Tylenol

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For detailed information about the active ingredient in Tylenol, see paracetamol, also known as acetaminophen
Tylenol PM (left) and Tylenol (right)
Acetaminophen (paracetamol), in line-angle representation (aromatic ring in Kekulé form).
Acetaminophen (paracetamol), in ball-and-stick representation (aromatic ring indicating resonance/bond equivalence)

Tylenol /ˈtlənɒl/ is an American brand of drugs advertised for reducing pain, reducing fever, and relieving the symptoms of allergies, cold, cough, and influenza. The active ingredient of its original flagship product is acetaminophen, an analgesic and antipyretic; it is commonly known elsewhere in the world by its international nonproprietary name, paracetamol. Like the words "acetaminophen" and "paracetamol", the brand name "Tylenol" is derived from the chemical name for the compound, N-aceTYL-para-aminophENOL (APAP).[1] The brand name "Tylenol" is owned by McNeil Consumer Healthcare, a subsidiary of Johnson & Johnson.[2]

Medical uses[edit]

Fever[edit]

Acetaminophen is approved for reducing fever in people of all ages.[3] The World Health Organization (WHO) recommends that acetaminophen only be used to treat fever in children if their temperature is greater than 38.5 °C (101.3 °F).[4] The efficacy of acetaminophen by itself in children with fevers appears to be better than placebo [5] but less effective than ibuprofen.[6]

Pain[edit]

Acetaminophen is used for the relief of pains associated with many parts of the body. It has analgesic properties comparable to those of aspirin, while its anti-inflammatory effects are weaker. It is better tolerated than aspirin in patients in whom excessive gastric acid secretion or prolongation of bleeding time may be a concern. Available without a prescription since 1959,[7] it has since become a common household drug.[8]

Acetaminophen has relatively little anti-inflammatory activity, unlike other common analgesics such as the NSAIDs aspirin and ibuprofen, but ibuprofen and acetaminophen have similar effects in the treatment of headache. Acetaminophen can relieve pain in mild arthritis, but has no effect on the underlying inflammation, redness, and swelling of the joint.[9]

Regarding comparative efficacy, studies show conflicting results when compared to NSAIDs. A randomised controlled trial of chronic pain from osteoarthritis in adults found similar benefit from acetaminophen and ibuprofen.[10][11]

The efficacy of acetaminophen when used in combination with weak opioids (such as codeine) was assessed in data studies in 1996 and 2009,[12][13] which found improved efficacy for approximately 50% of patients but increases in the number of patients experiencing adverse effects. Combination drugs of acetaminophen and strong opioids like morphine reduce the amount of opioid needed and improve analgesic effect.[14]

The American College of Rheumatology recommends acetaminophen as one of several treatment options for patients with arthritis pain of the hip, hand, or knee that is refractory to non-pharmacological interventions such as exercise and weight loss.[15]

A joint statement of the German, Austrian, and Swiss headache societies and the German Society of Neurology recommends the use of acetaminophen in combination with caffeine as one of several first line therapies for treatment of tension or migraine headache.[16] In the treatment of acute migraine, it is superior to placebo, with 39% of people experiencing pain relief at 1 hour compared to 20% in the control group.[17]

Based on a systematic review, acetaminophen is recommended by the American College of Physicians and the American Pain Society as a first line treatment for low back pain.[18][19] However a systematic review published by other authors concluded that evidence for its efficacy is lacking.[20]

The combination of acetaminophen with caffeine is superior to acetaminophen alone for the treatment of common pain conditions including dental pain, postpartum pain, and headache.[21]

Special Populations[edit]

Experimental studies in animals and cohort studies in humans indicate no detectable increase in congenital malformations associated with acetaminophen use during pregnancy.[22] Additionally, acetaminophen does not affect the closure of the fetal ductus arteriosus as NSAIDs can.[23] However, acetaminophen use by mother during pregnancy is associated with an increased risk of childhood asthma.[24]

Adverse Effects[edit]

In recommended doses and for a limited course of treatment, the side effects of acetominophen are mild to non-existent.[25]

Liver damage[edit]

