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Combination of
HydrocodoneOpioid analgesic
ParacetamolAnilide analgesic
Trade namesLorcet, Norco, Vicodin, others
Other namesHydrocodone/acetaminophen, hydrocodone/APAP
Clinical data
  • US: C (Risk not ruled out)
Routes of
By mouth
Defined daily dosenot established[1]
External links
AHFS/Drugs.comFDA Professional Drug Information
Legal status
MetabolismHydrocodone: extensively liver, primarily CYP3A4;
Acetaminophen: liver, CYP2E1
Elimination half-lifefor hydrocodone: 228–294 mins (3.8–4.9 hrs); for paracetamol: 120–240 mins (2–4 hrs)
Excretionfor hydrocodone: urinary; for paracetamol: urinary (10–15% unchanged)

Hydrocodone/paracetamol, also known as hydrocodone/acetaminophen, is the combination of the pain medications hydrocodone and paracetamol (acetaminophen).[2] It is used to treat moderate to severe pain.[2][3] It is taken by mouth.[2] Recreational use is common in the United States.[4][5]

Common side effects include dizziness, sleepiness, constipation, and vomiting.[2][3] Serious side effects include addiction, decreased rate of breathing, low blood pressure, serotonin syndrome, severe allergic reactions, and liver failure.[2] Use during pregnancy may harm the baby.[2] Use with alcohol is not recommended.[3] Hydrocodone works by binding to the mu-opioid receptor.[2] How acetaminophen works is unclear but may involve blocking the creation of prostaglandins.[2][6]

Hydrocodone/paracetamol was approved for medical use in the United States in 1982.[2] In the United States, it is a schedule II controlled substance.[2] In 2017, it was the thirteenth most commonly prescribed medication in the United States, with more than 40 million prescriptions.[7][8] It is not available in the United Kingdom,[9] though the combination codeine/paracetamol is.[10] It is sold under the brand names Vicodin and Norco among others.[2]



Hydrocodone/acetaminophen is a two-ingredient combination formula consisting of the opioid hydrocodone and the non-opioid analgesic acetaminophen. It is indicated for relief of moderate to severe pain of acute, chronic, or postoperative types.[11] Hydrocodone/acetaminophen comes in oral solution and tablet formulations; however strength of each component may vary.[12] In October 2014, the Drug Enforcement Administration rescheduled hydrocodone combination drugs from schedule III to schedule II due to its risk for misuse, abuse, and diversions.[13]


the defined daily dose is not established.[1]


Hydrocodone diversion and recreational use has escalated in recent years due to its opioid effects.[14] In 2009 and 2010, hydrocodone was the second most frequently encountered opioid pharmaceutical in drug evidence submitted to U.S. federal, state, and local forensic laboratories as reported by DEA's National Forensic Laboratory Information System (NFLIS) and System to Retrieve Information from Drug Evidence (STRIDE).[15]

Pregnancy and breastfeeding

Pregnancy category C: Risk in pregnancy cannot be ruled out. Animal controlled studies have not been conducted with this medication.[16]

Low concentrations of acetaminophen is excreted through breast milk, however, hydrocodone's excretion is unknown.[16]

Kidney and liver impairment

Use with caution due to possible risk of toxicity.[16]

Side effects

Most common

Less common

  • Central nervous system: drowsiness, confusion, lethargy, anxiety, fear, unease, dependence, mood changes, impairment of mental and physical performance[11]
  • Gastrointestinal system: constipation[11]
  • Genitourinary system: inability to urinate, bladder spasms[11]
  • Respiratory depression: decreased rate and effort of breathing[11]
  • Hearing impairment, permanent hearing loss[11]
  • Dermatological: rash, itching[11]

Black box warning

"Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant or death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product."[11]

Allergy warning

"Do not take hydrocodone bitartrate and acetaminophen tablets if you are allergic to any of its ingredients. If you develop signs of allergy such as a rash or difficulty breathing stop taking hydrocodone bitartrate and acetaminophen tablets and contact your healthcare provider immediately."[11]


Hydrocodone: Respiratory depression, extreme somnolence progressing towards coma, muscle limpness, cold and clammy skin, slow heart rate, low blood pressure, abrupt loss of heart function, and death may occur.[11]

Acetaminophen: Liver and kidney failure, low blood sugar coma may occur.[11]


Hydrocodone may demonstrate an enhanced respiratory depressant effect when combined with other sedatives such as other opioids, benzodiazepines, nonbenzodiazepine sedatives, psychotropics, and anticonvulsants.[17]

Concurrent use of paracetamol with alcohol products may increase the risk of acute liver failure.[11]


Laboratory function tests should be used to monitor therapy in people with severe liver or renal disease.[11]



