Wikipedia

Tapentadol

Tapentadol, sold under the brand names Nucynta and Palexia among others, is a synthetic opioid analgesic of the benzenoid class with a dual mode of action as a highly selective full agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI).[7] Tapentadol is used medically for the treatment of moderate to severe pain.[3] It is addictive, a commonly abused drug,[3][9][10] and poses a high risk of physical and/or mental dependence.[11][12]

Tapentadol
Clinical data
Trade namesNucynta, Palexia, Yantil, Tapenta, Tapal, Aspadol, others
Other namesBN-200
CG-5503
R-331333
AHFS/Drugs.comMonograph
MedlinePlusa610006
Pregnancy
category
  • AU: C
Dependence
liability		Very High[1]
Addiction
liability		High[2][3]
Routes of
administration		By mouth
Drug classOpioid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability32% (oral)[7]
Protein binding20%[8]
MetabolismHepatic (mostly via glucuronidation but also by CYP2C9, CYP2C19, CYP2D6)[7]
Onset of action~30 minutes
Elimination half-life4 hours
Duration of action4-6 hours[7]
ExcretionUrine and faeces (1%)[7]
Identifiers
  • 3-[(1R,2R)-3-(Dimethylamino)-1-ethyl-2-methylpropyl]phenol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.131.247 Edit this at Wikidata
Chemical and physical data
FormulaC14H23NO
Molar mass221.344 g·mol−1
3D model (JSmol)
Boiling point(decomposes)
  • Oc1cc(ccc1)[C@@H]([C@@H](C)CN(C)C)CC
  • InChI=1S/C14H23NO/c1-5-14(11(2)10-15(3)4)12-7-6-8-13(16)9-12/h6-9,11,14,16H,5,10H2,1-4H3/t11-,14+/m0/s1 checkY
  • Key:KWTWDQCKEHXFFR-SMDDNHRTSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.[13] It is taken by mouth, and is available in immediate-release and controlled-release formulations.[14] It is similar to tramadol in its dual mechanism of action; namely, its ability to activate the μ-opioid receptor and inhibit the reuptake of norepinephrine.[13] Unlike tramadol, it has only weak effects on the reuptake of serotonin and is a significantly more potent opioid with no known active metabolites.[13][15]

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 CYP3A4 and CYP2D6), as well as providing a more consistent dosage-response range among the patient population.[16]

The potency of tapentadol is somewhere between that of tramadol and morphine,[17] with an analgesic efficacy comparable to that of oxycodone despite a lower incidence of side effects.[7] It is generally regarded as a moderately strong opioid. The CDC Opioid Guidelines Calculator estimates a conversation rate of 50mg of tapentadol equaling 10 mg of oral oxycodone in terms of opioid receptor activation.[18]

Tapentadol was approved by the US Food and Drug Administration in November 2008,[19] by the Therapeutic Goods Administration of Australia in December 2010[20] and by the MHRA of the UK in February 2011.[21] In India, the Central Drug Standard Control Organisation approved tapentadol immediate-release (IR) and extended-release (ER) preparations for severe acute pain in April 2011 and December 2013 respectively.[22]

Tapentadol is a Schedule II controlled substance in the United States,[23] a Schedule 8 controlled drug in Australia,[24] and a Class A controlled substance in the United Kingdom.[25]

Medical use

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Tapentadol is used for the treatment of moderate to severe pain for both acute (following, for example, injury or surgery) and chronic musculoskeletal pain.[26] It is also specifically indicated for controlling the pain of diabetic neuropathy when around-the-clock opioid medication is required.

Extended-release formulations of tapentadol are not indicated for use in the management of acute pain and are instead indicated only for the relief of severe, disabling pain, that is long-term in nature and cannot be controlled by any other pharmacological means.[7][27][28]

Tapentadol is pregnancy category C. There are no adequate and well-controlled studies of tapentadol in pregnant women, and tapentadol is not recommended for use in women during and immediately prior to labor and delivery.[28]

There are no adequate and well-controlled studies of tapentadol in children.[28]

Contraindications

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Tapentadol is contraindicated in people with epilepsy or who are otherwise prone to seizures. It raises intracranial pressure so should not be used in people with head injuries, brain tumors, or other conditions which increase intracranial pressure. It increases the risk of respiratory depression so should not be used in people with asthma.[26]

