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Created February 8, 2021, last updated almost 4 years ago.
Collection: 140, Score: 1060, Trend score: 0, Read count: 1446, Articles count: 4, Created: 2021-02-08 23:22:42 UTC. Updated: 2021-02-09 11:04:35 UTC.Notes
Tapentadol (Paliex™, Nucynta™) is a synthetic opioid agonist and noradrenaline-reuptake inhibitor. Similar to and based upon tramadol, although with much weaker inhibition (by design) of serotonin reuptake.
A. Physiochemistry
- Synthetic analgesic of 'amino-cyclo-hexanol' group.
- Unlike tramadol, prepared as only the (R,R) stereoisomer (weakest opioid activity).
- Oral: 50, 75 & 100 mg immediate release, and 50,100,150 & 200 mg extended release preparations.
- No parenteral preparation is approved for use.
B. Pharmacokinetics
- Dose: 50-200 mg bd/qid for immediate release preparations, 50-200mg bd for extended release.
- approximately double potency of tramadol, similar to oxycodone and between tramadol and morphine.
- Absorption - po (only 32% biov)
- increasing doses have a non-linear effect on increasing peak plasma concentration, thus higher doses result in disproportionately higher Cmax.
- Distribution - ~8 L/kg (higher than tramadol).
- Protein binding - 20% (low!)
- Onset 30 min; Offset 4-6 h
- Metabolism - t½ 4h
- hepatic conjugation with glucuronic acid → glucuronides is main pathway (tapentadol-O-glucuronide); p450 metabolism to N-desmethyl tapentadol and hydroxyl tapentadol.
- No known active metabolites
- 99% excreted in urine, 1% in faecies.
- Clearance - 22 mL/kg/min
C. Pharmacodynamics
- Mech - weak mu agonists (30% of action / 18x less affinity than morphine) ; inhibits NAd reuptake (through indirect activation of post-synaptic alpha-2 adrenoreceptors), activating descending NAd (70%) modulating pain pathways.
- CNS - analgesia, good for neuropathic pain, low(er) incidence of tolerance & dependence, lowers seizure threshold, dizziness, sweating, ⇡ ICP.
- CVS - few CVS effects. Some tachycardia and flushing.
- Resp - little respiratory depression.
- Renal - possible caution in renal failure, although no active metabolites even if 99% renal excreted.
- GIT - Nausea & vomiting (less than tramadol), minimal constipation, more biliary spasm than tramadol.
- SEs - interacts with MAOI (adrenergic storm), SSRIs (serotonin syndrome).
- Although thought to have less abuse potential than other common opioids, it is still classed as a Schedule 2 drug in the US, Schedule 1 in Canada, Class A controlled drug in the UK and S8 in Australia.
- Safety of tapentadol in pregnant, lactating women, and pediatric patients is not yet established.
Daniel Jolley
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Collected Articles
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Tapentadol exerts its analgesic effects through micro opioid receptor agonism and noradrenaline reuptake inhibition in the central nervous system. Preclinical studies demonstrated that tapentadol is effective in a broad range of pain models, including nociceptive, inflammatory, visceral, mono- and polyneuropathic models. ⋯ In addition, it was reported to be associated with significantly fewer treatment discontinuations due to a significantly lower incidence of gastrointestinal-related adverse events compared with equivalent doses of oxycodone. The combination of these reduced treatment discontinuation rates and tapentadol efficacy for the relief of moderate to severe nociceptive and neuropathic pain may offer an improvement in pain therapy by increasing patient compliance with their treatment regimen.
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Tapentadol is a novel, centrally acting analgesic with dual mechanism of action, combining mu-opioid receptor agonism with noradrenaline reuptake inhibition in the same molecule. It has an improved side effect profile when compared to opioids and nonsteroidal anti-inflammatory drugs. The dual mechanism of action makes Tapentadol a useful analgesic to treat acute, chronic, and neuropathic pain.
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Int J Clin Pharm Th · Apr 2013
Randomized Controlled Trial Comparative StudyComparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations.
To evaluate the bioavailability and pharmacokinetics of orally administered tapentadol immediate release (IR) compared with tapentadol prolonged release (PR). ⋯ Absolute bioavailability for both tapentadol IR and tapentadol PR was ~ 32% under fasted conditions. Extent of exposure (AUC) for tapentadol PR was very similar to tapentadol IR, whereas Cmax was lower and HVD/MRT longer for the prolonged-release formulation. Overall, the pharmacokinetic characteristics of tapentadol PR enable a twice-daily dosing regimen to be used; such a regimen is expected to improve patient compliance during chronic use.
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Moderate-to-severe pain represents a heavy burden in patients' quality of life, and ultimately in the society and in healthcare costs. The aim of this review was to summarize data on tramadol and tapentadol adverse effects, toxicity, potential advantages and limitations according to the context of clinical use. We compared data on the pharmacological and toxicological profiles of tramadol and tapentadol, after an extensive literature search in the US National Library of Medicine (PubMed). ⋯ In addition, it leads to less side effects and lower abuse liability. However, in vivo and in vitro studies have shown that tramadol and tapentadol cause similar toxicological damage. In this context, it is important to underline that the choice of opioid should be individually balanced and a tailored decision, based on previous experience and on the patient's profile, type of pain and context of treatment.