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Tapentadol Vs Tramadol- Detailed Comparison Of Uses, Pharmacokinetics, And Toxicology

Tapentadol Vs Tramadol- Detailed Comparison Of Uses, Pharmacokinetics, And Toxicology


The comparative study of Tapentadol vs. Tramadol indicates that Tapentadol is two to three times more potent than Tramadol. It has a quicker onset of action and is a safer analgesic option with a lower risk of side effects, drug interaction, addiction, and dependency.



Tapentadol vs. Tramadol is an extensively discussed opioid analgesic comparison due to its high potency in treating chronic pain. 

Suffering from severe chronic pain is one of the most common reasons for people seeking medical help, as it restricts their mobility. A survey report by the CDC states that about 20.8% of American adults struggle with body pain [1]. Most chronic pain does not respond well to the conventional analgesic and requires more potent treatment options. 

Two common FDA-approved analgesics to be prescribed for severe pain are Tapentadol and Tramadol. This pharmacological comparison is to help readers make a better decision between the two extensively popular opioid pain medications.


Tramadol And Aspadol (Tapentadol)- An Overview

Tramadol is a centrally-acting analgesic used for moderate to severe pain. Its medical use was first approved in Germany in 1977 by the pharmaceutical company Grünenthal GmbH after being developed and patented in 1962. 

Under the brand Ultram (NDA 020281), Tramadol hydrochloride was approved by the FDA for medical use on March 3, 1995. In 2020, it was the 35th most commonly prescribed medication in the United States and considered the second option for pain treatment by WHO (World Health Organisation) [2].

Tapentadol is a novel opioid analgesic developed in 1980 to address the adverse effects associated with Tramadol. Its clinical use was approved in 2008 by the FDA and in Europe in 2010. It is an advanced pain management option where a single molecule can deliver analgesia through two working mechanisms. Available under the brand names Nucynta and Aspadol, this orange painkiller is effective across a broad spectrum of pain, from nociceptive to diabetic neuropathy. Tapentadol also treats dental pain following surgery, diabetes neuropathy, and muscle pain. 

The composition of Tapentadol brand drugs includes Tapentadol hydrochloride as the active compound along with other inactive compounds necessary for its formulation and stability. Currently there are no generic Tapentadol tablets available in the market. 

Tramadol Vs Tapentadol- Structural Differences

Tapentadol and Tramadol analgesics are phenypropylamines, a drug class that is used as a decongestant for nasal and bronchial issues and also as an appetite suppressant.

The Tramadol and Tapentadol structure, as shown below, indicates that Tramadol is a 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol with a chemical formula of C16H25NO2 and molecular weight 263.37 g/mol. 


Tapentadol Structure-

Tapentadol (3-((1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl) phenol hydrochloride), which suggests that the main part of the structure of Tapentadol is a phenol group (aromatic carbon that is derived from alcohol) that can also be called as its core structure. 

  • It also has a hydrochloride group that contributes to its water-soluble property, further increasing its ability to get absorbed by the body. 

  • The side chain: 3-(dimethylamino)-1-ethyl-2-methylpropyl indicates that there is a chain of carbon atoms with each carbon atom being attached to a hydrogen, methyl (CH3) groups, and dimethylamino group respectively.


Similarities Between Tramadol And Tapentadol 

Tapentadol and Tramadol analgesics showcase resemblances on specific comparative grounds, making it hard for most users to decide. Two distinct similarities between them are listed below. 

Drug Class:

Tapentadol and Tramadol are opioid pain medications. These are powerful pain medications that work with the brain cells.

Clinical uses: 

They are approved for treating moderate to severe acute and chronic pain that do not respond well to non-opioid analgesics. 

Tapentadol is also officially approved by the FDA as an alternative treatment of diabetic peripheral neuropathy in the USA. Whereas a few randomized controlled trials suggest that the evidence supporting using Tramadol for neuropathy is very low. The use of Tapentadol for treating dental pain is gradually gaining momentum.

Further depression associated with body pain can be treated with Tapentadol

A study by Srinivas Kalyanaraman Iye et al. on patients after cardiac surgery demonstrates that Tapentadol is a more potent pain medication than Tramadol for postoperative discomfort. Tramadol patients needed a higher level of "rescue analgesic" for better pain relief than Tapentadol, as shown below. 




Medical experts often provide rescue analgesics when the primary pain medication fails to deliver effective results, indicating Tapentadol is a better analgesic choice for post-operative body pain. 


Difference Between Tramadol And Tapentadol

Apart from the similarities, a few notable differences between them are listed below. 

Effectiveness And Potency

Tapentadol is two to three times more effective and potent than Tramadol, states Lucien Roulet et al. in a 2021 study. 

Legal Status

Tapentadol is a controlled substance and is classified as a Schedule II prescription drug by the Drug Enforcement Administration (DEA). Tramadol, on the other hand, is a Schedule IV drug in the USA. 

The legal status of Tapentadol and Tramadol in three other countries is listed below. 






Controlled drug

Prescription only.


Schedule I

Prescription only.


Schedule II

Schedule III


Availability And Prescription Modalities

Tramadol is available in 40 countries around the world, including Canada, Australia, the USA, China, Russia, Japan, and India. Meanwhile, Tapentadol is available in 28 countries. 

Both these medications are available through medical prescription in most countries and cannot be bought over the counter. 

Cost and Affordability

The cost of Aspadol 100 mg and Tramadol may vary depending on factors such as pharmacy, available offers and discounts, and pill packages. 

Generic Tapentadol tablets are unavailable; thus, Healthnaturo retails Aspasol 100 mg tablets at $2.77 per pill

The cost of Tramadol (Ultram) 50mg in some of the local pharmacies in the US is listed below. 



The cost of 60 pills 

Cost per pill














Mechanism Of Action Of Tapentadol And Tramdol 

Both pain medications act like messengers that specifically target a certain part of the body and block the pain signals from reaching the brain receptors. 

Further, It also helps in boosting the body's natural pain control system, thus reducing the overall feeling of pain.

Pharmacokinetics Differentiation 

Following an Orally administration, the absorption of Tapentadol is about 32%, which is not affected by stomach acidity and changes in gastric motility, unlike Tramadol. 





Onset of action

30 minutes

60 minutes (1 hour).

Maximum blood concentration

Sixty minutes (1 hour).

120 minutes (1 and a half hours).

Active metabolite

Active drug


T ½ (Half-Life)

4 hours

6 hours


Kidneys (99%)

Kidneys (90%).

Main metabolic pathways

Liver  P450 (CYP) enzymes.

Liver  P450 (CYP) enzymes.


Tapentadol Vs Tramadol- Dosing Guidelines 

The recommended dose of Tapentadol and Tramadol is 100mg every 4 to 6 hours. Meanwhile, the extended-release formula should be taken every 12 hours. 

  • Dosage form- Tapentadol is available as an oral tablet, whereas Tramadol is available as an injection and an oral tablet. 

  • Strengths- Tramadol is available in four dosages: 50mg, 100mg, 150mg, and 200mg. However, only 50 mg and 100mg of Tapentadol tablets are available. 

  • Maximum Dosage- The maximum daily dose of Tapentadol is 700 mg and 400 mg for Tramadol. 


Scientific Data On The Conversion Of Tramadol To Tapentadol

Several studies incorporate the safety guidelines in patients switching from Tramadol to Tapentadol. A survey by H.G. Kress on cancer patients shows people with prior Tramadol therapy can directly switch to Tapentadol, with 70 percent of the patients experiencing improved results. 

The reasons to discontinue Tramadol in such patients are lack of efficacy and high risk of acquiring dependency. 


Abuse Potential- Tapentadol Vs Tramadol High

The risk of abuse and dependency with Tapentadol and Tramadol is considered to be lower than most other opioid pain medications. 

The Tramadol extended-release form is taken in doses up to 600 mg per day. However, a recent 2019 study by Cornelius A. Thiels et al. found that Tramadol was associated with a much higher risk of dependency in patients after elective surgery. 

Intake of these pain medications in higher doses and their abrupt cessation can increase the risk of dependency and withdrawal symptoms. 

A recent 2023 study by Joana Barbosa et al. approached a test called Conditioned Place Preference (CPP) in animal models to evaluate the abuse potential of these two analgesics. The three significant findings of the study are listed below. 

  • Both these opioid medications have structural similarities with morphine, which is known to activate brain receptors associated with the feeling of "pleasure," raising concern for their use.  

  • Tapentadol has a lower abuse risk than Tramadol. 

  • Tramadol seemed to have a longer-lasting memory effect than Tapentadol. 

Signs of abuse of Tapentadol and Tramadol in users are-

  • Pupil becoming small 

  • Chest pain

  • Nausea 

  • Clammy skin

  • Trouble breathing

  • Loss of consciousness 

  • Drowsiness

  • Dizzines


Side Effects  

The frequency of occurrence of adverse effects reported from Tapentadol and Tramadol is highly variable across studies, thus reflecting the wide range of doses, indications, and populations studied. 

Vomiting and Nausea

Both vomiting and Nausea are frequently associated with Tramadol and Tapentadol. The frequency of these side effects is dose and time-dependent and can be reduced by starting with a lower dose and gradually increasing it every 4 days. 


Tramadol is associated with a lower incidence of constipation. A clinical trial by C H Wilder-Smith and A Bettiga in 1997 suggested minor Tramadol interference with gastrointestinal motility. 

A comparative study of Tapentadol with Oxycodone suggests that Tapentadol has a lower risk for constipation. However, its occurrence in people taking Tapentadol cannot be completely ruled out. 


In a clinical investigation by Srinivas Kalyanaraman Iye et al., 30 people taking Tramadol experienced Psychosis. Meanwhile, people taking Tapentadol showed no signs of the condition. 

Serotonin Syndrome

Cases of serotonin syndrome have been reported with Tramadol in patients when exposed to other drugs with serotonergic properties. It can also induce serotonin syndrome in case of overdose. 

Tapentadol, on the other hand, has a lower serotonergic effect than Tramadol.

Cardiovascular Effects

Reports of rhythm disturbances, including bradycardia, tachycardia, and atrial fibrillation, have been reported with the intake of Tramadol by Florence Moulis et al. in a 2017 study. 

Cases of cardiac arrests have been reported after Tramadol overdose in patients with a previous history of heart conditions. 

In comparison, Tapentadol, when taken from 200 mg to 500mg per day, is not associated with significant changes in blood pressure or heart rate in patients. The overall cardiovascular safety of Tapentadol reassures these findings; however, its noradrenergic activity can induce serious tachycardia in a few cases. 


Tapentadol Vs Tramadol - Drug Interactions

Using these medications with other treatments can induce drug interaction. It can cause unpredicted side effects with diminished or heightened drug action possibilities. 

Tramadol drug interaction is known to interact with 644 medications, whereas Tapentadol may interact with 372 drugs. 

  • Tramadol Drug Interaction: 302 major drug interactions, 340 moderate drug interactions, and 2 minor drug interactions.

  • Tapentadol Interaction: 183 major interactions, 188 moderate interactions, and 1 minor interaction. 

Can You Take Tapentadol With Tramadol?

Taking Tapentadol and Tramadol together is known to cause major drug interaction resulting in central nervous system depression, causing coma, profound sedation, respiratory distress, and death in rare and extremely severe cases. 

If coadministration is necessary, such patients should be monitored for signs of sedation and respiratory depression and are advised not to use hazardous machinery and to avoid driving. 


Is Nucynta Stronger Than Tramadol- Our Final Thoughts 

Tapentadol is considered to be a compound with a better clinical and safety profile as it overcomes some of the limitations of Tramadol, such as the likelihood of abuse, drug interaction, lower effectiveness, and longer onset of action. 

Tapentadol's efficacy in treating a wide range of acute and chronic pain and its better tolerability profile than traditional opioids give it the upper hand over Tramadol. 

Let us further sum up all the benefits and demerits of both Tapentadol and Tramadol to understand the right analgesic choice. 






  • Tapentadol has a lower potency for drug interaction than Tramadol. 

  • It is more potent and effective than Tramadol, according to a  2021 study by Lucien Roulet et al. 

  • The onset of action of Tapentadol is shorter than that of Tramadol. 

  • Tapentadol is more affordable. 

  • Tapentadol is more likely to result in respiratory depression and constipation than Tramadol. 

  • Generic Tapentadol is not available. 


  • Available in generic tablets. 

  • Better user rating. 

  • It has a slightly longer duration of action in some individuals. 

  • More widely available globally. 

  • Tramadol is less effective than Tapentadol for treating Cancer pain.

  • It has a higher risk of drug interaction. 

  • Has a higher risk of abuse potential.  


Taking Tramadol and Tapenatdol together is not advisable and causes central nervous system depression causing respiratory distress or coma in severe cases. 


Two stronger analgesic than Tramadol are Tapentadol and Oxycodone. 


Tapentadol is two to three times stronger and more potent than Tramadol. 


Tapentadol is an effective treatment option for chronic and acute pain. 


Studies show that the use of Tapentadol helps in reducing 80% of sleep disturbance.


No, Palexia is a Tapentadol brand name manufactured by Grünenthal Ltd and is not structurally similar to Tramadol. However, they are both opioid pain medications approved by the FDA for treating acute and chronic pain.

Yes, Palexia is the same as Tapentadol and is the brand name of the analgesic, which is manufactured by Grünenthal Ltd. Thus, Palexia showcases a similar medical uses and safety profile as its active ingredient, Tapentadol Hydrochloride.


  1. Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults- United States , 2016, CDC, 2018.

  2. Tramadol, Drugbank.

  3. Classification of controlled drugs,

  4. Can you buy tramadol online legally, bonfire.