^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 and pediatric patients aged 6 years and older with a body weight of at least 40kg.
^ Opioid-induced Hyperalgesia And Allodynia
Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect [see Dependence (9.3)]. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.
Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching the patient to a different opioid moiety) [see Dosage and Administration (2.7); Warnings and Precautions (5.13)].
^7 Drug Interactions
Table 2 includes clinically significant drug interactions with NUCYNTA tablets.
^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.
^ Mechanism Of Action
Tapentadol is a centrally-acting synthetic analgesic. The exact mechanism of action is unknown. Although the clinical relevance is unclear, preclinical studies have shown that tapentadol is a mu-opioid receptor (MOR) agonist and a norepinephrine reuptake inhibitor (NRI). Analgesia in animal models is derived from both of these properties.
^ 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:
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.
^ Description
NUCYNTA (tapentadol) tablets are a mu-opioid receptor agonist, available in immediate-release film-coated tablets for oral administration, containing 58.24, 87.36 and 116.48 mg of tapentadol hydrochloride in each tablet strength, equivalent to 50, 75, and 100 mg of tapentadol free-base, respectively. The chemical name is 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol monohydrochloride, and it has the following chemical structure:
The molecular weight of tapentadol HCl is 257.80, and the molecular formula is C14H23NO∙HCl. The n-octanol:water partition coefficient log P value is 2.87. The pKa values are 9.34 and 10.45.
The inactive ingredients in NUCYNTA tablets include: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone. The film coatings for all tablet strengths contain polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and the colorant FD&C Yellow #6 aluminum lake; the film coatings for the 50 mg and 75 mg tablets also contain the additional colorant D&C Yellow #10 aluminum lake.
^ Risks Of Use In Patients With Gastrointestinal Conditions
NUCYNTA tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The tapentadol in NUCYNTA tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Regularly evaluate patients with biliary tract disease, including acute pancreatitis for worsening symptoms.
^ Withdrawal
Do not abruptly discontinue NUCYNTA tablets in a patient physically dependent on opioids. When discontinuing NUCYNTA tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of tapentadol in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration (2.7), Drug Abuse and Dependence (9.3)].
Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including NUCYNTA tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].
^ Risks From Concomitant Use With Benzodiazepines Or Other Cns Depressants
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions (7)].
If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation).
If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.2), Overdosage (10)].
Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7)].
^ Renal Impairment
Use of NUCYNTA tablets in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) is not recommended. No dosage adjustment is recommended in patients with mild or moderate renal impairment (creatinine clearance 30-90 mL/minute) [see Warnings and Precautions (5.18), Clinical Pharmacology (12.1)].
^ Life-threatening Respiratory Depression In Patients With Chronic Pulmonary Disease Or In Elderly, Cachectic, Or Debilitated Patients
The use of NUCYNTA tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
^ 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.
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 total daily dose of opioid (including 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, evaluate 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 an extended period of time 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 (5.14), Drug Abuse and Dependence (9.3)].
^ Clinical Study In Pediatric Patients
The efficacy and safety of NUCYNTA (tapentadol) tablets for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate in pediatric patients who are 6 years and older and weigh at least 40 kg have been established based on one randomized, double-blind, placebo-controlled, multiple-dose study of NUCYNTA (tapentadol) oral solution in pediatric patients ages birth to 17 years who had undergone surgery that would reliably produce moderate to severe acute post-operative pain.
Patients who had undergone surgery that would reliably produce moderate to severe acute pain requiring opioid treatment via nurse-controlled analgesia (NCA) or patient-controlled analgesia (PCA), had received postoperative morphine or hydromorphone by NCA or PCA, and were able to tolerate liquids were randomized to either NUCYNTA (tapentadol) oral solution or placebo (2:1 allocation). Patients from 6 months to 17 years of age were administered NUCYNTA (tapentadol) oral solution 1.25 mg/kg body weight (maximum single dose 100 mg) or the same volume of placebo every four hours for the first 24 hours with dose reduction to 1.0 mg/kg body weight after 24 hours if there was a reduced need for analgesia at the investigator's discretion.