As with other μ-opioid agonists, tapentadol may cause spasms of the sphincter of Oddi, and is therefore discouraged for use in patients with biliary tract disease such as both acute and chronic pancreatitis. People who are rapid or ultra rapid metabolizers for the CYP2C9, CYP2C19, and CYP2D6 enzymes may not respond adequately to tapentadol therapy. Due to reduced clearance, tapentadol should be administered with caution to people with moderate liver disease and not at all in people with severe liver disease.[28]

Adverse effects

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The most commonly reported side effects of tapentadol therapy in clinical trials were nausea, vomiting, dizziness, sleepiness, itchiness, dry mouth, headache, and fatigue.[7][29] However, several studies have found that tapentadol causes less constipation and nausea compared with oxycodone.[30] It has been noted that due to this, treatment adherence may be improved, with fewer people discontinuing tapentadol (when compared with oxycodone).[30]

The World Health Organization determined that there was little evidence to judge the abuse potential of tapentadol when it was introduced.[31] Although early pre-clinical animal trials suggested that tapentadol had a reduced abuse liability compared to other opioid analgesics,[7] the US Drug Enforcement Agency placed tapentadol into Schedule II,[32] the same category as stronger opioids more commonly used recreationally, such as morphine, oxycodone, and fentanyl.[28][33] Since these initial trials, however, evidence has shown that tapentadol is commonly abused, misused and diverted,[11] that it is addictive, and that it poses a high risk of physical and/or mental dependence.[3][9][10]

Given that tapentadol is a highly selective full agonist of the μ-opioid receptor, and given that is not a pro-drug, with a relatively high ceiling effect, studies have found that it is significantly more abusable than tramadol,[34] and similar to hydrocodone and other full agonists of the μ-opioid receptor (such as oxycodone and hydromorphone) in terms of addiction and dependence liability.[35][36] There have been reports of users crushing, chewing, inhaling or injecting immediate-release tapentadol tablets, which can lead to respiratory depression, coma and death.[37][38]

Tapentadol has been demonstrated to reduce the seizure threshold in patients. Tapentadol should be used cautiously in patients with a history of seizures, and in patients who are also taking one or more other drugs which have also been demonstrated to reduce the seizure threshold. Patients at high risk include those using other serotogenic and adrenergic medications, as well as patients with head trauma, metabolic disorders, and those in alcohol and/or drug withdrawals.[39]

Tapentadol has been demonstrated to potentially produce hypotension (low blood pressure), and should be used with caution in patients with low blood pressure, and patients who are taking one or more other medications which are also known to reduce blood pressure.[39]

Interactions

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Combination with selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, serotonin releasing agents, and serotonin receptor agonists may lead to potentially lethal serotonin syndrome.[40] Combination with MAOIs may also result in an adrenergic storm. Use of tapentadol with alcohol or other central nervous system depressants such as benzodiazepines, barbiturates, nonbenzodiazepines, phenothiazines, gabapentinoids and other opiates may result in increased impairment, sedation, respiratory depression, and death.[7][41]

Tapentadol is partially metabolized by the hepatic enzymes CYP2C9, CYP2C19, and CYP2D6 so it innately has interactions with drugs that enhance or repress the activity/expression of one or more of these enzymes, as well as with substrates of these enzymes (due to competition for the enzyme); some enzyme mediators/substrates require dosing adjustments to one or both medications.[42][7]

The combination of tapentadol and alcohol may result in increased plasma concentrations of tapentadol and produce respiratory depression to a degree greater than the sum of the two drugs when administered separately; patients should be cautioned against alcohol consumption when taking tapentadol as the combination may be fatal.[39]

Tapentadol should be used with caution in patients who are taking one or more anticholinergic drugs, as this combination may result in urine retention (which can result in serious renal damage and is considered a medical emergency).[39]

Pharmacology

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Tapentadol is a high affinity agonist of the μ-opioid receptor and a norepinephrine reuptake inhibitor (NRI). Drugs that bind to the μ-opioid receptor (MOR) with high affinity have similar abuse potential to drugs such as morphine, oxycodone and hydromorphone. Receptor binding studies show that tapentadol has a higher affinity for MOR than for kappa and delta opioid receptors.

