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

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H25NO4
Molecular Weight 403.4703
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BENZHYDROCODONE

SMILES

[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=VPMRSLWWUXNYRY-PJCFOSJUSA-N
InChI=1S/C25H25NO4/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/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

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

2013
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

2019
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
[Longitudinal study of parameters of respiratory function tests and blood gas analysis in patients with progressive systemic scleroderma].
2001
Opioid formulations: tailoring to the needs in chronic pain.
2001
Harmonic Scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation.
2001 Apr
Do gender and race affect decisions about pain management?
2001 Apr
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
Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults.
2001 Feb
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
Who's feeling no pain?
2001 Mar 19
Evaluation of urinary dihydrocodeine excretion in human by gas chromatography-mass spectrometry.
2001 Mar 5
Narcotic analgesics for dental pain: available products, strengths, and formulations.
2001 Mar-Apr
Important drugs for cough in advanced cancer.
2001 Nov
Acetaminophen, aspirin, or Ibuprofen in combination analgesic products.
2001 Nov-Dec
Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.
2001 Sep
Engineering novel biocatalytic routes for production of semisynthetic opiate drugs.
2001 Sep
[Lung function tests and bronchoalveolar lavage (BAL) findings in patients with primary biliary cirrhosis].
2002
The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid.
2002 Apr
[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
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
A double-blind, single-dose comparison of the analgesic efficacy of tramadol/acetaminophen combination tablets, hydrocodone/acetaminophen combination tablets, and placebo after oral surgery.
2002 Jun
Simultaneous determination of hydrocodone and hydromorphone in human plasma by liquid chromatography with tandem mass spectrometric detection.
2002 Mar 25
Exacerbation of panic disorder symptoms following Vicodin exposure.
2002 Nov-Dec
A field evaluation of five on-site drug-testing devices.
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
Adverse drug reactions to oxycodone and hydrocodone in CYP2D6 ultrarapid metabolizers.
2003 Aug
I am following a health care professional who, I think, has a drug problem.
2003 Jan
Hair analysis for opiates: evaluation of washing and incubation procedures.
2003 Jun 5
Current concepts in acute pain management.
2003 May
[Spanish scientific production in anesthesiology and resuscitation 1983-1995].
2003 Nov
Carisoprodol withdrawal syndrome.
2004 Dec
A message of hope.
2004 Fall
Postoperative pain management after anterior cruciate ligament reconstruction.
2004 Jan
Fatal intravenous fentanyl abuse: four cases involving extraction of fentanyl from transdermal patches.
2004 Jun
[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
6-oxo-morphinane oximes: pharmacology, chemistry and analytical application.
2004 Oct
Continuous local anesthetic infusion for pain management after outpatient inguinal herniorrhaphy.
2004 Oct
Cough suppression during flexible bronchoscopy using combined sedation with midazolam and hydrocodone: a randomised, double blind, placebo controlled trial.
2004 Sep
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
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 02:52:53 GMT 2023
Edited
by admin
on Sat Dec 16 02:52:53 GMT 2023
Record UNII
75MS0AAZ9I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BENZHYDROCODONE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
benzhydrocodone [INN]
Common Name English
6,7-Didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6-yl benzoate
Systematic Name English
MORPHINAN-6-OL, 6,7-DIDEHYDRO-4,5-EPOXY-3-METHOXY-17-METHYL-, 6-BENZOATE, (5.ALPHA.)-
Systematic Name English
BENZHYDROCODONE [USAN]
Common Name English
Benzhydrocodone [WHO-DD]
Common Name English
KP201 FREE BASE
Code English
KP-201 FREE BASE
Code English
Code System Code Type Description
EVMPD
SUB182762
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
INN
9897
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
DRUG BANK
DB15465
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
CAS
1259440-61-3
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
DAILYMED
75MS0AAZ9I
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
ChEMBL
CHEMBL3137321
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
WIKIPEDIA
Benzhydrocodone
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
FDA UNII
75MS0AAZ9I
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
PUBCHEM
49836084
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
EPA CompTox
DTXSID201027932
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
RXCUI
2001352
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
SMS_ID
100000169102
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
USAN
AB-10
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
NCI_THESAURUS
C166992
Created by admin on Sat Dec 16 02:52:54 GMT 2023 , Edited by admin on Sat Dec 16 02:52:54 GMT 2023
PRIMARY
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