Tapentadol

Structural formula
General
Non-proprietary name	Tapentadol
other names	3 - [(1 R , 2 R ) -3- (Dimethylamino) -1-ethyl-2-methylpropyl] phenol ( IUPAC )
Molecular formula	C 14 H 23 NO
External identifiers / databases
CAS number 175591-23-8 EC number 605-757-6 ECHA InfoCard 100.131.247 PubChem 9838022 ChemSpider 8013742 DrugBank DB06204 Wikidata Q414463
Drug information
ATC code	N02 AX06
Drug class	Analgesics
properties
Molar mass	221.34 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tapentadol is a centrally acting, pain relieving agent that was developed by Grünenthal GmbH . On the one hand it acts as an agonist on the μ-opioid receptor and on the other hand as a selective noradrenaline reuptake inhibitor on the noradrenaline transporter .

Tapentadol is a highly effective opioid analgesic , which in principle is to be assigned to level III in the WHO level scheme (classification of pain therapy). However, this assignment is only valid to a limited extent, as there were no randomized, controlled comparative studies with the similar tramadol or other opioids available until 2014 .

Pharmacological properties

Mechanism of action

Tapentadol is an agonist on the μ-opioid receptor and also acts as a selective norepinephrine reuptake inhibitor . The mechanism of noradrenaline reuptake inhibition is also used in adjuvant drug pain therapy with antidepressants .

The affinity of tapentadol for the μ-opioid receptors (rat, human) is about 15 to 20 times higher than that of the structurally related tramadol , but is 2.7 times lower than that of its pharmacologically active metabolite (+) - O -Desmethyltramadol. In comparison to tramadol, there are differences in the ratio of accumulation in the CNS to μ-receptor activity and noradrenaline reuptake inhibition, which suggest that the two mechanisms of action differ in terms of their synergistic effect for tapentadol and tramadol.

Unlike tramadol, tapentadol does not inhibit serotonin recovery .

Absorption and distribution in the body

Tapentadol is approximately 30% absorbed in the gastrointestinal tract . In the liver occurs glucuronidation and sulfation . The metabolite is excreted 95% via the kidneys. The plasma half-life is four hours. The water-soluble tapentadol hydrochloride is used medicinally.

Clinical information

Application areas (indications)

Tapentadol is approved for the treatment of severe, chronic pain ( sustained release formulation ) and moderately severe to severe acute pain (rapid-release formulation) that can only be adequately treated with opioid analgesics. In 2012, the National Association of Statutory Health Insurance Physicians (KBV) in Germany recommended that tapentadol should only be used in patients with severe, non- tumor-related chronic pain, in whom prolonged-release morphine did not have an adequate effect or morphine was not tolerated, due to a lack of data in cancer patients .

Contraindications and restrictions on use

The contraindications correspond to those of the other opioids (intolerance of the active substance, risk of respiratory depression , not in ileus conditions , intoxication by centrally active substances).

The restrictions on use (use only possible under special observation) largely correspond to those of the other opioids (children and adolescents under 18 years of age, coma, severe craniocerebral injuries, brain tumors, advanced kidney failure, severe liver diseases, opiate addiction, severe respiratory disorders, hypotension, urination disorders, Diseases of the pancreas and biliary tract, pheochromocytoma ).

Respiratory depression of the fetus cannot be ruled out during pregnancy . Tapentadol can pass into breast milk and cause respiratory depression in the infant.

Because of the central depressant effect it can reduce the ability to drive affect. Patients with mild renal impairment or the elderly do not require dose adjustment. Interactions with other drugs, in addition to those of other opioids, are in particular the interaction with serotoninergic substances in drugs with e.g. B. selective serotonin reuptake and monoamine oxidase inhibitors to be observed.

Adverse effects, interactions with other drugs

Tapentadol has the usual adverse effects of opioids . The very common side effects include dizziness, somnolence , headache, nausea, and constipation. As often be specified decreased appetite, anxiety, depression, insomnia, restlessness, tremor , involuntary muscle contractions, flushing, dyspnea , vomiting, diarrhea, gastrointestinal disorders, itching, sweating, rash, fatigue, discomfort in body temperature, dry mucous membranes and edema.

There is a potential for addiction .

Taking tapentadol and MAO inhibitors or serotonin reuptake inhibitors together can lead to sharp increases in blood pressure. The intake with alcohol or other CNS depressants increases the negative impact on the ability to drive .

Effectiveness and tolerance

The analgesic potency of tapentadol is 0.3–0.5 and thus between that of tramadol (0.1) and morphine (sample substance, analgesic potency 1.0) Tapentadol was found in an approval study by the manufacturer for chronic osteoarthritis and back pain more tolerable than oxycodone in terms of nausea, constipation and vomiting . The number of discontinuations of therapy due to side effects with tapentadol was half as high as that with oxycodone. It is critical that, according to the study protocol, the dose of oxycodone could not be reduced and it was probably overdosed.

A superiority of tapentadol over pure opioids or tramadol in terms of efficacy or tolerability has not been proven by randomized, controlled studies.

