Tapentadol

Tapentadol

Clinical data
Trade names	Nucynta, Palexia, Yantil, Tapenta, Tapal, Aspadol, others
Other names	BN-200 CG-5503 R-331333
AHFS/Drugs.com	Monograph
MedlinePlus	a610006
Pregnancy category	AU: C
Dependence liability	Very High[1]
Addiction liability	High[2][3]
Routes of administration	By mouth
Drug class	Opioid
ATC code	N02AX06 (WHO)
Legal status
Legal status	AU: S8 (Controlled drug) BR: Class A1 (Narcotic drugs)[4] CA: Schedule I DE: Anlage III (Special prescription form required) UK: Class A (Schedule 2 CD) US: Schedule II UN: Unscheduled EU: Rx-only[5]
Pharmacokinetic data
Bioavailability	32% (oral)[6]
Protein binding	20%[7]
Metabolism	Hepatic (mostly via glucuronidation but also by CYP2C9, CYP2C19, CYP2D6)[6]
Onset of action	~30 minutes
Elimination half-life	4 hours
Duration of action	4-6 hours[6]
Excretion	Urine and faeces (1%)[6]
Identifiers
IUPAC name 3-[(1R,2R)-3-(Dimethylamino)-1-ethyl-2-methylpropyl]phenol
CAS Number	175591-23-8 Y HCl: 175591-09-0 Y
PubChem CID	9838022
IUPHAR/BPS	7477
DrugBank	DB06204 N
ChemSpider	8013742 Y
UNII	H8A007M585 HCl: 71204KII53 Y
KEGG	D06007 N
ChEMBL	ChEMBL1201776 N
CompTox Dashboard (EPA)	DTXSID30170003
ECHA InfoCard	100.131.247
Chemical and physical data
Formula	C14H23NO
Molar mass	221.344 g·mol−1
3D model (JSmol)	Interactive image
Boiling point	(decomposes)
SMILES Oc1cc(ccc1)[C@@H]([C@@H](C)CN(C)C)CC
InChI 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 Y Key:KWTWDQCKEHXFFR-SMDDNHRTSA-N Y
NY (what is this?)  (verify)

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 an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI).^[6] Tapentadol is used medically for the treatment of moderate to severe pain.^[3] Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.^[8] Tapentadol poses a high risk of abuse, misuse and diversion,^[9] along with a high risk of physical and/or mental dependence.^[3][10][11]

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.^[8] Unlike tramadol, it has only weak effects on the reuptake of serotonin and is a significantly more potent opioid with no known active metabolites.^[8][12]

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.^[13]

The potency of tapentadol is somewhere between that of tramadol and morphine,^[14] with an analgesic efficacy comparable to that of oxycodone despite a lower incidence of side effects.^[6] 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.^[15]

Tapentadol was approved by the US FDA in November 2008,^[16] by the TGA of Australia in December 2010^[17] and by the MHRA of the UK in February 2011.^[18] In India, the Central Drug Standard Control Organisation (CDSCO) approved tapentadol immediate-release (IR) and extended-release (ER) preparations for severe acute pain in April 2011 and December 2013 respectively.^[19]

Tapentadol is a Schedule II controlled substance in the United States,^[20] a Schedule 8 controlled drug in Australia,^[21] and a Class B controlled substance in the United Kingdom.