(ta PEN ta dol)
- Tapentadol HCl
- Tapentadol Hydrochloride
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Nucynta: 50 mg, 75 mg, 100 mg
Tablet Extended Release 12 Hour, Oral:
Nucynta ER: 50 mg
Nucynta ER: 100 mg, 150 mg [contains fd&c blue #2 aluminum lake]
Nucynta ER: 200 mg, 250 mg [scored; contains fd&c blue #2 aluminum lake]
Brand Names: U.S.
- Nucynta ER
- Analgesic, Opioid
Binds to μ-opiate receptors in the CNS causing inhibition of ascending pain pathways, altering the perception of and response to pain; also inhibits the reuptake of norepinephrine, which also modifies the ascending pain pathway
Rapid and complete
Vd: IV: 442-638 L
Extensive metabolism, including first pass metabolism; metabolized primarily via phase 2 glucuronidation to glucuronides (major metabolite: tapentadol-O-glucuronide); minimal phase 1 oxidative metabolism; also metabolized to a lesser degree by CYP2C9, CYP2C19, and CYP2D6; all metabolites pharmacologically inactive
Urine (99%: 70% conjugated metabolites; 3% unchanged drug)
Time to Peak
Plasma: Immediate release: 1.25 hours; Long acting formulations: 3-6 hours
Immediate release: ~4 hours; Long acting formulations: ~5-6 hours
Special Populations: Renal Function Impairment
In subjects with mild, moderate, and severe renal impairment, the AUC of tapentadol-O-glucuronide are 1.5-, 2.5-, and 5.5-fold higher, respectively, compared with healthy renal function.
Special Populations: Hepatic Function Impairment
Administration of tapentadol resulted in higher exposures to and serum levels of tapentadol in subjects with impaired hepatic function The rate of formation of tapentadol-O-glucuronide was lower in subjects with increased liver impairment. Tapentadol has not been studied in patients with severe hepatic impairment.
Special Populations: Elderly
Cmax is 16% lower than in younger subjects.
Use: Labeled Indications
Immediate release formulations: Management of moderate-to-severe acute pain in adults
Extended release formulation: Pain or neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long-term opioid analgesia and for which alternative treatments are inadequate.
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 tapentadol ER for use in patients for whom alternative treatment options (eg, nonopioid analgesics, immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Tapentadol ER is not indicated as an as-needed analgesic.
Hypersensitivity to tapentadol or any component of the formulation; significant respiratory depression; acute or severe asthma or hypercapnia in unmonitored settings or in absence of resuscitative equipment or ventilatory support; known or suspected paralytic ileus; use with or within 14 days of MAO inhibitors
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to opioids; acute respiratory depression, cor pulmonale; obstructive airway; known or suspected gastrointestinal obstruction or any disease/condition that affects bowel transit (eg, ileus of any type, strictures); severe renal impairment (CrCl <30 mL/minute); severe hepatic impairment (Child-Pugh class C); mild, intermittent, or short-duration pain that can be managed with alternative pain medication; management of perioperative pain (extended-release tablets); acute alcoholism, delirium tremens, and seizure disorders; severe CNS depression, increased cerebrospinal or intracranial pressure or head injury; pregnancy; breast-feeding; use during labor/delivery
Dose and dosage intervals should be individualized according to pain severity with respect to patient’s previous experience with similar opioid analgesics. In patients receiving extended release tapentadol, immediate-release opioid or nonopioid medication may be used for rescue relief of breakthrough pain and during dosage adjustments.
Acute moderate-severe pain: Oral: Immediate release tablets and solution: Day 1: 50 to 100 mg (2.5 to 5 mL) every 4 to 6 hours as needed; may administer a second dose ≥1 hour after the initial dose (maximum dose on first day: 700 mg daily); Day 2 and subsequent dosing: 50 to 100 mg (2.5 to 5 mL) every 4 to 6 hours as needed (maximum: 600 mg daily)
Chronic pain, neuropathic pain associated with diabetic peripheral neuropathy: Oral: Extended release:
Opioid naive (use as the first opioid analgesic or use in patients who are not opioid tolerant): Initial: 50 mg twice daily (recommended interval: every 12 hours) Note: Opioid tolerance is defined as: Patients already taking at least 60 mg of oral morphine daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone daily, 8 mg oral hydromorphone daily, 25 mg oral oxymorphone daily, or an equivalent dose of another opioid for at least 1 week.
Conversion from other oral opioids to extended release tapentadol: Discontinue all other around-the-clock opioids when extended release tapentadol is initiated. Substantial interpatient variability exists in relative potency. Therefore, it is safer to underestimate a patient’s daily oral tapentadol requirement and provide breakthrough pain relief with rescue medication (eg, immediate release opioid) than to overestimate requirements. In general, begin with a dose that is 50% of the estimated daily tapentadol requirement and use immediate release rescue medications to supplement dose.
Conversion from tapentadol immediate release to extended release: Convert using same total daily dose but divide into 2 equal doses and administer twice daily (recommended interval: ~12 hours) (maximum dose: 500 mg daily).