The study was statistically powered to evaluate the efficacy of NUCYNTA (tapentadol) oral solution across the pediatric age range from 2 to 17 years of age. Efficacy was evaluated by comparing the total amount of supplemental opioid analgesic medication (morphine equivalents in mg/kg body weight) used within 12 hours and 24 hours following initiation of study drug between the NUCYNTA (tapentadol) oral solution and placebo groups. Overall, statistically significantly more supplemental opioid analgesic medication was used in the placebo group than in the NUCYNTA (tapentadol) oral solution group during the first 12 and 24 hours after first dose of study drug. However, a descriptive analysis of supplemental opioid analgesic medication used by age subgroup demonstrated lack of efficacy of NUCYNTA (tapentadol) oral solution in pediatric patients 2 to less than 6 years of age [see Pediatric Use (8.4)].
The descriptive analysis of supplemental opioid analgesic medication use showed the following results (see Table 4):
NUCYNTA (tapentadol) tablets are not approved for use in pediatric patients less than 6 years of age or who weigh less than 40 kg [see Pediatric Use (8.4)].
The efficacy and safety of NUCYNTA (tapentadol) tablets at doses higher than 1.25 mg/kg body weight (maximum single dose of 100 mg) have not been studied; therefore, the use of NUCYNTA (tapentadol) tablets at doses higher than 1.25 mg/kg body weight is not recommended [see Dosage and Administration (2.4)].
^ Animal Toxicology And/or Pharmacology
In toxicological studies with tapentadol, the most common systemic effects of tapentadol were related to the mu-opioid receptor agonist and norepinephrine reuptake inhibition pharmacodynamic properties of the compound. Transient, dose-dependent and predominantly CNS-related findings were observed, including impaired respiratory function and convulsions, the latter occurring in the dog at plasma levels (Cmax) which are in the range associated with the maximum recommended human dose (MRHD).
^ Important Dosage And Administration Instructions
^Principal Display Panel - Mg Tablet Bottle Label
NDC 24510-075-10100 Tablets
NUCYNTA® (tapentadol) Tablets
75 mg
CII
Each tablet contains:tapentadol 75 mg
Caution: Federal law prohibits the transferof this drug to any person other than the patientfor whom it was prescribed.
Dispense the accompanying Medication Guide to each patient.
Rev Dec 2018NUC-006-C.4
^ Controlled Substance
NUCYNTA tablets contain tapentadol, a Schedule II controlled substance.
^ Severe Hypotension
NUCYNTA tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7)]. Regularly evaluate these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA tablets. In patients with circulatory shock, NUCYNTA tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA tablets in patients with circulatory shock.
^ Post-marketing Experience
The following additional adverse reactions have been identified during post approval use of tapentadol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Gastrointestinal disorders: diarrhea
Nervous system disorders: headache
Psychiatric disorders: hallucination, suicidal ideation, panic attack
Cardiac disorders: palpitations
Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Anaphylaxis: Anaphylaxis has been reported with ingredients contained in NUCYNTA tablets.
Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids for an extended period of time [see Clinical Pharmacology (12.2)].
Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions (5.5)]
Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).
^ Pediatric Use
The safety and effectiveness of NUCYNTA (tapentadol) tablets in pediatric patients ages 6 years and older who weigh at least 40 kg have been established. Use of NUCYNTA (tapentadol) tablets in pediatric patients ages 6 years and older who weigh at least 40 kg is based on one randomized, double-blind, placebo-controlled, multiple-dose efficacy and safety study of NUCYNTA (tapentadol) oral solution in 175 pediatric patients from birth to 17 years of age who had undergone surgery that would reliably produce moderate to severe pain and supported by pharmacokinetic and safety data from three open-label, single-dose studies of NUCYNTA (tapentadol) oral solution in 129 patients from birth to 17 years of age with moderate to severe acute pain from a surgical procedure [see Clinical Studies (14.2)].
