Hydrocodone

Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat pain and as a cough suppressant.[10] It is taken by mouth.[10] Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid[11][12] and in combination with homatropine methylbromide to relieve cough.[10] It is also available by itself in a long-acting form under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration.[10][13] Hydrocodone is a controlled drug, in the United States a Schedule II Controlled Substance.

Not to be confused with Dihydrocodeine.

Hydrocodone
Clinical data
Trade namesHysingla ER, Zohydro ER
Other namesDihydrocodeinone, hydrocodone bitartrate
AHFS/Drugs.comMonograph
MedlinePlusa601006
License data
Dependence
liability		High[1]
Routes of
administration		Clinical: by mouth[2]
Others: intranasal, rectal
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityBy mouth: 70%[4]
Protein bindingLow[4][5]
MetabolismLiver: CYP3A4 (major), CYP2D6 (minor)[6]
Metabolites• Norhydrocodone[6]
• Hydromorphone[6]
• Others[6]
Onset of action10–20 minutes[2]
Elimination half-lifeAverage: 3.8 hours[7]
Range: 3.3–4.4 hours[2]
Duration of action4–8 hours[2]
ExcretionUrine[8][9]
Identifiers
  • 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.004.304
Chemical and physical data
FormulaC18H21NO3
Molar mass299.370 g·mol−1
3D model (JSmol)
  • O=C4[C@@H]5Oc1c2c(ccc1OC)C[C@H]3N(CC[C@]25[C@H]3CC4)C
  • InChI=1S/C18H21NO3/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/t11-,12+,17-,18-/m0/s1 checkY
  • Key:LLPOLZWFYMWNKH-CMKMFDCUSA-N checkY
  (verify)

Side effects and mechanisms

Common side effects include dizziness, sleepiness, nausea, and constipation.[10] Serious side effects may include low blood pressure, seizures, QT prolongation, respiratory depression, and serotonin syndrome.[10] Rapidly decreasing the dose may result in opioid withdrawal.[10] Use during pregnancy or breastfeeding is generally not recommended.[14] Hydrocodone is believed to work by activating opioid receptors, mainly in the brain and spinal cord.[10] Hydrocodone 10 mg is equivalent to about 10 mg of morphine by mouth.[15]

History and culture

Hydrocodone was patented in 1923, while the long-acting formulation was approved for medical use in the United States in 2013.[10][16] It is most commonly prescribed in the United States, which consumed 99% of the worldwide supply as of 2010.[17] In 2018, it was the 402nd most commonly prescribed medication in the United States, with more than 400,000 prescriptions.[18] Hydrocodone is a semisynthetic opioid, converted from codeine[19][20] or less often from thebaine.[21] Production using genetically engineered yeasts has been developed but is not used commercially.[22][23][24]

Medical uses

Hydrocodone is used to treat moderate to severe pain. In liquid formulations, it is used to treat cough.[10] In one study comparing the potency of hydrocodone to that of oxycodone, it was found that it took 50% more hydrocodone to achieve the same degree of miosis (pupillary contraction).[25] The investigators interpreted this to mean that oxycodone is about 50% more potent than hydrocodone.

However, in a study of emergency department patients with fractures, it was found that an equal amount of either drug provided about the same degree of pain relief, indicating that there is little practical difference between them when used for that purpose.[26] Some references state that the analgesic action of hydrocodone begins in 20–30 minutes and lasts about 4–8 hours.[27] The manufacturer's information says onset of action is about 10-30 minutes and duration is about 4-6 hours.[28] Recommended dosing interval is 4–6 hours.

Available forms
See also: Hydrocodone/paracetamol, Hydrocodone/ibuprofen, and Hydrocodone/aspirin

Hydrocodone is available in a variety of formulations for oral administration:[29][30][31]

