WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, ACCIDENTAL EXPOSURE, and INTERACTION WITH ALCOHOL
NUCYNTA® ER contains tapentadol, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit. Assess each patient’s risk for opioid abuse or addiction prior to prescribing NUCYNTA® ER. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depressive disorder). Routinely monitor all patients receiving NUCYNTA® ER for signs of misuse, abuse, and addiction during treatment.
Life-threatening Respiratory Depression
Respiratory depression, including fatal cases, may occur with use of NUCYNTA® ER, even when the drug has been used as recommended and not misused or abused. Proper dosing and titration are essential, and NUCYNTA® ER should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Monitor for respiratory depression, especially during initiation of NUCYNTA® ER or following a dose increase. Instruct patients to swallow NUCYNTA® ER tablets whole. Crushing, dissolving, or chewing NUCYNTA® ER can cause rapid release and absorption of a potentially fatal dose of tapentadol.
Accidental ingestion of NUCYNTA® ER, especially in children, can result in a fatal overdose of tapentadol.
Interaction With Alcohol
The co-ingestion of alcohol with NUCYNTA® ER may result in an increase of plasma levels and potentially fatal overdose of tapentadol. Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol while on NUCYNTA® ER.
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.
Life-threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA® ER, the risk is greatest during the initiation of therapy or following a dose increase. When converting patients from another opioid product, overestimating the NUCYNTA® ER dose can result in a fatal overdose that can manifest as respiratory depression, with the first dose.
Accidental Exposure: Instruct patients against use by individuals other than the patient for whom NUCYNTA® ER was prescribed and to keep NUCYNTA® ER out of the reach of children as inappropriate use may result in fatal respiratory depression.
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. Monitor these patients closely, particularly when initiating and titrating NUCYNTA® ER and when 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 particularly when initiating therapy and titrating with NUCYNTA® ER. Consider the use of alternative nonopioid analgesics in these patients.
Interactions With CNS Depressants and Illicit Drugs: Concomitant use with other CNS depressants may result in hypotension and profound sedation, coma, or respiratory depression. If NUCYNTA® ER therapy is to be initiated in a patient taking a CNS depressant, start NUCYNTA® ER 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: NUCYNTA® ER may cause severe hypotension; there is an increased risk in patients whose ability to maintain blood pressure has already been compromised by reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor for signs of hypotension during dose initiation or titration. Avoid the 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, particularly when initiating therapy. NUCYNTA® ER 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® ER 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® ER therapy.
Serotonin Syndrome Risk: Cases of life-threatening serotonin syndrome have been reported with the concurrent use of NUCYNTA® ER 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® ER in physically dependent patients. When discontinuing NUCYNTA® ER, 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® ER. Avoid the use of mixed agonists/antagonists and partial agonists with NUCYNTA® ER.
- 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: NUCYNTA® ER 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® ER and know how they will react to the medication.
Renal and Hepatic Impairment:
- Renal: Use of NUCYNTA® ER 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.
- Hepatic: Avoid use of NUCYNTA® ER in patients with severe hepatic impairment (Child-Pugh Score 10-15); reduce the dose in patients with moderate impairment (Child-Pugh Score 7-9); and monitor for respiratory and CNS depression when initiating and titrating NUCYNTA® ER.
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 of NUCYNTA® ER with anticholinergic products may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Pregnancy/Neonates/Nursing Mothers: Pregnancy Category C. NUCYNTA® ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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® ER 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 Trials: The most common (≥10%) adverse reactions were nausea, constipation, vomiting, dizziness, somnolence, and headache.
Select Postmarketing Adverse Reactions: Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA® ER. Advise patients how to recognize such reactions and when to seek medical attention. Panic attack has also been very rarely reported.