In receptor binding studies on cloned human MOR labeled with titrated naloxone, tapentadol showed affinity with a Ki of 60 nM. It showed strong agonist activity comparable to morphine in stimulating MOR opioid receptor mediated G-protein activation using agonist stimulated [35S]GTPyS binding in cells expressing the cloned human MOR.[43] In addition to its opioid activity, tapentadol inhibits the reuptake of norepinephrine with Ki of 480 nM and was demonstrated to have a weak inhibitory activity on the serotonin reuptake of rat’s brain synaptosomes.[43][7]

Analgesia occurs within 32 minutes after oral administration, and lasts for 4–6 hours.[13] It is 18 times less potent than morphine in terms of binding to human μ-opioid receptors in in vitro research on human tissue.[44] In vivo, only 32% of an oral dose of tapentadol will survive first pass metabolism and proceed to the bloodstream to produce its effects on the central and peripheral nervous systems of the patient.[7]

It is similar to tramadol in its dual mechanism of action but unlike tramadol, it has much weaker effects on the reuptake of serotonin and is a significantly more potent opioid (around 2-3 times stronger) with no known active metabolites.[13][15][45]

Commercial preparations contain only the (R,R) stereoisomer, which is the weakest isomer in terms of opioid activity.[31] The free base conversion ratio for salts includes 0.86 for the hydrochloride.[46]

The peak plasma concentration (Cmax; amount of active drug in the bloodstream) when taken after food is increased by 8% and 18% for tapentadol IR and ER preparations, respectively. This difference is not clinically significant;[47] tapentadol may therefore be administered orally with or without food as circumstances allow, and the patient will generally not notice any change in the efficacy and/or duration of analgesic effects if the drug is not consistently administered in fasting or fed states.[48][49]

The plasma concentration of tapentadol differs to a relevant degree based on the administered dose, with the highest tested dose (250mg) resulting in a higher Cmax than would be expected via the dose-proportionate plasma concentration expectations.[39] Increased doses of tapentadol should be anticipated to be slightly stronger than predicted by linear functions of the previous dose-response relation.

History

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75 mg Nucynta (tapentadol) tablets

Tapentadol was invented at the German pharmaceutical company Grünenthal in the late 1980s led by Helmut Buschmann;[50] the team started by analyzing the chemistry and activity of tramadol, which had been invented at the same company in 1962.[51]

Tramadol has several enantiomers, and each forms metabolites after processing in the liver. These tramadol variants have varying activities at the μ-opioid receptor, the norepinephrine transporter, and the serotonin transporter, and differing half-lives, with the metabolites having the best activity. Using tramadol as a starting point, the team aimed to discover a single molecule that minimized the serotonin activity, had strong μ-opioid receptor agonism and strong norepinephrine reuptake inhibition, and would not require metabolism to be active; the result was tapentadol.[51]: 301–302 

In 2003 Grünenthal partnered with two Johnson & Johnson subsidiaries, Johnson & Johnson Pharmaceutical Research and Development and Ortho-McNeil Pharmaceutical to develop and market tapentadol; Johnson & Johnson had exclusive rights to sell the drug in the US, Canada, and Japan while Grünenthal retained rights elsewhere.[52] In 2008 tapentadol received approval by the US Food and Drug Administration; in 2009 it was classified by US Drug Enforcement Agency as a Schedule II drug, and entered the US market.[52] Tapentadol was reported to be the "first new molecular entity of oral centrally acting analgesics" class approved in the United States in more than 25 years.[53]

In 2010 Grünenthal granted Johnson & Johnson the right to market tapentadol in about 80 additional countries.[54] Later that year, tapentadol was approved in Europe.[55] In 2011, Nucynta ER, an extended release formulation of tapentadol, was released in the United States for management of moderate to severe chronic pain and received Food and Drug Administration approval the following year for the treatment of neuropathic pain associated with diabetic peripheral neuropathy.[56][57]

After annual sales of $166 million, in January 2015, Johnson & Johnson sold its rights to market tapentadol in the US to Depomed for $1 billion.[58] The drug was manufactured at a plant located on the island of Puerto Rico that was hit by Hurricane Maria in 2017 causing a major shortage in the drug's availability.[59] In January 2018 Depomed sold off the manufacturing of the drug and licensed it to Collegium Pharmaceutical for $10 million up front with an annual royalty payment of a minimum $135 million for the next 4 years.[60] This combination of events has caused additional short supply of the drug leaving patients who depend on it to seek alternative treatments.