  • The original oral form of hydrocodone alone, Dicodid, as immediate-release 5- and 10-mg tablets is available for prescription in Continental Europe per national drug control and prescription laws and Title 76 of the Schengen Treaty, but dihydrocodeine has been more widely used for the same indications since the beginning in the early 1920s, with hydrocodone being regulated the same way as morphine in the German Betäubungsmittelgesetz, the similarly named law in Switzerland and the Austrian Suchtmittelgesetz, whereas dihydrocodeine is regulated like codeine. For a number of decades, the liquid hydrocodone products available have been cough medicines.
  • Hydrocodone plus homatropine (Hycodan) in the form of small tablets for coughing and especially neuropathic moderate pain (the homatropine, an anticholinergic, is useful in both of those cases and is a deterrent to intentional overdose) was more widely used than Dicodid and was labelled as a cough medicine in the United States whilst Vicodin and similar drugs were the choices for analgesia.
  • Extended-release hydrocodone in a time-release syrup also containing chlorphenamine/chlorpheniramine is a cough medicine called Tussionex in North America. In Europe, similar time-release syrups containing codeine (numerous), dihydrocodeine (Paracodin Retard Hustensaft), nicocodeine (Tusscodin), thebacon, acetyldihydrocodeine, dionine, and nicodicodeine are used instead.
  • Immediate-release hydrocodone with paracetamol (acetaminophen) (Vicodin, Lortab, Lorcet, Maxidone, Norco, Zydone)
  • Immediate-release hydrocodone with ibuprofen (Vicoprofen, Ibudone, Reprexain)
  • Immediate-release hydrocodone with aspirin (Alor 5/500, Azdone, Damason-P, Lortab ASA, Panasal 5/500)
  • Controlled-release hydrocodone (Hysingla ER by Purdue Pharma, Zohydro ER)[32]

Hydrocodone is not available in parenteral or any other non-oral forms.[5][2]

Side effects

Common side effects of hydrocodone are nausea, vomiting, constipation, drowsiness, dizziness, lightheadedness, anxiety, abnormally happy or sad mood, dry throat, difficulty urinating, rash, itching, and contraction of the pupils. Serious side effects include slowed or irregular breathing and chest tightness.[33]

Several cases of progressive bilateral hearing loss unresponsive to steroid therapy have been described as an infrequent adverse reaction to hydrocodone/paracetamol misuse. This adverse effect has been considered by some to be due to the ototoxicity of hydrocodone.[34][35] Other researchers have suggested that paracetamol is the primary agent responsible for the ototoxicity.[36][37]

Hydrocodone is in U.S. Food and Drug Administration (FDA) pregnancy category C. No adequate and well-controlled studies in humans have been conducted. A newborn of a mother taking opioid medications regularly prior to the birth will be physically dependent.[38][39] The baby may also exhibit respiratory depression if the opioid dose was high.[40] An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects.[41]

Symptoms of hydrocodone overdose include narrowed or widened pupils; slow, shallow, or stopped breathing; slowed or stopped heartbeat; cold, clammy, or blue skin; excessive sleepiness; loss of consciousness; seizures; or death.[33]

Hydrocodone can be habit forming, causing physical and psychological dependence. Its abuse liability is similar to morphine and less than oxycodone.[42]

Interactions

Hydrocodone is metabolized by the cytochrome P450 enzymes CYP2D6 and CYP3A4, and inhibitors and inducers of these enzymes can modify hydrocodone exposure.[43] One study found that combination of paroxetine, a selective serotonin reuptake inhibitor (SSRI) and strong CYP2D6 inhibitor, with once-daily extended-release hydrocodone, did not modify exposure to hydrocodone or the incidence of adverse effects.[43][44] These findings suggest that hydrocodone can be coadministered with CYP2D6 inhibitors without dosage modification.[43][44] Conversely, combination of hydrocodone/acetaminophen with the antiviral regimen of ombitasvir, paritaprevir, ritonavir, and dasabuvir for treatment of hepatitis C increased peak concentrations of hydrocodone by 27%, total exposure by 90%, and elimination half-life from 5.1 hours to 8.0 hours.[45] Ritonavir is a strong CYP3A4 inhibitor as well as inducer of CYP3A and other enzymes, and the other antivirals are known to inhibit drug transporters like organic anion transporting polypeptide (OATP) 1B1 and 1B3, P-glycoprotein, and breast cancer resistance protein (BCRP).[45] The changes in hydrocodone levels are consistent with CYP3A4 inhibition by ritonavir.[45] Based on these findings, a 50% lower dose of hydrocodone and closer clinical monitoring was recommended when hydrocodone is used in combination with this antiviral regimen.[45]

People consuming alcohol, other opioids, anticholinergic antihistamines, antipsychotics, anxiolytics, or other central nervous system (CNS) depressants together with hydrocodone may exhibit an additive CNS depression.[40] Hydrocodone taken concomitantly with serotonergic medications like SSRI antidepressants may increase the risk of serotonin syndrome.[46]

