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
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
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 |
|---|---|---|
| Exacerbation of panic disorder symptoms following Vicodin exposure. | 2002 Nov-Dec |
|
| Rational use of analgesic combinations. | 2002 Oct |
|
| [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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Misuse of prescribed controlled substances defined by urinalysis. | 2003 Mar-Apr |
|
| Current concepts in acute pain management. | 2003 May |
|
| [Spanish scientific production in anesthesiology and resuscitation 1983-1995]. | 2003 Nov |
|
| Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study. | 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 |
|
| Patterns and trends in opioid use among individuals with back pain in the United States. | 2004 Apr 15 |
|
| 1000 office-based hysteroscopies prior to in vitro fertilization: feasibility and findings. | 2004 Apr-Jun |
|
| Carisoprodol withdrawal syndrome. | 2004 Dec |
|
| A message of hope. | 2004 Fall |
|
| Refractory status epilepticus. | 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 |
|
| Dose-response relationship between opioid use and adverse effects after ambulatory surgery. | 2004 Jul |
|
| 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 |
|
| [Detection of thyroid pathology during surgical exploration of the neck for primary hyperthyroidism]. | 2004 Mar-Apr |
|
| [Gender and health in the daily press]. | 2004 May |
|
| Patient-controlled ropivacaine analgesia after arthroscopic subacromial decompression. | 2004 May |
|
| Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing. | 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 |
|
| Fracture of an endoluminal nitinol stent used in the treatment of tracheal collapse in a dog. | 2004 Oct 15 |
|
| Metaxalone (Skelaxin)-related death. | 2004 Sep |
|
| 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 |
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
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Benzhydrocodone
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C166992
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SUBSTANCE RECORD
