Class: Opioid analgesic
- Tablets, oral 50 mg
- Tablets, oral 75 mg
- Tablets, oral 100 mg
- Tablets ER, oral 50 mg
- Tablets ER, oral 100 mg
- Tablets ER, oral 150 mg
- Tablets ER, oral 200 mg
- Tablets ER, oral 250 mg
Binds to certain opioid receptors and inhibits reuptake of norepinephrine; exact mechanism of action is unknown.
Mean absolute bioavailability is 32%. High-fat meals increased C max and AUC by 16% and 25%, respectively (immediate release) and 17% and 6%, respectively (ER). T max is 1.25 h (immediate release) and 3 to 6 h (ER). Steady-state of the ER tablet is attained after the third dose.
Vd is approximately 540 L. Protein binding is approximately 20%.
Tapentadol is mainly metabolized by conjugation with glucuronic acid to produce glucuronides. Tapentadol is also metabolized to a lesser extent by CYP2C9 and CYP2C19 (13%) and CYP2D6 (2%), which are further metabolized by conjugation. None of the metabolites contribute to its pharmacologic activity.
99% of a dose is excreted in urine; 3% is unchanged drug. The half-life is 4 and 5 h for immediate release and ER, respectively. Total Cl is approximately 1,530 mL/min and 1,603 mL/min for immediate release and ER, respectively.
Special PopulationsRenal 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.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.Elderly
C max is 16% lower than in younger subjects.
Indications and Usage
Relief of moderate to severe acute pain in patients 18 y and older (immediate release only); for the management of moderate to severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period of time (ER only).
Significant respiratory depression in unmonitored settings or in the absence of resuscitative equipment; acute or severe bronchial asthma or hypercapnia in unmonitored settings or in the absence of resuscitative equipment; paralytic ileus; concomitant use with MAOIs or MAOI use within the last 14 days.
Dosage and AdministrationAcute pain
Adults Immediate release
PO 50 to 100 mg every 4 to 6 h. On the first day of dosing, the second dose may be administered as soon as 1 h after the first dose if adequate pain relief is not attained with the first dose (max, 700 mg on the first day of therapy and 600 mg on subsequent days).Chronic pain
PO 50 mg twice per day (approximately every 12 h) initially in patients not currently taking analgesics. In patients previously taking other opioids, initiate at 50 mg and titrate to an effective dose. Titrate with dose increases of 50 mg no more than twice daily every 3 days. Usual dosage is 100 mg to 250 mg twice daily (max, 500 mg daily). Patients should discontinue all other tapentadol and tramadol products when beginning and while taking tapentadol ER.Hepatic Function Impairment
Adults Immediate release
PO For patients with moderate hepatic impairment, initiate at 50 mg, not more frequently than every 8 h (max, 3 doses in 24 h). Adjust subsequent doses by shortening or lengthening the dosing interval to maintain adequate analgesia and acceptable tolerability. Not recommended for use in patients with severe hepatic impairment.ER
PO For patients with moderate hepatic impairment, initiate at 50 mg, not more frequently than once every 24 h (max, 100 mg once daily). Not recommended for use in patients with severe hepatic impairment.Conversion
PO Patients can be converted from tapentadol to tapentadol ER by using the equivalent total daily dose of tapentadol and dividing it into 2 equal doses of tapentadol ER separated by approximately 12-hour intervals.
- Individualize according to severity of pain, previous experience with similar drugs, and the ability to monitor the patient. Dosage should be adjusted to maintain adequate analgesia with acceptable tolerability.
- May be given with or without food.
- Periodically reassess the need for continued treatment during long-term therapy.
- Withdrawal symptoms may occur if tapentadol is discontinued abruptly. Withdrawal symptoms may be reduced by tapering tapentadol.
- Tapentadol ER tablets must be swallowed whole and must not be split, broken, chewed, dissolved, or crushed. Taking split, broken, chewed, dissolved, or crushed tapentadol ER tablets could lead to rapid release and absorption of a potentially fatal dose of tapentadol.
- Tapentadol ER tablets must be taken 1 tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth.
Store between 59° and 86°F. Protect from moisture.
Drug InteractionsAnticholinergic agents
The risk of urinary retention and severe constipation, which may lead to paralytic ileus, may be increased. Avoid coadministration.CNS depressants (eg, alcohol, anesthetics, narcotics, phenothiazines, sedative-hypnotics, tranquilizers)
Risk of CNS and respiratory depression may be increased. Consider a dose reduction in one or both agents. Avoid concomitant use with alcohol.Iobenguane
Tapentadol may reduce uptake and diagnostic efficacy of iobenguane. False-negative iobenguane imaging tests may result. Discontinue tapentadol at least 5 biological half-lives (approximately 24 h) prior to iobenguane administration.MAOIs
Concomitant use or use within 14 days of each other is contraindicated because of possible additive adverse CV effects.Mixed agonist/antagonist opioid analgesics (eg, buprenorphine, butorphanol, nalbuphine, pentazocine)
The analgesic effect of tapentadol may be reduced by competitive blocking of opioid receptors. In addition, opioid withdrawal symptoms may occur. Concurrent use is not recommended.Naltrexone
The analgesic effect of tapentadol may be reduced by competitive blocking of opioid receptors. In addition, opioid withdrawal symptoms may occur. Close clinical monitoring for signs of opioid withdrawal or reduced tapentadol efficacy is warranted. Opioid-dependent patients should be detoxified before treatment with naltrexone.Serotonergics (eg, mirtazapine, SNRIs, SSRIs, tricyclic antidepressants, tramadol, trazodone, triptans)
Serotonin syndrome (eg, agitation, coma, hallucinations, hyperreflexia, hyperthermia, tachycardia) may occur with coadministration. Coadminister with caution. Closely observe the patient, particularly during the start of treatment and with dose increases.
Dizziness (24%); headache, somnolence (15%); fatigue (9%); insomnia (4%); anxiety, asthenia, lethargy, vertigo (2%); abnormal dreams, confusional state, depressed mood, depression, disturbance in attention, tremor (1%); hallucination, suicidal ideation (postmarketing).
Hyperhidrosis, pruritus (5%); rash (1%).
Blurred vision, nasopharyngitis (1%).
Nausea (30%); vomiting (18%); constipation (17%); dry mouth (7%); dyspepsia (3%); diarrhea (postmarketing).
Erectile dysfunction, UTI (1%).
Dyspnea, upper respiratory tract infection (1%).
Decreased appetite, hot flush (2%); arthralgia, chills, feeling hot (1%); angioedema, palpitation (postmarketing).
WarningsER tablets only
Tapentadol ER is a mu-opioid agonist and a Schedule II controlled substance with an abuse liability similar to other opioid analgesics. Tapentadol ER can be abused in a manner similar to other opioid agonists, legal or illicit. Consider these risks when prescribing or dispensing tapentadol ER in situations in which the health care provider or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Tapentadol ER is indicated for the management of moderate to severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. Tapentadol ER is not intended for use as an as-needed analgesic. Tapentadol ER is not intended for the management of acute or postoperative pain. Tapentadol ER tablets are to be swallowed whole and are not to be split, broken, chewed, dissolved, or crushed. Taking split, broken, chewed, dissolved, or crushed tapentadol ER tablets could lead to rapid release and absorption of a potentially fatal dose of tapentadol. Patients must not consume alcoholic beverages or prescription or nonprescription medications containing alcohol.
Monitor patients for breakthrough pain and adverse effects of tapentadol.
Category C . Use is not recommended during and immediately prior to labor and delivery. Long-term maternal use of opiates or opioids during pregnancy coexposes the fetus. The newborn may experience subsequent neonatal withdrawal syndrome. Manifestation of neonatal withdrawal syndrome includes irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, weight loss, and failure to gain weight.
Safety and efficacy not established in children younger than 18 y.
