPCG. Emphasize to patients and their
`
`caregivers the importance of reading the Medication Guide that they will receive
`
`from their pharmacist every time an opioid analgesic is dispensed to them.
`
`
` Consider using other tools to improve patient, household, and community safety, such as
`patient-prescriber agreements that reinforce patient-prescriber responsibilities.
`
`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.
`
`
` 5.3 Life-Threatening Respiratory Depression
`Serious, life-threatening, or fatal respiratory depression has been reported with the use of
`opioids, even when used as recommended. Respiratory depression, if not immediately
`recognized and treated, may lead to respiratory arrest and death. Management of respiratory
`depression may include close observation, supportive measures, and use of opioid antagonists,
`depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention
`from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
`
`While serious, life-threatening, or fatal respiratory depression can occur at any time during the
`use of NUCYNTA tablets, the risk is greatest during the initiation of therapy or following a
`dosage increase. Monitor patients closely for respiratory depression, especially within the first
`
`
`24-72 hours of initiating therapy with and following dosage increases of NUCYNTA tablets.
`
`To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA tablets
`are essential [see Dosage and Administration (2.3)]. Overestimating the NUCYNTA tablets
`dosage when converting patients from another opioid product can result in a fatal overdose with
`the first dose.
`
`Accidental ingestion of even one dose of NUCYNTA tablets, especially by children, can result in
`respiratory depression and death due to an overdose of tapentadol.
`
`Educate patients and caregivers on how to recognize respiratory depression and emphasize the
`importance of calling 911 or getting emergency medical help right away in the event of a known
`
`or suspected overdose [see Patient Counseling Information (17)].
`
`Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and
`sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In
`patients who present with CSA, consider decreasing the opioid dosage using best practices for
`opioid taper [see Dosage and Administration (2.6)].
`
`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 tablets. Inform patients and caregivers about the
`various ways to obtain naloxone as permitted by individual state naloxone dispensing and
`
`prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as
`part of a community-based program). Educate patients and caregivers on how to recognize
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`respiratory depression and emphasize the importance of calling 911 or getting emergency
`
` medical help, even if naloxone is administered [see Patient Counseling Information (17)].
`
`
`
`Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as
`concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose.
`The presence of risk factors for overdose should not prevent the proper management of pain in
`any given patient. Also consider prescribing naloxone if the patient has household members
`(including children) or other close contacts at risk for accidental ingestion or overdose. If
`
`naloxone is prescribed, educate patients and caregivers on how to treat with naloxone. [see
`
`
`Warnings and Precautions (5.1, 5.5), Patient Counseling Information (17)].
`
`5.4 Neonatal Opioid Withdrawal Syndrome
`Prolonged use of NUCYNTA tablets during pregnancy can result in withdrawal in the neonate.
`Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be
`life-threatening if not recognized and treated, and requires management according to protocols
`developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal
`syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged
`period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment
`will be available [see Use in Specific Populations (8.1), Patient Counseling Information (17)].
`
`5.5 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
`Profound sedation, respiratory depression, coma, and death may result from the concomitant u