Pharmacology

Pharmacodynamics
Hydrocodone (and metabolite) at opioid receptors
CompoundAffinities (KiTooltip Inhibitor constant)RatioRef
MORTooltip μ-Opioid receptorDORTooltip δ-Opioid receptorKORTooltip κ-Opioid receptorMOR:DOR:KOR
Hydrocodone11.1 nM962 nM501 nM1:87:45[47]
Hydromorphone0.47 nM18.5 nM24.9 nM1:39:53[48]

Equianalgesic doses[49][50][51]
CompoundRouteDose
CodeinePO200 mg
HydrocodonePO20–30 mg
HydromorphonePO7.5 mg
HydromorphoneIV1.5 mg
MorphinePO30 mg
MorphineIV10 mg
OxycodonePO20 mg
OxycodoneIV10 mg
OxymorphonePO10 mg
OxymorphoneIV1 mg

Hydrocodone is a highly selective full agonist of the μ-opioid receptor (MOR).[27][52][47] This is the main biological target of the endogenous opioid neuropeptide β-endorphin.[53] Hydrocodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly.[47]

Studies have shown hydrocodone is stronger than codeine but only one-tenth as potent as morphine at binding to receptors and reported to be only 59% as potent as morphine in analgesic properties. However, in tests conducted on rhesus monkeys, the analgesic potency of hydrocodone was actually higher than morphine.[7] Oral hydrocodone has a mean equivalent daily dosage (MEDD) factor of 0.4, meaning that 1 mg of hydrocodone is equivalent to 0.4 mg of intravenous morphine. However, because of morphine's low oral bioavailability, there is a 1:1 correspondence between orally administered morphine and orally administered hydrocodone.[54]

Absorption

Hydrocodone is only pharmaceutically available as an oral medication.[2] It is well-absorbed, but the oral bioavailability of hydrocodone is only approximately 25%.[4][5] The onset of action of hydrocodone via this route is 10 to 20 minutes, with a peak effect (Tmax) occurring at 30 to 60 minutes,[55] and it has a duration of 4 to 8 hours.[2] The FDA label for immediate-release hydrocodone with acetaminophen does not include any information on the influence of food on its absorption or other pharmacokinetics.[56] Conversely, coadministration with a high-fat meal increases peak concentrations of different formulations of extended-release hydrocodone by 14 to 54%, whereas area-under-the-curve levels are not notably affected.[57][58][59][60]

Distribution

The volume of distribution of hydrocodone is 3.3 to 4.7 L/kg.[5] The plasma protein binding of hydrocodone is 20 to 50%.[27]

Metabolism

In the liver, hydrocodone is transformed into several metabolites, including norhydrocodone, hydromorphone, 6α-hydrocodol (dihydrocodeine), and 6β-hydrocodol.[6] 6α- and 6β-hydromorphol are also formed, and the metabolites of hydrocodone are conjugated (via glucuronidation).[61][62] Hydrocodone has a terminal half-life that averages 3.8 hours (range 3.3–4.4 hours).[7][2] The hepatic cytochrome P450 enzyme CYP2D6 converts hydrocodone into hydromorphone, a more potent opioid (5-fold higher binding affinity to the MOR).[6][63] However, extensive and poor cytochrome 450 CYP2D6 metabolizers had similar physiological and subjective responses to hydrocodone, and CYP2D6 inhibitor quinidine did not change the responses of extensive metabolizers, suggesting that inhibition of CYP2D6 metabolism of hydrocodone has no practical importance.[64][65] Ultra-rapid CYP2D6 metabolizers (1–2% of the population) may have an increased response to hydrocodone; however, hydrocodone metabolism in this population has not been studied.[66]

Norhydrocodone, the major metabolite of hydrocodone, is predominantly formed by CYP3A4-catalyzed oxidation.[6] In contrast to hydromorphone, it is described as inactive.[63] However, norhydrocodone is actually a MOR agonist with similar potency to hydrocodone, but has been found to produce only minimal analgesia when administered peripherally to animals (likely due to poor blood–brain barrier and thus central nervous system penetration).[67] Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of hydrocodone.[68] Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome P450-catalyzed reactions.[69]

Elimination

Hydrocodone is excreted in urine, mainly in the form of conjugates.[8][9]

Chemistry

Detection in body fluids

Hydrocodone concentrations are measured in blood, plasma, and urine to seek evidence of misuse, to confirm diagnoses of poisoning, and to assist in investigations into deaths. Many commercial opiate screening tests react indiscriminately with hydrocodone, other opiates, and their metabolites, but chromatographic techniques can easily distinguish hydrocodone uniquely. Blood and plasma hydrocodone concentrations typically fall into the 5–30 µg/L range among people taking the drug therapeutically, 100–200 µg/L among recreational users, and 100–1,600 µg/L in cases of acute, fatal overdosage. Co-administration of the drug with food or alcohol can very significantly increase the resulting plasma hydrocodone concentrations that are subsequently achieved.[70][71]

Synthesis

Hydrocodone is most commonly synthesized from thebaine, a constituent of opium latex from the dried poppy plant. Once thebaine is obtained, the reaction undergoes hydrogenation using a palladium catalyst.[72]

Structure

There are three important structures in hydrocodone: the amine group, which binds to the tertiary nitrogen binding site in the central nervous system's opioid receptor, the hydroxy group that binds to the anionic binding side, and the phenyl group which binds to the phenolic binding site.[73] This triggers a G protein activation and subsequent release of dopamine.[74]

History

Hydrocodone was first synthesized in Germany in 1920 by Carl Mannich and Helene Löwenheim.[75] It was approved by the Food and Drug Administration on 23 March 1943 for sale in the United States and approved by Health Canada for sale in Canada under the brand name Hycodan.[76][77]

Hydrocodone was first marketed by Knoll as Dicodid, starting in February 1924 in Germany. This name is analogous to other products the company introduced or otherwise marketed: Dilaudid (hydromorphone, 1926), Dinarkon (oxycodone, 1917), Dihydrin (dihydrocodeine, 1911), and Dimorphan (dihydromorphine). Paramorfan is the trade name of dihydromorphine from another manufacturer, as is Paracodin, for dihydrocodeine.[78][79]

The name Dicodid was registered in the United States and appears without a monograph as late as 1978 in the Physicians' Desk Reference; Dicodid may have been marketed to one extent or another in North America in the 1920s and early 1930s. The drug was pure hydrocodone in small 5 and 10 mg tablets, physically similar to the Dilaudid tablets. It is no longer manufactured by Knoll in Germany, nor is a generic available. Hydrocodone was never as common in Europe as it is in North America—dihydrocodeine is used for its spectrum of indications. Germany was the number two consumer of hydrocodone until the manufacture of the drug was discontinued there. Now, the world outside the United States accounts for less than 1% of annual consumption. It was listed as a Suchtgift under the German Betäubungsmittelgesetz and regulated like morphine. It became available in the Schengen Area of the European Union as of 1 January 2002 under Title 76 of the Schengen Treaty.

Society and culture

Formulations

Several common imprints for hydrocodone are M365, M366, M367.[80]

Combination products
Main articles: Hydrocodone/paracetamol and Hydrocodone/ibuprofen
Hydrocodone and paracetamol (acetaminophen) 10-325 tablets (Mallinckrodt)

Most hydrocodone formulations include a second analgesic, such as paracetamol (acetaminophen) or ibuprofen. Examples of hydrocodone combinations include Norco, Vicodin, Vicoprofen and Riboxen.[81]

United States

The US government imposed tougher prescribing rules for hydrocodone in 2014, changing the drug from Schedule III to Schedule II.[82][83][84][85] In 2011, hydrocodone products were involved in around 100,000 abuse-related emergency department visits in the United States, more than double the number in 2004.[86]

