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Systematic (IUPAC) name
Clinical data
  • Category C (USA)
Routes of
oral, intranasal, rectal
Legal status
Legal status
Pharmacokinetic data
Bioavailability High (80% +)
Metabolism Hepatic
Biological half-life 3.8–6 hours
Excretion Renal
CAS Number 125-29-1
ATC code R05DA03 (WHO)
PubChem CID 5284569
DrugBank DB00956
ChemSpider 4447623
Synonyms dihydrocodeinone
Chemical data
Formula C18H21NO3
Molar mass 299.368 g/mol[[Script error: No such module "String".]]
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Indicated for:

Other uses:

  • Alcohol
  • Amphetamines
  • Barbiturates
  • Benzodiazapines
  • Cocaine
  • Methylphenidate
Non-medical use/abuse:
  • Used as a euphoriant
Side effects:


Atypical sensations:


  • N/A

Ear, nose, and throat:

  • Hearing loss (with prolonged use)


  •  ?


  • N/A





  • Anxiety, mood swings


  • Depressed respiration


  • Itching, rash

Urogenital and reproductive:

  •  ?


  • Allergic reaction, ,

Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates - codeine and thebaine. Hydrocodone is an orally active narcotic analgesic (pain reliever) and antitussive (cough suppressant). It is commonly available in tablet, capsule, and syrup form, and is often compounded with other, generally less effective non-opioid compounds such as paracetamol (also known as acetaminophen) or ibuprofen, often added to both discourage recreational use (as paracetamol can cause potentially fatal liver toxicity at high doses), and to provide a possible synergy of analgesic effects between hydrocodone and the non-opioid compounds present. However, the effectiveness and safety of hydrocodone compound products versus hydrocodone-only products remains a highly debated issue.

The particular niche in which hydrocodone is most commonly used is as an intermediate centrally acting analgesic and strong cough suppressant, especially in those for whom histamine release and attendant itching from codeine is a problem. For the latter indication, at the 5 to 10 mg dose range hydrocodone is more powerful than most cough suppressants, being roughly equal to its derivative dihydrocodeinone enol acetate, with the top of the list being morphine and hydromorphone and methadone (methadone linctus, about 33 percent the concentration of the liquid used for opioid physical dependence maintenance or detoxification) and dihydrocodeine being right below. The experiments in dogs conducted by Winder and Rosière in the mid-1950s reported in the Journal of Pharmacology in 1955 indicate that hydrocodone is 12 times stronger than codeine as an antitussive (morphine 14×, methadone 9×), and other tests from 1920 forward showed it was about six times stronger as an analgesic.


Hydrocodone was first synthesized in Germany in 1920[1] and 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.[2][3]

Hydrocodone and compounds containing it are marketed, in varying forms, under a number of trademarks, including Vicodin, Hydrococet, Symtan, Anexsia, Damason-P, Dicodid, Hycodan (or generically Hydromet), Hycomine, Hycet, Lorcet, Lortab, Norco, Novahistex, Hydrovo, Duodin, Kolikodol, Orthoxycol, Panacet, Zydone, Mercodinone, Synkonin, Norgan, Xodol and Hydrokon. Hycodan was the original trade name. The trade name Dicodid was chosen because hydrocodone is the codeine analogue of hydromorphone (Dilaudid and the naming scheme extended to related drugs like Dihydrin (dihydrocodeine) and Dinarkon (oxycodone). The trade name Vicodin refers to hydrocodone being six times stronger than codeine by mouth, as in the Roman numeral VI.


Hydrocodone Bitartrate 10mg/
Acetaminophen 650mg

As a narcotic, hydrocodone relieves pain by binding to opioid receptors in the brain and spinal cord. It can be taken with or without food as desired. When taken with alcohol, it can intensify drowsiness. It may interact with monoamine oxidase inhibitors, as well as other drugs that cause drowsiness. It is in FDA pregnancy category C. Animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. In addition, a newborn of a mother taking the medication may exhibit breathing problems or withdrawal symptoms.

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 found to be higher than that of morphine.[4] Per os hydrocodone has a MEDD factor of .4, meaning that 1mg of hydrocodone is equivalent to .4mg 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.[5]

Hydrocodone can be habit-forming, which leads to physical and psychological dependence, but the potential for addiction varies from individual to individual depending on unique biological differences. Sales and production of this drug have increased significantly in recent years, as have diversion and illicit use. In the U.S., (however the latter do not exist in the U.S.-- see comment below). Hydrocodone in a form by itself (with no added components) is considered a C-II controlled substance (Also known as a schedule II). This means that its prescription and distribution are heavily monitored by the FDA. C-II substances are the most heavily controlled substances available for prescription in the US. Most C-II substances have a high risk of addiction and have a marked affect on the CNS (Central Nervous System). With a C-II, a doctor cannot permit refills of the prescription. You must receive the prescription by hand from your doctor and they may only write one prescription at a time. You must also present the hard copy of your prescription to the pharmacist. As with all C-II substances, it is illegal for the doctor to fax and/or phone in the prescription to the pharmacy (except in limited 'emergency' situations defined by regulation, which limit quantities to those needed until a written prescription can be obtained and provided to the pharmacy.) Most state laws put a 3 month "half life" on the prescription, meaning that a pharmacy cannot legally fill the prescription if the date on the prescription is beyond the 3 month mark.

As with many other opioids, it is quite possible to reduce the amount of hydrocodone needed to stop a certain level of pain by having the patient take the hydrocodone along with one of the medications with analgesic-sparing properties, also known as potentiators. The most common, one of the most effective with hydrocodone, and safest is hydroxyzine (often marketed under the brand name Vistaril). Orphenadrine, nefopam, carisoprodol, and antihistamines also potentiate most opioids. Especially in the case of carisoprodol, it is imperative that the titration and addition of the potentiator be done under strict supervision of a physician.

Hydrocodone also interacts relatively well with most adjuvant and atypical analgesics used for severe and neuropathic pain such as first-generation anti-depressants, anticholinergics, anticonvulsants, centrally acting stimulants, NMDA antagonists, etc. Hydrocodone can usually be successfully used with duloxetine (Cymbalta) for neuropathic pain, especially that from diabetic neuropathy, provided that the patient has normal relative and absolute levels of Cytochrome P450-related liver enzymes.


Hydrocodone and paracetamol (acetaminophen) 5-500 tablets (Mallinckrodt).
When sold commercially in the United States, hydrocodone is always combined with another medication. Those combined with paracetamol (acetaminophen) are known by various trademark names, such as Vicodin and Lortab. Hydrocodone also can be combined with aspirin (e.g., Lortab ASA), and ibuprofen (e.g., Vicoprofen).

Combining an opioid such as hydrocodone with another analgesic can increase the effectiveness of the drug without increasing opioid-related side effects (e.g., nausea, constipation, sedation). Another argument for combining hydrocodone with paracetemol (acetaminophen) is that it limits the potential for misuse. As with other opioid analgesics, with a few exceptions, there is no ceiling dose for hydrocodone in users tolerant to its effects; however the hepatotoxicity of the acetaminophen it is often combined with begins to manifest itself with doses of around 4,000mg/day.[6]


Hydrocodone is used to treat moderate to severe pain and is also used as an antitussive to treat cough in formulations such as Codiclear and Tussionex. Tussionex has a timed-release formulation containing both hydrocodone polistirex and chlorpheniramine polistirex (a sulfonated styrene-divinylbenzene copolymer complex) at concentrations equivalent to 10 mg/5 mL hydrocodone bitartrate and 8 mg/5 mL of chlorpheniramine maleate. Its strength, pleasant taste and extended duration of action make it both a good antitussive and an easily ingestible recreational drug. Due to the ease of administration, the potenital for misuse may resemble that of the more potent opioids.[7][8]

Contraindications and interactions

Mixing hydrocodone with alcohol, cocaine, amphetamines, methylphenidate, benzodiazapines, barbiturates, and a number of other medication can have severe adverse reactions including but not limited to heart failure, heart attack, respiratory distress, pulmonary failure, liver or kidney failure, jaundice, amnesia, seizures, blackouts, and coma.[citation needed] Also, hydrocodone can cause false indications on blood and urinalysis testing for morphine, codeine, hydromorphone and cocaine depending on usage and dosing. Generally this effect is only present when doses are taken for long periods of time, and the effect ceases after cessation of use.


Because all commercially available hydrocodone compounds prescribed in the United States contain secondary analgesics, there are serious health risks posed by concurrently consuming any amount of alcohol with hydrocodone compounds.

The most common medication compounded with hydrocodone is APAP (acetaminophen), which is metabolized solely by the liver. Therefore the risk of fatal overdose due to hepatotoxicity can occur with significantly lower levels of APAP when mixed with ethanol. Also the mixture can potentially cause serious damage to the liver, kidneys, and stomach wall. Acetaminophen may increase the potential for coma, respiratory problems, and can damage the CNS.[9]


Hydrocodone is biotransformed by the liver into several metabolites, and has a serum half-life that averages 3.8 hours.[4] The hepatic cytochrome P450 enzyme CYP2D6 converts it into hydromorphone, a more potent opioid. CYP2D6 poor metabolizers (~10% of the Caucasian population) have a reduced capacity for this metabolic pathway, and so might receive a reduced analgesic benefit from the drug. However, the pharmacodynamic profile of the drug in these individuals indicates that the effects of hydrocodone are largely independent of its conversion to hydromorphone.[10]

Adverse effects

File:Side effects of Hydrocodone.png
Main side effects of hydrocodone.[11] The respiratory effects are most serious, requiring immediate contact with health provider.[11]

Common side effects include dizziness, itching, lightheadedness, nausea, sweating, drowsiness, constipation, vomiting, and euphoria. Vomiting in some patients is so severe that hospitalization is required.[citation needed] Some less common side effects are allergic reaction, blood disorders, changes in mood, racing heartbeat, mental fogginess, anxiety, lethargy, difficulty urinating, spasm of the ureter, irregular or depressed respiration, and rash.

