HYDROCODONE BITARTRATE ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H21NO3.C4H6O6
Molecular Weight	449.4511
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of HYDROCODONE BITARTRATE ANHYDROUS

Structure Search

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.COC1=C2O[C@H]3C(=O)CC[C@H]4[C@H]5CC(C=C1)=C2[C@@]34CCN5C

InChI

InChIKey=OJHZNMVJJKMFGX-BWCYBWMMSA-N

InChI=1S/C18H21NO3.C4H6O6/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;5-1(3(7)8)2(6)4(9)10/h3,6,11-12,17H,4-5,7-9H2,1-2H3;1-2,5-6H,(H,7,8)(H,9,10)/t11-,12+,17-,18-;1-,2-/m01/s1

HIDE SMILES / InChI

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

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

Description
Sources: https://www.ncbi.nlm.nih.gov/books/NBK501225/ | https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208653s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/30140595 | https://www.ncbi.nlm.nih.gov/pubmed/29092079

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

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1b89a045-d552-40b6-a717-09858b5e6239	Primary		Approved 8583	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
Acute pain 17 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208653s000lbl.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
13 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
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
16.04 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208653s007lbl.pdf#page=30	6.12 mg single, oral dose: 6.12 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
19.18 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208653s007lbl.pdf#page=30	6.12 mg single, oral dose: 6.12 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
33.95 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=25	12.24 mg 6 times / day multiple, oral dose: 12.24 mg route of administration: Oral experiment type: MULTIPLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
62.79 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=25	12.24 mg 6 times / day multiple, oral dose: 12.24 mg route of administration: Oral experiment type: MULTIPLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
208 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=27	73.44 mg single, oral dose: 73.44 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=29	6.12 mg single, nasal dose: 6.12 mg route of administration: Nasal experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
27 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=29	24.48 mg single, nasal dose: 24.48 mg route of administration: Nasal experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
25.6 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=31 \| https://pubmed.ncbi.nlm.nih.gov/29092079/	12.24 mg single, nasal dose: 12.24 mg route of administration: Nasal experiment type: SINGLE co-administered:		HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
40.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29025138/	12.24 mg single, oral dose: 12.24 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
34.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29025138/	12.24 mg single, nasal dose: 12.24 mg route of administration: Nasal experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
269 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
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
130.91 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208653s007lbl.pdf#page=30	6.12 mg single, oral dose: 6.12 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
125.73 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208653s007lbl.pdf#page=30	6.12 mg single, oral dose: 6.12 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
92.94 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=25	12.24 mg 6 times / day multiple, oral dose: 12.24 mg route of administration: Oral experiment type: MULTIPLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
195.07 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=25	12.24 mg 6 times / day multiple, oral dose: 12.24 mg route of administration: Oral experiment type: MULTIPLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1272 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=27	73.44 mg single, oral dose: 73.44 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
194.7 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=31 \| https://pubmed.ncbi.nlm.nih.gov/29092079/	12.24 mg single, nasal dose: 12.24 mg route of administration: Nasal experiment type: SINGLE co-administered:		HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
252.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29025138/	12.24 mg single, oral dose: 12.24 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
278.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29025138/	12.24 mg single, nasal dose: 12.24 mg route of administration: Nasal experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10.5 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
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
4.51 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208653s007lbl.pdf#page=30	6.12 mg single, oral dose: 6.12 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
4.33 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208653s007lbl.pdf#page=30	6.12 mg single, oral dose: 6.12 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
4.45 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=25	12.24 mg 6 times / day multiple, oral dose: 12.24 mg route of administration: Oral experiment type: MULTIPLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.87 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=25	12.24 mg 6 times / day multiple, oral dose: 12.24 mg route of administration: Oral experiment type: MULTIPLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=27	73.44 mg single, oral dose: 73.44 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.29 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208653Orig1s000ClinPharmR.pdf#page=31 \| https://pubmed.ncbi.nlm.nih.gov/29092079/	12.24 mg single, nasal dose: 12.24 mg route of administration: Nasal experiment type: SINGLE co-administered:		HYDROCODONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse events
30 mg multiple, oral Overdose Dose: 30 mg Route: oral Route: multiple Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/20837591	unhealthy, 5 years Health Status: unhealthy Age Group: 5 years Sex: F 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	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000MedR.pdf	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
13.34 mg 1 times / day steady-state, intranasal Studied dose Dose: 13.34 mg, 1 times / day Route: intranasal Route: steady-state Dose: 13.34 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29025138/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29025138/	Other AEs: Nasal discomfort, Nasal congestion... Other AEs: Nasal discomfort (16 patients) Nasal congestion (7 patients) Rhinorrhea (7 patients) Throat irritation (6 patients) Oropharyngeal pain (1 pt) Dry throat (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/29025138/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 776 CYP2C19 1119

