Tramadol versus Tapentadol
Table 1. Comparison of tramadol and tapentadol
|Brand names||Ultram®, Ultram® ER||Nucynta®, Nucynta® ER|
|Drug class||Centrally acting synthetic analgesic|
|Legal status||Controlled Substance Schedule IV||Controlled Substance Schedule II|
|FDA-approved Indications for Immediate-release formulation||Moderate to moderately severe pain in adults.||Moderate to severe acute pain in patients aged > or =18 years.|
|FDA-approved Indications for Extended-release formulation||• Moderate to moderately severe chronic pain in adults, requiring around-the-clock, long-term treatment||• Severe pain requiring daily, around-the-clock, long-term opioid treatment and for which alternative treatments are inadequate;
• Severe diabetic peripheral neuropathic pain in adults requiring daily, around-the-clock, long-term opioid treatment and for which alternative treatments are inadequate
|Mechanism of action||Dual mechanism of action:
weak µ-opioid receptor agonism,
and norepinephrine and serotonin reuptake inhibition
|Dual mechanism of action:
µ-opioid receptor agonism and norepinephrine reuptake inhibition
|Onset of action||1 hour||20-40 min|
|Duration of action||4-6 hours||4-6 hours|
(7.4 hours for metabolite)
|Metabolism, Elimination||Undergoes CYP3A4- and CYP2D6 metabolism in the liver.
Excreted primarily through liver metabolism and the metabolites are eliminated primarily by the kidneys.
|Predominantly metabolized by liver by phase 2 glucuronidation.
Excreted in urine 99%.
Analgesic efficacy is not altered by metabolic factors.
|Contraindications||• Hypersensitivity to tramadol
• Acute intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs5
|• Hypersensitivity to tapentadol
• Significant respiratory depression
• Acute or severe bronchial asthma or hypercarbia
• Paralytic ileus
• Monoamine oxidase (MAO) inhibitors therapy4
|Warnings & precautions||• Abuse potential
• Interactions with alcohol, other opioids, CNS depressants
• Patients with increased intracranial pressure or head injury
• Serotonin syndrome risk
• Withdrawal symptoms
• Impairment of mental or physical abilities
|• Respiratory depression
• Seizures risk - seizures have been reported with the recommended dosages
• Suicide risk
• Concomitant use with MAO inhibitors and SSRIs
• Anaphylactoid reactions have been reported
• Renal and hepatic disease - dosing reduction is recommended
|• Life threatening respiratory depression; elderly and debilitated patients are particularly vulnerable
• Seizures risk - has not been studied in patients with patients with a predisposition to seizures
• Chronic pulmonary disease
• Hypotensive effect
• Hepatic impairment - avoid in severe hepatic impairment; dosing reduction is recommended in moderate hepatic disease
• Renal impairment - avoid tapentadol in severe renal impairment
• Spasm of the sphincter of Oddi risk
|Abuse potential||Low risk of physical/psychological dependence||Physical/psychological dependence similar to schedule II potent opioids|
|Drug interactions||• CYP2D6 and CYP3A4 inhibitors (e.g. ketoconazole, erythromycin) may affect the metabolism of tramadol.
• Carbamazepine significantly increases tramadol metabolism.
|• Does not inhibit or induce cytochrome P450 enzymes.
Minimal potential for pharmacokinetic drug interactions.
• Anticholinergics may increase the risk of urinary retention.
|Monoamine oxidase inhibitors, serotonergic medications|
|Molecule||• Racemic mixture
|• Single enantiomer
• Active molecule, not a prodrug
Tapentadol and Tramadol are similar in that they are considered “different” than the classic opioids. Both tramadol and tapentadol are centrally-acting analgesics that combine opioid and non-opioid activities, which synergistically produce analgesia. In contrast to pure opioid agonists, both drugs have lower risks of respiratory depression, tolerance, and dependence.
Tapentadol has an open-chain molecule, while tramadol has a 2-ring cyclic structure, resulting in distinct pharmacological properties.
Tapentadol has no active metabolites and does not require metabolic activation to exert its analgesic effects. Tramadol requires metabolism by the CYP450 complex to its active metabolite O-desmethyltramadol to be completely effective.
The µ-opioid receptor agonist activity of tapentadol is several-fold greater than that of tramadol. Also, tapentadol exerts noticeable norepinephrine reuptake inhibition but minimal serotonin effect 2. Tramadol notably inhibits both norepinephrine and serotonin reuptake.
Tramadol is a good choice for pain conditions for which a strong opioid action is not necessary. On the other hand, tapentadol is a suitable choice for pain conditions requiring a strong opioid action2.
Main Tapentadol advantages over Tramadol:
- Lack of cytochrome P450 drug interactions
- Lower risk of seizures (no listed risk of idiopathic seizures in the FDA labeling4)
- Lower risk of serotonin syndrome6
- Better analgesia thanks to stronger binding affinity for µ-opioid receptors
- Earlier onset of action
- No individual variation in drug response
- Lesser incidence of nausea and vomiting
Main Tramadol advantages over Tapentadol:
- Lower risk of respiratory depression, drowsiness, and lethargy7
- Less abuse potential
- Not contraindicated in patients with asthma, hypercarbia, and paralytic ileus
- Inexpensive - wide availability of generic formulations
Tolerability: According to the indirect comparison1 between oral tramadol and oral tapentadol patients treated with tramadol have a significantly higher risk of constipation and vomiting; patients treated with tapentadol have a slightly higher risk of dizziness.
Effectiveness: Recent 2014 meta-analysis1 suggests that tramadol provides slightly better pain management than tapentadol. However, as mentioned above, tramadol opioid analgesia depends on CYP2D6 genotype.
Analgesia after cardiac surgery
Tapentadol is a better analgesic than tramadol8.
- 1. Mercier F, Claret L, Prins K, Bruno R. A Model-Based Meta-analysis to Compare Efficacy and Tolerability of Tramadol and Tapentadol for the Treatment of Chronic Non-Malignant Pain. Pain Ther. 2014 Jun;3(1):31-44. PubMed
- 2. Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, Hertrampf T, Kögel B, Schiene K, Straßburger W, Terlinden R, Tzschentke TM. Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother. 2012 Jul;13(10):1437-49. PubMed
- 3. Vadivelu N, Timchenko A, Huang Y, Sinatra R. Tapentadol extended-release for treatment of chronic pain: a review. J Pain Res. 2011;4:211-8 PubMed
- 4. Prescribing Information for NUCYNTA® (tapentadol) with 2013 updates PDF
- 5. Prescribing Information for ULTRAM® (tramadol hydrochloride) PDF
- 6. T.L. Lemke, D.A. Williams Foye's Principles of Medicinal Chemistry. 7th ed. Philadelphia, Wolters Kluwer/Williams; p.689
- 7. Tsutaoka BT, Ho RY, Fung SM, Kearney TE. Comparative Toxicity of Tapentadol and Tramadol Utilizing Data Reported to the National Poison Data System. Ann Pharmacother. 2015 Dec;49(12):1311-6. PubMed
- 8. Iyer SK, Mohan G, Ramakrishnan S, Theodore S. Comparison of tapentadol with tramadol for analgesia after cardiac surgery. Ann Card Anaesth. 2015 Jul-Sep;18(3):352-60. PubMed
Published: January 16, 2015
Last updated: February 22, 2017