Tapentadol
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TAPENTADOL EXTENDED-RELEASE TABLETS Addiction, Abuse, and Misuse Because the use of tapentadol extended-release tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death assess, each patient's risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1) ] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of tapentadol extended-release tablets, especially during initiation or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of tapentadol extended-release tablets are essential. Instruct patients to swallow tapentadol extended-release tablets whole; crushing, chewing, or dissolving tapentadol extended-release tablets can cause rapid release and absorption of a potentially fatal dose of tapentadol [see Warnings and Precautions (5.2) ] . Accidental Ingestion Accidental ingestion of even one dose of tapentadol extended-release tablets, especially by children, can result in a fatal overdose of tapentadol [see Warnings and Precautions (5.2) ] .
Interaction with Alcohol Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking tapentadol extended-release tablets. The co-ingestion of alcohol with tapentadol extended-release tablets may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol [see Warnings and Precautions (5.2 , 5.3) ] . Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of tapentadol extended-release tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3) , Drug Interactions (7) ] . Neonatal Opioid Withdrawal Syndrome (NOWS) If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions (5.4) ] . Opioid Analgesic Risk Evaluation and…
Handling and access
REMS
RequiredStated in the label quoted on this page.
- Prescriber education
- Medication Guide
Dosing in kidney impairment
Renal Impairment Use of tapentadol extended-release tablets in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) is not recommended. No dosage adjustment is recommended in patients with mild or moderate renal impairment (creatinine clearance 30-90 mL/minute) [see Warnings and Precautions , Clinical Pharmacology ] .
Dosing in liver impairment
Dosage Modification in Patients with Hepatic Impairment The use of tapentadol extended-release tablets in patients with severe hepatic impairment (Child-Pugh Score 10-15) is not recommended [see Warnings and Precautions ] . In patients with moderate hepatic impairment (Child-Pugh Score 7 to 9), initiate treatment using 50 mg tapentadol extended-release tablets, administer no more frequently than once every 24 hours, and regularly evaluate for respiratory and central nervous system depression, particularly during initiation and titration of tapentadol extended-release tablets.
The maximum recommended dose for patients with moderate hepatic impairment is 100 mg of tapentadol extended-release tablets per day. Regularly evaluate patients for respiratory and central nervous system depression [see Clinical Pharmacology ] . No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5 to 6) [see Warnings and Precautions , Use in Specific Populations , Clinical Pharmacology ].
Preparation and administration
Important Dosage and Administration Instructions Tapentadol extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions ] .
Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of tapentadol extended-release tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ].
Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with tapentadol extended-release tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions ] . Instruct patients to swallow tapentadol extended-release tablets whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth.
Crushing, chewing, or dissolving tapentadol extended-release tablets will result in uncontrolled delivery of tapentadol and can lead to overdose or death [see Warnings and Precautions ]. Discontinue all other tapentadol and tramadol products when beginning and while taking tapentadol extended-release tablets [see Warnings and Precautions ] .
Although the maximum approved total daily dose of tapentadol immediate-release formulation is 600 mg per day, the maximum total daily dose of tapentadol extended-release tablets is 500 mg. Do not exceed a total daily dose of tapentadol extended-release tablets of 500 mg.
Drug interactions
Check tapentadol against a medication listLabel text (5 paragraphs)
Table 3 includes clinically significant drug interactions with tapentadol extended-release tablets. Table 3. Clinically Significant Drug Interactions with tapentadol extended-release tablets Alcohol Clinical Impact: Concomitant use of alcohol with tapentadol extended-release tablets can result in an increase of tapentadol plasma levels and potentially fatal overdose of tapentadol. Intervention: Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on tapentadol extended-release tablet therapy [see Warnings and Precautions (5.3) ] .
Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death [see Warnings and Precautions (5.3) ] . Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation).
If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) , Warnings and Precautions (5.1 , 5.2 , 5.3) ]. Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions (5.7) ].
Intervention: If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue tapentadol extended-release tablet if serotonin syndrome is suspected.
Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2) ]. Intervention: Do not use tapentadol extended-release tablet in patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of tapentadol extended-release tablets and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Tapentadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Because respiratory depression may be greater than otherwise expected, decrease the dosage of tapentadol extended-release tablets and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) , Warnings and Precautions (5.2 , 5.3) ] Examples: cyclobenzaprine, metaxalone Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Evaluate patients for signs of urinary retention or reduced gastric motility when tapentadol extended-release tablets are used concomitantly with anticholinergic drugs. Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics : Avoid use with tapentadol extended-release tablets because they may reduce analgesic effect of tapentadol extended-release tablets or precipitate withdrawal symptoms. ( 5.13 , 7 )
Contraindications
Tapentadol extended-release tablets are contraindicated in patients with: Significant respiratory depression Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment Known or suspected gastrointestinal obstruction, including paralytic ileus Hypersensitivity (e.g., anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product [see Adverse Reactions (6.2) ] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Drug Interactions (7) ] Significant respiratory depression ( 4 ) Acute or severe bronchial asthma ( 4 ) Known or suspected paralytic ileus ( 4 ) Hypersensitivity to tapentadol or to any other ingredients of the product ( 4 ) Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for tapentadol. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4) ]. Available data with tapentadol extended-release tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. In animal reproduction studies, embryofetal mortality and structural malformations were observed with subcutaneous administration of tapentadol during organogenesis to rabbits and delays in skeletal maturation were observed in rats at exposures equivalent to and less than the maximum recommended human dose (MRHD), respectively.
When administered to pregnant rats during organogenesis and through lactation, increased pup mortality was noted following oral tapentadol exposures to doses equivalent to the MRHD [see Data ] . Based on animal data, advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse reaction. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Fetal/neonatal adverse reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. 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 the newborn.
Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.4) ]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psychophysiological effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. tapentadol extended-release tablets are not recommended for use in pregnant women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more…
Breastfeeding (LactMed)
Maternal use of oral opioids during breastfeeding can cause infant drowsiness, which may progress to rare but severe central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Little information is available on the use of tapentadol during breastfeeding. Because it has opioid agonist activity, an alternate drug is preferred, especially when nursing a newborn or preterm infant. Monitor infants for excess sedation and respiratory depression. If tapentadol is required by the mother of a newborn, it is not a reason to discontinue breastfeeding; however, once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of oral tapentadol to 2 to 3 days at a low dose with close infant monitoring.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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