ta-PEN-ta-dol

Therapeutic Classification: analgesics (centrally acting), opioid analgesics

Pharmacologic Classification: opioid agonists

• Acute pain that is severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
• Moderate to severe chronic pain in opioid-tolerant patients requiring use of daily, around-the-clock long-term opioid treatment and for which alternative treatment options are inadequate (extended-release only).
• Diabetic pain associated with diabetic peripheral neuropathy in patients requiring around-the-clock opioid analgesia for an extended time (extended-release only).

• Acts as a mu-opioid receptor agonist.
• Also inhibits the reuptake of norepinephrine.

• Decrease in pain severity.

Absorption: 32% absorbed following oral administration.

Distribution: Widely distributed.

Metabolism/Excretion: Undergoes extensive first-pass hepatic metabolism (97%); metabolites have no analgesic activity; metabolized drug is 99% renally excreted.

Half-life: 4 hr.

(analgesic effect)

Contraindicated in:

• Hypersensitivity
• Significant respiratory depression in unmonitored settings or where resuscitative equipment is not readily available
• Paralytic ileus
• Severe renal impairment
• Severe hepatic impairment
• Concurrent use of MAO inhibitors or use of MAO inhibitors in the preceding 2 wk
• Acute or severe bronchial asthma
• Acute, mild, intermittent, or postoperative pain (extended-release only)
• OB: Not recommended for use during labor and delivery
• Pedi: Children 6 yr and 40 kg with renal or hepatic impairment.

Use Cautiously in:

• Conditions associated with hypoxia, hypercapnea, or ↓ respiratory reserve, including asthma, chronic obstructive pulmonary disease, cor pulmonale, extreme obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression, use of other CNS depressants, or coma (↑ risk of further respiratory depression); use smallest effective dose
• History of substance abuse or addiction disorder
• Seizure disorders
• Moderate hepatic impairment
• OB: Prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children <18 yr (extended release) or <6 yr and <(immediate release)
• Geri: ↑risk of respiratory depression in older adults (dose ↓ suggested).

CV: hypotension.

Endo: adrenal insufficiency.

GI: diarrhea, nausea, vomiting.

GU: ↓fertility.

Neuro: allodynia, dizziness, headache, hyperalgesia, SEIZURES, somnolence.

Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA).
Misc: (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• Concurrent use of MAO inhibitors or use of MAO inhibitors in the preceding 2 wk can result in potentially life-threatening adverse cardiovascular reactions due to additive effects on norepinephrine levels; concurrent use or use of MAO inhibitors in preceding 2 wk contraindicated.
• Use with benzodiazepines or other CNS depressants, including other opioids, non-benzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
• Alcohol may ↑ levels and ↑ the risk of toxicity
• Mixed agonist/antagonist analgesics, including nalbuphine or butorphanol, and partial agonist analgesics, including buprenorphine, may ↓ tapentadol's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
• Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5-HT₃ receptor antagonists, linezolid, methylene blue, and triptans, ↑ risk of serotonin syndrome.

When switching from immediate-release to extended-release product, the same total daily dose can be used.

• PO (Adults): Immediate release: 50 mg, 75 mg, or 100 mg initially, then every 4–6 hr as needed and tolerated. If adequate analgesia is not achieved within first hr of first dose, additional dose may be given. Doses should not exceed 700 mg on the first day or 600 mg/day thereafter; Extended release: 50 mg twice daily; titrate dose up to 100–250 mg twice daily (not to exceed dose of 500 mg/day).
• PO (Children 6 yr and 80 kg): Immediate release: 50 mg every 4 hr; may ↑ to 75 mg every 4 hr as needed and tolerated. If adequate analgesia still not achieved, may ↑ to 100 mg every 4 hr to maintain analgesia without intolerable side effects (not to exceed 7.5 mg/kg/day). Duration of treatment should not exceed 3 days.
• PO (Children 6 yr and 60–79 kg): Immediate release: 50 mg every 4 hr; may ↑ to 75 mg every 4 hr as needed and tolerated (not to exceed 7.5 mg/kg/day). Duration of treatment should not exceed 3 days.
• PO (Children 6 yr and 40–59 kg): Immediate release: 50 mg every 4 hr (not to exceed 7.5 mg/kg/day). Duration of treatment should not exceed 3 days.

