Dosing and uses of Tapentadol (Nucynta, Nucynta ER)
Adult dosage forms and strengths
tablet, immediate release: Schedule II
- 50mg
- 75mg
- 100mg
tablet, extended release: Schedule II
- 50mg
- 100mg
- 150mg
- 200mg
- 250mg
Acute Moderate-to-Severe Pain
Immediate-release tablet or oral solution: 50-100 mg PO q4-6hr PRN; not to exceed 700 mg on day 1 and 600 mg/day thereafter
Chronic (extended-release tablet)
- 50-250 mg PO q12hr PRN; not to exceed 500 mg/day
- Opioid-naive patients: 50 mg PO q12hr; titrated to optimal dosage as needed; not to exceed 500 mg/day
Chronic Severe Pain
Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
50-250 mg PO q12hr PRN; not to exceed 500 mg/day
Opioid-naive patients: 50 mg PO q12hr; titrated to optimal dosage as needed; not to exceed 500 mg/day
Opioid-naive definition
- Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
- Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid
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
Treatment of pain associated with diabetic peripheral neuropathy when continuous, around-the-clock opioid analgesic is needed for extended period
Extended release: 50 mg PO q12hr initially; titrated to balance individual tolerance with efficacy; typical range, 100-250 mg PO q12hr
Dosing Modifications
Renal impairment
- CrCl ≥30 mL/min : Dosage adjustment not required
- CrCl <30 mL/min: Not recommended
Hepatic impairment
- Mild: Dosage adjustment not required
- Moderate: 50 mg immediate release q8hr initially; dosing frequency not to exceed 3 times daily; alternatively, 50 mg PO q24hr extended release; not to exceed 100 mg/day
- Severe: Not recommended
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Initiate dosage at lower end of range
Tapentadol (Nucynta, Nucynta ER) adverse (side) effects
>10%
Nausea (30%)
Dizziness (24%)
Vomiting (18%)
Somnolence (15%)
1-10% (selected)
Constipation (8%)
Pruritus (5%)
Xerostomia (4%)
Fatigue (3%)
Hyperhidrosis (3%)
Anorexia (2%)
Dyspepsia (2%)
Insomnia (2%)
Postmarketing Reports
Anaphylaxis, angioedema, anaphylactic shock
Psychiatric disorders: Hallucinations, suicidal ideation, panic attack
Nervous system disorders: Headache
Gastrointestinal disorders: Diarrhea
Cardiac disorders: Palpitations
Warnings
Black box warnings
Addiction, abuse, and misuse
- Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
- Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions
Life-threatening respiratory depression
- Serious, life-threatening, or fatal respiratory depression may occur
- Monitor for respiratory depression, especially during initiation or following a dose increase Instruct patients to swallow tablet/capsule whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal dose
Accidental exposure
- Accidental of even 1 dose, especially by children, can result in a fatal overdose
Neonatal opioid withdrawal syndrome
- Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
- Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
- 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 the newborn
- If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Interaction with alcohoL
- Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol
- Coingestion of alcohol may cause rapid release of opioid content from long-acting tablet/capsule and result in increased plasma levels and a potentially fatal overdose
Contraindications
Hypersensitivity (eg, anaphylaxis, angioedema)
Significant respiratory depression
Acute or severe asthma
Hypercarbia in unmonitored setting or in absence of resuscitative equipment
Paralytic ileus
Coadministration with monoamine oxidase inhibitors (MAOIs) or use within 14 days
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)
May increase intracranial pressure
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
May cause serotonin syndrome
May cause severe hypotension; avoid use in patients with circulatory shock or taking hypotensive agents
May cause spasms of sphincter of Oddi
May prevent/obscure diagnosis of acute abdominal conditions
Potential for addiction and misuse exist
Abrupt discontinuance may precipitate withdrawal symptoms (eg, anxiety, sweating, insomnia, rigors, pain, nausea, tremors, hallucinations)
Use caution in adrenal insufficiency, CNS depression, head trauma, hepatic/renal impairment, hypothyroidism, prostatic hyperplasia, respiratory disease, or seizures
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 opioid 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 (see Black box warnings)
- Serious, life-threatening, or fatal respiratory depression reported (see Black box warnings)
- Accidental exposure reported, including fatalities (see Black box warnings)
- Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black box warnings)
- Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase 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
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown whether drug is distributed in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tapentadol (Nucynta, Nucynta ER)
Mechanism of action
Mu-opioid agonist; inhibits ascending pain pathways, thus altering response to pain; produces analgesia, respiratory depression, and sedation; also inhibits reuptake of norepinephrine, which also affects ascending pain pathways
Absorption
Bioavailability: 32% (single dose, fasting)
Peak plasma time: Immediate release, 1.25 hr; extended release, 3-6 hr
Distribution
Protein bound: 20%
Vd: 540 L (IV)
Metabolism
Metabolized via glucuronidation (97%)
Elimination
Half-life: Immediate release, 4 hr; extended release, 5-6 hr
Excretion: Urine (99%)
