FDA

Tapentadol Hydrochloride

Approved 27 Jan 2026OralTablet

The FDA lists this product in 10 strengths and forms.

Indications

Tapentadol tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate in adults. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dose or duration [see Warnings and Precautions (5.1 )], and persist over the course of therapy, reserve opioid analgesics, including tapentadol tablets for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Pediatric use information is approved for Collegium Pharmaceutical, Inc.’s NUCYNTA tablets. However, due to Collegium Pharmaceutical, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Tapentadol tablets are an opioid analgesic indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate in adults.

( 1 ) Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration, and persist over the course of therapy, reserve opioid analgesics, including tapentadol tablets for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. (1, 5.1)

Contraindications

Tapentadol tablets are contraindicated in patients with:

Significant respiratory depression [see Warnings and Precautions (5.2) ]
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.8) ]
Known or suspected gastrointestinal obstruction, including suspected paralytic ileus [see Warnings and Precautions (5.12) ]
Hypersensitivity to tapentadol (e.g. anaphylaxis, angioedema) 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 in an unmonitored setting or in absence of resuscitative equipment. ( 4 )
Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 )
Hypersensitivity to tapentadol ( 4 )
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days. ( 4 )

At a glance

Brand name: Tapentadol Hydrochloride
Route: Oral
Dosage form: Tablet
Applicant: Humanwell
Status: Prescription
FDA approval: 27 Jan 2026
Application: ANDA214378-002

Indications

Contraindications

Tapentadol tablets are contraindicated in patients with:

Significant respiratory depression [see Warnings and Precautions (5.2) ]
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.8) ]
Known or suspected gastrointestinal obstruction, including suspected paralytic ileus [see Warnings and Precautions (5.12) ]
Hypersensitivity to tapentadol (e.g. anaphylaxis, angioedema) 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 in an unmonitored setting or in absence of resuscitative equipment. ( 4 )
Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 )
Hypersensitivity to tapentadol ( 4 )
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days. ( 4 )

Interactions

Table 2 includes clinically significant drug interactions with tapentadol tablets. Table 2: Clinically Significant Drug Interactions with Tapentadol Tablets 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, increases the risk of 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 recommending or prescribing an opioid overdose reversal agent [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, gabapentinoids (gabapentin or pregabalin), 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 tablets 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 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 (5.3) ] Intervention: Do not use tapentadol tablets in patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of tapentadol 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 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 recommending or prescribing an opioid overdose reversal agent [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 tablets is used concomitantly with anticholinergic drugs. Alcohol, Other Opioids, and Drugs of Abuse Clinical Impact: Due to its mu-opioid agonist activity, tapentadol tablets may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression, respiratory depression, hypotension, and profound sedation, coma or death [see Warnings and Precautions (5.16) ].

Intervention: Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products containing alcohol, other opioids, or drugs of abuse while on tapentadol tablets therapy. Examples: Alcohol, other opioids, illicit drugs

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics : Avoid use with tapentadol tablets because they reduce analgesic effect of tapentadol tablets or precipitate withdrawal symptoms. ( 7 ).

Pregnancy and breastfeeding

8.1Pregnancy 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 tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. There are risks to the mother and infant associated with the use of tapentadol tablets for an extended period of time during pregnancy (see Clinical Considerations).

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 2-4% and 15-20%, 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 psycho-physiologic effects in neonates.

An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. Tapentadol tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including tapentadol tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions.

However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Animal Data Tapentadol hydrochloride was evaluated for teratogenic effects in pregnant rats and rabbits following subcutaneous exposure during organogenesis. When tapentadol was administered twice daily by the subcutaneous route in rats at dose levels of 10, 20, or 40 mg/kg/day [producing up to 1 times the plasma exposure at the maximum recommended human dose (MRHD) of 700 mg/day based on an area under the time-curve (AUC) comparison], no teratogenic effects were observed.

Evidence of embryofetal toxicity included transient delays in skeletal maturation (i.e. reduced ossification) at the 40 mg/kg/day dose which was associated with significant maternal toxicity. Administration of tapentadol HCl in rabbits at doses of 4, 10, or 24 mg/kg/day by subcutaneous injection [producing 0.2, 0.6, and 1.85 times the plasma exposure at the MRHD based on an AUC comparison] revealed embryofetal toxicity at doses ≥10 mg/kg/day.

Findings included reduced fetal viability, skeletal delays and other variations. In addition, there were multiple malformations including gastroschisis/thoracogastroschisis, amelia/phocomelia, and cleft palate at doses ≥10 mg/kg/day and above, and ablepharia, encephalopathy, and spina bifida at the high dose of 24 mg/kg/day. Embryofetal toxicity, including malformations, may be secondary to the significant maternal toxicity observed in the study.

In a study of pre- and postnatal development in rats, oral administration of tapentadol at doses of 20, 50, 150, or 300 mg/kg/day to pregnant and lactating rats during the late gestation and early postnatal period [resulting in up to 1.7 times the plasma exposure at the MRHD on an AUC basis] did not influence physical or reflex development, the outcome of neurobehavioral tests or reproductive parameters. Treatment-related developmental delay was observed, including incomplete ossification, and significant reductions in pup body weights and body weight gains at doses associated with maternal toxicity (150 mg/kg/day and above).

At maternal tapentadol doses ≥150 mg/kg/day, a dose-related increase in pup mortality was observed through postnatal Day 4.

Adverse reactions

The following adverse reactions are discussed, or described in greater detail, in other sections:

Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ]
Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2) ]
Interactions with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions (5.3) ]
Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4 )]
Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.6)].
Serotonin Syndrome [see Warnings and Precautions (5.7) ]
Adrenal Insufficiency [see Warnings and Precautions (5.9) ]
Severe Hypotension [see Warnings and Precautions (5.10) ]
Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.12) ]
Seizures [see Warnings and Precautions (5.13) ]
Withdrawal [see Warnings and Precautions (5.14) ] The most common adverse reactions were Adults (incidence ≥10%) were nausea, dizziness, vomiting and somnolence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Epic Pharma, LLC at 1-888-374-2791 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Adults

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Based on data from nine Phase 2/3 studies that administered multiple doses (seven placebo- and/or active-controlled, one noncontrolled and one Phase 3 active-controlled safety study) the most common adverse reactions (reported by ≥10% in any tapentadol tablets dose group) were: nausea, dizziness, vomiting and somnolence.

The most common reasons for discontinuation due to adverse reactions in the studies described above (reported by ≥1% in any tapentadol tablets dose group) were dizziness (2.6% vs. 0.5%), nausea (2.3% vs. 0.6%), vomiting (1.4% vs. 0.2%), somnolence (1.3% vs. 0.2%) and headache (0.9% vs. 0.2%) for tapentadol- and placebo-treated patients, respectively. Seventy-six percent of tapentadol-treated patients from the nine studies experienced adverse events.

Tapentadol tablets were studied in multiple-dose, active- or placebo-controlled studies, or noncontrolled studies (n = 2178), in single-dose studies (n = 870), in open-label study extension (n = 483) and in Phase 1 studies (n = 597). Of these, 2034 patients were treated with doses of 50 mg to 100 mg of tapentadol tablets dosed every 4 to 6 hours. The data described below reflect exposure to tapentadol tablets in 3161 patients, including 449 exposed for 45 days.

Tapentadol tablets were studied primarily in placebo- and active- controlled studies (n = 2266, and n = 2944, respectively). The population was 18 to 85 years old (mean age 46 years), 68% were female, 75% white and 67% were postoperative. Most patients received tapentadol tablets doses of 50 mg, 75 mg, or 100 mg every 4 to 6 hours. Table 1 Adverse Reactions Reported by ≥1% of Tapentadol-Treated Patients In Seven Phase 2/3 Placebo- and/or Oxycodone-Controlled, One Non-controlled, and One Phase 3 Oxycodone-Controlled Safety, Multiple-Dose Clinical Studies System Organ Class MedDRA Preferred Term Tapentadol 21 mg – 120 mg (n = 2178) % Placebo (n = 619) % Gastrointestinal Disorders Nausea 30 13 Vomiting 18 4 Constipation 8 3 Dry mouth 4 <1 Dyspepsia 2 <1 General disorders and administration site conditions Fatigue 3 <1 Feeling hot 1 <1 Infections and infestations Nasopharyngitis 1 <1 Upper respiratory tract infection 1 <1 Urinary tract infection 1 <1 Metabolism and nutrition disorders Decreased appetite 2 0 Nervous system disorders Dizziness 24 8 Somnolence 15 3 Tremor 1 <1 Lethargy 1 <1 Psychiatric disorders Insomnia 2 <1 Confusional state 1 0 Abnormal dreams 1 <1 Anxiety 1 <1 Skin and subcutaneous tissue disorders Pruritus 5 1 Hyperhidrosis 3 <1 Pruritus generalized 3 <1 Rash 1 <1 Vascular disorders Hot flush 1 <1 The following adverse drug reactions occurred in less than 1% of tapentadol-treated patients in the pooled safety data from nine Phase 2/3 clinical studies: Cardiac disorders : heart rate increased, heart rate decreased Eye disorders : visual disturbance Gastrointestinal disorders : abdominal discomfort, impaired gastric emptying General disorders and administration site conditions : irritability, edema, drug withdrawal syndrome, feeling drunk Immune system disorders : hypersensitivity Investigations : gamma-glutamyltransferase increased, alanine aminotransferase increased, aspartate aminotransferase increased Musculoskeletal and connective tissue disorders : involuntary muscle contractions, sensation of heaviness Nervous system disorders : hypoesthesia, paresthesia, disturbance in attention, sedation, dysarthria, depressed level of consciousness, memory impairment, ataxia, presyncope, syncope, coordination abnormal, seizure Psychiatric disorders : euphoric mood, disorientation, restlessness, agitation, nervousness, thinking abnormal Renal and urinary disorders : urinary hesitation, pollakiuria Respiratory, thoracic and mediastinal disorders : oxygen saturation decreased, cough, dyspnea, respiratory depression Skin and subcutaneous tissue disorders : urticaria Vascular disorders : blood pressure decreased In the pooled safety data, the overall incidence of adverse reactions increased with increased dose of tapentadol tablets, as did the percentage of patients with adverse reactions of nausea, dizziness, vomiting, somnolence, and pruritus.

6.2Post-marketing Experience

The following additional adverse reactions have been identified during post‐approval use of tapentadol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disorders : diarrhea Nervous system disorders : headache Psychiatric disorders : hallucination, suicidal ideation, panic attack Cardiac disorders : palpitations Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis : Anaphylaxis has been reported with ingredients contained in tapentadol tablets. Androgen deficiency : Cases of androgen deficiency have occurred with chronic use of opioids for an extended period of time [see Clinical Pharmacology (12.2) ]. Hyperalgesia and Allodynia : Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions (5.6) ] Hypoglycemia : Cases of hypoglycemia have been reported in patients taking opioids.

Most reports were in patients with at least one predisposing risk factor (e.g., diabetes). Opioid-induced esophageal dysfunction (OIED) : Cases of OIED have been reported in patients taking opioids and may occur more frequently in patients taking higher doses of opioids, and/or in patients taking opioids longer term [ see Warnings and Precautions (5.12) ]. Adverse Reactions from Observational Studies A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021.

Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-r

Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA

Tapentadol Hydrochloride

Indications

Contraindications

At a glance

Two medicines in one question?

Tapentadol Hydrochloride

Indications

Contraindications

At a glance

Two medicines in one question?

Warnings and precautions

5.1Addiction, Abuse, and Misuse

5.2Life-Threatening Respiratory Depression

5.3Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Use

Adverse reactions

6.1Clinical Trials Experience Adults

6.2Post-marketing Experience

Composition

Strengths and forms

Official product information