Hydrocodone in particular, and the -codone family of opioids in general, have been shown to have a liability to cause long term hearing loss over periods of use.[12][13]

Some of the effects of hydrocodone come from the fact that a fraction of it is changed to hydromorphone in the liver, as is the case with all codeine-based analgesics (codeine into morphine, dihydrocodeine into dihydromorphine, nicocodeine into nicomorphine etc.). The percentage can vary based on both other medications taken and inherited metabolic quirks involving the Cytochrome P450 metabolic pathways — some cannot process it at all, whereas a smaller percentage can get even more strength from it than usual. These factors can also cause hydrocodone and related drugs to have a threshold effect, cause significant lengthening or shortening of the duration of effects in the absence of tolerance, and increase or decrease the de facto conversion ratio between hydrocodone and other drugs like morphine, hydromorphone, and synthetics like levorphanol and methadone.


Hydrocodone, along with most other opioids, may also severely decrease testosterone levels in men and may cause menstrual irregularities in women. Short-term use of opioids will usually result in a decrease in testosterone with a subsequent rebound post-cessation. However, chronic use is much more dangerous. In a study on cancer survivors using opioids for chronic pain relief, 90% of the subjects had hypogonadal levels of testosterone. It is believed that this occurs due to both a negative feedback at both the hypothalamus-pituitary and at the gonadal (testicular) level. This is known as "central hypogonadism". Patients using opioid therapy should be screened for such endocrinological problems periodically through blood tests and inquiry of symptoms, which include loss of libido, erectile dysfunction, anxiety, fatigue, loss of muscle mass, and infertility. Treatment should first consist of opioid rotation. If that does not work, then testosterone replacement should commence.[14]


File:Main symptoms of Hydrocodone overdose.png
Main symptoms of hydrocodone overdose. If severe, death may result.[15]

Symptoms of hydrocodone overdose include respiratory depression; extreme somnolence; blue, clammy, or cold skin; narrowed or widened pupils; bradycardia; coma; seizures; cardiac arrest; and death.[15]

Daily consumption of hydrocodone should not exceed 40 milligrams in patients not tolerant to opiates.[citation needed] The 2006 Physicians Desk Reference states that Norco 10, containing 10 milligrams of hydrocodone and 325 mg of APAP can be taken at a dosage of up to twelve tablets per day (120 mg of hydrocodone). This restriction is only limited by the fact that twelve tablets, each containing 325 mg of APAP, puts the patient right below the 24-hour FDA maximum of 4,000 mg of APAP.[16] Some specially compounded products are routinely given to chronic pain patients in doses of up to 180 mg of hydrocodone per day.[citation needed]

Presence in body fluids

Hydrocodone may be quantitated in blood, plasma or urine to monitor for abuse, 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 0.1-2.0 mg/L in cases of acute fatal overdosage.[17][18]

Recreational use and dependency

Due to its opiate-related side effects such as euphoria, sedation and somnolence, hydrocodone is now one of the most common recreational prescription drugs in America, along with oxycodone. Recreational hydrocodone use is particularly prevalent among teenagers and young adults because of the drug's widespread availability.[19] Like other opioids, long-term use of hydrocodone may cause physical dependency leading to a severe withdrawal syndrome when the dose is lowered or discontinued. Withdrawal effects 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, and extreme drug cravings, among others. The presence of acetaminophen in hydrocodone-containing products allegedly deters many users, at least in theory, from taking excessive amounts. However, some users will bypass this danger by using cold water extraction to extract and dispose of a portion of the acetaminophen, taking advantage of the water-soluble element of the drug. It is not uncommon for users to have liver problems from consuming excessive amounts of acetaminophen over a long period of time; taking 10,000 to 15,000 milligrams (10 to 15 grams) of acetaminophen in a period of 24 hours typically results in severe hepatotoxicity, and doses in the range of 15,000–20,000 milligrams a day have been reported as fatal.[20] It is this factor that leads many recreational users to use only single-entity opioids such as oxycodone. One of the major problems today with the illicit use of hydrocodone, especially in younger populations, is that users may not be aware that hydrocodone pills contain acetaminophen. Consuming more than 4,000 milligrams of acetaminophen a day can cause liver damage, jaundice, and even liver failure[6] if the drug is being taken in excessive dosages for an extended period of time.