The safety and effectiveness of NUCYNTA (tapentadol) tablets in pediatric patients less than 6 years of age have not been established. In pediatric patients less than 6 years of age, NUCYNTA (tapentadol) oral solution did not demonstrate efficacy compared to placebo when evaluated in one randomized, double-blind, placebo-controlled, multiple-dose study in 175 pediatric patients from birth to 17 years of age who had undergone surgery that would reliably produce moderate to severe pain [see Clinical Studies (14.2)].
The safety and effectiveness of NUCYNTA (tapentadol) tablets in pediatric patients who weigh less than 40 kg have not been established because the recommended dosage cannot be achieved with available tablet strengths. Consider use of another NUCYNTA product, such as NUCYNTA (tapentadol) oral solution, in patients who cannot swallow oral tablets or who weigh less than 40 kg [see Dosage and Administration (2.3)].
NUCYNTA (tapentadol) tablets have not been studied in pediatric patients with hepatic or renal impairment; therefore, use in these populations is not recommended [see Dosage and Administration (2.4)].
^ Risk Of Toxicity In Patients With Renal Impairment
Use of NUCYNTA tablets in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known [see Clinical Pharmacology (12.3)].
^Principal Display Panel - Mg Tablet Bottle Label
NDC 24510-100-10100 Tablets
NUCYNTA® (tapentadol) Tablets
100 mg
CII
Each tablet contains:tapentadol 100 mg
Caution: Federal law prohibits the transferof this drug to any person other than the patientfor whom it was prescribed.
Dispense the accompanying Medication Guide to each patient.
Rev Dec 2018NUC-009-C.4
^ 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.
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.
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)].
^ Adrenal Insufficiency
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
^ Risk Of Toxicity In Patients With Hepatic Impairment
A study with NUCYNTA tablets in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA tablets in patients with severe hepatic impairment. Reduce the dose of NUCYNTA tablets in patients with moderate hepatic impairment [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. Regularly evaluate patients with moderate hepatic impairment for respiratory and central nervous system depression when receiving NUCYNTA tablets.
^ 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)].
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, 5.2, 5.3)].
Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.
^ Serotonin Syndrome With Concomitant Use Of Serotonergic Drugs
Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions (7)]. This may occur within the recommended dosage range.
Serotonin syndrome symptoms may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) and can be fatal. The onset of symptoms generally occurs within several hours to a few days of concomitant use but may occur later than that. Discontinue NUCYNTA tablets if serotonin syndrome is suspected.
^ Dosage Modifications In Adult Patients With Hepatic Impairment
The safety and efficacy of NUCYNTA tablets have 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. Regularly evaluate patients 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)].
^ Increased Risk Of Seizures In Patients With Seizure Disorders
The tapentadol in NUCYNTA tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Regularly evaluate patients with a history of seizure disorders for worsened seizure control during NUCYNTA tablets therapy.
^ Interactions With Alcohol, Other Opioids, And Drugs Of Abuse
Due to its mu-opioid agonist activity, NUCYNTA tablets may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression, respiratory depression, hypotension, and profound sedation, coma or death [see Drug Interactions (7)]. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol, other opioids, or drugs of abuse while on NUCYNTA tablets therapy [see Drug Interactions (7)].
^ Geriatric Use
Of the total number of patients in Phase 2/3 double-blind, multiple-dose clinical studies of NUCYNTA tablets, 19% were 65 and over, while 5% were 75 and over. No overall differences in effectiveness were observed between these patients and younger patients. The rate of constipation was higher in subjects greater than or equal to 65 years than those less than 65 years (12% vs. 7%).
Elderly patients (aged 65 years or older) may have increased sensitivity to tapentadol. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of NUCYNTA tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.2)].
Tapentadol is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.
^ Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
^ Risks Of Use In Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, Or Impaired Consciousness
In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NUCYNTA tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure.
Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA tablets.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA tablets in patients with impaired consciousness or coma.
^6 Adverse Reactions
The following adverse reactions are discussed, or described in greater detail, in other sections:
^ 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 reassess 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 frequent reevaluation 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 (5.2)].
Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. 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 careful storage of the drug during the course of treatment and on the proper disposal of unused drug. 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.
^Principal Display Panel - Mg Tablet Bottle Label
NDC 24510-050-10100 Tablets
NUCYNTA® (tapentadol) Tablets
50 mg
CII
Each tablet contains:tapentadol 50 mg
Caution: Federal law prohibits the transferof this drug to any person other than the patientfor whom it was prescribed.
Dispense the accompanying Medication Guide to each patient.
Rev Dec 2018NUC-003-C.4
^ Abuse
NUCYNTA tablets contain tapentadol, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1)].
Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.
Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
Misuse and abuse of NUCYNTA tablets increase risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of NUCYNTA tablets with alcohol and/or other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.
All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of NUCYNTA tablet abuse include those with a history of prolonged use of any opioid, including products containing tapentadol, those with a history of drug or alcohol abuse, or those who use NUCYNTA tablets in combination with other abused drugs.
"Drug-seeking" behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated "loss" of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.
NUCYNTA tablets, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
^ Titration And Maintenance Of Therapy
Individually titrate NUCYNTA tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving NUCYNTA tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as reassess for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1, 5.14)]. 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 after increase the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after a dosage increase), consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
^4 Contraindications
NUCYNTA tablets are contraindicated in patients with:
^ Risks Of Driving And Operating Machinery
NUCYNTA tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA tablets and know how they will react to the medication.
^ Dependence
Both tolerance and physical dependence can develop during use of opioid therapy.
Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.
Do not abruptly discontinue NUCYNTA tablets in a patient physically dependent on opioids. Rapid tapering of NUCYNTA tablets in a patient physically dependent on opioids may lead to 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.
When discontinuing NUCYNTA tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of NUCYNTA tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.7), and Warnings and Precautions (5.13)].
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].
^ Clinical Studies In Adult Patients
The efficacy and safety of NUCYNTA tablets in the treatment of acute pain has been established in two randomized, double-blind, placebo- and active-controlled studies of moderate to severe pain from first metatarsal bunionectomy and end-stage degenerative joint disease.
^ How Supplied/storage And Handling
NUCYNTA Tablets are available in the following strengths and packages. All tablets are round and biconvex-shaped.
50 mg tablets are yellow and debossed with "O-M" on one side and "50" on the other side, and are available in bottles of 100 (NDC 24510-050-10) and hospital unit dose blister packs of 10 (NDC 24510-050-01).
75 mg tablets are yellow-orange and debossed with "O-M" on one side and "75" on the other side, and are available in bottles of 100 (NDC 24510-075-10) and hospital unit dose blister packs of 10 (NDC 24510-075-01).
100 mg tablets are orange and debossed with "O-M" on one side and "100" on the other side, and are available in bottles of 100 (NDC 24510-100-10) and hospital unit dose blister packs of 10 (NDC 24510-100-01).
^ Hepatic Impairment
Administration of tapentadol resulted in higher exposures and serum levels of tapentadol in subjects with impaired hepatic function compared to subjects with normal hepatic function [see Clinical Pharmacology (12.3)]. Use of NUCYNTA tablets are not recommended in patients with severe hepatic impairment (Child-Pugh Score 10 to 15) [see Warnings and Precautions (5.17)]. The dose of NUCYNTA tablets should be reduced in patients with moderate hepatic impairment (Child-Pugh Score 7 to 9) [see Dosage and Administration (2.5)]. No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5 to 6) [see Warnings and Precautions (5.17), Clinical Pharmacology (12.3)].
^ Neonatal Opioid Withdrawal Syndrome
Use of NUCYNTA tablets for an extended period of time 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 an extended period of time of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1)].