U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula 2C14H23NO.2C4H4O4.H2O
Molecular Weight 692.8366
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of TAPENTADOL MALEATE HEMIHYDRATE

SMILES

O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.CC[C@H]([C@@H](C)CN(C)C)C1=CC=CC(O)=C1.CC[C@H]([C@@H](C)CN(C)C)C2=CC=CC(O)=C2

InChI

InChIKey=ZDYFCLLYJFXWDY-ALHIZKRASA-N
InChI=1S/2C14H23NO.2C4H4O4.H2O/c2*1-5-14(11(2)10-15(3)4)12-7-6-8-13(16)9-12;2*5-3(6)1-2-4(7)8;/h2*6-9,11,14,16H,5,10H2,1-4H3;2*1-2H,(H,5,6)(H,7,8);1H2/b;;2*2-1-;/t2*11-,14+;;;/m00.../s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C14H23NO
Molecular Weight 221.3385
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21476608 | https://www.nucynta.com/hcp/er/mechanism-of-action#isi-0

Tapentadol is the first US FDA-approved centrally acting analgesic having both μ-opioid receptor agonist and noradrenaline (norepinephrine) reuptake inhibition activity with minimal serotonin reuptake inhibition. Tapentadol is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate, neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.16 µM [Ki]
8.8 µM [Ki]
5.28 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NUCYNTA

Approved Use

NUCYNTA ER (tapentadol) is indicated for the management of: pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Launch Date

1.22713919E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
221.34 ng/mL
86 mg single, oral
dose: 86 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAPENTADOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
221.34 ng × h/mL
86 mg single, oral
dose: 86 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAPENTADOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.16 h
86 mg single, oral
dose: 86 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAPENTADOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAPENTADOL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
80%
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TAPENTADOL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Disc. AE: Nausea, Constipation...
AEs leading to
discontinuation/dose reduction:
Nausea (3.4%)
Constipation (1.6%)
Dizziness (3%)
Vomiting (2.6%)
Fatigue (1.8%)
Somnolence (3.4%)
Pruritus (0.6%)
Sources: Page: p.424
100 mg 6 times / day multiple, oral
Recommended
Dose: 100 mg, 6 times / day
Route: oral
Route: multiple
Dose: 100 mg, 6 times / day
Sources: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.7
Disc. AE: Dizziness, Nausea...
AEs leading to
discontinuation/dose reduction:
Dizziness
Nausea
Vomiting
Somnolence
Headache
Sources: Page: p.7
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Disc. AE: Respiratory depression, CNS disorder (NOS)...
AEs leading to
discontinuation/dose reduction:
Respiratory depression
CNS disorder (NOS)
Intracranial pressure increased
Abuse NOS
Mental function decreased
Physical impairment
Seizures
Serotonin syndrome (grade 4)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Pruritus 0.6%
Disc. AE
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Constipation 1.6%
Disc. AE
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Fatigue 1.8%
Disc. AE
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Vomiting 2.6%
Disc. AE
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Dizziness 3%
Disc. AE
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Nausea 3.4%
Disc. AE
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Somnolence 3.4%
Disc. AE
250 mg 2 times / day multiple, oral (max)
Recommended
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.424
unhealthy, 56.8
n = 894
Health Status: unhealthy
Condition: Chronic low back pain|Osteoarthritis pain
Age Group: 56.8
Sex: M+F
Population Size: 894
Sources: Page: p.424
Dizziness Disc. AE
100 mg 6 times / day multiple, oral
Recommended
Dose: 100 mg, 6 times / day
Route: oral
Route: multiple
Dose: 100 mg, 6 times / day
Sources: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.7
Headache Disc. AE
100 mg 6 times / day multiple, oral
Recommended
Dose: 100 mg, 6 times / day
Route: oral
Route: multiple
Dose: 100 mg, 6 times / day
Sources: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.7
Nausea Disc. AE
100 mg 6 times / day multiple, oral
Recommended
Dose: 100 mg, 6 times / day
Route: oral
Route: multiple
Dose: 100 mg, 6 times / day
Sources: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.7
Somnolence Disc. AE
100 mg 6 times / day multiple, oral
Recommended
Dose: 100 mg, 6 times / day
Route: oral
Route: multiple
Dose: 100 mg, 6 times / day
Sources: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.7
Vomiting Disc. AE
100 mg 6 times / day multiple, oral
Recommended
Dose: 100 mg, 6 times / day
Route: oral
Route: multiple
Dose: 100 mg, 6 times / day
Sources: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.7
Abuse NOS Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
CNS disorder (NOS) Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Intracranial pressure increased Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Mental function decreased Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Physical impairment Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Respiratory depression Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Seizures Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Serotonin syndrome grade 4
Disc. AE
700 mg 6 times / day multiple, oral (total)
Recommended
Dose: 700 mg, 6 times / day
Route: oral
Route: multiple
Dose: 700 mg, 6 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute pain
Sources: Page: p.1
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Single dose analgesic efficacy of tapentadol in postsurgical dental pain: the results of a randomized, double-blind, placebo-controlled study.
2008 Dec
Investigations into the drug-drug interaction potential of tapentadol in human liver microsomes and fresh human hepatocytes.
2008 Jan
Tapentadol a 'realistic alternative' to strong opioids for severe pain.
2008 Sep
Tapentadol approved as pain reliever.
2009 Jan 1
Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study.
2009 May
Schedules of controlled substances: placement of tapentadol into schedule II. Final rule.
2009 May 21
Efficacy and safety of Tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study.
2010
[Tapentadol. Opioid analgesic and norepinephrine reuptake inhibitors].
2010 Dec
Tapentadol immediate-release for acute pain.
2010 Jun
Determination of tapentadol (Nucynta®) and N-desmethyltapentadol in authentic urine specimens by ultra-performance liquid chromatography-tandem mass spectrometry.
2010 Oct
Tapentadol and its two mechanisms of action: is there a new pharmacological class of centrally-acting analgesics on the horizon?
2010 Sep
Long-term safety and tolerability of tapentadol extended release for the management of chronic low back pain or osteoarthritis pain.
2010 Sep-Oct
Comparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations.
2013 Apr
Tapentadol hydrochloride: A novel analgesic.
2013 Jul
Patents