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206627s007s008lbl.pdf#page=29 Page: 29.0	minor
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206627s007s008lbl.pdf#page=29 Page: 29.0	minor
CYP2D6 1388	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884456/; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206627s007s008lbl.pdf#page=30	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 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884456/; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206627s007s008lbl.pdf#page=30
CYP3A4 1946	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884456/; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206627s007s008lbl.pdf#page=30	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; Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884456/; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206627s007s008lbl.pdf#page=30

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206627Orig1s000PharmR.pdf#page=33 Page: 33.0

Sourcing

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

PubMed

Title	Date	PubMed
Opioid formulations: tailoring to the needs in chronic pain.	2001	11798229
Harmonic Scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation.	2001 Apr	11330583
Psychosis after ultrarapid opiate detoxification.	2001 Jun	11384923
Narcotic analgesics for dental pain: available products, strengths, and formulations.	2001 Mar-Apr	12004688
Important drugs for cough in advanced cancer.	2001 Nov	11762966
Acetaminophen, aspirin, or Ibuprofen in combination analgesic products.	2001 Nov-Dec	11704782
Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.	2001 Sep	11589259
Complications of intranasal prescription narcotic abuse.	2002 Feb	11860072
The effectiveness of an anesthetic continuous-infusion device on postoperative pain control.	2002 Jan	11774146
Synthesis and biological activity of 8beta-substituted hydrocodone indole and hydromorphone indole derivatives.	2002 Jan 21	11755345
Gateways to clinical trials.	2002 Jul-Aug	12224444
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	12117085
[Trends in the incidence of hepatic tumors in childhood].	2002 Mar-Apr	12053775
Detection of cocaine analytes and opiates in nails from postmortem cases.	2002 Oct	12423005
[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	12364952
Review of the analgesic efficacy of ibuprofen.	2003 Apr	12723741
Current concepts in acute pain management.	2003 May	12839235
[Spanish scientific production in anesthesiology and resuscitation 1983-1995].	2003 Nov	14753139
Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study.	2003 Nov	14636819
The influence of gender and race on physicians' pain management decisions.	2003 Nov	14636818
Refractory status epilepticus.	2004 Feb	15000791
Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor.	2004 Feb	14742366
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	14600248
Postoperative pain management after anterior cruciate ligament reconstruction.	2004 Jan	14971669
Patient characteristics and risks factors for development of dependence on hydrocodone and oxycodone.	2004 Jan-Feb	14704593
Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000.	2004 Jun	15157714
Hallucinations with zolpidem and fluoxetine in an impaired driver.	2004 Mar	15027567
CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes.	2004 Mar	14998425
[Gender and health in the daily press].	2004 May	15171880
[Origin and growth of the National Program of Continuous Academic Development for the General Physician].	2004 May-Jun	15646146
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	15352969
A 35-year-old physician with opioid dependence.	2004 Sep 15	15367558
Selective potentiation of opioid analgesia by nonsteroidal anti-inflammatory drugs.	2005 Apr 8	15804436
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Patents

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 `Mon Mar 31 20:06:33 GMT 2025` Edited by `admin` on `Mon Mar 31 20:06:33 GMT 2025`
Record UNII	9GU1G05Y03
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HYDROCODONE BITARTRATE ANHYDROUS

Common Name

English

4,5.ALPHA.-EPOXY-3-METHOXY-17-METHYLMORPHINAN-6-ONE TARTRATE (1:1)

Preferred Name

English

MORPHINAN-6-ONE, 4,5-EPOXY-3-METHOXY-17-METHYL-, (5.ALPHA.)-, (R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (1:1)

Common Name

English

HYDROCODONE BITARTRATE, ANHYDROUS

Common Name

English

HYDROCODONE BITARTRATE ANHYDROUS [MI]

Common Name

English

Code System Code Type Description

FDA UNII

9GU1G05Y03