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

Details

Stereochemistry ABSOLUTE
Molecular Formula C76H52O46.C18H21NO3
Molecular Weight 2000.5627
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HYDROCODONE TANNATE

SMILES

[H][C@@]12OC3=C(OC)C=CC4=C3[C@@]15CCN(C)[C@H](C4)[C@]5([H])CCC2=O.OC6=CC(=CC(O)=C6O)C(=O)OC7=CC(=CC(O)=C7O)C(=O)OC[C@H]8O[C@@H](OC(=O)C9=CC(O)=C(O)C(OC(=O)C%10=CC(O)=C(O)C(O)=C%10)=C9)[C@H](OC(=O)C%11=CC(O)=C(O)C(OC(=O)C%12=CC(O)=C(O)C(O)=C%12)=C%11)[C@@H](OC(=O)C%13=CC(O)=C(O)C(OC(=O)C%14=CC(O)=C(O)C(O)=C%14)=C%13)[C@@H]8OC(=O)C%15=CC(O)=C(O)C(OC(=O)C%16=CC(O)=C(O)C(O)=C%16)=C%15

InChI

InChIKey=MGLIXEAMASGXSI-KBXDZNRUSA-N
InChI=1S/C76H52O46.C18H21NO3/c77-32-1-22(2-33(78)53(32)92)67(103)113-47-16-27(11-42(87)58(47)97)66(102)112-21-52-63(119-72(108)28-12-43(88)59(98)48(17-28)114-68(104)23-3-34(79)54(93)35(80)4-23)64(120-73(109)29-13-44(89)60(99)49(18-29)115-69(105)24-5-36(81)55(94)37(82)6-24)65(121-74(110)30-14-45(90)61(100)50(19-30)116-70(106)25-7-38(83)56(95)39(84)8-25)76(118-52)122-75(111)31-15-46(91)62(101)51(20-31)117-71(107)26-9-40(85)57(96)41(86)10-26;1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h1-20,52,63-65,76-101H,21H2;3,6,11-12,17H,4-5,7-9H2,1-2H3/t52-,63-,64+,65-,76+;11-,12+,17-,18-/m10/s1

HIDE SMILES / InChI
Molecular Formula C18H21NO3
Molecular Weight 299.3642
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula C76H52O46
Molecular Weight 1701.1985
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 3
Optical Activity UNSPECIFIED

Description

Benzhydrocodone is a prodrug of hydrocodone. Benzhydrocodone is formed by covalently bonding hydrocodone to benzoic acid. Benzhydrocodone itself is not pharmacologically active, but must be metabolized to hydrocodone by enzymes in the intestinal tract to optimally deliver its pharmacologic effects. Hydrocodone is a full agonist of the opioid receptors with a higher affinity for the mu-opioid receptor. Upon binding, hydrocodone produces an analgesic effect with no ceiling. APADAZ a combination of benzhydrocodone and acetaminophen is FDA approved and indicated for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. APADAZ, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death.

CNS Activity

Approval Year

1943
64
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
ZOHYDRO ER

Approved Use

ZOHYDRO ER is an opioid agonist 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.

Launch Date

2013
Primary
Approved
8429
APADAZ

Approved Use

APADAZ is a combination of benzhydrocodone, a prodrug of the opioid agonist hydrocodone, and acetaminophen, and is indicated for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Launch Date

2019
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.1 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27138027/
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROCODONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
23.6 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/005213s039lbl.pdf
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROCODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
155 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27138027/
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROCODONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.2 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27138027/
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROCODONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/005213s039lbl.pdf
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROCODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
55%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/005213s039lbl.pdf
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROCODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
30 mg multiple, oral (total)
Overdose
Dose: 30 mg
Route: oral
Route: multiple
Dose: 30 mg
Co-administed with::
clarithromycin
valproic acid(250 mg, 2 times per day)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20837591
unhealthy, 5 years
n = 1
Health Status: unhealthy
Condition: cold
Age Group: 5 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/20837591
Other AEs: Adverse event...
Other AEs:
Adverse event (grade 5)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20837591
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Other AEs: Electrocardiogram QTc interval prolonged...
Other AEs:
Electrocardiogram QTc interval prolonged
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
Other AEs: Withdrawal syndrome neonatal...
Other AEs:
Withdrawal syndrome neonatal
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
Other AEs: Respiratory depression, Addiction...
Other AEs:
Respiratory depression (grade 5)
Addiction
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
20 mg 1 times / day multiple, oral
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
Disc. AE: Vomiting, Nausea...
AEs leading to
discontinuation/dose reduction:
Vomiting (1%)
Nausea (1%)
Headache (1%)
Dizziness (1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
AEs

AEs

AESignificanceDosePopulation
Adverse event grade 5
30 mg multiple, oral (total)
Overdose
Dose: 30 mg
Route: oral
Route: multiple
Dose: 30 mg
Co-administed with::
clarithromycin
valproic acid(250 mg, 2 times per day)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20837591
unhealthy, 5 years
n = 1
Health Status: unhealthy
Condition: cold
Age Group: 5 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/20837591
Electrocardiogram QTc interval prolonged
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Withdrawal syndrome neonatal
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
Addiction
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
Respiratory depression grade 5
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.pdf
Dizziness 1%
Disc. AE
20 mg 1 times / day multiple, oral
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
Headache 1%
Disc. AE
20 mg 1 times / day multiple, oral
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
Nausea 1%
Disc. AE
20 mg 1 times / day multiple, oral
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
Vomiting 1%
Disc. AE
20 mg 1 times / day multiple, oral
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf
Page: p. 115
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737
substrate
1217
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2B6
664

CYP2C19
991
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2B6
664
 minor
CYP2C19
991
 minor
CYP2D6
1217
 yes
yes (co-administration study)
Comment: The 90% confidence interval (CI) of the geometric means for hydrocodone AUCinf (98 to 115%), AUCt (98 to 115%), and Cmax (93 to 121%) values were within the range of 80 to 125% when a single dose of HYSINGLA ER 20 mg was co-administered with CYP2D6 inhibitor paroxetine
CYP3A4
1737
 yes
yes (co-administration study)
Comment: Co-administration of HYSINGLA ER and CYP3A4 inhibitor ketoconazole increased mean hydrocodone AUC and Cmax by 135% and 78%, respectively;
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:5779
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5779
ZINC
ZINC000001280665
http://zinc15.docking.org/substances/ZINC000001280665
eMolecules
29539213
https://www.emolecules.com/cgi-bin/more?vid=29539213
PubMed

PubMed

TitleDatePubMed
Opioid formulations: tailoring to the needs in chronic pain.
2001
Harmonic Scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation.
2001 Apr
[Does the inhalation of a 1% L-menthol solution in the premedication of fiberoptic bronchoscopy affect coughing and the sensation of dyspnea?].
2001 Mar
Acetaminophen, aspirin, or Ibuprofen in combination analgesic products.
2001 Nov-Dec
[Learning from experience. Analysis of claims submitted to the National Commission of Medical Arbitration].
2001 Sep-Oct
Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain.
2002 Jan
The effectiveness of an anesthetic continuous-infusion device on postoperative pain control.
2002 Jan
Synthesis and biological activity of 8beta-substituted hydrocodone indole and hydromorphone indole derivatives.
2002 Jan 21
Gateways to clinical trials.
2002 Jul-Aug
Gender differences in narcotic-induced emesis in the ED.
2002 May
Determination of 6-oxo-morphinans, as the oximes, by difference circular dichroism spectroscopy.
2002 Oct
Surveillance of drug identification calls: an overlooked poison center responsibility.
2002 Oct
Senate committee fights hydrocodone abuse.
2002 Sep
Quantification of the O- and N-demethylated metabolites of hydrocodone and oxycodone in human liver microsomes using liquid chromatography with ultraviolet absorbance detection.
2003 Feb 25
I am following a health care professional who, I think, has a drug problem.
2003 Jan
Rapid communication: laparoscopic Anderson-Hynes dismembered pyeloplasty using the da Vinci robot: technical considerations.
2003 Mar
Cognitive and motor function after administration of hydrocodone bitartrate plus ibuprofen, ibuprofen alone, or placebo in healthy subjects with exercise-induced muscle damage: a randomized, repeated-dose, placebo-controlled study.
2003 Mar
A message of hope.
2004 Fall
Refractory status epilepticus.
2004 Feb
Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor.
2004 Feb
Patient characteristics and risks factors for development of dependence on hydrocodone and oxycodone.
2004 Jan-Feb
Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000.
2004 Jun
Hallucinations with zolpidem and fluoxetine in an impaired driver.
2004 Mar
Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing.
2004 May
Local anesthetic infusion pumps improve postoperative pain after inguinal hernia repair: a randomized trial.
2004 Nov
Continuous local anesthetic infusion for pain management after outpatient inguinal herniorrhaphy.
2004 Oct
Detection of hypoventilation during thoracoscopy: combined cutaneous carbon dioxide tension and oximetry monitoring with a new digital sensor.
2005 Feb
A preclinical comparison between different opioids: antinociceptive versus adverse effects.
2005 Feb
Oral analgesics for acute nonspecific pain.
2005 Mar 1
Patents

Patents

04272541
12
07321038
10
08491935
42
08569329
42
JP2000501709A
75
JP2005506351A
26
JP2010163446A
20
JP2010509227A
64
JP2011511782A
10
JP2011520977A
49
JP2013241461A
10
JP4806507B2
10

Sample Use Guides

In Vivo Use Guide
APADAZ Immediate-release tablets: 6.12 mg benzhydrocodone (equivalent to 6.67 mg benzhydrocodone hydrochloride) and 325 mg acetaminophen. Initiate treatment with APADAZ at 1 or 2 tablets every 4 to 6 hours as needed for pain. Dosage should not exceed 12 tablets in a 24­ hour period.
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:10:54 GMT 2023
Edited
by admin
on Fri Dec 15 18:10:54 GMT 2023
Record UNII
68T7388F5H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
HYDROCODONE TANNATE
WHO-DD  
Common Name English
4,5.ALPHA.-EPOXY-3-METHOXY-17-METHYLMORPHINAN-6-ONE TANNATE
Common Name English
HYDROCODONE TANNATE [WHO-DD]
Common Name English
Code System Code Type Description
PUBCHEM
16208253
Created by admin on Fri Dec 15 18:10:54 GMT 2023 , Edited by admin on Fri Dec 15 18:10:54 GMT 2023
PRIMARY
FDA UNII
68T7388F5H
Created by admin on Fri Dec 15 18:10:54 GMT 2023 , Edited by admin on Fri Dec 15 18:10:54 GMT 2023
PRIMARY
RXCUI
597355
Created by admin on Fri Dec 15 18:10:54 GMT 2023 , Edited by admin on Fri Dec 15 18:10:54 GMT 2023
PRIMARY RxNorm
Related Record Type Details
Structure of HYDROCODONE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of HYDROCODONE
ACTIVE MOIETY
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