Hydrocodone/paracetamol, also known as hydrocodone/acetaminophen, is the combination of the pain medications hydrocodone and paracetamol (acetaminophen). It is used to treat moderate to severe pain. It is taken by mouth. Recreational use is common in the United States.
|Trade names||Lorcet, Norco, Vicodin, others|
|Other names||Hydrocodone/acetaminophen, hydrocodone/APAP|
|AHFS/Drugs.com||FDA Professional Drug Information|
|Metabolism||Hydrocodone: extensively liver, primarily CYP3A4;|
Acetaminophen: liver, CYP2E1
|Elimination half-life||for hydrocodone: 228–294 mins (3.8–4.9 hrs); for paracetamol: 120–240 mins (2–4 hrs)|
|Excretion||for hydrocodone: urinary; for paracetamol: urinary (10–15% unchanged)|
Common side effects include dizziness, sleepiness, constipation, and vomiting. Serious side effects include addiction, decreased rate of breathing, low blood pressure, serotonin syndrome, severe allergic reactions, and liver failure. Use during pregnancy may harm the baby. Use with alcohol is not recommended. Hydrocodone works by binding to the mu-opioid receptor. How acetaminophen works is unclear.
Hydrocodone/paracetamol was approved for medical use in the United States in 1982. In the United States, it is a schedule II controlled substance. In 2016, it was the 13th most prescribed medication in the United States, with more than 43 million prescriptions. It is not available in the United Kingdom, though the combination codeine/paracetamol is. It is sold under the trade name Vicodin among others.
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. Hydrocodone/acetaminophen comes in oral solution and tablet formulations; however strength of each component may vary. 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.
Hydrocodone diversion and recreational use has escalated in recent years due to its opioid effects. 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).
Pregnancy and breastfeeding
- Central nervous system: drowsiness, confusion, lethargy, anxiety, fear, unease, dependence, mood changes, impairment of mental and physical performance
- Gastrointestinal system: constipation
- Genitourinary system: inability to urinate, bladder spasms
- Respiratory depression: inadequate breaths
- Special senses: hearing impairment, permanent hearing loss
- Dermatological: rash, itching
* Exact prevalence (%) is unknown
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."
"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."
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.
Hydrocodone may demonstrate an enhanced respiratory depressant effect when combined with other sedatives such as other opioids, benzodiazepines, nonbenzodiazepine sedatives, psychotropics, and anticonvulsants.
Concurrent use of paracetamol with alcohol products may increase the risk of acute liver failure.
- 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.
- Absorption/distribution: The oral formulation can be absorbed from the gastrointestinal tract and remain 20–50% bound to plasma proteins. 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.
- Metabolism/excretion: It is metabolized to norhydrocodone by cytochrome P450 3A4 and to hydromorphone, also biologically active, by cytochrome P450 2D6. 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.
- Mechanism of action: Acetaminophen acts to inhibit COX enzyme, which is responsible for prostaglandin synthesis. Prostaglandins increase the perception of pain. Inhibition of prostaglandin production helps to alleviate pain.
- 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.
- 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. 85% of the oral dose is excreted renally. At high doses, the supply of glutathione cannot meet its demand, thus results in the accumulation of highly reactive compounds leading to liver damage.
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.
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". 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. Each year, acetaminophen overdose is linked to about 400 deaths and 42,000 hospitalizations.
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 3 years. 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.
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. In 2010, more than 16,000 deaths were attributed to abuse of opioid drugs. Even though there are legitimate medical uses for HCPs, data suggest that a significant number of individuals misuse HCPs.
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.
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