• Immediate-release tablets: 50 mg; 75 mg; 100 mg;
• Extended-release tablets: 50 mg; 100 mg; 150 mg; 200 mg; 250 mg;

• Assess type, location, and intensity of pain before and 1 hr (peak) after administration.
• Assess level of consciousness, BP, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Subsequent doses may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use. Monitor for respiratory depression, especially during initiation or following dose increase; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea, sleep-related hypoxemia).Geri: Pedi: Assess geriatric and pediatric patients frequently; more sensitive to the effects of opioid analgesics and may experience side effects and respiratory complications more frequently
• Patients taking extended-release tapentadol may require additional short-acting or rapid-onset opioid doses for breakthrough pain. Doses of short-acting opioids should be equivalent to 10–20% of 24 hr total and given every 2 hr as needed.
• Assess bowel function routinely. Prevention of constipation should be instituted with increased intake of fluids and bulk and with laxatives to minimize constipating effects. Administer stimulant laxatives routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid-induced constipation.
• Prolonged use may lead to physical and psychological dependence and tolerance, although these may be milder than with opioids. This should not prevent patient from receiving adequate analgesia. Patients who receive tapentadol for pain rarely develop psychological dependence.
• Monitor patient for seizures. May occur within recommended dose range. Risk is increased in patients with a history of seizures and in patients taking antidepressants (SSRIs, SNRIs, TCAs) or other drugs that decrease the seizure threshold.
• Monitor for serotonin syndrome (mental-status changes [agitation, hallucinations, coma]), autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or gastrointestinal symptoms [nausea, vomiting, diarrhea] in patients taking SSRIs, SNRIs, triptans, TCAs, or MAO inhibitors concurrently with tapentadol.
• Assess risk for opioid addiction, abuse, or misuse prior to administration. Abuse or misuse of extended-release preparations by crushing, chewing, snorting, or injecting dissolved product will result in uncontrolled delivery of tapentadol and can result in overdose and death.
• Monitor for symptoms of opioid-induced hyperalgesia (increased pain upon opioid dose increase, decreased pain upon opioid dose decrease, or pain from ordinarily nonpainful stimuli (allodynia). If a patient is suspected to be experiencing opioid-induced hyperalgesia, consider appropriately decreasing the dose of the current opioid analgesic, or using opioid rotation (safely switching patient to a different opioid moiety).

• Overdose may cause respiratory depression. Naloxone may reverse some, but not all, of the symptoms of overdose. Treatment should be symptomatic and supportive. Maintain adequate respiratory exchange.

• Explain therapeutic value of medication prior to administration to enhance the analgesic effect.
• Initial immediate-release dose of 50 mg, 75 mg, or 100 mg is individualized based on pain severity, previous experience with similar drugs, and ability to monitor patient. 2nd dose may be administered as soon as 1 hr after first dose if adequate pain relief is not obtained with first dose.
  • Medication should be discontinued gradually after long-term use to prevent withdrawal symptoms. For patients on long-acting agents who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 wk. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. Monitor frequently to manage pain and withdrawal symptoms (restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis, 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 occur, pause the taper for a period of time or raise the dose of opioid analgesic to the previous dose, and then proceed with a slower taper. Also, monitor patients for changes in mood, emergence of suicidal thoughts, or use of other substances. 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.
• PO: Tapentadol may be administered without regard to meals.
  • DNC: Swallow extended-release tablets whole; do not crush, break, or chew.
  • Use calibrated syringe to administer correct dose of oral solution.
• REMS: FDA strongly encourages health care professionals to complete a REMS-compliant education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain, available at OpioidAnalgesicREMSBlueprint. Information on programs can be found at 1-800-503-0784 or.
• Discuss availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing therapy, especially if patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. 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. However, the presence of risk factors for overdose should not prevent the proper management of pain in any patient.

• REMS: Instruct patient on how and when to ask for and take pain medication and to take tapentadol as directed; do not adjust dose without consulting health care professional. Report breakthrough pain and adverse reactions to health care professional. Do not take tapentadol if pain is mild or can be controlled with other pain medications such as NSAIDs or acetaminophen. Do not stop abruptly; may cause withdrawal symptoms (anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, hallucinations). Decrease dose gradually. Advise patient to read the Medication Guide prior to taking tapentadol and with each Rx refill, in case of changes. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide (PCG) is available at OpioidAnalgesicREMSPCG.
• Advise patient that tapentadol is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed; may be dangerous. Store out of sight and reach of children, and in a location not accessible by others.
• May cause dizziness and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Inform patient that tapentadol may cause seizures. Stop taking tapentadol and notify health care professional immediately if seizures occur.
• Advise patient to change positions slowly to minimize orthostatic hypotension.
• Caution patient to avoid concurrent use of alcohol or other CNS depressants, including other opioids, with this medication.
• 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. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (by prescription, directly from a pharmacist, or as part of a community-based program).
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to notify health care professional if signs of serotonin syndrome occur.
• Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
• Advise patient to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight); usually occur the first days after birth. Monitor infants exposed to tapentadol through breast milk for excess sedation and respiratory depression. Chronic use may reduce fertility in females and males.

• Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.

Nucynta, Nucynta ER

Nucynta IR

Schedule II (C-II)