United Kingdom

In the UK, it is listed as a Class A drug under the Misuse of Drugs Act 1971. In Germany and elsewhere, hydrocodone is available as single-active-ingredient tablets as Dicodid (by analogy to the original manufacturer's other products Dilaudid and Dinarkon and others) available in 5- and 10-mg strengths.

United States

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, 88% of the hydrocodone-containing medications have been removed from the market.[21]

At the present time, 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 Retard (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.

C-III and higher prescriptions are generally valid for 6 months (including any refills). In the U.S., hydrocodone is always found in combination with other drugs such as paracetamol, aspirin, ibuprofen and homatropine methylbromide due to compounding regulations. These combinations are considered C-III substances. 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 stated above, hydrocodone is not available in pure form in the United States due to a separate regulation, and is always sold with an NSAID, acetaminophen, antihistamine, expectorant, or homatropine. The cough preparation Codiclear DH is the purest US hydrocodone item, containing guaifenesin and small amounts of ethanol as active ingredients.

As of July 2010, the FDA is 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, dihydrocodeine, and propoxyphene products such as the Tylenol With Codeine and Panlor series of drugs and Darvocet. An extended-release hydrocodone-only product is apparently close to final approval for marketing in the United States, and single-ingredient tablets of oxycodone and codeine are currently marketed. Mixtures of these drugs with other drugs such as Vicoprofen (hydrocodone & ibuprofen), Combunox (ibuprofen and oxycodone), Synalgos DC (aspirin and dihydrocodeine), and the Emprin With Codeine series are also currently available.

See also


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External links


es:Hidrocodona fr:Hydrocodone ko:하이드로콘 it:Idrocodone hu:Hidrokodon nl:Hydrocodon pl:Hydrokodon pt:Diidrocodeína ru:Гидрокодон fi:Hydrokodoni sv:Hydrokodon

  1. Mannich, C.; Löwenheim, H. (1920). "Ueber zwei neue Reduktionsprodukte des Kodeins". Archiv der Pharmazie. 258: 295–316. doi:10.1002/ardp.19202580218. 
  2. "Drugs@FDA - Approval History: Hycodan". FDA. Retrieved 2006-01-07. 
  3. "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
  4. 4.0 4.1 Davis, Mellar P. (2005). "Hydrocodone". Opioids for cancer pain. Oxford UK: Oxford University Press. pp. 59–68. ISBN 0-19-852943-0. 
  5. "Instructions for Mean Equivalent Daily Dose (MEDD)" (PDF). Retrieved 2010-08-22. 
  6. 6.0 6.1 "Acetaminophen (Tylenol) - side effects, drug class, medical uses, and drug interactions by". Medicinenet.com. 2007-09-21. Retrieved 2010-08-22. 
  7. Tussionex Pennkinetic Extended-Release package insert, UCB, Inc. Smyrna, GA 30080, May, 2007
  8. Tussionex Abuse, Anesthesia Assisted Medical Opiate Detoxification, Inc. <http://www.opiates.com/tussionex/tussionex-abuse.html>
  9. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  10. "Inhibition of Cytochrome P450 2D6 Metabolism of Hydrocodone to Hydromorphone Does Not Importantly Affect Abuse Liability — JPET". Jpet.aspetjournals.org. 1997-04-01. Retrieved 2010-08-22. 
  11. 11.0 11.1 MedlinePlus (The American Society of Health-System Pharmacists) - Drug Information: Hydrocodone. Last Revised - 1 October 2008. Retrieved on 21 February 2009.
  12. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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  14. http://www.painmanagementrounds.org/crus/painmgt_09.pdf
  15. 15.0 15.1 "MedlinePlus drug information: Hydrocodone. Last revised: Last Revised - 10/01/2008. Retrieved on 15 Mars, 2009". Nlm.nih.gov. 2010-07-28. Retrieved 2010-08-22. 
  16. "Slide 1" (PDF). Retrieved 2010-08-22. 
  17. Spiller HA. Postmortem oxycodone and hydrocodone blood concentrations. J. Forensic Sci. 48: 429-431, 2003.
  18. R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 745-747.
  19. "Hydrocodone". http://www.justice.gov. United States Government. 2007-07-01. Archived from the original on 2007-07-01. Retrieved 2010-01-13.  |first1= missing |last1= in Authors list (help); External link in |work= (help)
  20. Rx List
  21. "Medical News: FDA Pulls Plug on 200-Plus Unapproved Cough Syrups With Hydrocodone - in Product Alert, Prescriptions from". MedPage Today. Retrieved 2010-08-22.