  • Mechanism of action: Hydrocodone acts primarily as an agonist at the mu-opioid receptors, but is also a weak agonist against the delta opioid and kappa opioid receptors.[18]
  • Absorption/distribution: The oral formulation can be absorbed from the gastrointestinal tract and remain 20–50% bound to plasma proteins.[18] The onset of analgesia is about 20 to 30 minutes with duration of 4 to 8 hours and t1/2 of 3 to 4 hours.[18]
  • Metabolism/excretion: It is metabolized to norhydrocodone by cytochrome P450 3A4 and to hydromorphone, also biologically active, by cytochrome P450 2D6.[19][20] For individuals who have a defect in the gene encoding CYP2D6, the clearance of the drug will be lower and less metabolite such as hydromorphone will be formed; however, the effect on analgesia remains unknown.[20]


  • Mechanism of action: Acetaminophen acts to inhibit COX enzyme, which is responsible for prostaglandin synthesis.[6] Prostaglandins increase the perception of pain. Inhibition of prostaglandin production helps to alleviate pain.[21]
  • Absorption/distribution: The half-life of oral acetaminophen is 1.25 to 3 hours and peak level is reached by 10–60 minutes after ingestion.[22]
  • Metabolism/excretion: Acetaminophen is metabolized primarily in the liver via glucuronidation and sulfation to mostly non-toxic metabolites and some highly reactive metabolites, which is inactivated by glutathione.[22] 85% of the oral dose is excreted renally.[11] At high doses, the supply of glutathione cannot meet its demand, thus results in the accumulation of highly reactive compounds leading to liver damage.[22]

Society and culture

In May 2017, professional golfer Tiger Woods was arrested by the police for driving under the influence. Woods said that this was due to four prescription drugs that he was taking for a back operation, one of which was Vicodin.[23][24]


In 2017, it was the thirteenth most commonly prescribed medication in the United States, with more than 40 million prescriptions.[7][8]


On June 30, 2009, a U.S. Food and Drug Administration (FDA) advisory panel voted by a narrow margin to advise the FDA to remove Vicodin and another opioid, Percocet, from the market because of "a high likelihood of overdose from prescription narcotics and acetaminophen products".[25] The panel also cited concerns of liver damage from their acetaminophen component, which is also the main ingredient in commonly used nonprescription drugs such as Tylenol.[25] Each year, acetaminophen overdose is linked to about 400 deaths and 42,000 hospitalizations.[26]

In January 2011, the FDA asked manufacturers of prescription combination products that contain acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet or capsule within three years.[27][28][29][30] The FDA also required manufacturers on all acetaminophen containing products to issue a black box warning indicating the potential risk for severe liver injury and a warning highlighting potential for allergic reactions.[27][28][30]

On August 22, 2014, the Drug Enforcement Administration (DEA) announced that all hydrocodone combination products (HCPs) will be rescheduled from Schedule III to Schedule II of the Controlled Substances Act (CSA), effective on October 6, 2014.[31] In 2010, more than 16,000 deaths were attributed to abuse of opioid drugs.[31] Even though there are legitimate medical uses for HCPs, data suggest that a significant number of individuals misuse them.[31]

Popular culture

Vicodin is mentioned in songs such as Eminem's "Kill You", Blackbear's "Sniffing Vicodin in Paris", Kendrick Lamar's "A.D.H.D", Future's "Lay Up", Lupe Fiasco's "Mural", Queens of the Stone Age's "Feel Good Hit of the Summer", A Winged Victory for the Sullen's "Steep Hills of Vicodin Tears" and The Wombats' "Give Me a Try". Vicodin use is a central theme in the 2004–2012 medical TV drama House, in which the lead character Dr. Gregory House is addicted to it.

Brand names

Brand names include Adol, Hycet, Lortab, Lorcet, Norco, and Vicodin among others.[32]