Conversion from methadone to extended release tapentadol: Close monitoring is required when converting methadone to another opioid. Ratio between methadone and other opioid agonists varies widely according to previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.
Dose titration: Titrate in increments of 50 mg no more frequently than twice daily every 3 days to effective dose (therapeutic range: 100 to 250 mg twice daily) (maximum dose: 500 mg daily).
Discontinuation of therapy: Gradually titrate dose downward to prevent withdrawal signs/symptoms. Do not abruptly discontinue.
Initial: Consider initiating at lower range of dosing. Refer to adult dosing.
Dosing: Renal Impairment
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use not recommended (not studied).
Dosing: Hepatic Impairment
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B):
Immediate release tablets and solution: Initial: 50 mg every 8 hours or longer (maximum: 3 doses/24 hours). Further treatment for maintenance of analgesia may be achieved by either shortening or lengthening the dosing interval.
Extended release: Initial: 50 mg every 24 hours or longer; maximum: 100 mg once daily
Severe impairment (Child-Pugh class C): Use not recommended (not studied).
Administer orally with or without food.
Tablets: Swallow whole; do not split, crush, break, chew, or dissolve. Administer 1 tablet at a time with sufficient water to ensure complete swallowing immediately after placing in mouth.
Oral solution: Always use the enclosed calibrated oral syringe to ensure the dose is measured and administered accurately.
May be taken without regard to meals.
Store at room temperature up to 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect tablets from moisture.
Alcohol (Ethyl): May enhance the CNS depressant effect of Tapentadol. Alcohol (Ethyl) may increase the serum concentration of Tapentadol. Specifically, alcohol may increase the maximum serum concentrations when used with extended-release tapentadol. Avoid combination
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Antiemetics (5HT3 Antagonists): May diminish the analgesic effect of Tapentadol. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
CNS Depressants: Tapentadol may enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Monitor therapy
Dimethindene (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Analgesics (Opioid) may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MAO Inhibitors: Tapentadol may enhance the adverse/toxic effect of MAO Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Consider therapy modification
Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy
Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Central nervous system: Dizziness (24%), drowsiness (15%)
Gastrointestinal: Nausea (30%), vomiting (18%)
1% to 10%:
Central nervous system: Fatigue (3%), insomnia (2%), abnormal dreams (1%), anxiety (1%), confusion (1%), lethargy (1%)
Dermatologic: Pruritus (3% to 5%), hyperhidrosis (3%), skin rash (1%)
Endocrine & metabolic: Hot flash (1%)
Gastrointestinal: Constipation (8%), xerostomia (4%), decreased appetite (2%), dyspepsia (2%)
Genitourinary: Urinary tract infection (1%)
Neuromuscular & skeletal: Arthralgia (1%), tremor (1%)
Respiratory: Nasopharyngitis (1%), upper respiratory tract infection (1%)
Central nervous system: Dizziness (17% to 18%), headache (10% to 15%), drowsiness (12% to 14%)
Gastrointestinal: Nausea (21% to 27%), constipation (13% to 17%), vomiting (8% to 12%)
1% to 10%:
Cardiovascular: Hypotension (1%)
Central nervous system: Fatigue (9%), anxiety (2% to 5%), insomnia (4%), irritability (2%), lethargy (2%), abnormal dreams (1% to 2%), vertigo (1% to 2%), chills (1%), depression (1%), hypoesthesia (1%), lack of concentration (1%), nervousness (1%), sedation (1%), withdrawal syndrome (1%)
Dermatologic: Pruritus (1% to 8%), hyperhidrosis (3% to 5%), skin rash (1%)
Endocrine & metabolic: Hot flash (2% to 3%)
Gastrointestinal: Diarrhea (7%), xerostomia (7%), decreased appetite (2% to 6%), dyspepsia (1% to 3%), abdominal distress (1%)
Genitourinary: Erectile dysfunction (1%)
Neuromuscular & skeletal: Tremor (1% to 3%), weakness (2%)
Ophthalmic: Blurred vision (1%)
Respiratory: Dyspnea (1%)
Immediate and/or extended release:<1% (Limited to important or life-threatening): Abnormality in thinking, altered mental status, anaphylaxis, angioedema, ataxia, decreased blood pressure, delayed gastric emptying, disorientation, drug withdrawal, dysarthria, euphoria, hallucination, hypersensitivity, hypogonadism (Brennan, 2013; Debono, 2011), impaired consciousness, intoxicated feeling, memory impairment, panic attack, pollakiuria, presyncope, respiratory depression, seizure, syncope, urinary hesitation, visual disturbance
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause severe hypotension; use with caution in patients with risk factors (eg, hypovolemia, concomitant use of other hypotensive agents). Avoid use in patients with circulatory shock.
• Respiratory depression: Extended release tablets: [U.S. Boxed Warning]: May cause serious, life-threatening, or fatal respiratory depression. Monitor closely for respiratory depression, especially during initiation or dose escalation. Patients should swallow tablets whole; crushing, chewing, or dissolving can cause rapid release and a potentially fatal dose. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with concomitant use of tapentadol and serotonergic agents (eg, SSRIs, SNRIs, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.