Sample Use Guides

As with many centrally-acting analgesic medications, the dosing regimen of NUCYNTA® should be individualized according to the severity of pain being treated, the previous experience with similar drugs and the ability to monitor the patient. Initiate NUCYNTA® with or without food at a dose of 50 mg, 75 mg, or 100 mg every 4 to 6 hours depending upon pain intensity. 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.
Route of Administration: Oral
Upon exposure to tramadol and tapentadol concentrations up to 600μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling. Tapentadol was observed to trigger much more prominent toxic effects than tramadol, ultimately leading to energy deficit and cell death.
Substance Class Chemical
Created
by admin
on Sat Dec 16 19:10:55 UTC 2023
Edited
by admin
on Sat Dec 16 19:10:55 UTC 2023
Record UNII
KX7V4GP9RS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TAPENTADOL MALEATE HEMIHYDRATE
Common Name English
3-((2R,3R)-1-(DIMETHYLAMINO)-2-METHYLPENTAN-3-YL) PHENOL MALEATE HEMIHYDRATE
Systematic Name English
3-((1R,2R)-3-(DIMETHYLAMINO)-1-ETHYL-2-METHYLPROPYL) PHENOL MALEATE HEMIHYDRATE
Systematic Name English
Code System Code Type Description
PUBCHEM
76903475
Created by admin on Sat Dec 16 19:10:55 UTC 2023 , Edited by admin on Sat Dec 16 19:10:55 UTC 2023
PRIMARY
SMS_ID
300000016880
Created by admin on Sat Dec 16 19:10:55 UTC 2023 , Edited by admin on Sat Dec 16 19:10:55 UTC 2023
PRIMARY
FDA UNII
KX7V4GP9RS
Created by admin on Sat Dec 16 19:10:55 UTC 2023 , Edited by admin on Sat Dec 16 19:10:55 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE
Related Record Type Details
ACTIVE MOIETY