Abuse and controls

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Palexia IR 50mg with Australian "controlled drug" warning

There have been calls for Tapentadol to be only marketed in countries where appropriate controls exist,[61] but after performing a critical review, the United Nations Expert Committee on Drug Dependence in 2014 advised that tapentadol not be placed under international control but remain under surveillance.[62]

CSS recognizes that tapentadol is available as an IR formula, and that in the past there was no requirement of a medication guide for immediate-release opioids. However, tapentadol exhibits several distinctive properties that makes it highly abusable. According to them:[43]

  1. Tapentadol is a novel opioid that displays high affinity and selectivity for the μ-opioid receptor;
  2. In a human liability pharmacology study conducted by the sponsor, it was found that tapentadol displays a high abuse potential similar to hydromorphone, a controlled substance with a similar risk of abuse, misuse and diversion; and
  3. Based on a human abuse liability study, 50 mg of tapentadol produces comparable opioid effects to that of 4 mg of hydromorphone.

Since 2009 the drug has been categorized in the US as a Schedule II Controlled Substance with ACSCN 9780; in 2014 it was allocated a 17,500 kg aggregate manufacturing quota.

In 2010, Australia made tapentadol a S8 controlled drug.[63] The following year, tapentadol was classified as a Class A controlled drug in the United Kingdom, and was also placed under national control in Cyprus, Estonia, Finland, Greece, Latvia and Spain.[64][65]

More recently, Canada made the opioid a Schedule I controlled drug, putting it in the same class as other prescription opioids such as morphine, fentanyl, tramadol, and heroin.[66]

In India (except the state of Punjab), multiple brands of Tapentadol remain available over the counter. Recent reports have suggested increasing Tapentadol abuse and dependence in India, where users have improvised injections with 50 and 100 mg tablets.[22] Furthermore, a large number of listings for Tapentadol sourced from India can be found internationally on illicit marketplaces on the dark web. There have been several reports of Tapentadol from Indian pharmacies being smuggled to the US, the EU, and Bangladesh, where they are distributed via the black market.[67]