Acute overdoses of acetominophen can cause potentially fatal liver damage. According to the US Food and Drug Administration, "Acetaminophen can cause serious liver damage if more than directed is used."[26] and in 2011 the FDA required manufacturers to update labels of all prescription combination acetaminophen products to warn of the potential risk for severe liver injury[27] and launched a public education program to help consumers avoid overdose.[28] [29] The risk may be heightened by chronic alcohol abuse. Acetominophen toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia and New Zealand.[30][31][32][33] According to the FDA, in the United States there were "56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year related to acetaminophen-associated overdoses during the 1990s. Within these estimates, unintentional acetaminophen overdose accounted for nearly 25 percent of the emergency department visits, 10 percent of the hospitalizations, and 25 percent of the deaths."[34]

Acetominophen is metabolised by the liver and is hepatotoxic; side effects are multiplied when combined with alcoholic drinks, and very likely in chronic alcoholics or patients with liver damage.[25][35] Some studies have suggested the possibility of a moderately increased risk of upper gastrointestinal complications such as stomach bleeding when high doses are taken chronically.[36] Kidney damage is seen in rare cases, most commonly in overdose.[37] The Food and Drug Administration has warned doctors against prescribing acetaminophen/narcotic combinations whose dosages exceed 325 mg of acetaminophen due to hepatoxicity risks of greater magnitude than the therapeutic benefits conferred.[38]

A report prepared by an internal FDA working group describes a history of FDA initiatives designed to educate consumers about the risk of acetominophen overdose, and notes that one challenge to the Agency has been "identifying the appropriate message about the relative safety of acetaminophen, especially compared to other OTC pain relievers (e.g., aspirin and other NSAIDs)". The report notes that "Chronic use of NSAIDs is also associated with significant morbidity and mortality. NSAID gastrointestinal risk is substantial, with deaths and hospitalization estimated in one publication as 3200 and 32,000 per year respectively. Possible cardiovascular toxicity with chronic NSAID use has been a major discussion recently", finally noting that "The goal of the educational efforts is not to decrease appropriate acetaminophen use or encourage substitution of NSAID use, but rather to educate consumers so that they can avoid unnecessary health risks."[39]

Skin reactions[edit]

On August 2, 2013, the U.S. Food and Drug Administration (FDA) issued a new warning about acetominophen. It stated that the drug could cause rare, and possibly fatal, skin reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis. Prescription-strength products will be required to carry a warning label about skin reactions, and the FDA has urged manufacturers to do the same with over-the-counter products.[40]

Asthma[edit]

There is an association between acetominophen use and asthma but the weight of evidence of the collected studies strongly suggests that the association reflects various forms of bias, the most prominent of which is confounding by indication.[41] The majority of the evidence does not support a causal role.[42]

As of 2014, the American Academy of Pediatrics and the National Institute for Health and Care Excellence (NICE) continue to recommend acetominophen for pain and discomfort in children,[43][44][45][46][47][48] but some experts have recommended that acetaminophen use by children with asthma, or at risk for asthma, should be avoided.[49][50]

Other factors[edit]

In contrast to aspirin, acetominophen does not prevent blood from clotting (it is not an antithrombotic), and thus may be used in patients where failure of blood coagulation is a concern; and it does not cause gastric irritation.[51] However, acetaminophen does not help reduce inflammation, while aspirin does.[52] Compared to ibuprofen—whose side effects may include diarrhea, vomiting and abdominal pain— acetaminophen has fewer adverse gastrointestinal effects.[53]

Unlike aspirin, acetominophen is generally considered safe for children, as it is not associated with a risk of Reye syndrome in children with viral illnesses.[54]

Overdose[edit]

Untreated overdose can lead to liver failure and death within days. Treatment is aimed at removing the acetominophen from the body and replacing glutathione.[55] Activated charcoal can be used to decrease absorption of acetominophen if the patient presents for treatment soon after the overdose. While the antidote, acetylcysteine, (also called N-acetylcysteine or NAC) acts as a precursor for glutathione, helping the body regenerate enough to prevent or at least decrease the possible damage to the liver, a liver transplant is often required if damage to the liver becomes severe.[30][56] NAC was usually given following a treatment nomogram (one for patients with risk factors, and one for those without) but the use of the nomogram is no longer recommended as evidence to support the use of risk factors was poor and inconsistent, and many of the risk factors are imprecise and difficult to determine with sufficient certainty in clinical practice.[57] NAC also helps in neutralizing the imidoquinone metabolite of acetaminophen.[55] Renal failure is also a possible side effect.

Products[edit]

Tylenol 3, a compound of acetaminophen (300 mg) and Codeine (30 mg)

Tylenol sells products to relieve pain, allergies, and cold- and flu- related symptoms. Allergy and cold products also contain dextromethorphan, antihistamines, and expectorants.[citation needed]

Tylenol is also sold as a class of stronger pain relievers containing codeine, known as co-codamols:

  • Tylenol 1 contains 325 mg acetaminophen and 8 mg codeine;
  • Tylenol 2 (300 mg/15 mg),
  • Tylenol 3 (300 mg/30 mg), and
  • Tylenol 4 (300 mg/60 mg).

In Canada, Tylenol 1, 2 and 3 all include 15 mg caffeine, in addition to the above ingredients; furthermore, Tylenol 1 is sold in Canada without a prescription, while all forms of Tylenol with codeine require a prescription in the US.[citation needed]

Acetaminophen is also found in other narcotic-based analgesics such as Percocet which additionally contains oxycodone, and Lortab/Vicodin which both additionally contain hydrocodone.[citation needed]

Tylenol PM[edit]

Tylenol PM is the trademark for a mixture of acetaminophen (paracetamol) and diphenhydramine, distributed by Johnson & Johnson. It is marketed as a combined analgesic and sedative. It is listed as non-habit forming.[58] Diphenhydramine is an anticholinergic used as the active ingredient in Benadryl, for its antihistamine properties, and Benylin, which is used in cough and cold therapy as an antitussive (anti-cough) medication.

History[edit]

Acetaminophen was first synthesized and evaluated as a pain reliever by Bayer in the 1890's. The presence of an impurity in the material prepared by Bayer led to a condition called methaemoglobinaemia, in which a chemical reaction involving the iron in hemoglobin causes darkening of the skin and blue lips. As a result of these studies, further work on acetominophen was not pursued until the 1940s.

The revival of interest in acetaminophen as a pain reliever was sparked by 1947 studies of the pain-relieving properties of a related compound, acetanilide. Researchers David Lester and Leon Greenberg identified acetaminophen as a major metabolite of acetanalide. Bernard Brodie and Julius Axelrod of the New York University College of Medicine confirmed this result. They published a paper suggesting that the potential of acetaminophen as a pain reliever should be revisited.[59]

Around this same time, U.S. gastroenterologist James Roth had been publishing a series of papers expressing concern regarding the safety profile of aspirin, particularly its tendency to promote stomach irriation, gastric bleeding, and inhibit blood clotting. In response to the publication of the Brodie and Axelrod paper, he became an advocate of acetaminophen. In 1953, McNeil Laboratories, where Roth served as a consultant, introduced its first acetominophen-containing product.[59] Algoson was a preparation containing acetaminophen together with sodium butabarbital, a sedative. Then in 1955, McNeil Laboratories introduced Tylenol Elixir for children, which contained acetaminophen as its sole active ingredient. It was originally marketed mainly towards children, but soon came to dominate the North American pain-killer market. Different varieties of Tylenol available today include extra-strength (with 500 milligrams of acetaminophen), children's doses, longer-lasting, and sleep aiding (in combination with diphenhydramine). In 2005, Tylenol Ultra was introduced in Canada, with 500 mg of acetaminophen and 65 mg of caffeine; caffeine has vasoconstricting effects, for which there is some disputed evidence for additional effectiveness.[60][61]

1982 Chicago Tylenol murders and first recall[edit]

On September 29, 1982, a "Tylenol scare" began when the first of seven individuals died in metropolitan Chicago, after ingesting Extra Strength Tylenol that had been deliberately contaminated with cyanide. Within a week, the company pulled 31 million bottles of tablets back from retailers, making it one of the first major recalls in American history.[62]

As a result of the crisis, all Tylenol capsules were discontinued, as were capsules of other brand names. Retained by McNeil President Joseph Chiesa, new product consultant Martin Calle and management strategist Calle & Company conceived the world's first tamper-proof gelatin-enrobed capsule called "Tylenol Gelcaps," which proved to resuscitate the 92% of capsule-segment sales lost to the recall. The tamper-proof, triple-sealed safety containers were swiftly placed on the shelves of retailers 10 weeks after the withdrawal, and other manufacturers followed suit. The crisis cost the company more than $100 million, but Tylenol regained 100% of the market share it had before the crisis. The Tylenol murderer was never found, and a $100,000 reward offered by Johnson & Johnson remains unclaimed.