See also


  1. 1.0 1.1 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 1 July 2021. Retrieved 9 September 2020.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 "Hydrocodone and Acetaminophen – FDA prescribing information". Drugs.com. Archived from the original on 23 December 2018. Retrieved 23 December 2018.
  3. 3.0 3.1 3.2 Mancano, Michael; Gallagher, Jason (2010). Frequently Prescribed Medications. Jones & Bartlett Learning. p. 7. ISBN 9780763781170. Archived from the original on 2020-08-01. Retrieved 2020-08-09.
  4. Parrillo, Vincent N. (2008). Encyclopedia of Social Problems. SAGE. p. 262. ISBN 9781412941655. Archived from the original on 2020-08-01. Retrieved 2020-08-09.
  5. Singla A, Sloan P (2013). "Pharmacokinetic evaluation of hydrocodone/acetaminophen for pain management". Journal of Opioid Management. 9 (1): 71–80. doi:10.5055/jom.2013.0149. PMID 23709306.
  6. 6.0 6.1 Graham GG, Scott KF (2005-02-01). "Mechanism of action of paracetamol". American Journal of Therapeutics. 12 (1): 46–55. doi:10.1097/00045391-200501000-00008. PMID 15662292.
  7. 7.0 7.1 "The Top 300 of 2020". ClinCalc. Archived from the original on 12 February 2021. Retrieved 11 April 2020.
  8. 8.0 8.1 "Acetaminophen; Hydrocodone Bitartrate - Drug Usage Statistics". ClinCalc. 1 December 1981. Archived from the original on 11 April 2020. Retrieved 11 April 2020.
  9. Atkins, Lucy (16 August 2001). "Know what a Vike is?". The Guardian. Archived from the original on 23 December 2018. Retrieved 23 December 2018.
  10. "Co-codamol 30/500 Tablets - Summary of Product Characteristics (SmPC) - (eMC)". www.medicines.org.uk. Archived from the original on 7 August 2019. Retrieved 7 August 2019.
  11. 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 11.12 11.13 11.14 11.15 11.16 11.17 "Vicodin Prescribing Information for Health Care Professionals". www.vicodin.com. Archived from the original on 2015-11-03. Retrieved 2015-11-04.
  12. "Acetaminophen / Hydrocodone Dosage Guide with Precautions - Drugs.com". www.drugs.com. Archived from the original on 2015-11-02. Retrieved 2015-11-04.
  13. "Rules – 2014 – Rescheduling of Hydrocodone Combination Products From Schedule III to Schedule II". www.deadiversion.usdoj.gov. Archived from the original on 2015-10-08. Retrieved 2015-11-04.
  14. "Norco Addiction | The Fix". The Fix. 2015-01-21. Archived from the original on 2015-09-01. Retrieved 2015-11-04.
  15. "Hydrocodone (Trade Names: Vicodin, Lortab, Lorcet-HD, Hycodan, Vicoprofen)" (PDF). US DOJ – DEA. April 2013. Archived from the original (PDF) on 18 April 2013. Retrieved 21 May 2013.
  16. 16.0 16.1 16.2 "Norco – FDA prescribing information, side effects and uses". www.drugs.com. Archived from the original on 2015-11-08. Retrieved 2015-11-04.
  17. Becker DE (2011-01-01). "Adverse drug interactions". Anesthesia Progress. 58 (1): 31–41. doi:10.2344/0003-3006-58.1.31. PMC 3265267. PMID 21410363.
  18. 18.0 18.1 18.2 Vallejo R, Barkin RL, Wang VC (2011-08-01). "Pharmacology of opioids in the treatment of chronic pain syndromes". Pain Physician. 14 (4): E343-60. PMID 21785485.
  19. Cone EJ, Darwin WD, Gorodetzky CW, Tan T (1978-08-01). "Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog". Drug Metabolism and Disposition. 6 (4): 488–93. PMID 28931.
  20. 20.0 20.1 Kaye, Alan David (2015). Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care. Springer. pp. 134–13. ISBN 9781461489481.
  21. Golan, David E. (2008). Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Lippincott Williams & Wilkins. pp. 275–276. ISBN 978-0-7817-8355-2.
  22. 22.0 22.1 22.2 Sinatra, Raymond S. (2011). The Essence of Analgesia and Analgesics. Cambridge University Press. p. 256. ISBN 978-0-521-14450-6.
  23. "Police release dashcam footage of Tiger Woods' DUI arrest". Guardian. Associated press. 1 June 2017. Archived from the original on 1 June 2017. Retrieved 1 June 2017.
  24. Murray, Ewan (29 May 2017). "Tiger Woods says medication, not alcohol led to Florida DUI arrest". Guardian. Archived from the original on 31 May 2017. Retrieved 1 June 2017.
  25. 25.0 25.1 "FDA advisers vote to take Vicodin, Percocet off market". CNN. Archived from the original on 2018-04-22. Retrieved 2020-08-09.
  26. Harris, Gardiner (2011-01-13). "F.D.A. Plans New Limits on Prescription Painkillers". The New York Times. ISSN 0362-4331. Archived from the original on 2012-06-09. Retrieved 2015-11-04.
  27. 27.0 27.1 "FDA limits acetaminophen in prescription combination products; requires liver toxicity warnings" (Press release). U.S. Food and Drug Administration. January 13, 2011. Archived from the original on January 15, 2011. Retrieved January 13, 2011.
  28. 28.0 28.1 "FDA Drug Safety Communication: Prescription Acetaminophen Products to be Limited to 325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure". U.S. Food and Drug Administration (FDA). January 13, 2011. Archived from the original on April 23, 2019. Retrieved January 13, 2011.
  29. Perrone, Matthew (January 13, 2011). "FDA orders lowering pain reliever in Vicodin". The Boston Globe. Associated Press. Archived from the original on March 5, 2016. Retrieved January 13, 2011.
  30. 30.0 30.1 Harris, Gardiner (January 13, 2011). "F.D.A. Plans New Limits on Prescription Painkillers". The New York Times. Archived from the original on June 9, 2012. Retrieved January 13, 2011.
  31. 31.0 31.1 31.2 "Federal Register – Schedules of Controlled Substances: Rescheduling of Hydrocodone Combination Products From Schedule III to Schedule II". usa.gov. 2014-08-22. Archived from the original on 2016-03-05. Retrieved 2020-08-09.
  32. "Adol (Hydrocodone-Acetaminoph) Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD". WebMD. Archived from the original on 6 August 2017. Retrieved 26 July 2017.

External links