Pharmaceutical information

Tapentadol was granted market access in EU countries through a decentralized approval process that was completed in August 2010. In the same month tapentadol came onto the market in Germany in the form of prolonged-release tablets; In 2014, an oral solution for the treatment of acute pain followed. In the US, tapentadol was approved as Nucynta 2008.

Tapentadol has been the first new active ingredient to be launched on the market for the oral treatment of moderate to severe acute and chronic pain in 25 years . According to a report by the health insurance companies, however, it is not very innovative, significantly more expensive than existing therapy options (such as tramadol or morphine ) and is not recommended for the treatment of tumor pain due to a lack of study data.

Tapentadol is subject to narcotics regulations; in Germany it is classified as a marketable and prescription drug . In Switzerland it is also covered by the Narcotics Act , and in Austria by the Narcotics Act .

Tapentadol increases the cost of therapy in an equivalent dose to morphine by a factor of around 2.5 (as of 2012).

Trade names

Palexia ( D , A , CH ), Yantil ( DK , ES ), Nucynta ( USA )

literature

• R. Terlinden, J. Ossig, F. Fliegert, K. Gohler: Pharmacokinetics, excretion and metabolism of tapentadol HCl, a novel centrally acting analgesic in healthy subjects. In: Program and abstracts of the 25th Annual Scientific Meeting of the American Pain Society. May 3-6, 2006; San Antonio, Texas. Poster 689.
• S. Daniels, D. Upmalis, A. Okamoto, C. Lange, J. Haeussler: A Randomized, Double-Blind, Phase III Study Comparing Multiple Doses of Tapentadol IR, Oxycodone IR, and Placebo for Postoperative (bunionectomy) Pain. In: Current Medical Research and Opinion. Vol. 25, No. 3, 2009, pp. 765-776.
• C. Hartrick, I. van Hove, J. Stegmann, C. Oh, D. Upmalis: Efficacy and Tolerability of tapentadol Immediate Release and Oxycodone HCl Immediate Release in Patients Awaiting Primary Join Replacement Surgery for End-Stage Joint Disease: A 10- day, Phase III, Randomized, Double-Blind, Active and Placebo Controlled Study. In: Clinical Therapeutics . Vol 31, No. 2, 2009.
• R. Kleinert, C. Lange, A. Steup, P. Black, J. Goldberg, P. Dejardins: Single Dose Analgesic Efficacy of Tapentadol in Postsurgical Dental Pain: The Results of a Randomized, Double-Blind, Placebo-Controlled Study. In: International Anesthesia Research Society. Vol. 107, No. 6, December 2008.

Web links

• Red list online, Palexia, restricted access e.g. B. via DocCheck
• Specialist information Palexia retard. As of August 2010 ( RTF ; 164 kB)
• Entries in the NIH study registry

Individual evidence

1. ↑ There is not yet a harmonized classification for this substance . A labeling of phenol, 3 - [(1R, 2R) -3- (dimethylamino) -1-ethyl-2-methylpropyl] - derived from a self-classification by the distributor is reproduced in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA) on May 11, 2020.
2. ↑ TM Tzschentke, T. Christoph, B. Kögel, K. Schiene, HH Hennies, W. Englberger, M. Haurand, U. Jahnel, TI Cremers, E. Friderichs, J. De Vry: (1R, 2R) -3 - (3-Dimethylamino-1-ethyl-2-methyl-propyl) -phenol Hydrochloride (Tapentadol HCl): a Novel μ-Opioid Receptor Agonist / Norepinephrine Reuptake Inhibitor with Broad-Spectrum Analgesic Properties. In: Journal of Pharmacology and Experimental Therapeutics . 323 (1), 2007 Oct, pp. 265-276. PMID 17656655 doi: 10.1124 / jpet.107.126052
3. ↑ ^{a b} Pain therapy with opioids. ( Memento from February 22nd, 2014 in the Internet Archive ) In: Der Arzneimittelbrief. No. 45/2011, accessed on February 7, 2014.
4. ↑ ^{a b} Public assessment report Palexia / Yantil film-coated tablets
5. ↑ Active ingredient CURRENT ( Memento from October 19, 2012 in the Internet Archive ) (PDF; 935 kB) information from the KBV in cooperation with the AkdÄ , accessed on February 7, 2014.
6. ↑ B. Lange, B. Kuperwasser, A. Okamoto, A. Steup, T. Haulel, J. Ashworth et al: Efficacy and Safety of Tapentadol Prolonged Release for Chronic Osteoarthritis Pain and Low Back Pain. In: Adv Ther . 27 (6), 2010, pp. 381-399.
7. ↑ OPIOIDANALGETIC TAPENTADOL (PALEXIA RETARD). In: arznei-telegram online. 2010, accessed February 7, 2014.
8. ↑ Specialist information Palexia 20 mg / ml oral solution ( Memento of February 22, 2014 in the Internet Archive ), accessed on February 15, 2014.
9. ↑ Innovation Report 2013 ( Memento from February 22, 2014 in the Internet Archive ) on: tk.de (PDF; 20.6 MB)
10. ↑ Appendix III of the Narcotics Act .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !