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Systematic (IUPAC) name
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a601006
Pregnancy cat. C (US)
Legal status Controlled (S8) (AU) Schedule I (CA) Class A (CD) (UK) Schedule II in bulk quantities or as stand-alone product; Schedule III when in combination product with no more than 15mg per dose unit (USA)
Dependence liability Moderate
Routes oral, intranasal, rectal
Pharmacokinetic data
Bioavailability High (80% +)
Metabolism Hepatic
Half-life 3.8–6 hours
Excretion Renal
CAS number 125-29-1 YesY
ATC code R05DA03
PubChem CID 5284569
DrugBank DB00956
ChemSpider 4447623 YesY
KEGG D08045 YesY
Synonyms dihydrocodeinone
Chemical data
Formula C18H21NO3 
Mol. mass 299.368 g/mol
 YesY (what is this?)  (verify)

Hydrocodone is a semi-synthetic opioid derived from codeine. Hydrocodone is used orally as a narcotic analgesic and antitussive (cough medicine), often in combination with paracetamol (acetaminophen) or ibuprofen.[1] Hydrocodone is prescribed predominantly in the United States. The International Narcotics Control Board reported 99% of the worldwide supply in 2007 was consumed in the United States.[2]

Medical uses[edit]

Hydrocodone is used to treat moderate to severe pain and as an antitussive to treat cough.[1] 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).[3] The investigators interpreted this to mean that oxycodone is about 50% more potent than hydrocodone, however, in a study of emergency room 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.[4] Some references state that the analgesic action of hydrocodone begins in 20-30 minutes and lasts about 4-8 hours.[5] The manufacturer's information says onset of action is about 10-30 minutes and duration is about 4-6 hours.[6] Recommended dosing interval is 4-6 hours.

Adverse effects[edit]

Common side effects of hydrocodone are nausea, vomiting, constipation, drowsiness, dizziness, lightheadedness, fuzzy thinking, anxiety, abnormally happy or sad mood, dry throat, difficulty urinating, rash, itching, and narrowing of the pupils. Serious side effects include slowed or irregular breathing and chest tightness.[7]

Several cases of progressive bilateral hearing loss unresponsive to steroid therapy have been described as an infrequent adverse reaction to hydrocodone/acetaminophene abuse. This adverse effect has been considered due to the ototoxicity of hydrocodone.[8][9] Recently, researchers suggested that acetaminophen is the primary agent responsible for the ototoxicity.[10][11]

It is in 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. The baby may also exhibit respiratory depression if the opioid dose was high.[12] An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects.[13]

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.[7]

Hydrocodone can be habit-forming, causing physical and psychological dependence. Its abuse liability is similar to morphine and less than oxycodone.[14]

Contraindications and interactions[edit]

Patients consuming alcohol, other opioids, antihistamines, antipsychotics, antianxiety agents, or other central nervous system (CNS) depressants together with hydrocodone may exhibit an additive CNS depression.[12] Hydrocodone may interact with serotonergic medications.[15]


As a narcotic, hydrocodone relieves pain by binding to opioid receptors in the CNS. It acts primarily on μ-opioid receptors, with about six times lesser affinity to δ-opioid receptors. In blood, 20–50% of hydrocodone is bound to protein.[5][16]

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.[17] Per os 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.[18]


Hydrocodone is biotransformed by the liver into several metabolites, and has a serum half-life that averages 3.8 hours.[17] The hepatic cytochrome P450 enzyme CYP2D6 converts it into hydromorphone, a more potent opioid. 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.[19][20] Ultrarapid CYP2D6 metabolizers (1-2% of the population) may have an increased response to hydrocodone; however, hydrocodone metabolism in this population has not been studied.[21]

A major metabolite, norhydrocodone, is predominantly formed by CYP3A4-catalyzed oxidation. Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of hydrocodone.[22] Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome catalyzed reactions.[23]


Hydrocodone and paracetamol (acetaminophen) 5-500 tablets (Mallinckrodt)

