Tapentadol; Uses, Dosage, Side Effects, Interactions

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Tapentadol is an Opioid Agonist. The mechanism of action of tapentadol is as an Opioid Agonist. Opioid analgesic for the treatment of moderate to severe pain.

Tapentadol is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration and lasts for 4–6 hours.

It is similar to tramadol in its dual mechanism of action; namely, its ability to activate the mu opioid receptor and inhibit the reuptake of norepinephrine. Unlike tramadol, it has only weak effects on the reuptake of serotonin and is a significantly more potent opioid with no known active metabolites. Tapentadol is not a pro-drug and therefore does not rely on metabolism to produce its therapeutic effects; this makes it a useful moderate-potency analgesic option for patients who do not respond adequately to more commonly used opioids due to genetic disposition poor metabolizers of , as well as providing a more consistent dosage-response range among the patient population.

Mechanism of Action of Tapentadol

Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central mu-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurons of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in a dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbinereversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and a2-adrenoceptors seen at spinal levels but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain.


Tapentadol acts on the opioid receptors through its major active metabolite desmetapentadol, which has as much as 700-fold higher affinity for the MOR relative to tapentadol. Moreover, tapentadol itself has been found to possess no efficacy in activating the MOR in functional activity assays, whereas desme tapentadol activates the receptor with high intrinsic activity ( equal to that of morphine). As such, desme tapentadol is exclusively responsible for the opioid effects of tapentadol. Both tapentadol and desme tapentadol have pronounced selectivity for the MOR over the DOR and KOR in terms of binding affinity. Tramadol has been found to possess the following actions

  • Agonist of the μ-opioid receptor (MOR) and to a far lesser extent of the δ-opioid receptor (DOR) and κ-opioid receptor (KOR)
  • Serotonin reuptake inhibitor (SRI) and norepinephrine reuptake inhibitor (NRI); hence, an SNRI
  • Serotonin 5-HT2C receptor antagonist
  • M1 and M3 muscarinic acetylcholine receptor antagonist
  • α7 nicotinic acetylcholine receptor antagonist
  • NMDA receptor antagonist (very weak)
  • TRPA1 inhibitor
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Indications of Tapentadol

Therapeutic Uses of Tapentadol

Contra-Indications of Tapentadol

Tapentadol is contraindicated in those with hypersensitivity,

Dosage of Tapentadol

Strenghts: 50 mg, 75 mg, or 100 mg


Immediate release

  • 50 mg, 75 mg, or 100 mg orally every 4 to 6 hours depending upon pain intensity, with or without food.
  • On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability. Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are, therefore, not recommended.

Extended release

  • Initial: 50 mg twice daily (recommended interval: 12 hours); titrate in increments of 50 mg no more frequently than twice daily every 3 days to the effective dose (therapeutic range: 100 to 250 mg twice daily) (maximum dose: 500 mg/day)
  • Initial: 50 mg titrated to an effective dose; titrate in increments of 50 mg no more frequently than twice daily every 3 days (therapeutic range: 100 to 250 mg twice daily) (maximum dose: 500 mg/day). Note: No adequate data on converting patients from other opioids to tapentadol extended release.
  • Conversion from immediate release to extended release: Convert using same total daily dose but divide into two equal doses and administer twice daily (recommended interval: 12 hours) (maximum dose: 500 mg/day).

Side effects of Tapentadol

The most common

More common

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Drug Interactions of Tapentadol

Tapentadol may interact with following drugs, supplements & may change the efficacy of drugs

Pregnancy & Lactation of Tapentadol

FDA Pregnancy Category C


This medication should not be used during pregnancy, prior to or during labour. If you become pregnant while taking this medication, contact your doctor immediately.


It is not known if tapentadol passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.


  1. https://pubchem.ncbi.nlm.nih.gov

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