Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C18H21NO3.ClH.2H2O |
| Molecular Weight | 371.856 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.O.Cl.[H][C@@]12OC3=C4C(C[C@@]5([H])N(C)CC[C@@]14[C@@]5([H])CCC2=O)=CC=C3OC
InChI
InChIKey=HEUMIQUBXVWULP-GXTZACRKSA-N
InChI=1S/C18H21NO3.ClH.2H2O/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;2*1H2/t11-,12+,17-,18-;;;/m0.../s1
| 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 | 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 | H2O |
| Molecular Weight | 18.0153 |
| 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
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | ZOHYDRO ER Approved UseZOHYDRO 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 Date2013 |
|||
| Primary | APADAZ Approved UseAPADAZ 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 Date2019 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Dose | Population | Adverse events |
|---|---|---|
30 mg multiple, oral (total) Overdose Dose: 30 mg Route: oral Route: multiple Dose: 30 mg Co-administed with:: clarithromycin Sources: valproic acid(250 mg, 2 times per day) |
unhealthy, 5 years n = 1 Health Status: unhealthy Condition: cold Age Group: 5 years Sex: F Population Size: 1 Sources: |
Other AEs: Adverse event... |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Electrocardiogram QTc interval prolonged... Other AEs: Electrocardiogram QTc interval prolonged Sources: |
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... Other AEs: Withdrawal syndrome neonatal Sources: |
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 Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Respiratory depression, Addiction... Other AEs: Respiratory depression (grade 5) Sources: Addiction |
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%) Sources: Page: p. 115Nausea (1%) Headache (1%) Dizziness (1%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Adverse event | grade 5 | 30 mg multiple, oral (total) Overdose Dose: 30 mg Route: oral Route: multiple Dose: 30 mg Co-administed with:: clarithromycin Sources: valproic acid(250 mg, 2 times per day) |
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 Dose: 160 mg, 1 times / day Route: oral Route: multiple Dose: 160 mg, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
|
| 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 Health Status: unhealthy Age Group: adult Sources: |
|
| 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 Health Status: unhealthy Age Group: adult Sources: |
| 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
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical 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
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Profound hearing loss associated with hydrocodone/acetaminophen abuse. | 2000 Mar |
|
| Harmonic Scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation. | 2001 Apr |
|
| Randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerin ointment on pain after hemorrhoidectomy. | 2001 Aug |
|
| Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. | 2001 Feb |
|
| Evaluation of urinary dihydrocodeine excretion in human by gas chromatography-mass spectrometry. | 2001 Mar 5 |
|
| Important drugs for cough in advanced cancer. | 2001 Nov |
|
| Cellulose granulomatosis presenting as centrilobular nodules: CT and histologic findings. | 2001 Nov |
|
| Acetaminophen, aspirin, or Ibuprofen in combination analgesic products. | 2001 Nov-Dec |
|
| Simultaneous determination of hydrocodone and hydromorphone in human plasma by liquid chromatography with tandem mass spectrometric detection. | 2002 Mar 25 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers. | 2003 Jan |
|
| Hair analysis for opiates: evaluation of washing and incubation procedures. | 2003 Jun 5 |
|
| Current concepts in acute pain management. | 2003 May |
|
| The influence of gender and race on physicians' pain management decisions. | 2003 Nov |
|
| Postoperative pain management after anterior cruciate ligament reconstruction. | 2004 Jan |
|
| Dose-response relationship between opioid use and adverse effects after ambulatory surgery. | 2004 Jul |
|
| 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 |
|
| 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 |
|
| Patient-controlled ropivacaine analgesia after arthroscopic subacromial decompression. | 2004 May |
|
| Selective potentiation of opioid analgesia by nonsteroidal anti-inflammatory drugs. | 2005 Apr 8 |
|
| 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 |
|
| Oral analgesics for acute nonspecific pain. | 2005 Mar 1 |
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
Edited
Sat Dec 16 10:15:08 GMT 2023
by
admin
on
Sat Dec 16 10:15:08 GMT 2023
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| Record UNII |
PPK4BVC0DX
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
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Download
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PPK4BVC0DX
Created by
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Created by
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ANHYDROUS->SOLVATE | |||
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PARENT -> SALT/SOLVATE |
APPROXIMATE PURE ANHYDROUS DRUG CONTENT (IN PERCENT)
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|---|---|---|---|---|
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ACTIVE MOIETY |