The FDA has approved and released a new product, by Zogenix Pharmaceuticals, by the brand name of Zohydro(R). It is the first ever pure hydrocodone product in the US. It comes as a capsule with hydrocodone powder inside. They are available now by prescription and come in Extended-release capsules: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg and 50 mg. This is 5 times as much active opioid as the highest strength Hydrocodone/APAP product (10mg/325mg).Zohydro™ ER (hydrocodone bitartrate) is 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. Zohydro(R) is schedule II controlled substance under the CSA. http://www.zogenix.com/content/products/zohydro.htm

Rya W. Zobel has indicated that she may allow the distribution of Zohydro in Massachusetts.[24]

Recreational use[edit]

Many users of hydrocodone report a sense of satisfaction (euphoria), especially at higher doses. A number of users also report a warm or pleasant numbing sensation throughout the body, one of the best known effects of narcotics.[25][medical citation needed] Withdrawal symptoms may include, but are not limited to; severe pain, pins and needles sensation throughout body, sweating, extreme anxiety and restlessness, sneezing, watery eyes, fever, depression, stomach cramps, diarrhea, and extreme drug cravings, among others.[26][unreliable medical source?]

Taking hydrocodone with grapefruit juice is one of the measures believed to enhance its narcotic effect. It is believed that CYP3A4 inhibitors in grapefruit juice may decrease metabolism of hydrocodone,[27] although there has been no research into this issue. Additionally, many medications are either substrates (competing for metabolism and exhausting available enzymes) or direct inhibitors or CYP3A4. Inhibition of CYP2D6 would also increase the duration of hydrocodones effects and its concentration in the blood, leading to exaggerated effects. Complete inhibition of both enzymes would theoretically inhibit 60% of the factors involved in hydrocodones metabolism.

Detection in body fluids[edit]

Hydrocodone may be quantitated in blood, plasma or urine to monitor for misuse, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Many commercial opiate screening tests cross-react appreciably with hydrocodone and its metabolites, but chromatographic techniques can easily distinguish hydrocodone from other opiates. Blood or plasma hydrocodone concentrations are typically in the 5–30 µg/L range in persons taking the drug therapeutically, 100–200 µg/L in abusers and 100–1,600 µg/L in cases of acute fatal overdosage.[28][29]



In Australia, hydrocodone is a Schedule 8 (S8) or Controlled Drug.


Hydrocodone is regulated in the same fashion as in Germany (see below) under the Austrian Suchtmittelgesetz; since 2002 it has been available in the form of German products and those produced elsewhere in the European Union under Article 76 of the Schengen Treaty—prior to this, no Austrian companies produced hydrocodone products, with dihydrocodeine and nicomorphine being more commonly used for the same levels of pain and the former for coughing.


In Belgium, hydrocodone is no longer available for medical use.


In France, hydrocodone (Vicodin) is no longer available for medical use. Hydrocodone is a prohibited narcotic.


In Germany, hydrocodone is no longer available for medical use. Hydrocodone is listed under the Betäubungsmittelgesetz as a Suchtgift in the same category as morphine.


In Luxembourg, hydrocodone is available by prescription under the name Biocodone. Prescriptions are more commonly given for use as a cough suppressant (antitussive) rather than for pain relief (analgesic).

The Netherlands

In the Netherlands, hydrocodone is not available for medical use and is classified as a List 1 drug under the Opium Law.


Hydrocodone is no longer available for medical use. The last remaining formula was banned in 1967.

United Kingdom

In the UK, hydrocodone is not available for medical use and is listed as a Class A drug under the Misuse of Drugs Act 1971. Various formulations of dihydrocodeine, a weaker opioid, are frequently used as an alternative for the aforementioned indications of hydrocodone use.

