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

Details

Stereochemistry ABSOLUTE
Molecular Formula C18H21NO3.ClH
Molecular Weight 335.825
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HYDROCODONE HYDROCHLORIDE

SMILES

Cl.[H][C@@]12OC3=C(OC)C=CC4=C3[C@@]15CCN(C)[C@H](C4)[C@]5([H])CCC2=O

InChI

InChIKey=GCJAEXSZUXBMFS-RNWHKREASA-N
InChI=1S/C18H21NO3.ClH/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19;/h3,6,11-12,17H,4-5,7-9H2,1-2H3;1H/t11-,12+,17-,18-;/m0./s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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.

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1.38257275E12
Primary
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

1.54647357E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.1 ng/mL
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
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
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
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
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%
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:
unhealthy, 5 years
n = 1
Health Status: unhealthy
Condition: cold
Age Group: 5 years
Sex: F
Population Size: 1
Sources:
Other AEs: Adverse event...
Other AEs:
Adverse event (grade 5)
Sources:
160 mg 1 times / day multiple, oral
Highest studied dose
unhealthy, adult
Other AEs: Electrocardiogram QTc interval prolonged...
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:
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
Other AEs: 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:
unhealthy, adult
Other AEs: Respiratory depression, Addiction...
Other AEs:
Respiratory depression (grade 5)
Addiction
Sources:
20 mg 1 times / day multiple, oral
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources: Page: p. 115
Disc. AE: Vomiting, Nausea...
AEs leading to
discontinuation/dose reduction:
Vomiting (1%)
Nausea (1%)
Headache (1%)
Dizziness (1%)
Sources: 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:
unhealthy, 5 years
n = 1
Health Status: unhealthy
Condition: cold
Age Group: 5 years
Sex: F
Population Size: 1
Sources:
Electrocardiogram QTc interval prolonged
160 mg 1 times / day multiple, oral
Highest studied dose
unhealthy, adult
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:
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
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:
unhealthy, adult
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:
unhealthy, adult
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: Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources: 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: Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources: 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: Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources: 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: Page: p. 115
unhealthy, adult
n = 296
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 296
Sources: Page: p. 115
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
minor
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
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
PubMed

