Acetaminophen (Tylenol)

1. Health Canada Product Monograph — Acetaminophen

• Acetaminophen is used for temporary relief of mild to moderate pain, including headache, migraine, tension headache, earache, low back pain, arthritis pain, menstrual cramps (dysmenorrhea), muscle aches, and nerve pain.
• Acetaminophen is used to reduce fever caused by the common cold, flu, and other viral or bacterial infections.
• Acetaminophen should not be taken for pain for more than 5 days, or for fever for more than 3 days, without consulting a doctor, and combining more than one acetaminophen-containing product at a time should be avoided.

• There are no well-controlled clinical studies of acetaminophen in pregnant women, but large observational studies have not found an association between acetaminophen use and birth defects or growth problems.
• Acetaminophen is generally considered a suitable option in pregnancy at recommended doses, but as with any medicine, pregnant patients should consult a physician before use.
• An acetaminophen overdose during pregnancy should be treated the same as in any other patient, with prompt antidote treatment, since delayed treatment, not the overdose itself, is the main risk to the pregnancy.

• Acetaminophen passes into breast milk only in very small amounts.
• Acetaminophen is considered compatible with breastfeeding.

• No dose reduction is necessary for older adults at currently recommended doses.
• Older adults who need acetaminophen for longer than 5 days should check in with their doctor to monitor their condition, though the dose itself does not need to change.

• Dosing for children should be based on body weight where possible, using the product's pediatric dosing chart, rather than age alone.
• Solid dosage forms such as tablets may not be appropriate for children under 2 years of age.
• Consumer labeling for infant and children's products does not provide dosing guidance for infants younger than 4 months; use in very young infants should be guided by a healthcare professional.

• For adults and children 12 years and older, the standard immediate-release dose is 325 mg to 1000 mg every 4 to 6 hours as needed, not exceeding 4000 mg (4 g) in 24 hours.
• For children under 12, the dose is 10 to 15 mg/kg every 4 to 6 hours as needed, based on body weight, not exceeding 5 doses in 24 hours.
• Extended-release caplets (Arthritis Pain and Muscle & Body formulations) are dosed at up to 2 caplets every 8 hours, not exceeding 6 caplets in 24 hours; these must be swallowed whole on an empty stomach and never crushed, chewed, or dissolved.
• Regular immediate-release forms may be taken with or without food.
• The total daily dose limit of 4000 mg includes all acetaminophen-containing products used together, including combination cough, cold, and pain products.
• No dose adjustment is required for chronic kidney disease, chronic stable liver disease, obesity, or older age at standard recommended doses.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Acetaminophen overdose is a medical emergency because it can cause serious, potentially fatal liver damage, even when early symptoms are mild or absent.
• Early symptoms of overdose may include loss of appetite, nausea, vomiting, sweating, and general malaise, typically appearing within the first 24 hours.
• A misleading "recovery" phase can follow, where symptoms improve temporarily even as liver enzyme levels and blood clotting times continue to worsen.
• If untreated, severe overdose can progress to right upper abdominal pain, confusion, jaundice, bleeding problems, low blood sugar, kidney failure, and life-threatening liver failure.
• In children, a single overdose of less than 150 mg/kg is less likely to cause liver toxicity than in adults, but any suspected overdose should still be assessed promptly by a healthcare professional.
• N-acetylcysteine (NAC) is a specific antidote that should be given as early as possible, ideally within 8 hours of a significant overdose, without waiting for blood test results to confirm the diagnosis.
• Anyone with a suspected acetaminophen overdose should be evaluated immediately in a medical setting, since blood levels are compared against a treatment nomogram to guide antidote therapy.

• Acetaminophen is generally well tolerated at recommended doses, with true side effects being uncommon.
• Mild, reversible increases in liver enzyme levels can occasionally occur even at labeled doses, without signs of liver damage.
• Mild stomach upset may occur in some people.
• A mild skin rash may occur rarely, even at labeled doses.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Severe liver damage (hepatotoxicity) can occur with overdose and, very rarely, has been reported with recommended doses.
• Serious allergic reactions, including rash, hives, difficulty breathing, low blood pressure, swelling of the throat (laryngeal edema), or anaphylaxis, may occur rarely.
• Serious skin reactions, including acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely.
• Blood disorders, including low platelet counts, low white blood cell counts, and reduced blood cell production (pancytopenia or agranulocytosis), have been reported rarely.
• Seek urgent medical attention for yellowing of the skin or eyes, unexplained bleeding or bruising, a widespread rash or skin peeling, facial or throat swelling, or any suspected overdose, even without symptoms.

• Use with caution in people who regularly drink three or more alcoholic drinks per day, since chronic heavy alcohol use may increase the risk of liver toxicity from acetaminophen.
• Use with caution in patients with chronic liver disease; while studies have not shown increased risk at recommended doses, a doctor should be consulted before regular use.
• Use with caution in patients with chronic kidney disease, particularly with long-term regular use, and a doctor should supervise ongoing therapy.
• Use with caution in patients taking warfarin or other coumarin-type blood thinners, since regular acetaminophen use has occasionally been linked to increased INR; periodic monitoring is reasonable.
• Use with caution in patients taking long-term anticonvulsant medications such as phenytoin or carbamazepine, since altered liver metabolism may affect the risk of toxicity if an overdose occurs.
• Use with caution in patients on isoniazid therapy, particularly in the 12 to 48 hours after stopping isoniazid, when liver enzyme changes could increase overdose risk.
• Do not use with any other product that also contains acetaminophen, to avoid unintentionally exceeding the maximum daily dose.

• Contraindicated in patients with known hypersensitivity to acetaminophen or to any ingredient in the specific product formulation.

• Warfarin and other coumarin-type anticoagulants may show increased INR (a measure of blood clotting time) with regular acetaminophen use; periodic monitoring is advised with concurrent use.
• Diflunisal can raise acetaminophen blood levels by about half; caution and monitoring are advised if these are used together.
• Isoniazid can affect the metabolism of acetaminophen, with the period shortly after stopping isoniazid carrying a theoretically higher risk if an acetaminophen overdose occurs.
• Alcohol competes with acetaminophen for the same liver enzyme pathway; while occasional alcohol use does not significantly increase risk at recommended doses, chronic heavy use raises the risk of liver toxicity.
• Combining acetaminophen with other analgesics should be done cautiously, since combining multiple pain relievers can increase the risk of side effects such as stomach irritation or kidney strain.

• Standard immediate-release acetaminophen tablets, caplets, liquid gels, chewables, and liquid formulations can be taken with or without food.
• Extended-release acetaminophen caplets (Arthritis Pain and Muscle & Body formulations) should be swallowed whole on an empty stomach, and never crushed, chewed, or dissolved.

• Immediate-release acetaminophen may be taken at any time of day, with or without food, spaced 4 to 6 hours apart as needed.
• Extended-release acetaminophen should be taken on an empty stomach, spaced about 8 hours apart, to ensure the tablet releases the medication as intended.

• Store acetaminophen products at room temperature (15°C to 30°C).
• Rapid Release gelcaps should additionally be protected from high heat and humidity.
• Infants' and Children's suspensions should additionally be protected from light.

• Acetaminophen is a widely used pain reliever and fever reducer that is safe when taken at the recommended dose, but dangerous in overdose.
• Never take more than 4000 mg (4 g) total in 24 hours from all sources, and always check other medicines for hidden acetaminophen before combining them.
• Extended-release arthritis and muscle formulations must be swallowed whole on an empty stomach, never crushed or chewed.
• Seek medical help immediately for any suspected overdose, even if you feel fine, since early treatment with the antidote can prevent serious liver damage.