References

edit
  1. ^ "Tapentadol (Monograph)". American Society of Health-System Pharmacists (AHFS) – via Drugs.com.
  2. ^ Basu D, Mahintamini T, Ghosh A, Roub F, Subodh BN, Mattoo SK, et al. (2020). "Tapentadol, the new kid on the block in India: Is it time to worry?". Indian Journal of Psychiatry. 62 (6): 697–702. doi:10.4103/psychiatry.IndianJPsychiatry_332_20. PMC 8052882. PMID 33896976.
  3. ^ a b c d "Tapentadol Consumer Medicine Information". NPS MedicineWise. September 2020 – via nps.org.au.
  4. ^ "Tapentadol". MedLine Plus. 2024-03-15. Retrieved 2024-11-25.
  5. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  6. ^ "Active substance(s): tapentadol" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 21 July 2022. Archived (PDF) from the original on 2022-09-06. Retrieved 2022-09-06.
  7. ^ a b c d e f g h i j k l m Smit JW, Oh C, Rengelshausen J, Terlinden R, Ravenstijn PG, Wang SS, et al. (January 2010). "Effects of acetaminophen, naproxen, and acetylsalicylic acid on tapentadol pharmacokinetics: results of two randomized, open-label, crossover, drug-drug interaction studies". Pharmacotherapy. 30 (1): 25–34. doi:10.1592/phco.30.1.25. PMC 2888545. PMID 20030470.
  8. ^ Brayfield A, ed. (14 November 2011). "Tapentadol". Martindale: The Complete Drug Reference. Pharmaceutical Press. Archived from the original on 29 August 2021. Retrieved 2 April 2014.
  9. ^ a b "Tapentadol". Health Direct. 23 October 2024 – via healthdirect.gov.au.
  10. ^ a b Khaja M, Lominadze G, Millerman K (July 2017). "Cardiac Arrest Following Drug Abuse with Intravenous Tapentadol: Case Report and Literature Review". The American Journal of Case Reports. 18: 817–821. doi:10.12659/AJCR.904695. PMC 5536129. PMID 28729524.
  11. ^ a b Kathiresan P, Pakhre A, Kattula D, Sarkar S (October 2019). "Tapentadol Dependence: A Case Series". The Primary Care Companion for CNS Disorders. 21 (5): 23400. doi:10.4088/PCC.19l02444. PMID 31682335.
  12. ^ Drug Enforcement Agency (US) (2019-09-18). "Label: Nucynta - Tapentadol hydrochloride tablet, film coated". DailyMed. Retrieved 2024-11-24.
  13. ^ a b c d e Singh DR, Nag K, Shetti AN, Krishnaveni N (July 2013). "Tapentadol hydrochloride: A novel analgesic". Saudi Journal of Anaesthesia. 7 (3): 322–326. doi:10.4103/1658-354X.115319. PMC 3757808. PMID 24015138.
  14. ^ Etropolski MS, Okamoto A, Shapiro DY, Rauschkolb C (2010). "Dose conversion between tapentadol immediate and extended release for low back pain". Pain Physician. 13 (1): 61–70. doi:10.36076/ppj.2010/13/61. PMID 20119464.
  15. ^ a b Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, et al. (July 2012). "Mechanistic and functional differentiation of tapentadol and tramadol". Expert Opinion on Pharmacotherapy. 13 (10): 1437–1449. doi:10.1517/14656566.2012.696097. PMID 22698264. S2CID 24226747.
  16. ^ Chang EJ, Choi EJ, Kim KH (July 2016). "Tapentadol: Can It Kill Two Birds with One Stone without Breaking Windows?". The Korean Journal of Pain. 29 (3): 153–157. doi:10.3344/kjp.2016.29.3.153. PMC 4942642. PMID 27413479.
  17. ^ Tschentke TM, De Vry J, Terlinden R, Hennies HH, Lange C, Strassburger W, et al. (2006). "Tapentadol Hydrochloride". Drugs of the Future. 31 (12): 1053. doi:10.1358/dof.2006.031.12.1047744.
  18. ^ "CDC Opioid Calculator". 13 October 2022.
  19. ^ "Nucynta History". drugs.com. Archived from the original on April 12, 2015. Retrieved April 5, 2015.
  20. ^ "Palexia SR Product Information" (PDF). TGA eBusiness Services. CSL Limited. 26 June 2013. Archived from the original on 6 April 2017. Retrieved 2 April 2014.
  21. ^ "Palexia film coated tablets". electronic Medicines Compendium. Grunenthal Ltd. 13 November 2013. Archived from the original on 7 April 2014. Retrieved 2 April 2014.
  22. ^ a b Mukherjee D, Shukla L, Saha P, Mahadevan J, Kandasamy A, Chand P, et al. (March 2020). "Tapentadol abuse and dependence in India". Asian Journal of Psychiatry. 49: 101978. doi:10.1016/j.ajp.2020.101978. PMID 32120298. S2CID 211834859. Archived from the original on 2021-12-20. Retrieved 2021-10-10.
  23. ^ "Schedules of Controlled Substances: Placement of Tapentadol Into Schedule II". Federal Register • U.S. FDA. 2009. Retrieved 21 November 2024.
  24. ^ "Schedule 8 Medicines". Health NSW. 2024. Retrieved 21 November 2024.
  25. ^ "List of most commonly encountered drugs currently controlled under the misuse of drugs legislation". gov.uk. Retrieved 2024-11-23.
  26. ^ a b Polati E, Canonico PL, Schweiger V, Collino M (2019-05-16). "Tapentadol: an overview of the safety profile". Journal of Pain Research. 12: 1569–1576. doi:10.2147/JPR.S190154. PMC 6529613. PMID 31190968.
  27. ^ "Medscape-Nucynta". Archived from the original on 2017-12-22. Retrieved 2012-12-09.
  28. ^ a b c d e "Nucynta Label" (PDF). Archived from the original (PDF) on 2021-03-30.
  29. ^ Roulet L, Rollason V, Desmeules J, Piguet V (2021-07-01). "Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients". Drugs. 81 (11): 1257–1272. doi:10.1007/s40265-021-01515-z. ISSN 0012-6667. PMC 8318929. PMID 34196947.
  30. ^ a b Oliveira M, Moisés MC, Dias EC, dos Santos MV, Schmidt AP (2024-12-01). "Treatment-emergent adverse events of tapentadol or oxycodone in pain management after orthopedic surgeries: A systematic review and meta-analysis of randomized clinical trials". JCA Advances. 1 (3): 100024. doi:10.1016/j.jcadva.2024.100024. ISSN 2950-5534.
  31. ^ a b 35th Expert Committee on Drug Dependence, Hammamet, Tunisia (June 2012). "Tapentadol: Expert peer review on pre-review report" (PDF). World Health Organization. Archived (PDF) from the original on 16 March 2014. Retrieved 16 March 2014.
  32. ^ Leonhart MM, Deputy Administrator, Drug Enforcement Administration (May 2009). "Schedules of Controlled Substances: Placement of Tapentadol Into Schedule II". Federal Register. 74 (97): 23790–93.
  33. ^ "DEA Diversion Control – Controlled Substances Schedules". US Federal Government. Archived from the original on 2021-04-25. Retrieved 2012-05-16.
  34. ^ Roulet L, Rollason V, Desmeules J, Piguet V (July 2021). "Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients". Drugs. 81 (11): 1257–1272. doi:10.1007/s40265-021-01515-z. PMC 8318929. PMID 34196947.
  35. ^ Roulet L, Rollason V, Desmeules J, Piguet V (July 2021). "Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients". Drugs. 81 (11): 1257–1272. doi:10.1007/s40265-021-01515-z. PMC 8318929. PMID 34196947.
  36. ^ Vosburg SK, Severtson SG, Dart RC, Cicero TJ, Kurtz SP, Parrino MW, et al. (April 2018). "Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion and Addiction-Related Surveillance System". The Journal of Pain. 19 (4): 439–453. doi:10.1016/j.jpain.2017.11.007. PMID 29224919.
  37. ^ Khaja M, Lominadze G, Millerman K (July 2017). "Cardiac Arrest Following Drug Abuse with Intravenous Tapentadol: Case Report and Literature Review". The American Journal of Case Reports. 18: 817–821. doi:10.12659/AJCR.904695. PMC 5536129. PMID 28729524.
  38. ^ Dart RC, Bartelson BB, Adams EH (August 2014). "Nonmedical use of tapentadol immediate release by college students". The Clinical Journal of Pain. 30 (8): 685–692. doi:10.1097/AJP.0000000000000001. PMID 24042351.
  39. ^ a b c d e "Nucynta CR" (PDF). Janssen Inc. Archived (PDF) from the original on 2016-08-15. Retrieved 2016-06-21.
  40. ^ Nossaman VE, Ramadhyani U, Kadowitz PJ, Nossaman BD (December 2010). "Advances in perioperative pain management: use of medications with dual analgesic mechanisms, tramadol & tapentadol". Anesthesiology Clinics. 28 (4): 647–666. doi:10.1016/j.anclin.2010.08.009. PMID 21074743.
  41. ^ Alshehri FS (2023-03-21). "Tapentadol: A Review of Experimental Pharmacology Studies, Clinical Trials, and Recent Findings". Drug Design, Development and Therapy. 17: 851–861. doi:10.2147/DDDT.S402362. PMC 10039632. PMID 36974332.
  42. ^ Ramaswamy S, Chang S, Mehta V (2015-05-01). "Tapentadol - the evidence so far". Anaesthesia. 70 (5): 518–522. doi:10.1111/anae.13080. ISSN 0003-2409. PMID 25866038.
  43. ^ a b c "Tapentadol Post Marketing Requirement" (PDF). Center for Drug Evaluation and Research (CDER). FDA. 4 November 2008.
  44. ^ "Tapentadol". PubChem. U.S. National Library of Medicine. Archived from the original on August 9, 2016. Retrieved June 14, 2016.  This article incorporates text from this source, which is in the public domain.
  45. ^ Roulet L, Rollason V, Desmeules J, Piguet V (July 2021). "Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients". Drugs. 81 (11): 1257–1272. doi:10.1007/s40265-021-01515-z. PMC 8318929. PMID 34196947.
  46. ^ "2014 - Final Adjusted Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2014". Deadiversion.usdoj.gov. Archived from the original on 2016-03-04. Retrieved 2018-09-22.
