NUCYNTA® INDICATIONS AND USAGE
NUCYNTA® (tapentadol) is an opioid analgesic indicated for the management of moderate to severe acute pain in adults.
NUCYNTA® IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS: Significant respiratory depression; acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity to tapentadol or to any other ingredients of the product; concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days.
WARNINGS AND PRECAUTIONS
Abuse Potential: NUCYNTA® contains tapentadol, an opioid agonist and a Schedule II controlled substance that can be abused in a manner similar to other opioid agonists, legal or illicit. Misuse or abuse of NUCYNTA® by crushing, chewing, snorting, or injecting will pose a significant risk that could result in overdose and death. Assess risk for opioid abuse or addiction prior to prescribing NUCYNTA®. Routinely monitor for signs of misuse, abuse, and addiction because these drugs carry a risk for addiction even under appropriate medical use.
Life-threatening Respiratory Depression: Respiratory depression is the chief hazard of opioid agonists, including NUCYNTA® which, 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.
Accidental Exposure: Instruct patients against use by individuals other than the patient for whom NUCYNTA® was prescribed and to keep NUCYNTA® out of the reach of children, as such inappropriate use may result in fatal respiratory depression.
Interactions with Alcohol, Other Opioids, and Drugs of Abuse: Due to its mu-opioid agonist activity, NUCYNTA® 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.
Elderly, Cachectic, or Debilitated Patients: Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Closely monitor these patients, particularly when NUCYNTA® is given concomitantly with other drugs that depress respiration.
Use in Patients With Chronic Pulmonary Disease: Patients with significant chronic obstructive pulmonary disease or cor pulmonale and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre-existing respiratory depression, should be monitored for respiratory depression. Consider the use of alternative nonopioid analgesics in these patients.
Interactions With Central Nervous System (CNS) Depressants and Illicit Drugs: Concomitant use with other CNS depressants may result in hypotension and profound sedation, coma, or respiratory depression. If NUCYNTA® therapy is to be initiated in a patient taking a CNS depressant, start NUCYNTA® at 1/3 to 1/2 of the usual dosage and monitor patients for signs of sedation and respiratory depression; consider using a lower dose of the concomitant CNS depressant.
Hypotensive Effect: May cause severe hypotension; there is an 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). Monitor for signs of hypotension. Avoid use in patients with circulatory shock; may cause vasodilation that can further reduce cardiac output and blood pressure.
Use in Patients With Head Injury or Increased Intracranial Pressure: Monitor patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression. NUCYNTA® may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury.
Seizures: NUCYNTA® may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA® therapy.
Serotonin Syndrome Risk: Cases of life-threatening serotonin syndrome have been reported with the concurrent use of NUCYNTA® and serotonergic drugs. Serotonergic drugs comprise selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, drugs that affect the serotonergic neurotransmitter system, and drugs that impair metabolism of serotonin (including MAOIs). This may occur within the recommended dose. Serotonin syndrome 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. If concomitant treatment with SSRIs, SNRIs, TCAs, or triptans is clinically warranted, careful observation of the patient is advised.
Use in Patients With Gastrointestinal (GI) Conditions: Contraindicated in patients with GI obstruction, including paralytic ileus; may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
Withdrawal: Withdrawal symptoms (e.g., anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely, hallucinations) may occur:
- After abrupt discontinuation or a significant dose reduction of NUCYNTA® in physically dependent patients. When discontinuing NUCYNTA®, gradually taper the dose.
- If mixed agonists/antagonists (e.g., butorphanol, nalbuphine, pentazocine) and partial agonists (e.g., buprenorphine) are used in patients who have received or are receiving NUCYNTA®. Avoid use with mixed agonists/antagonists and partial agonists.
- If opioid antagonists (e.g., naloxone, nalmefene) are administered in physically dependent patients. Administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.
Driving and Operating Heavy Machinery: 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® and know how they will react to the medication.
Hepatic and Renal Impairment:
- Hepatic: Avoid use of NUCYNTA® in patients with severe hepatic impairment (Child-Pugh Score 10-15). In patients with moderate impairment (Child-Pugh Score 7-9), initiate treatment with 50 mg no more frequently than once every 8 hours (maximum of 3 doses in 24 hours). Further treatment should reflect maintenance of analgesia with acceptable tolerability, to be achieved by either shortening or lengthening the dose interval.
- Renal: Use of NUCYNTA® in patients with severe renal impairment (CLCR <30 mL/min) is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.
Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients in the lower range of recommended doses.
Anticholinergics: Use with anticholinergic products may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
USE IN SPECIFIC POPULATIONS
Pregnancy/Labor and Delivery/Neonates/Nursing Mothers: Pregnancy Category C. NUCYNTA® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. NUCYNTA® is not for use in women during and immediately prior to labor. Neonates born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms. Neonatal opioid withdrawal syndrome may be life-threatening and should be treated according to protocols developed by neonatology experts. Closely monitor infants of nursing mothers receiving NUCYNTA® because of the potential for adverse reactions (e.g., withdrawal symptoms).
OVERDOSAGE: Institute supportive measures to manage respiratory depression, circulatory shock, and pulmonary edema as required. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression.
ADVERSE REACTIONS: In clinical studies, the most common (≥10%) adverse reactions were nausea, dizziness, vomiting, and somnolence.
Select Postmarketing Adverse Reactions: Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA®. Advise patients how to recognize such reactions and when to seek medical attention. Panic attack has also been reported.
Please see full Prescribing Information for more information about NUCYNTA®.