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Hydrocodone/paracetamol (also known as hydrocodone/acetaminophen) is the combination of the
pain medication An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
s
hydrocodone Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe en ...
and
paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
(acetaminophen). It is used to treat moderate to severe
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
. It is taken
by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...
.
Recreational use Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...
is common in the United States. Common side effects include dizziness, sleepiness,
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
, and vomiting. Serious side effects include
addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
, decreased rate of breathing,
low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
,
serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...
, severe allergic reactions, and liver failure. Use during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
may harm the fetus. Use with
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
is not recommended. Hydrocodone works by binding to the mu-opioid receptor. How paracetamol works is unclear but may involve blocking the creation of
prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
. Hydrocodone/paracetamol was approved for medical use in the United States in 1982. In the United States, it is a
schedule II controlled substance The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States ...
. In 2020, it was the sixteenth most commonly prescribed medication in the United States, with more than 30million prescriptions. It is not available in the United Kingdom, though the similar combination
codeine/paracetamol Codeine/paracetamol, also known as codeine/acetaminophen and co-codamol, is a compound analgesic consisting of a combination of codeine phosphate and paracetamol (acetaminophen). Codeine/paracetamol is used for the relief of mild to moderate pai ...
(co-codamol) is. It is sold under the brand names Vicodin and Norco among others.


Uses


Medical

Hydrocodone/paracetamol is a
fixed-dose combination A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC pr ...
consisting of the
opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
hydrocodone and the non-opioid analgesic paracetamol. It is indicated for relief of moderate to severe pain of acute, chronic, or postoperative types. Hydrocodone/paracetamol comes in oral solution and tablet formulations; however strength of each component may vary. In October 2014, the
Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within th ...
rescheduled hydrocodone combination drugs from schedule III to schedule II due to its risk for misuse, abuse, and diversions.


Recreational

Hydrocodone diversion and recreational use has escalated 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 Forensic science, also known as criminalistics, is the application of science to Criminal law, criminal and Civil law (legal system), civil laws, mainly—on the criminal side—during criminal investigation, as governed by the legal standard ...
laboratories as reported by the
Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within th ...
's National Forensic Laboratory Information System (NFLIS) and System to Retrieve Information from Drug Evidence (STRIDE).


Pregnancy and breastfeeding

Prolonged use of hydrocodone/paracetamol during pregnancy can result in neonatal opioid withdrawal syndrome. Hydrocodone/paracetamol passes into breast milk and may harm the baby.


Kidney and liver impairment

Use with caution due to possible risk of toxicity.


Side effects


Most common

* Lightheadedness * Dizziness * Euphoria * Sedation * Nausea and vomiting * Headaches


Less common

* 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: decreased rate and effort of breathing * Hearing impairment, permanent hearing loss * Dermatological: rash, itching


Black box warning

"Paracetamol 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 paracetamol at doses that exceed 4000 milligrams per day, and often involve more than one paracetamol-containing product."


Overdose

Hydrocodone:
Respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...
, extreme
somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
progressing towards coma, muscle limpness, cold and clammy skin, slow heart rate, low blood pressure, abrupt loss of heart function, and death may occur. Paracetamol: Liver and kidney failure, low blood sugar coma may occur.


Interactions

Hydrocodone may demonstrate an enhanced respiratory depressant effect when combined with other
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...
s such as other
opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
s,
benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...
s, nonbenzodiazepine sedatives,
psychotropics A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. T ...
, and
anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s. Concurrent use of paracetamol with alcohol products may increase the risk of
acute liver failure Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...
.


Monitoring

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


Pharmacology


Hydrocodone

* 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 Norhydrocodone is the major metabolite of the opioid analgesic hydrocodone. It is formed from hydrocodone in the liver via N-demethylation predominantly by CYP3A4. Unlike hydromorphone, a minor metabolite of hydrocodone, norhydrocodone is describ ...
by
cytochrome P450 3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
and to
hydromorphone Hydromorphone, also known as dihydromorphinone, and sold under the brand name Dilaudid among others, is an opioid used to treat moderate to severe pain. Typically, long-term use is only recommended for pain due to cancer. It may be used by mou ...
, 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.


Paracetamol

* Mechanism of action: Paracetamol acts to inhibit
COX Cox may refer to: * Cox (surname), including people with the name Companies * Cox Enterprises, a media and communications company ** Cox Communications, cable provider ** Cox Media Group, a company that owns television and radio stations ** ...
enzyme, which is responsible for prostaglandin synthesis.
Prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
s increase the perception of pain. Inhibition of prostaglandin production helps to alleviate pain. * Absorption/distribution: The half-life of oral paracetamol is 1.25 to 3 hours and peak level is reached by 10–60 minutes after ingestion. * Metabolism/excretion: Paracetamol is metabolized primarily in the liver via
glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosid ...
and
sulfation Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...
to mostly non-toxic metabolites and some highly reactive metabolites, which is inactivated by
glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...
. 85% of the oral dose is excreted via the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s. 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


Legal status

On 30 June 2009, a U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) advisory panel voted by a narrow margin to advise the FDA to remove Vicodin and another opioid,
Percocet Oxycodone/paracetamol, sold under the brand name Percocet among others, is a fixed-dose combination of the opioid oxycodone with paracetamol (acetaminophen), used to treat moderate to severe pain. In 2020, it was the 69th most commonly prescri ...
, 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 paracetamol component, which is also the main ingredient in commonly used nonprescription drugs such as Tylenol. Each year,
paracetamol overdose Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These include ...
is linked to about 400 deaths and 42,000 hospitalizations. In January 2011, the FDA asked manufacturers of prescription combination products that contain paracetamol to limit the amount of paracetamol to no more than 325 mg in each tablet or capsule within three years. The FDA also required manufacturers on all paracetamol 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 22 August 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 6 October 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 them.


