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

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H25NO4.ClH
Molecular Weight 439.931
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BENZHYDROCODONE HYDROCHLORIDE

SMILES

Cl.[H][C@@]12OC3=C(OC)C=CC4=C3[C@@]15CCN(C)[C@]([H])(C4)[C@]5([H])CC=C2OC(=O)C6=CC=CC=C6

InChI

InChIKey=VVCUIDHKAHHSAN-RFIUKBLMSA-N
InChI=1S/C25H25NO4.ClH/c1-26-13-12-25-17-9-11-20(29-24(27)15-6-4-3-5-7-15)23(25)30-22-19(28-2)10-8-16(21(22)25)14-18(17)26;/h3-8,10-11,17-18,23H,9,12-14H2,1-2H3;1H/t17-,18+,23-,25-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C25H25NO4
Molecular Weight 403.4703
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

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

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
[Lung function tests and bronchoalveolar lavage (BAL) findings in patients with primary biliary cirrhosis].
2002
Photodynamic therapy for Barrett's esophagus and high grade dysplasia: results of a patient satisfaction survey.
2002 Jul-Aug
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
A field evaluation of five on-site drug-testing devices.
2002 Oct
Detection of cocaine analytes and opiates in nails from postmortem cases.
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
Adverse drug reactions to oxycodone and hydrocodone in CYP2D6 ultrarapid metabolizers.
2003 Aug
The synergistic analgesic interactions between hydrocodone and ibuprofen.
2003 Dec
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
Trials and tribulations: current challenges in conducting clinical trials.
2003 Jan
Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers.
2003 Jan
[Maternal and fetal morbidity in patients with premature rupture of the membrane after 27-week gestation. Causes and costs].
2003 Jul
Hair analysis for opiates: evaluation of washing and incubation procedures.
2003 Jun 5
Rapid communication: laparoscopic Anderson-Hynes dismembered pyeloplasty using the da Vinci robot: technical considerations.
2003 Mar
Postmortem oxycodone and hydrocodone blood concentrations.
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
[Spanish scientific production in anesthesiology and resuscitation 1983-1995].
2003 Nov
The influence of gender and race on physicians' pain management decisions.
2003 Nov
Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.
2003 Nov-Dec
Evaluation of postoperative bupivacaine infusion for pain management after anterior cruciate ligament reconstruction.
2003 Oct
Carisoprodol withdrawal syndrome.
2004 Dec
Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor.
2004 Feb
Activation of G-proteins by morphine and codeine congeners: insights to the relevance of O- and N-demethylated metabolites at mu- and delta-opioid receptors.
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
Efficacy of ibuprofen-hydrocodone for the treatment of postoperative pain after periodontal surgery.
2004 Jun
Fatal intravenous fentanyl abuse: four cases involving extraction of fentanyl from transdermal patches.
2004 Jun
Persistent nonmalignant pain and analgesic prescribing patterns in elderly nursing home residents.
2004 Jun
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
CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes.
2004 Mar
[Gender and health in the daily press].
2004 May
[Origin and growth of the National Program of Continuous Academic Development for the General Physician].
2004 May-Jun
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
Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects.
2004 Oct
Fracture of an endoluminal nitinol stent used in the treatment of tracheal collapse in a dog.
2004 Oct 15
Cough suppression during flexible bronchoscopy using combined sedation with midazolam and hydrocodone: a randomised, double blind, placebo controlled trial.
2004 Sep
A 35-year-old physician with opioid dependence.
2004 Sep 15
Selective potentiation of opioid analgesia by nonsteroidal anti-inflammatory drugs.
2005 Apr 8
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
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
A 46-year-old man with excruciating shoulder pain.
2005 Mar
Oral analgesics for acute nonspecific pain.
2005 Mar 1
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 Sat Dec 16 02:11:00 UTC 2023
Edited
by admin
on Sat Dec 16 02:11:00 UTC 2023
Record UNII
I894QAU7FJ
Record Status Validated (UNII)
Record Version
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Name Type Language
BENZHYDROCODONE HYDROCHLORIDE
USAN   WHO-DD  
USAN  
Official Name English
BENZHYDROCODONE HYDROCHLORIDE [USAN]
Common Name English
Hydrochloride of 6,7-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6-yl benzoate
Common Name English
MORPHINAN-6-OL, 6,7-DIDEHYDRO-4,5-EPOXY-3-METHOXY-17-METHYL-, 6-BENZOATE, HYDROCHLORIDE (1:1), (5.ALPHA.)-
Systematic Name English
Benzhydrocodone hydrochloride [WHO-DD]
Common Name English
KP201
Code English
BENZHYDROCODONE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
KP-201
Code English
Classification Tree Code System Code
NCI_THESAURUS C67413
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
Code System Code Type Description
USAN
AB-11
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
RXCUI
2122776
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
NCI_THESAURUS
C142951
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
PUBCHEM
72736244
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
SMS_ID
300000039349
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
FDA UNII
I894QAU7FJ
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
DAILYMED
I894QAU7FJ
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
ChEMBL
CHEMBL3137321
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
EPA CompTox
DTXSID901027933
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
CAS
1379679-42-1
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
DRUG BANK
DBSALT002879
Created by admin on Sat Dec 16 02:11:00 UTC 2023 , Edited by admin on Sat Dec 16 02:11:00 UTC 2023
PRIMARY
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