Tapentadol

Tapentadol is a prescription medicine used to treat moderate to severe pain and diabetic peripheral neuropathy.

• Tapentadol is available under the following different brand names: Nucynta, Nucynta ER

Adult dosage

Tablet, immediate release: Schedule II

• 50mg
• 75mg
• 100mg

Tablet, extended-release: Schedule II

• 50mg
• 100mg
• 150mg
• 200mg
• 250mg

Acute Moderate-to-Severe Pain

Adult dosage

• Immediate-release tablet or oral solution: 50-100 mg orally every 4-6 hours as needed; not to exceed 700 mg on day 1 and 600 mg/day thereafter

Chronic (extended-release tablet)

• 50-250 mg orally every 12 hours as needed; not to exceed 500 mg/day
• Opioid-naive patients: 50 mg orally every 12 hours; titrated to optimal dosage as needed; not to exceed 500 mg/day

Chronic Severe Pain

Adult dosage

• 50-250 mg orally every 12 hours as needed; not to exceed 500 mg/day
• Opioid-naive patients: 50 mg orally every 12 hours; titrated to optimal dosage as needed; not to exceed 500 mg/day

Limitations of Use

• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
• Not indicated as a PRN analgesic

Diabetic Peripheral Neuropathy

Adult dosage

• Extended-release: 50 mg orally every 12 hours initially; titrated to balance individual tolerance with efficacy; typical range, 100-250 mg orally every 12 hours

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Tapentadol include:

• constipation, 
• nausea, 
• vomiting, 
• stomach pain,
• headache, 
• feeling tired,
• drowsiness, and
• dizziness.

Serious side effects of Tapentadol include:

• noisy breathing, 
• sighing, 
• shallow breathing, breathing that stops,
• a light-headed feeling, 
• agitation, 
• feeling hot,
• severe drowsiness or dizziness, 
• confusion, 
• problems with speech or balance,
• seizure,
• serotonin syndrome--agitation, hallucinations, fever, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, diarrhea, and
• low cortisol levels-- nausea, vomiting, loss of appetite, dizziness, worsening tiredness, or weakness.

Rare side effects of Tapentadol include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Tapentadol has severe interactions with the following drugs:
  • alvimopan
  • rasagiline
  • safinamide
  • selegiline
• Tapentadol has serious interactions with at least 30 other drugs.
• Tapentadol has moderate interactions with at least 220 other drugs.
• Tapentadol has minor interactions with the following drugs:
  • brimonidine
  • dextroamphetamine
  • eucalyptus
  • lidocaine
  • sage
• ziconotide 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Hypersensitivity (eg, anaphylaxis, angioedema)
• Significant respiratory depression
• Acute or severe asthma
• Hypercarbia in an unmonitored setting or absence of resuscitative equipment
• Gastrointestinal obstruction, including suspected paralytic ileus
• Coadministration with monoamine oxidase inhibitors (MAOIs) or use within 14 days

Effects of drug abuse

• Addiction
• Overdose
• Death

Short-Term Effects

• See “What Are Side Effects Associated with Using Tapentadol?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Tapentadol?”

Cautions

• Conditions with risk for respiratory depression (particularly in patients who are elderly or debilitated or have comorbid conditions with hypoxia, hypercarbia, or airway obstruction)
• 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 opioid dosage using best practices for opioid taper
• Avoid dosing errors that may result from confusion between mg and mL when prescribing, dispensing, and administering oral solution; ensure the dose is communicated clearly and dispensed accurately; always use the enclosed calibrated syringe when administering the drug to ensure the dose is measured and administered accurately; do not use teaspoon or tablespoon to measure a dose; a household teaspoon or tablespoon is not an adequate measuring device; health care providers should recommend a calibrated device that can measure and deliver prescribed dose accurately, and instruct caregivers to use extreme caution in measuring dosage
• In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure the clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma
• May cause drowsiness (use with caution when driving or operating machinery)
• Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products containing alcohol, other opioids, or drugs of abuse
• Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected
• Therapy 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); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock
• Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of the sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms
• May prevent/obscure diagnosis of acute abdominal conditions
• 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; mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms
• Addiction can occur in patients appropriately prescribed therapy; addiction can occur at recommended dosages and if the drug is misused or abused
• While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, the risk is greatest during initiation of therapy or following dosage increase; monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases; accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to overdose of opioid
• Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concomitant use with benzodiazepine or muscle relaxant is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
• Abrupt discontinuance may precipitate withdrawal symptoms (eg, anxiety, sweating, insomnia, rigors, pain, nausea, tremors, hallucinations)
• Do not abruptly discontinue therapy in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
• Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; 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
• Use caution in CNS depression, hepatic/renal impairment, hypothyroidism, prostatic hyperplasia, respiratory disease, or seizures
• 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
  • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
  • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
  • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
  • To obtain further information on 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
• Long-acting opioids
• Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioids present (see Black Box Warnings)
• Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary
• Serious, life-threatening, or fatal respiratory depression reported; 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; follow patients closely for signs and symptoms of respiratory depression and sedation
• Accidental exposure was reported, including fatalities
• Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy
• Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase the risk for respiratory depression, profound sedation, and hypotension
• Life-threatening 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
• Patient access to naloxone for emergency treatment of opioid overdose
  • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
  • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
  • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose

Pregnancy and Lactation

• Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there is no available data in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with opioids and major birth defects
• Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly Severe fetal bradycardia reported when administered during labor; naloxone may reverse these effects; although there are no reports of fetal bradycardia earlier in pregnancy, it may occur; the drug should be used in pregnancy only if needed if the potential benefit outweighs the risk to the fetus and if appropriate measures such as fetal monitoring are taken to detect and manage the potential adverse effect on the fetus
• Labor and delivery
  • Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; the drug is not recommended for use in women during and immediately before labor when the use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression
• Infertility
  • Due to the effects of androgen deficiency, chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible
• Lactation
  • The drug is present in breast milk; published lactation studies report variable concentrations of drug in breast milk with administration of immediate-release formulation to nursing mothers in the early postpartum period
  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy; capsules and any potential adverse effects on the breastfed infant from therapy or underlying maternal condition
  • Monitor infants exposed to the drugs through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped