Opioid analgesic with dual mechanism
Brand names: Palexia, Nucynta, Yantil, Palexia Retard
Updated · Methodology
Second line
In acute moderate-to-severe pain (postoperative, musculoskeletal), the immediate-release form is used at 50–100 mg every 4–6 hours. Course is limited to a few days to prevent dependence. Not first-line – paracetamol and adequate NSAID dosing come first.
ICD-10: R52 · ICD-11: MG31
Second line
Used in moderate-to-severe chronic pain, particularly with mixed nociceptive-neuropathic components. NG193 (2021) does not place opioids as first-line in chronic non-cancer pain; they are considered when alternatives fail. Extended-release starting dose 50 mg twice daily, titrated to 250 mg twice daily. Compared with oxycodone, less constipation and nausea.
ICD-10: R52.2 · ICD-11: MG30
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Tapentadol is an opioid analgesic with additional norepinephrine reuptake inhibitor activity. It is prescribed for moderate-to-severe chronic pain when other drugs are ineffective (AEMPS Ficha Técnica). For chronic fatigue without a confirmed pain syndrome, tapentadol is strictly not indicated. The drug has serious risks: opioid dependence formation ( boxed warning), respiratory depression (life-threatening, especially combined with other CNS depressants), serotonin syndrome with other serotonergic drugs, sedation, constipation, and nausea. If tapentadol was prescribed for fatigue, seek a second opinion immediately.
Sources
ICD-10: R53 · ICD-11: MG22
Dual mechanism: μ-opioid agonist and noradrenaline reuptake inhibitor. The combination yields analgesia comparable to oxycodone with 30–50% lower typical opioid side effects (nausea, vomiting, constipation) per the Riemsma 2011 meta-analysis. No active metabolites, so less affected by CYP polymorphism than tramadol. Half-life 4 hours for immediate-release, 5–6 hours for extended-release.
Boxed warning
FDA boxed warning: risk of addiction, abuse, severe respiratory depression, and death. Combination with benzodiazepines, alcohol, gabapentin, or pregabalin is hazardous. Prescribe only for clear indications, at minimum effective dose, with scheduled review.
Long-term use in T3 carries neonatal abstinence syndrome risk. For chronic pain in pregnancy, non-opioid measures are first-line; when an opioid is needed, short-term lowest-effective dose is preferred.
Limited data. Use cautiously in lactation with monitoring of infant sedation and activity.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Verbatim lines from the interaction sections, in the language of the label
«CONTRAINDICATIONS: Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Drug Interactions (7)] .»FDA, section 4 · Open on DailyMed
«Debe evitarse el tratamiento con tapentadol en los pacientes que reciben inhibidores de la monoaminooxidasa (MAO) o que los han tomado en los últimos 14 días, debido a que pueden incrementar más las…»AEMPS, section 4.5 · Open on CIMA
«El uso concomitante de tapentadol con medicamentos sedantes como las benzodiazepinas u otros depresores respiratorios o del SNC (otros opioides, antitusígenos o tratamientos de sustitución…»AEMPS, section 4.5 · Open on CIMA
«El uso concomitante de tapentadol con medicamentos sedantes como las benzodiazepinas u otros depresores respiratorios o del SNC (otros opioides, antitusígenos o tratamientos de sustitución…»AEMPS, section 4.5 · Open on CIMA
«El uso concomitante de tapentadol con medicamentos sedantes como las benzodiazepinas u otros depresores respiratorios o del SNC (otros opioides, antitusígenos o tratamientos de sustitución…»AEMPS, section 4.5 · Open on CIMA
«El uso concomitante de tapentadol con medicamentos sedantes como las benzodiazepinas u otros depresores respiratorios o del SNC (otros opioides, antitusígenos o tratamientos de sustitución…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Intervention: Because respiratory depression may be greater than otherwise expected, decrease the dosage of tapentadol hydrochloride oral solution and/FDA, section 7 · Open on DailyMed
«En pacientes que están en tratamiento con tapentadol, debe procederse con precaución si se inicia o se suspende la administración concomitante de medicamentos que sean inductores enzimáticos potentes…»AEMPS, section 4.5 · Open on CIMA
«En pacientes que están en tratamiento con tapentadol, debe procederse con precaución si se inicia o se suspende la administración concomitante de medicamentos que sean inductores enzimáticos potentes…»AEMPS, section 4.5 · Open on CIMA
«Tapentadol puede provocar convulsiones e incrementar el potencial de originar convulsiones de los inhibidores selectivos de la recaptación de serotonina (ISRS), inhibidores de la recaptación de…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Benzodiazepines and other sedatives/FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Benzodiazepines and other Central Nervous System (CNS) Depressants»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Diuretics»FDA, section 7 · Open on DailyMed
«La principal vía de eliminación de tapentadol es la conjugación con el ácido glucurónico mediado vía uridina difosfato glucuronil transferasa (UGT) principalmente las isoformas UGT1A6, UGT1A9 y…»AEMPS, section 4.5 · Open on CIMA
«El uso concomitante de opioides y gabapentinoides (gabapentina y pregabalina) aumenta el riesgo de sobredosis de opioides, depresión respiratoria y muerte.»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Benzodiazepines and other sedatives/FDA, section 7 · Open on DailyMed
«Tapentadol puede provocar convulsiones e incrementar el potencial de originar convulsiones de los inhibidores selectivos de la recaptación de serotonina (ISRS), inhibidores de la recaptación de…»AEMPS, section 4.5 · Open on CIMA
«La principal vía de eliminación de tapentadol es la conjugación con el ácido glucurónico mediado vía uridina difosfato glucuronil transferasa (UGT) principalmente las isoformas UGT1A6, UGT1A9 y…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor…»FDA, section 7 · Open on DailyMed
«Se han notificado casos de síndrome serotoninérgico coincidiendo temporalmente con el tratamiento de tapentadol en combinación con medicamentos serotoninérgicos tales como, inhibidores selectivos de…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Clinical Impact: Tapentadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: phenelzine, tranylcypromine, linezolid»FDA, section 7 · Open on DailyMed
«El uso concomitante de opioides y gabapentinoides (gabapentina y pregabalina) aumenta el riesgo de sobredosis de opioides, depresión respiratoria y muerte.»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Benzodiazepines and other sedatives/FDA, section 7 · Open on DailyMed
«La administración concomitante de tapentadol con anticolinérgicos o medicamentos con actividad anticolinérgica (p. ej., antidepresivos tricíclicos, antihistamínicos, antipsicóticos, relajantes…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Serotonergic Drugs»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: phenelzine, tranylcypromine, linezolid»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor…»FDA, section 7 · Open on DailyMed
«Combination with Certain Drugs: carbamazepine meperidine tapentadol»FDA, section 4 · Open on DailyMed
«Drugs Having Clinically Important Interactions with Alprazolam: Examples Morphine, buprenorphine, hydromorphone, oxymorphone, oxycodone, fentanyl, methadone, alfentanil, butorpenol, codeine…»FDA, section 7 · Open on DailyMed
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Tapentadol is evaluated for the following indications with varying evidence strength: Mild to moderate pain in adults (evidence tier B), Moderate-to-severe chronic pain (evidence tier B), Chronic fatigue (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Tapentadol (≥ 1 in 100): Nausea, Constipation, Drowsiness, Dizziness, Dry mouth, Pruritus. See the Safety section for uncommon and serious reactions.
Long-term use in T3 carries neonatal abstinence syndrome risk. For chronic pain in pregnancy, non-opioid measures are first-line; when an opioid is needed, short-term lowest-effective dose is preferred.
Limited data. Use cautiously in lactation with monitoring of infant sedation and activity.
Do not combine with alcohol, benzodiazepines, or gabapentinoids – risk of severe respiratory depression.
Tapentadol is contraindicated in: Tapentadol hypersensitivity; Severe respiratory failure, acute bronchospasm; Severe hepatic impairment; Acute alcohol or opioid intoxication; Concurrent MAO inhibitors or within 14 days of stopping. Full list in the Safety section.
FDA boxed warning: risk of addiction, abuse, severe respiratory depression, and death. Combination with benzodiazepines, alcohol, gabapentin, or pregabalin is hazardous. Prescribe only for clear indications, at minimum effective dose, with scheduled review.
Direct links to regulator labels. Open in a new tab.
Tramadol, Tramadol + Paracetamol, Zolmitriptan, Almotriptan, Ergotamine, Metamizole sodium, Oxycodone + Naloxone, Buprenorphine (transdermal)