PubMed

TitleDatePubMed
Profound hearing loss associated with hydrocodone/acetaminophen abuse.
2000 Mar
Opioid formulations: tailoring to the needs in chronic pain.
2001
Randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerin ointment on pain after hemorrhoidectomy.
2001 Aug
Persistently elevated acetaminophen concentrations for two days after an initial four-hour non-toxic concentration.
2001 Aug
A retrospective study of the effect of postoperative indomethacin rectal suppositories on the need for narcotic analgesia in patients who had a cesarean delivery while they were under regional anesthesia.
2001 Jun
Psychosis after ultrarapid opiate detoxification.
2001 Jun
[Does the inhalation of a 1% L-menthol solution in the premedication of fiberoptic bronchoscopy affect coughing and the sensation of dyspnea?].
2001 Mar
Narcotic analgesics for dental pain: available products, strengths, and formulations.
2001 Mar-Apr
Important drugs for cough in advanced cancer.
2001 Nov
Cellulose granulomatosis presenting as centrilobular nodules: CT and histologic findings.
2001 Nov
Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.
2001 Sep
[Learning from experience. Analysis of claims submitted to the National Commission of Medical Arbitration].
2001 Sep-Oct
[Lung function tests and bronchoalveolar lavage (BAL) findings in patients with primary biliary cirrhosis].
2002
[Hospital maternal mortality: causes and consistency between clinical and autopsy diagnosis at the Northeastern Medical Center of the IMSS, Mexico].
2002 Feb
Esophageal cancer and the esophagus: challenges and potential strategies for selective cytoprotection of the tumor-bearing organ during cancer treatment.
2002 Jan
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
A phase II study of hydrocodone for cough in advanced cancer.
2002 Jan-Feb
Effect of narcotic pain reliever on pulp tests in women.
2002 Jul
Gateways to clinical trials.
2002 Jul-Aug
Photodynamic therapy for Barrett's esophagus and high grade dysplasia: results of a patient satisfaction survey.
2002 Jul-Aug
Gender differences in narcotic-induced emesis in the ED.
2002 May
Exacerbation of panic disorder symptoms following Vicodin exposure.
2002 Nov-Dec
Rational use of analgesic combinations.
2002 Oct
Simultaneous quantitation of opioids in blood by GC-EI-MS analysis following deproteination, detautomerization of keto analytes, solid-phase extraction, and trimethylsilyl derivatization.
2002 Oct
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
Effect of gastrointestinal bleeding and oral medications on acquisition of vancomycin-resistant Enterococcus faecium in hospitalized patients.
2002 Oct 15
Senate committee fights hydrocodone abuse.
2002 Sep
[Hypoxic brain damage in victims of fatal road traffic accident: prevalence, distribution and association with survival time and other head and extracranial injuries].
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
Trials and tribulations: current challenges in conducting clinical trials.
2003 Jan
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
Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study.
2003 Nov
Evaluation of postoperative bupivacaine infusion for pain management after anterior cruciate ligament reconstruction.
2003 Oct
Refractory status epilepticus.
2004 Feb
Postoperative pain management after anterior cruciate ligament reconstruction.
2004 Jan
Loss prevention case of the month. Monitoring remains critical.
2004 Jan
Patient characteristics and risks factors for development of dependence on hydrocodone and oxycodone.
2004 Jan-Feb
Dose-response relationship between opioid use and adverse effects after ambulatory surgery.
2004 Jul
Hallucinations with zolpidem and fluoxetine in an impaired driver.
2004 Mar
CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes.
2004 Mar
[Detection of thyroid pathology during surgical exploration of the neck for primary hyperthyroidism].
2004 Mar-Apr
[Origin and growth of the National Program of Continuous Academic Development for the General Physician].
2004 May-Jun
Continuous local anesthetic infusion for pain management after outpatient inguinal herniorrhaphy.
2004 Oct
The GC-MS detection and characterization of neopine resulting from opium use and codeine metabolism and its potential as an opiate-product-use marker.
2005 Jun
Patents

Sample Use Guides

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 Thu Jul 06 01:06:42 UTC 2023
Edited
by admin
on Thu Jul 06 01:06:42 UTC 2023
Record UNII
QKZ0920OV3
Record Status Validated (UNII)
Record Version
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Name Type Language
HYDROCODONE HYDROCHLORIDE
MART.   MI   WHO-DD  
Common Name English
HYDROCODONE HYDROCHLORIDE [MI]
Common Name English
NSC-35549
Code English
Hydrocodone hydrochloride [WHO-DD]
Common Name English
7,8-DIHYDROCODEINONE HYDROCHLORIDE
Common Name English
NSC-117856
Code English
HYDROCODONE HYDROCHLORIDE [MART.]
Common Name English
DIHYDROCODEINONE HYDROCHLORIDE
Common Name English
MORPHINAN-6-ONE, 4,5-EPOXY-3-METHOXY-17-METHYL-, HYDROCHLORIDE (1:1), (5.ALPHA.)-
Common Name English
MORPHINAN-6-ONE, 4,5.ALPHA.-EPOXY-3-METHOXY-17-METHYL-, HYDROCHLORIDE
Systematic Name English
MORPHINAN-6-ONE, 4,5-EPOXY-3-METHOXY-17-METHYL-, HYDROCHLORIDE, (5.ALPHA.)-
Systematic Name English
HYDROCODONE HCL
Common Name English
Code System Code Type Description
NSC
117856
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
SMS_ID
100000077616
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
PUBCHEM
12358607
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
DRUG BANK
DBSALT002210
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
RXCUI
236931
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY RxNorm
CAS
25968-91-6
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
EVMPD
SUB14131MIG
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
ECHA (EC/EINECS)
247-382-7
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
FDA UNII
QKZ0920OV3
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
NSC
35549
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
EPA CompTox
DTXSID80180632
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY
MERCK INDEX
M6093
Created by admin on Thu Jul 06 01:06:42 UTC 2023 , Edited by admin on Thu Jul 06 01:06:42 UTC 2023
PRIMARY Merck Index
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ACTIVE MOIETY