• Abdominal conditions: Opioids may obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan, 2013).
• Biliary tract impairment: Use caution in patients with biliary tract dysfunction or acute pancreatitis; opioids may cause spasm of the sphincter of Oddi.
• CNS depression/coma: Use with caution in patients with CNS depression; avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO2 retention.
• Drug abuse: Use opioids for chronic pain with caution in patients at increased risk for misuse; factors associated with increased risk include previous substance use disorder, younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.
• Hepatic impairment: Serum concentrations are increased in hepatic impairment; use with caution in patients with moderate hepatic impairment (dosage adjustment required). Not recommended for use in severe hepatic impairment (not studied).
• Hypothyroidism: Use with caution in patients with hypothyroidism.
• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Renal impairment: Use with caution in patients with mild-to-moderate renal impairment; no dosage adjustments recommended. Not recommended for use in severe renal impairment (not studied).
• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or preexisting respiratory depression, particularly when initiating therapy and titrating with tapentadol; even therapeutic doses may decrease respiratory drive to the point of apnea. Consider the use of alternative nonopioid analgesics in these patients.
• Seizures: Use caution in patients with a history of seizures or conditions predisposing patients to seizures; patients with a history of seizures were excluded in clinical trials of tapentadol. Tramadol, an analgesic with similar pharmacologic properties to tapentadol, has been associated with seizures, particularly in patients with predisposing factors.
• Sleep-disordered breathing: Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).
Concurrent drug therapy issues:
• Ethanol use: Extended release tablets: [U.S. Boxed Warning]: Patients should not consume alcoholic beverages or medication containing ethanol while taking tapentadol ER; ethanol may increase tapentadol plasma levels resulting in a potentially fatal overdose.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Sedatives: Effects may be potentiated when used with other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). In the setting of chronic pain, avoid prescribing opioids and benzodiazepines concurrently whenever possible; epidemiologic studies suggest there is an increased risk for potentially fatal overdose with concurrent use (Dowell [CDC 2016]).
• Cachectic or debilitated patients: Use with caution in debilitated or cachectic patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• Elderly: Use opioids with caution in the elderly; consider decreasing initial dose. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]).
• Neonates: Neonatal withdrawal syndrome: Extended release tablets: [U.S. Boxed Warning]: Prolonged maternal use of opioids during pregnancy can cause neonatal withdrawal syndrome in the newborn which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If prolonged opioid therapy is required in a pregnant woman, ensure treatment is available and warn patient of risk to the neonate. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.
Dosage form specific issues:
• Extended release tablets: Therapy should only be prescribed by healthcare professionals familiar with the use of potent opioids for chronic pain.
• Oral solution: In order to avoid dosing errors, include the dose in mL and mg when writing prescriptions. Instruct patients to always use the enclosed calibrated oral syringe to ensure the dose is measured and administered accurately.
• Abuse/misuse/diversion: Extended release tablets: [U.S. Boxed Warning]: Users are exposed to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient’s risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions.
• Accidental exposure: Extended release tablets: [U.S. Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of tapentadol.
• Appropriate use:
- Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, NSAIDs, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).
- Prolonged use increases risk of abuse, addiction, and withdrawal symptoms. An opioid-containing regimen should be tailored to each patient’s needs with respect to degree of tolerance for opioids (naïve versus chronic user), age, weight, and medical condition.
• Withdrawal: Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Taper dose gradually when discontinuing.
Respiratory and cardiovascular status, blood pressure, heart rate; signs of misuse, abuse, or addiction; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)
Extended release tablets: Monitor for respiratory depression for 72 hours of initiating dose.
Alternate recommendations: Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and re-checking should be considered at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (Dowell [CDC 2016]).
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies. Opioids cross the placenta. Tapentadol is not recommended for use during labor and delivery and if exposure occurs the neonate should be monitored for respiratory depression.
US Boxed Warning]: Prolonged maternal use of opioids during pregnancy can cause neonatal withdrawal syndrome in the newborn which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If prolonged opioid therapy is required in a pregnant woman, ensure treatment is available and warn patient of risk to the neonate. If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur; monitoring of the neonate is recommended. The minimum effective dose should be used if opioids are needed (Chou, 2009). Neonatal abstinence syndrome following opioid exposure may present with autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, increased muscle tone, irritability, seizure, tremor) symptoms (Dow, 2012; Hudak, 2012).
Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility (Brennan, 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, vomiting, itching, dry mouth, headache, or loss of strength and energy. Have patient report immediately to prescriber difficulty breathing, slow breathing, shallow breathing, severe dizziness, passing out, seizures, severe constipation, burning or numbness feeling, angina, sensation of cold, difficult urination, polyuria, shortness of breath, bradycardia, memory impairment, mood changes, severe abdominal pain, suicidal ideation, abnormal movements, twitching, change in balance, difficulty speaking, dysphagia, vision changes, severe fatigue, sweating a lot, feeling overheated, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, severe diarrhea) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.