United States

In the U.S., formulations containing more than 15 mg per dosage unit are considered Schedule II drugs, as would any formulation consisting of just hydrocodone alone. Those containing less than or equal to 15 mg per dosage unit in combination with acetaminophen or another non-controlled drug are called hydrocodone compounds and are currently considered Schedule III drugs, although that is likely to change in 2014. Hydrocodone is typically found in combination with other drugs such as acetaminophen, aspirin, ibuprofen and homatropine methylbromide. The purpose of the non-controlled drugs in combination is often twofold: 1) To provide increased analgesia via drug synergy. 2) To limit the intake of hydrocodone by causing unpleasant and often unsafe side effects at higher-than-prescribed doses. Hydrocodone is not commercially available in pure form in the United States due to a separate regulation, and is always sold with an NSAID, paracetamol, antihistamine, expectorant, or homatropine. Pure hydrocodone is a more strictly controlled Schedule II drug[30] and sold by compounding pharmacies. The cough preparation Codiclear DH is the purest commercial US hydrocodone item, containing guaifenesin and small amounts of ethanol as active ingredients.

Under the Controlled Substances Act (CSA), hydrocodone is currently listed as both a Schedule II and Schedule III substance depending on the formulation.

  • Schedule II lists hydrocodone in pure form and any formulations of combination products containing more than 15 mg hydrocodone per dosage unit.
  • Schedule III lists hydrocodone in formulations of combination products containing up to 15 mg hydrocodone per dosage unit.

On 25-Oct-2013 the U.S. Food & Drug Administration recommended tighter controls of the drug by reclassifying all formulations of hydrocodone as Schedule II. The change would take place as early as 2014.[31]

Hydrocodone was until recently the active antitussive in more than 200 formulations of cough syrups and tablets sold in the United States. In late 2006, the FDA began forcing the recall of many of these formulations due to reports of deaths in infants and children under the age of six. The legal status of drug formulations originally sold between 1938 and 1962—before FDA approval was required—was ambiguous. As a result of FDA enforcement action, by August 2010, 88% of the hydrocodone-containing medications had been removed from the market.[32][not in citation given]

At the present time[when?], doctors, pharmacists, and codeine-sensitive or allergic patients or sensitive to the amounts of histamine released by its metabolites must choose among rapidly dwindling supplies of the Hycodan-Codiclear-Hydromet type syrups, Tussionex—an extended-release suspension similar to the European products Codipertussin (codeine hydrochloride), Paracodin suspension (dihydrocodeine hydroiodide), Tusscodin (nicocodeine hydrochloride) and others—and a handful of weak dihydrocodeine syrups. The low sales volume and Schedule II status of Dilaudid cough syrup predictably leads to under-utilisation of the drug. There are several conflicting views concerning the US availability of cough preparations containing ethylmorphine (also called dionine or codethyline)—Feco Syrup and its equivalents were first marketed circa 1895 and still in common use in the 1940s and 1950s, and the main ingredient is treated like codeine under the Controlled Substances Act of 1970.[citation needed]

In the U.S., hydrocodone is always found in combination with other drugs such as paracetamol (also called acetaminophen), aspirin, an NSAID, ibuprofen, an antihistamine, an expectorant, or homatropine methylbromide due to compounding regulations. These combinations are considered C-III substances, prescriptions for which are generally valid for 6 months, including refills. The purpose of the non-controlled drugs in combination is often twofold:

  1. To provide increased analgesia via drug synergy.
  2. To limit the intake of hydrocodone by causing unpleasant and often unsafe side effects at higher-than-prescribed doses (see below).

As of July 2010, the FDA was considering banning some hydrocodone and oxycodone fixed-combination proprietary prescription drugs—based on the paracetamol content and the widespread occurrence of liver problems. FDA action on this suggestion would ostensibly also affect codeine and dihydrocodeine products such as the Tylenol With Codeine and Panlor series of drugs.[citation needed] In 2010, it was the most prescribed drug in the USA, with 131.2 million prescriptions of hydrocodone (combined with paracetamol) being written.[33]

By itself, hydrocodone is a Schedule II drug. The commercial hydrocodone preparations that have been approved by the US Food and Drug Administration are almost always combined with another medication, which is often a painkiller and is most frequently acetaminophen. The additional drug is primarily there as an abuse deterrent, although they may also increase efficacy. These compound medications are classified as Schedule III.[27]

The rationale of combining hydrocodone with other pain-killers is that the combination may increase efficacy, and the adverse effects may be reduced as compared with an equally effective dose of a single agent.[34][35] A combination of hydrocodone and ibuprofen was more effective than either of the drugs on their own in relieving postoperative pain. The overall effect of the combination could be presented as a sum of the effects of ibuprofen and hydrocodone, which is consistent with differing mechanisms of action of these drugs.[36][37][38] Similar results were observed for hydrocodone-acetaminophen combination.[34]

Four pharmaceutical companies (Purdue Pharma, Cephalon, Egalet and Zogenix) are developing extended-release formulations of hydrocodone by itself; the Zogenix product was approved by the US FDA on October 25, 2013 and is expected to be launched 1Q2014. These formulations are expected to avoid the issue of hepatotoxicity of acetaminophen containing formulations. They may also have lower abuse potential.[39] A group of 40 health care, consumer and addiction treatment groups have called on the FDA to withdraw its approval.[40]


Hydrocodone was first synthesized in Germany in 1920 by Carl Mannich and Helene Löwenheim.[41] 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.[42][43]

See also[edit]


  1. ^ a b Karch, Steven B. (2008). Pharmacokinetics and pharmacodynamics of abused drugs. Boca Raton: CRC Press. pp. 55–56. ISBN 1-4200-5458-9. 
  2. ^ International Narcotics Control Board Report 2008.. United Nations Pubns. 2009. p. 20. ISBN 9211482321. 
  3. ^ Zacny, J. P.; Gutierrez, S. (2009). "Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers". Drug and Alcohol Dependence 101 (1–2): 107–114. doi:10.1016/j.drugalcdep.2008.11.013. PMID 19118954.  edit
  4. ^ Marco, C. A.; Plewa, M. C.; Buderer, N; Black, C; Roberts, A (2005). "Comparison of oxycodone and hydrocodone for the treatment of acute pain associated with fractures: A double-blind, randomized, controlled trial". Academic Emergency Medicine 12 (4): 282–8. doi:10.1197/j.aem.2004.12.005. PMID 15805317.  edit
  5. ^ a b Vallejo, R.; Barkin, R. L.; Wang, V. C. (2011). "Pharmacology of opioids in the treatment of chronic pain syndromes". Pain physician 14 (4): E343–E360. PMID 21785485.  edit
  6. ^ "Opioid (Narcotic Analgesics and Acetaminophen Systemic )". Retrieved 2014-03-22. 
  7. ^ a b MedlinePlus; Drug Information: Hydrocodone. Last Revised—1 October 2008. Retrieved on 20 April 2013.
  8. ^ Friedman RA, House JW, Luxford WM, Gherini S, Mills D (Mar 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. 
  9. ^ Ho T, Vrabec JT, Burton AW (May 2007). "Hydrocodone use and sensorineural hearing loss". Pain Physician 10 (3): 467–72. PMID 17525781. 
  10. ^ Yorgason, J. G.; Kalinec, G. M.; Luxford, W. M.; Warren, F. M.; Kalinec, F. (2010). "Acetaminophen ototoxicity after acetaminophen/hydrocodone abuse: Evidence from two parallel in vitro mouse models". Otolaryngology - Head and Neck Surgery 142 (6): 814–819, 819.819–2. doi:10.1016/j.otohns.2010.01.010. PMID 20493351.  edit
  11. ^ Curhan, S. G.; Eavey, R.; Shargorodsky, J.; Curhan, G. C. (2010). "Analgesic Use and the Risk of Hearing Loss in Men". The American Journal of Medicine 123 (3): 231–237. doi:10.1016/j.amjmed.2009.08.006. PMC 2831770. PMID 20193831.  edit
  12. ^ a b "REPREXAIN(hydrocodone bitartrate, ibuprofen) tablet, film coated". http://dailymed.nlm.nih.gov. NIH. Retrieved April 27, 2013. 
  13. ^ Broussard, C. S.; Rasmussen, S. A.; Reefhuis, J.; Friedman, J. M.; Jann, M. W.; Riehle-Colarusso, T.; Honein, M. A.; National Birth Defects Prevention Study (2011). "Maternal treatment with opioid analgesics and risk for birth defects". American Journal of Obstetrics and Gynecology 204 (4): 314.3e1–11. doi:10.1016/j.ajog.2010.12.039. PMID 21345403.  edit
  14. ^ Wightman, R.; Perrone, J.; Portelli, I.; Nelson, L. (2012). "Likeability and Abuse Liability of Commonly Prescribed Opioids". Journal of Medical Toxicology 8 (4): 335–340. doi:10.1007/s13181-012-0263-x. PMID 22992943.  edit
  15. ^ Gnanadesigan N, Espinoza RT, Smith RL (June 2005). "The serotonin syndrome". N Engl J Med 352 (23): 2454–6; author reply 2454–6. doi:10.1056/NEJM200506093522320. PMID 15948273. 
  16. ^ Thompson, C. M.; Wojno, H.; Greiner, E.; May, E. L.; Rice, K. C.; Selley, D. E. (2003). "Activation of G-Proteins by Morphine and Codeine Congeners: Insights to the Relevance of O- and N-Demethylated Metabolites at  - and  -Opioid Receptors". Journal of Pharmacology and Experimental Therapeutics 308 (2): 547–554. doi:10.1124/jpet.103.058602. PMID 14600248.  edit
  17. ^ a b Davis, Mellar P. (2005). "Hydrocodone". Opioids for cancer pain. Oxford UK: Oxford University Press. pp. 59–68. ISBN 0-19-852943-0. 
  18. ^ "Instructions for Mean Equivalent Daily Dose (MEDD)" (PDF). Retrieved 2010-08-22. 
  19. ^ Kaplan, H. L.; Busto, U. E.; Baylon, G. J.; Cheung, S. W.; Otton, S. V.; Somer, G.; Sellers, E. M. (1997). "Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability". The Journal of pharmacology and experimental therapeutics 281 (1): 103–108. PMID 9103485.  edit
  20. ^ Gardiner, S. J.; Begg, E. J. (2006). "Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice". Pharmacological Reviews 58 (3): 521–590. doi:10.1124/pr.58.3.6. PMID 16968950.  edit
  21. ^ Crews, K. R.; Gaedigk, A.; Dunnenberger, H. M.; Klein, T. E.; Shen, D. D.; Callaghan, J. T.; Kharasch, E. D.; Skaar, T. C.; Clinical Pharmacogenetics Implementation Consortium (2011). "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype". Clinical Pharmacology & Therapeutics 91 (2): 321–326. doi:10.1038/clpt.2011.287. PMC 3289963. PMID 22205192.  edit
  22. ^ Madadi, P; Hildebrandt, D; Gong, I. Y.; Schwarz, U. I.; Ciszkowski, C; Ross, C. J.; Sistonen, J; Carleton, B. C.; Hayden, M. R.; Lauwers, A. E.; Koren, G (2010). "Fatal hydrocodone overdose in a child: Pharmacogenetics and drug interactions". PEDIATRICS 126 (4): e986–9. doi:10.1542/peds.2009-1907. PMID 20837591.  edit
  23. ^ Landau, R.; Stamer, U. M.; Landau, R. (2012). "Pharmacogenomic considerations in opioid analgesia". Pharmacogenomics and Personalized Medicine 5: 73–87. doi:10.2147/PGPM.S23422. PMC 3513230. PMID 23226064.  edit
  24. ^ Valencia, Milton J. (8 April 2014). "Zobel signals she’ll reject Patrick’s action on Zohydro". www.bostonglobe.com. Boston Globe Media Partners, LLC. Retrieved 09 April 2014. 
  25. ^ "Hydrocodone". http://www.justice.gov. United States Government. 2007-07-01. Archived from the original on 2007-07-01. Retrieved 2010-01-13. 
  26. ^ "Hydrocodone Withdrawal Symptoms". Retrieved 2012-07-24. 
  27. ^ a b Hernandez, S. H.; Nelson, L. S. (2010). "Prescription Drug Abuse: Insight into the Epidemic". Clinical Pharmacology & Therapeutics 88 (3): 307–317. doi:10.1038/clpt.2010.154. PMID 20686478.  edit
  28. ^ Spiller HA. Postmortem oxycodone and hydrocodone blood concentrations. J. Forensic Sci. 48: 429–431, 2003.
  29. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 812–814.
  30. ^ "Controlled Substances Act". Wikipedia. Retrieved 8 February 2012. 
  31. ^ "F.D.A. Urging a Tighter Rein on Painkillers — NYTimes.com, U.S. Edition &lquot;Business Day,&rquot; from". The New York Times on NYTimes.com. 2013-10-25. Retrieved 2013-10-26. 
  32. ^ "Medical News: FDA Pulls Plug on 200-Plus Unapproved Cough Syrups With Hydrocodone—in Product Alert, Prescriptions from". MedPage Today. Retrieved 2010-08-22. 
  33. ^ DeNoon, Daniel J. (April 20, 2011). "The 10 Most Prescribed Drugs". eMedicineHealth. Retrieved 16 August 2012. 
  34. ^ a b Beaver, W. T.; McMillan, D. (1980). "Methodological considerations in the evaluation of analgesic combinations: Acetaminophen (paracetamol) and hydrocodone in postpartum pain". British journal of clinical pharmacology. 10 Suppl 2 (Suppl 2): 215S–223S. PMC 1430165. PMID 7192153.  edit
  35. ^ Raffa, R. B. (2001). "Pharmacology of oral combination analgesics: Rational therapy for pain". Journal of clinical pharmacy and therapeutics 26 (4): 257–264. doi:10.1046/j.1365-2710.2001.00355.x. PMID 11493367.  edit
  36. ^ Wideman, G.; Keffer, M.; Morris, E.; Doylejr, R.; Jiang, J.; Beaver, W. (1999). "Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain". Clinical Pharmacology & Therapeutics 65 (1): 66–76. doi:10.1016/S0009-9236(99)70123-2. PMID 9951432.  edit
  37. ^ Sunshine, A.; Olson, N. Z.; O'Neill, E.; Ramos, I.; Doyle, R. (1997). "Analgesic efficacy of a hydrocodone with ibuprofen combination compared with ibuprofen alone for the treatment of acute postoperative pain". Journal of clinical pharmacology 37 (10): 908–915. doi:10.1002/j.1552-4604.1997.tb04265.x. PMID 9505982.  edit
  38. ^ Betancourt, J. W.; Kupp, L. I.; Jasper, S. J.; Farooqi, O. A. (2004). "Efficacy of Ibuprofen-Hydrocodone for the Treatment of Postoperative Pain After Periodontal Surgery". Journal of Periodontology 75 (6): 872–876. doi:10.1902/jop.2004.75.6.872. PMID 15295955.  edit
  39. ^ Trescot, A.; Krashin, D.; Murinova, A. M. (2013). "Extended-release hydrocodone – gift or curse?". Journal of Pain Research 6: 53–57. doi:10.2147/JPR.S33062. PMC 3555555. PMID 23358452.  edit
  40. ^ Smith, Stephanie (26 February 2014). "New pain pill's approval: 'Genuinely frightening'". www.cnn.com. CNN. Retrieved 26 February 2014. 
  41. ^ Mannich, C.; Löwenheim, H. (1920). "Ueber zwei neue Reduktionsprodukte des Kodeins". Archiv der Pharmazie 258 (2–4): 295–316. doi:10.1002/ardp.19202580218. 
  42. ^ "Drugs@FDA—Approval History: Hycodan". FDA. Retrieved 2006-01-07. 
  43. ^ "FDA Docket No. 2007N-0353, Drug Products Containing Hydrocodone; Enforcement Action Dates". FDA. Retrieved 2006-01-07.  See section I. B., DESI Review of Hydrocodone Products

External links[edit]