  47. ^ Peter N Zannikos P, Johan W Smit P, Hans-Jürgen Stahlberg MD, Birger Wenge P, Vera M Hillewaert M, Mila S Etropolski MD (2013-07-01). "Pharmacokinetic evaluation of tapentadol extended-release tablets in healthy subjects". Journal of Opioid Management. 9 (4): 291–300. doi:10.5055/jom.2013.0171. ISSN 1551-7489. PMID 24353023.
  48. ^ Singh DR, Nag K, Shetti AN, Krishnaveni N (2013-07-01). "Tapentadol hydrochloride: A novel analgesic". Saudi Journal of Anaesthesia. 7 (3): 322–326. doi:10.4103/1658-354X.115319. PMC 3757808. PMID 24015138.
  49. ^ "Tapentadol (oral route)". Mayo Clinic. Retrieved 2024-11-27.
  50. ^ US 6248737, "1-phenyl-3-dimethylaminopropane compounds with a pharmacological effects" 
  51. ^ a b Helmut Buschmann. Tapentadol – From Morphine and Tramadol to the Discovery of Tapentadol. Chapter 12 in Analogue-based Drug Discovery III, First Edition. Edited by Janos Fischer, C. Robin Ganellin, and David P. Rotella. Wiley-VCH Verlag GmbH & Co. KGaA. 2013. ISBN 9783527651108
  52. ^ a b Dan Froicu and Raymond S Sinatra. Tapentadol. Chapter 31 in The Essence of Analgesia and Analgesics, Eds. Raymond S. Sinatra, Jonathan S. Jahr, J. Michael Watkins-Pitchford. Cambridge University Press, 2010. ISBN 9781139491983
  53. ^ "Grünenthal GmbH Presents Tapentadol, a Novel Centrally Acting Analgesic, at the 25th Annual Scientific Meeting of The American Pain Society". PR Newswire. 6 June 2006. Archived from the original on 2012-02-07. Retrieved 2007-09-20.
  54. ^ "Janssen Pharmaceutica N.V. Announces Expansion of Licensing Agreement for Tapentadol". J&J Press Release. 7 June 2010. Archived from the original on 2018-09-23.
  55. ^ Dutton G (1 June 2012). "Pain Management Market Ripe with Immediate Opportunities". Genetic Engineering & Biotechnology News. Archived from the original on 2018-09-23.
  56. ^ "Nucynta (tapentadol) FDA Approval History – Drugs.com". www.drugs.com. Archived from the original on 2015-04-12. Retrieved 2016-03-09.
  57. ^ "FDA Approves Nucynta ER (tapentadol) Extended-Release Oral Tablets for the Management of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy". Archived from the original on 2021-03-05. Retrieved 2018-01-23.
  58. ^ Staff (16 January 2015). "Depomed pays over $1 billion for US rights to Janssen's Nucynta franchise". The Pharma Letter. Archived from the original on 2016-03-08.
  59. ^ Byrne M, Pallaria F. "Dealing with Prescription Drug Shortages". www.iwpharmacy.com. Archived from the original on 2019-10-15. Retrieved 2019-10-15.
  60. ^ "Troubled Depomed sells off Nucynta, axes 40% of workforce to pare down costs". FiercePharma. 5 December 2017. Archived from the original on 2019-10-15. Retrieved 2019-10-15.
  61. ^ "Supplemental data for World Health Organization (Expert Committee on Drug Dependence) Critical Review on drug dependence of tapentadol" (PDF). World Health Organization. 23 May 2014. p. 18. Archived (PDF) from the original on 29 August 2021. Retrieved 12 March 2014.
  62. ^ "World Health Organization: Reports of advisory bodies" (PDF). World Health Organization. 22 January 2015. pp. 2, 4. Archived (PDF) from the original on 8 September 2015. Retrieved 12 March 2016.
  63. ^ "Australian Public Assessment Report for Tapentadol" (PDF). Therapeutic Goods Administration. February 2011. Archived from the original on 23 September 2018. Retrieved 12 March 2016.
  64. ^ "The Misuse of Drugs Act 1971 (Amendment) Order 2011". www.legislation.gov.uk. Archived from the original on 2021-05-03. Retrieved 2011-03-26.
  65. ^ "International Narcotics Control Board Report 2012" (PDF). International Narcotics Control Board. 5 March 2013. p. 99. Archived (PDF) from the original on 18 August 2016. Retrieved 12 March 2016.
  66. ^ "Canada Gazette – Regulations Amending the Narcotic Control Regulations (Tapentadol) – (Archived)". Canada Gazette. Government of Canada, Public Works and Government Services Canada, Public Services and Procurement Canada, Integrated Services Branch, Canada. 29 July 2015. Archived from the original on 2016-03-13. Retrieved 2016-03-12.
  67. ^ "71 arrested in DMP's anti-narcotics drive". BanglaNews24.com (in Bengali). 2021-12-14. Archived from the original on 2021-12-30. Retrieved 2021-12-30.
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