• 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).

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.

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

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.

Nucynta, Nucynta ER

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

• Decrease in pain severity.

Therapeutic Classification: analgesics (centrally acting), opioid analgesics

Pharmacologic Classification: opioid agonists

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.

Schedule II (C-II)

Nucynta IR

(analgesic effect)

• 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.

ta-PEN-ta-dol