Tylenol remains a top seller, controlling about 35% of the pain killer market in North America, according to a study published in 2003.[63]

2010 Tylenol recall[edit]

On January 15, 2010, 20 months after first receiving consumer complaints, Johnson & Johnson announced a voluntary recall of several hundred batches of popular medicines, including Benadryl, Motrin, Rolaids, Simply Sleep, St. Joseph Aspirin and Tylenol.[64] The recall was due to complaints of a musty smell which is suspected to be due to contamination of the packaging with the chemical 2,4,6-tribromoanisole.[65] The full health effects of 2,4,6-tribromoanisole are not known but no serious events have been documented in medical literature.[66] The recall came 20 months after McNeil first began investigating consumer complaints about moldy-smelling bottles of Tylenol Arthritis Relief caplets, according to the United States Food and Drug Administration. The recall included 53 million bottles of over-the-counter products including Tylenol, Motrin and Rolaids, Benadryl and St. Joseph's Aspirin, involving lots in the Americas, the United Arab Emirates and Fiji.[67]

On April 30, 2010, another recall was issued for 40 products including liquid infant and children's pain relievers, Tylenol, and Motrin and allergy medications Zyrtec and Benadryl.[67] A Food and Drug Administration report said its inspectors found thick dust and grime covering certain equipment, a hole in the ceiling and duct tape-covered pipes at the Fort Washington, Pennsylvania, facility that made 40 products recalled. New testing regulations were enacted after the recall to ensure product quality and safety. [68]

On Wednesday, May 5, 2010, the Food and Drug Administration (FDA) confirmed[69] that the bacteria found at the Johnson & Johnson plant that made the recalled Children's Tylenol was Burkholderia cepacia, a bacteria often resistant to common antibiotics.[70] The bacteria was found on the outside of certain product-containing drums, but not in the finished product. The CDC has stated that Burkholderia cepacia is not likely to cause health problems for those with healthy immune systems, but those with weaker ones and those with chronic lung diseases, such as cystic fibrosis, could be more susceptible to infection.

Advertising[edit]

Tylenol has many different advertisement approaches. One of these advertisement campaigns focuses on "getting you back to normal", whereas the other commercials focus on Tylenol's current slogan, "Feel better, Tylenol". In the "Feel better, Tylenol" commercials, Tylenol places emphasis on the importance of sleep; various people are seen sleeping in this commercial while a voiceover describes how sleep can help repair and heal the human body during times of aches and pains.[71] In the "getting you back to normal" commercial, Tylenol places more emphasis on helping its consumers get back to their daily routines; many different people are shown first experiencing headaches and other sorts of body pain, where a voiceover then states that Tylenol Rapid Release can help rid aches and pains; the various people are then showed enjoying their everyday lives, and are seen as "back to normal".[72]

In an older commercial from 1986, Tylenol emphasized that it is the drug that American hospitals trust the most. In this ad, Susan Sullivan told the consumer that Tylenol was a drug that could be trusted by Americans since many doctors also trusted it; she went on to state that doctors prescribed Tylenol four times more often than the other leading pain relieving drugs combined.[73]

See also[edit]

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  66. ^ McNeil Consumer Healthcare Announces Voluntary Recall of Certain Over-The-Counter (OTC) Products In The Americas, UAE, and Fiji
  67. ^ a b FACTBOX-Johnson & Johnson's recent product recalls
  68. ^ Grime, dust, bacteria found at J&J plant: FDA (Reuters, May 4, 2010
  69. ^ Bacteria Identified in Recall, CNN, First Published: May 5, 2010
  70. ^ Kavilanz, Parija (6 May 2010). "Bacteria identified in Tylenol recall". CNN. Retrieved 21 July 2010. 
  71. ^ Midori's Tylenol Commercial
  72. ^ Tylenol Rapid Release Commercial
  73. ^ Tylenol Commercial (1986)

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