Consider starting at the low end of the dosage range because of the greater frequency of hepatic or renal impairment. Respiratory depression occurs more frequently in elderly patients.
Angioedema has been reported.
Not recommended in patients with severe renal impairment.
Use with caution in patients with moderate hepatic impairment. Not recommended in patients with severe hepatic impairment.
Special Risk Patients
Use tapentadol ER with caution in adrenocortical insufficiency (eg, Addison disease), delirium tremens, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, or toxic psychosis.
May impair judgment, thinking, or motor skills.
Tapentadol is a controlled substance and may cause addiction. Use with caution in opioid-dependent patients.
Do not use in patients with increased intracranial pressure or head trauma; use with caution in patients with intracranial lesions.
Tapentadol ER may cause severe hypotension.
Pancreatic/Biliary tract disease
May cause spasm of the sphincter of Oddi; use with caution in patients with biliary tract disease, including acute pancreatitis.
May occur. Administer with caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve, such as asthma, COPD, cor pulmonale, severe obesity, or sleep apnea.
Use with caution in patients with a history of a seizure disorder or any condition that would put the patient at risk of seizures.
Potentially life-threatening serotonin syndrome may develop, particularly when combined with serotonergic agents (eg, SNRIs, SSRIs, triptans).
If tapentadol is discontinued abruptly, withdrawal symptoms may occur.
Coma, convulsions, CV collapse, miosis, respiratory arrest, respiratory depression, vomiting.
- Advise patients to read the Medication Guide before starting therapy and with each refill.
- Advise patients to take tapentadol only as directed and to report episodes of breakthrough pain and adverse events during therapy to their health care provider. Individualization of dosage is essential to make optimal use of this medication. Advise patients not to adjust the dose of tapentadol without consulting their health care provider. Advise patients that it may be appropriate to taper dosing when discontinuing treatment with tapentadol because withdrawal symptoms may occur. The health care provider can provide a dose schedule to accomplish a gradual discontinuation of the medication.
- Advise patients that tapentadol is a potential drug of abuse. Advise patients to protect tapentadol from theft and not to give tapentadol to anyone other than the individual for whom tapentadol was prescribed.
- Because tapentadol has the potential to impair judgment, thinking, or motor skills, caution patients about operating hazardous machinery, including automobiles.
- Advise patients to notify their health care provider if they become pregnant or intend to become pregnant during treatment with tapentadol.
- Advise patients not to breast-feed an infant during treatment with tapentadol.
- Inform patients not to take tapentadol while using any MAOI, and not to start any new medication while taking tapentadol until they are assured by their health care provider that the new medication is not an MAOI.
- Inform patients that tapentadol could cause seizures if they are at risk for seizures or have epilepsy. Advise patients to use tapentadol with care. Advise patients to stop taking tapentadol if they have a seizure while taking tapentadol and to call their health care provider right away.
- Inform patients that tapentadol could cause rare but potentially life-threatening conditions resulting from coadministration of serotonergic drugs (including serotonin reuptake inhibitors, SNRIs, and tricyclic antidepressants).
- Advise patients to inform their health care provider if they are taking or planning to take any prescription or nonprescription drugs because there is a potential for interactions.
- Advise patients to avoid alcohol while taking tapentadol.
- Advise patients to inform their health care provider if they are experiencing changes in their pain level or if they feel they need a change in dosage.
- Advise patients that tapentadol ER must be swallowed whole. The ER tablets may release all of their contents at once if split, broken, chewed, crushed, or dissolved, resulting in a risk of fatal overdose of tapentadol.
- Advise patients that tapentadol ER tablets should be taken one at a time. Patients should not pre-soak, lick, or otherwise wet the tablet prior to placing it in the mouth. Advise patients to take each tablet with enough water to ensure complete swallowing immediately after placing it in the mouth.
- Tapentadol ER tablets are intended for oral use only and must not be administered by any other route. If abused by parenteral route, this may result in serious or even fatal complications.
- Advise patients that tapentadol can cause respiratory depression and hypotension.
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