References
  1. Bonewit-West K, Hunt SA, Applegate E (2012). Today's Medical Assistant: Clinical and Administrative Procedures. Elsevier Health Sciences. p. 571. ISBN 9781455701506.
  2. Jennifer A. Elliott; Howard S. Smith (19 April 2016). Handbook of Acute Pain Management. CRC Press. pp. 79–. ISBN 978-1-4665-9635-1.
  3. Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  4. Gary S. Firestein; Ralph Budd; Sherine E. Gabriel; Iain B. McInnes; James R. O'Dell (21 June 2016). Kelley and Firestein's Textbook of Rheumatology. Elsevier Health Sciences. pp. 1081–. ISBN 978-0-323-41494-4.
  5. Bruce A. Chabner; Dan L. Longo (8 November 2010). Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott Williams & Wilkins. pp. 700–. ISBN 978-1-60547-431-1.
  6. Shufeng Zhou (6 April 2016). Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism. CRC Press. pp. 164–. ISBN 978-1-4665-9788-4.
  7. Mellar P. Davis; Paul Glare; Janet Hardy (2005). Opioids in Cancer Pain. Oxford University Press. pp. 59–68. ISBN 978-0-19-852943-9.
  8. Martin H. Bluth (16 November 2016). Toxicology and Drug Testing, An Issue of Clinics in Laboratory Medicine, E-Book. Elsevier Health Sciences. pp. 85–. ISBN 978-0-323-47795-6.
  9. Howard S. Smith (21 February 2013). Opioid Therapy in the 21st Century. OUP USA. pp. 68–. ISBN 978-0-19-984497-5.
  10. "Hydrocodone Bitartrate Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 April 2019.
  11. Mallinckrodt (10 March 2021). "HYDROCODONE BITARTRATE AND ACETAMINOPHEN tablet (label)". National Institutes of Health DailyMed. Retrieved 6 November 2021.
  12. Briggs GG, Freeman RK, Yaffe SJ (2011). Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Lippincott Williams & Wilkins. p. 692. ISBN 9781608317080.
  13. "Hydrocodone: MedlinePlus Drug Information". medlineplus.gov. Retrieved 15 April 2019.
  14. "Hydrocodone Use During Pregnancy". Drugs.com. Retrieved 15 April 2019.
  15. "Opioid Dose Calculator". Agency Medical Directors' Group. Archived from the original on 10 February 2016. Retrieved 15 April 2019.
  16. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 526. ISBN 9783527607495.
  17. "Making Some Painkillers Harder to Get". The New York Times. 21 February 2013. Archived from the original on 3 January 2022. Retrieved 15 April 2019.
  18. "Hydrocodone - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  19. Stoker HS (2012). General, Organic, and Biological Chemistry. Cengage Learning. p. 567. ISBN 9781133711285.
  20. Vardanyan R, Hruby V (10 March 2006). Synthesis of Essential Drugs. Elsevier. ISBN 978-0-08-046212-7.
  21. Narcotic Drugs 2020, Estimated World Requirements for 2021, Statistics for 2019 (PDF). International Narcotics Control Board. 2020. p. 37. ISBN 978-92-1-148355-0. Thebaine itself is not used in therapy, but it is an important starting material for the manufacture of a number of opioids, mainly codeine, dihydrocodeine, etorphine, hydrocodone, oxycodone and oxymorphone...
  22. Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD (September 2015). "Complete biosynthesis of opioids in yeast". Science. 349 (6252): 1095–1100. Bibcode:2015Sci...349.1095G. doi:10.1126/science.aac9373. PMC 4924617. PMID 26272907.
  23. Thodey K, Galanie S, Smolke CD (October 2014). "A microbial biomanufacturing platform for natural and semisynthetic opioids". Nature Chemical Biology. 10 (10): 837–844. doi:10.1038/nchembio.1613. PMC 4167936. PMID 25151135.
  24. Nakagawa A, Matsumura E, Koyanagi T, Katayama T, Kawano N, Yoshimatsu K, et al. (February 2016). "Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli". Nature Communications. 7 (1): 10390. Bibcode:2016NatCo...710390N. doi:10.1038/ncomms10390. PMC 4748248. PMID 26847395.
  25. Zacny JP, Gutierrez S (April 2009). "Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers". Drug Alcohol Depend. 101 (1–2): 107–14. doi:10.1016/j.drugalcdep.2008.11.013. PMID 19118954.
  26. Marco CA, Plewa MC, Buderer N, Black C, Roberts A (April 2005). "Comparison of oxycodone and hydrocodone for the treatment of acute pain associated with fractures: a double-blind, randomized, controlled trial". Acad Emerg Med. 12 (4): 282–8. doi:10.1197/j.aem.2004.12.005. PMID 15805317.
  27. Vallejo R, Barkin RL, Wang VC (2011). "Pharmacology of opioids in the treatment of chronic pain syndromes". Pain Physician. 14 (4): E343–60. doi:10.36076/ppj.2011/14/E343. PMID 21785485.
  28. "Opioid (Narcotic Analgesics and Acetaminophen Systemic )". Retrieved 22 March 2014.
  29. Mary Lynn McPherson (24 August 2009). Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. ASHP. pp. 187–188. ISBN 978-1-58528-297-5.
  30. Jan Odom-Forren; Cecil Drain (11 February 2008). PeriAnesthesia Nursing: A Critical Care Approach. Elsevier Health Sciences. pp. 751–. ISBN 978-1-4377-2610-7.
  31. Linda Skidmore-Roth (27 June 2013). Mosby's Drug Guide for Nursing Students, with 2014 Update. Elsevier Health Sciences. pp. 524–. ISBN 978-0-323-22268-6.
  32. Vadivelu N, Schermer E, Kodumudi G, Berger JM (July 2016). "The Clinical Applications of Extended-Release Abuse-Deterrent Opioids". CNS Drugs. 30 (7): 637–646. doi:10.1007/s40263-016-0357-0. PMID 27290716. S2CID 26878027.
  33. MedlinePlus; Drug Information: Hydrocodone. Last Revised—1 October 2008. Retrieved on 20 April 2013.
  34. Friedman RA, House JW, Luxford WM, Gherini S, Mills D (March 2000). "Profound hearing loss associated with hydrocodone/acetaminophen abuse". Am J Otol. 21 (2): 188–91. doi:10.1016/S0196-0709(00)80007-1. PMID 10733182.
  35. Ho T, Vrabec JT, Burton AW (May 2007). "Hydrocodone use and sensorineural hearing loss". Pain Physician. 10 (3): 467–72. PMID 17525781. Archived from the original on 23 July 2011.
  36. Yorgason JG, Kalinec GM, Luxford WM, Warren FM, Kalinec F (June 2010). "Acetaminophen ototoxicity after acetaminophen/hydrocodone abuse: evidence from two parallel in vitro mouse models". Otolaryngol Head Neck Surg. 142 (6): 814–9, 819.e1–2. doi:10.1016/j.otohns.2010.01.010. PMID 20493351. S2CID 25083914.
  37. Curhan SG, Eavey R, Shargorodsky J, Curhan GC (March 2010). "Analgesic use and the risk of hearing loss in men". Am. J. Med. 123 (3): 231–7. doi:10.1016/j.amjmed.2009.08.006. PMC 2831770. PMID 20193831.
  38. "Neonatal abstinence syndrome: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 11 January 2022.
  39. "Opioid Use and Opioid Use Disorder in Pregnancy". www.acog.org. Retrieved 11 January 2022.
  40. "REPREXAIN (hydrocodone bitartrate, ibuprofen) tablet, film coated". dailymed.nlm.nih.gov. NIH. Retrieved 27 April 2013.
  41. Broussard CS, Rasmussen SA, Reefhuis J, Friedman JM, Jann MW, Riehle-Colarusso T, Honein MA (April 2011). "Maternal treatment with opioid analgesics and risk for birth defects". Am. J. Obstet. Gynecol. 204 (4): 314.e1–11. doi:10.1016/j.ajog.2010.12.039. PMID 21345403.
  42. Wightman R, Perrone J, Portelli I, Nelson L (December 2012). "Likeability and abuse liability of commonly prescribed opioids". J Med Toxicol. 8 (4): 335–40. doi:10.1007/s13181-012-0263-x. PMC 3550270. PMID 22992943.
  43. Feng XQ, Zhu LL, Zhou Q (2017). "Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management". J Pain Res. 10: 1225–1239. doi:10.2147/JPR.S138698. PMC 5449157. PMID 28579821.
  44. Kapil RP, Friedman K, Cipriano A, Michels G, Shet M, Mondal SA, Harris SC (October 2015). "Effects of paroxetine, a CYP2D6 inhibitor, on the pharmacokinetic properties of hydrocodone after coadministration with a single-entity, once-daily, extended-release hydrocodone tablet". Clin Ther. 37 (10): 2286–96. doi:10.1016/j.clinthera.2015.08.007. PMID 26350273.
  45. Polepally AR, King JR, Ding B, Shuster DL, Dumas EO, Khatri A, Chiu YL, Podsadecki TJ, Menon RM (August 2016). "Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers". Clin Pharmacokinet. 55 (8): 1003–14. doi:10.1007/s40262-016-0373-8. PMC 4933729. PMID 26895022.
  46. "What is Hydrocodone Bitartrate and Acetaminophen Tablet". American Society of Health-System Pharmacists. Retrieved 15 April 2023. {{cite journal}}: Cite journal requires |journal= (help)
  47. Codd EE, Shank RP, Schupsky JJ, Raffa RB (September 1995). "Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception". J. Pharmacol. Exp. Ther. 274 (3): 1263–70. PMID 7562497.
  48. Filizola M, Villar HO, Loew GH (January 2001). "Molecular determinants of non-specific recognition of delta, mu, and kappa opioid receptors". Bioorg. Med. Chem. 9 (1): 69–76. doi:10.1016/S0968-0896(00)00223-6. PMID 11197347.
  49. King (25 October 2010). Pharmacology for Women's Health. Jones & Bartlett Publishers. pp. 332–. ISBN 978-1-4496-1073-9.
  50. David H. Chestnut; Cynthia A Wong; Lawrence C Tsen; Warwick D Ngan Kee; Yaakov Beilin; Jill Mhyre, eds. (28 February 2014). Chestnut's Obstetric Anesthesia: Principles and Practice E-Book. Elsevier Health Sciences. pp. 611–. ISBN 978-0-323-11374-8.
  51. Adriana P. Tiziani (1 June 2013). Havard's Nursing Guide to Drugs. Elsevier Health Sciences. pp. 933–. ISBN 978-0-7295-8162-2.
  52. Thompson CM, Wojno H, Greiner E, May EL, Rice KC, Selley DE (February 2004). "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". J. Pharmacol. Exp. Ther. 308 (2): 547–54. doi:10.1124/jpet.103.058602. PMID 14600248. S2CID 22492018.
  53. Nicholas J Talley; Brad Frankum; David Currow (10 February 2015). Essentials of Internal Medicine 3e. Elsevier Health Sciences. pp. 491–. ISBN 978-0-7295-8081-6.
  54. "Instructions for Mean Equivalent Daily Dose (MEDD)" (PDF). Archived from the original (PDF) on 27 July 2011. Retrieved 22 August 2010.
  55. Mary C. Brucker; Tekoa L. King (8 September 2015). Pharmacology for Women's Health. Jones & Bartlett Publishers. pp. 322–. ISBN 978-1-284-05748-5.
  56. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/040099s023lbl.pdf
  57. Raffa RB, Colucci R, Pergolizzi JV (September 2017). "The effects of food on opioid-induced nausea and vomiting and pharmacological parameters: a systematic review". Postgrad Med. 129 (7): 698–708. doi:10.1080/00325481.2017.1345282. PMID 28635354.
  58. Bond M, Rabinovich-Guilatt L, Selim S, Darwish M, Tracewell W, Robertson P, Yang R, Malamut R, Colucci P, Ducharme MP, Spiegelstein O (December 2017). "Effect of Food on the Pharmacokinetics of Single- and Multiple-Dose Hydrocodone Extended Release in Healthy Subjects". Clin Drug Investig. 37 (12): 1153–1163. doi:10.1007/s40261-017-0575-3. PMID 28948482.
  59. Farr SJ, Robinson CY, Rubino CM (2015). "Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers". Clin Pharmacol. 7: 1–9. doi:10.2147/CPAA.S70831. PMC 4307648. PMID 25653563.
  60. Devarakonda K, Kostenbader K, Giuliani MJ, Young JL (November 2015). "Single-dose pharmacokinetics of 2 or 3 tablets of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) under fed and fasted conditions: two randomized open-label trials". BMC Pharmacol Toxicol. 16: 31. doi:10.1186/s40360-015-0032-y. PMC 4662814. PMID 26614499.
  61. Steven B. Karch (9 October 2007). Pharmacokinetics and Pharmacodynamics of Abused Drugs. CRC Press. pp. 56–. ISBN 978-1-4200-5460-6.
  62. Amitava Dasgupta; Jorge L. Sepulveda (22 January 2013). Accurate Results in the Clinical Laboratory: A Guide to Error Detection and Correction. Newnes. pp. 239–. ISBN 978-0-12-415858-0.
  63. Amitava Dasgupta; Loralie J. Langman (23 April 2012). Pharmacogenomics of Alcohol and Drugs of Abuse. CRC Press. pp. 175–. ISBN 978-1-4398-5611-6.
  64. Kaplan HL, Busto UE, Baylon GJ, Cheung SW, Otton SV, Somer G, Sellers EM (April 1997). "Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability". J. Pharmacol. Exp. Ther. 281 (1): 103–8. PMID 9103485.
  65. Gardiner SJ, Begg EJ (September 2006). "Pharmacogenetics, drug-metabolizing enzymes, and clinical practice". Pharmacol. Rev. 58 (3): 521–90. doi:10.1124/pr.58.3.6. PMID 16968950. S2CID 25747320.
  66. Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, Kharasch ED, Skaar TC (February 2012). "Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype". Clin. Pharmacol. Ther. 91 (2): 321–6. doi:10.1038/clpt.2011.287. PMC 3289963. PMID 22205192.
  67. Navani DM, Yoburn BC (November 2013). "In vivo activity of norhydrocodone: an active metabolite of hydrocodone". The Journal of Pharmacology and Experimental Therapeutics. 347 (2): 497–505. doi:10.1124/jpet.113.207548. PMID 23995596. S2CID 31072872.
  68. Madadi P, Hildebrandt D, Gong IY, Schwarz UI, Ciszkowski C, Ross CJ, Sistonen J, Carleton BC, Hayden MR, Lauwers AE, Koren G (October 2010). "Fatal hydrocodone overdose in a child: pharmacogenetics and drug interactions". Pediatrics. 126 (4): e986–9. doi:10.1542/peds.2009-1907. PMID 20837591. S2CID 42365304.
  69. Vuilleumier PH, Stamer UM, Landau R (2012). "Pharmacogenomic considerations in opioid analgesia". Pharmgenomics Pers Med. 5: 73–87. doi:10.2147/PGPM.S23422. PMC 3513230. PMID 23226064.
  70. Spiller HA (March 2003). "Postmortem oxycodone and hydrocodone blood concentrations". J. Forensic Sci. 48 (2): 429–31. doi:10.1520/JFS2002309. PMID 12665006.
  71. Randall C. Baselt (2017). Disposition of Toxic Drugs and Chemicals in Man. Biomedical Publications. pp. 1050–1052. ISBN 978-0-692-77499-1.
  72. Carroll RJ, Leisch H, Rochon L, Hudlicky T, Cox DP (January 2009). "One-pot conversion of thebaine to hydrocodone and synthesis of neopinone ketal". The Journal of Organic Chemistry. 74 (2): 747–752. doi:10.1021/jo802454v. PMID 19072148.
  73. Sinatra RS (6 December 2010). The Essence of Analgesia and Analgesics. Cambridge: Cambridge University Press. pp. 73, 81. ISBN 9780511841378.
  74. Cruz SL (27 October 2016). Neuroscience in the 21st Century. New York, NY: Springer. pp. 3626, 3657. ISBN 978-1-4939-3474-4.
  75. Mannich C, Löwenheim H (1920). "Ueber zwei neue Reduktionsprodukte des Kodeins". Archiv der Pharmazie. 258 (2–4): 295–316. doi:10.1002/ardp.19202580218. ISSN 0365-6233. S2CID 97513395.
  76. "Drugs@FDA—Approval History: Hycodan". FDA. Retrieved 7 January 2006.
  77. "FDA Docket No. 2007N-0353, Drug Products Containing Hydrocodone; Enforcement Action Dates". FDA. Retrieved 7 January 2006. See section I. B., DESI Review of Hydrocodone Products
  78. "Dihydromorphine". PubChem. U.S. National Library of Medicine. Retrieved 21 May 2021.
  79. "Dihydrocodeine". PubChem. U.S. National Library of Medicine. Retrieved 21 May 2021.
  80. International Narcotics Control Board Report 2008. United Nations Pubns. 2009. p. 20. ISBN 978-9211482324.
  81. "Hydrocodone Combination Products". MedlinePlus. The American Society of Health-System Pharmacists, Inc. Retrieved 14 July 2018.
  82. McCarthy M (January 2016). "Prescriptions for hydrocodone plummet after US tightens prescribing rules". BMJ. 352: i549. doi:10.1136/bmj.i549. PMID 26819247. S2CID 45954090.
  83. Jones CM, Lurie PG, Throckmorton DC (March 2016). "Effect of US Drug Enforcement Administration's Rescheduling of Hydrocodone Combination Analgesic Products on Opioid Analgesic Prescribing". JAMA Internal Medicine. 176 (3): 399–402. doi:10.1001/jamainternmed.2015.7799. PMID 26809459.
  84. Chambers J, Gleason RM, Kirsh KL, Twillman R, Webster L, Berner J, et al. (September 2016). "An Online Survey of Patients' Experiences Since the Rescheduling of Hydrocodone: The First 100 Days". Pain Medicine. 17 (9): 1686–1693. doi:10.1093/pm/pnv064. PMID 26814291.
  85. "Schedules of Controlled Substances: Rescheduling of Hydrocodone Combination Products From Schedule III to Schedule II". Federal Register. 22 August 2014. Retrieved 11 August 2017.
  86. "Drug-Related Hospital Emergency Room Visits". National Institute on Drug Abuse. Retrieved 11 August 2017.
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