Popular culture

In May 2017,
professional golfer A professional golfer is somebody who receives payments or financial rewards in the sport of golf that are directly related to their skill or reputation. A person who earns money by teaching or playing golf is traditionally considered a "golf pr ...
Tiger Woods Eldrick Tont "Tiger" Woods (born December 30, 1975) is an American professional golfer. He is tied for first in PGA Tour wins, ranks second in men's major championships, and holds numerous golf records. * * * Woods is widely regarded as ...
was arrested by the police for
driving under the influence Driving under the influence (DUI)—also called driving while impaired, impaired driving, driving while intoxicated (DWI), drunk driving, operating while intoxicated (OWI), operating under the influence (OUI), operating vehicle under the infl ...
. Woods said that this was due to four
prescription drugs A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
that he was taking for a back operation, one of which was Vicodin. Vicodin is mentioned in songs such as Juice Wrld's "Already Dead"
Eminem Marshall Bruce Mathers III (born October 17, 1972), known professionally as Eminem (; often stylized as EMINƎM), is an American rapper and record producer. He is credited with popularizing hip hop in middle America and is critically acclai ...
's " Kill You", Blackbear's "Sniffing Vicodin in Paris",
Kendrick Lamar Kendrick Lamar Duckworth (born June 17, 1987) is an American rapper and songwriter. Known for his Progressive rap, progressive musical styles and Social consciousness, socially conscious songwriting, he is often considered one of the most infl ...
's "
A.D.H.D Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise Development ...
",
Future The future is the time after the past and present. Its arrival is considered inevitable due to the existence of time and the laws of physics. Due to the apparent nature of reality and the unavoidability of the future, everything that currently ...
's "
Lay Up A layup in basketball is a two-point shot attempt made by leaping from below, laying the ball up near the basket, and using one hand to bounce it off the backboard and into the basket. The motion and one-handed reach distinguish it from a jump s ...
",
Lupe Fiasco Wasalu Muhammad Jaco (born February 16, 1982), better known by his stage name Lupe Fiasco ( ), is an American rapper, singer, record producer, and entrepreneur. He rose to fame in 2006 following the success of his debut album, ''Lupe Fiasco's ...
's "
Mural A mural is any piece of graphic artwork that is painted or applied directly to a wall, ceiling or other permanent substrate. Mural techniques include fresco, mosaic, graffiti and marouflage. Word mural in art The word ''mural'' is a Spani ...
",
Queens of the Stone Age Queens of the Stone Age (commonly abbreviated QOTSA) is an American rock band formed in 1996 in Palm Desert, California. The band was founded by vocalist and guitarist Josh Homme, who has been the only constant member throughout multiple line- ...
's "
Feel Good Hit of the Summer "Feel Good Hit of the Summer" is a song by American rock music, rock band Queens of the Stone Age and written by band members Josh Homme and Nick Oliveri. It is the opening track of their second album, ''Rated R (Queens of the Stone Age album), R ...
",
A Winged Victory for the Sullen A Winged Victory for the Sullen is an American ambient music duo composed of Dustin O'Halloran and Adam Wiltzie. They have released four studio albums, an EP, and one soundtrack album. In 2015, they performed at the Royal Albert Hall as part ...
's "Steep Hills of Vicodin Tears",
Death Grips Death Grips is an American experimental hip hop group formed in 2010 in Sacramento, California. The group consists of Stefan Burnett, also known as MC Ride (vocals, lyrics), Zach Hill (drums, production, lyrics), and Andy Morin (keyboards, produ ...
's "
Anne Bonny Anne Bonny (8 March 1697 – disappeared April 1721), sometimes Anne Bonney, was an Irish pirate operating in the Caribbean, and one of the few female pirates in recorded history. What little that is known of her life comes largely from Capta ...
" and
The Wombats The Wombats are an English indie rock band formed in Liverpool in 2003, consisting of Matthew Murphy (lead vocals, guitar, keyboards), Tord Øverland Knudsen (bass, backing vocals, keyboards), and Dan Haggis (drums, backing vocals, keyboards). ...
' " Give Me a Try". Vicodin use is a central theme in the 2004–2012 medical TV drama ''
House A house is a single-unit residential building. It may range in complexity from a rudimentary hut to a complex structure of wood, masonry, concrete or other material, outfitted with plumbing, electrical, and heating, ventilation, and air condi ...
'', in which the lead character Dr.
Gregory House Gregory House, M.D. is the titular protagonist of the American medical drama series ''House''. Created by David Shore and portrayed by English actor Hugh Laurie, he leads a team of diagnosticians and is the Head of Diagnostic Medicine at the f ...
is addicted to the drug combination.


Brand names

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


References


External links

*
Vicodin U.S. Federal Regulations
{{DEFAULTSORT:Hydrocodone Paracetamol Combination analgesics Euphoriants Hepatotoxins AbbVie brands Semisynthetic opioids Wikipedia medicine articles ready to translate