Acetaminophen

Name: Acetaminophen

What is acetaminophen? How does it work (mechanism of action)?

Acetaminophen belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers). The exact mechanism of action of acetaminophen is not known. It may reduce the production of prostaglandins in the brain. Prostaglandins are chemicals that cause inflammation and swelling. Acetaminophen relieves pain by elevating the pain threshold, that is, by requiring a greater amount of pain to develop before a person feels it. It reduces fever through its action on the heat-regulating center of the brain. Specifically, it tells the center to lower the body's temperature when the temperature is elevated. The FDA approved acetaminophen in 1951.

What brand names are available for acetaminophen?

Tylenol, Tylenol Arthritis Pain, Tylenol Ext, Little Fevers Children's Fever/Pain Reliever, Little Fevers Infant Fever/Pain Reliever, PediaCare Single Dose Acetaminophen Fever Reducer/Pain Reliever, Infants's Feverall, Acephen, Neopap, and others.

Cautions for Acetaminophen

Contraindications

  • Known hypersensitivity to acetaminophen or any ingredient in the formulation.207 222 300

  • Severe hepatic impairment or severe active liver disease.300

Warnings/Precautions

Warnings

Hepatic Effects

Ingestion of a single toxic dose or multiple excessive doses can result in hepatotoxicity.222 223 (See Boxed Warning.) About 50% of cases of acute liver failure in the US result from inadvertent overdosage.262 265 266 267 268 269 270 271 (See Advice to Patients.) Following suspected overdosage, evaluate necessity of antidote (acetylcysteine) therapy.222 223 225 229

Increased serum ALT concentrations reported in healthy individuals receiving oral acetaminophen 4 g daily for 14 days in 1 study.239 Increased AST or hepatic enzyme concentrations reported in patients receiving IV acetaminophen in clinical studies.300

Use with caution in patients with hepatic impairment, active liver disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., resulting from dehydration or blood loss), or severe renal impairment (Clcr ≤30 mL/minute).300 Contraindicated in those with severe hepatic impairment or severe active liver disease.300

Sensitivity Reactions

Hypersensitivity Reactions

Sensitivity reactions (e.g., anaphylaxis, urticaria, rash, pruritus, respiratory distress, swelling of the face, mouth, or throat) reported rarely.222 300 If such reactions occur, immediately discontinue the drug.207 222 300

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.a

Other Warnings/Precautions

Dermatologic Reactions

Serious, potentially fatal dermatologic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis) reported rarely.282 283 284 285 May occur at any time during therapy.282 Although NSAIAs may cause similar reactions, cross-sensitivity with acetaminophen does not appear to occur.282

Discontinue at the first appearance of rash or any other manifestation of hypersensitivity.300

Use of Multiple Acetaminophen-containing Preparations

Do not use multiple acetaminophen-containing preparations concomitantly.207 222 235 (See Boxed Warning.)

Use of Fixed Combinations

When used in fixed combination with other agents (e.g., aspirin, caffeine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, opiate agonists, phenylephrine, pseudoephedrine), consider the cautions, precautions, and contraindications associated with the concomitant agent(s).212 253 254 255 256 257 258 259

Because many OTC and prescription preparations contain acetaminophen,238 264 265 266 267 270 271 272 273 concomitant use of more than one acetaminophen-containing preparation can result in adverse consequences (e.g., acetaminophen overdosage).238 240 262 264 265 266 267 268 269 271 273 Avoid such concomitant use.238 262 264 265 266 267 268 269 271 273 (See Advice to Patients.)

When used in fixed combination with an opiate analgesic, an increase in dosage of the fixed combination (because of tolerance to the opiate) may increase risk of inadvertent acetaminophen overdosage.265 271 To minimize such risk, FDA has requested manufacturers to reformulate prescription combination preparations to limit the amount of acetaminophen to 325 mg per dosage unit.268 FDA recommends that health care providers stop prescribing and dispensing prescription combination preparations containing >325 mg of acetaminophen per dosage unit.286 287 (See Preparations and also see Dosage under Dosage and Administration.)

Masking of Fever

Antipyretic effects may mask the presence of fever.300

Specific Populations

Pregnancy

Epidemiologic data regarding oral acetaminophen use in pregnant women have shown no increased risk of major congenital malformations in infants exposed in utero.300

Commonly used during all stages of pregnancy for analgesia and antipyresis.293 299 Although thought not to be associated with risk in offspring, some recent reports have questioned this assessment, especially with frequent maternal use or in cases involving genetic variability.293 299 FDA reviewed data on a possible association between acetaminophen use during pregnancy and risk of ADHD in children and announced in January 2015 that the data were inclusive.299 Some experts state that as with all drug use during pregnancy, avoid routine acetaminophen use.293

Manufacturer states IV acetaminophen should be used during pregnancy only when clearly needed; IV acetaminophen not studied in pregnant women or in animal reproduction studies.300

Use IV acetaminophen during labor and delivery only after careful assessment of potential benefits and risks; IV acetaminophen not studied in this setting.300

Lactation

Distributed into milk in small quantities after oral administration;293 300 data suggest approximately 1–2% of maternal daily dosage is ingested by nursing infant.300

Maculopapular rash reported in a breast-fed infant; rash resolved when mother discontinued acetaminophen use and recurred when she resumed such use.293 300

AAP and other experts state acetaminophen is an acceptable choice for use in nursing women.293 294 Manufacturer states IV acetaminophen should be used with caution in nursing women.300

Pediatric Use

Severe hepatotoxicity and death reported in children who apparently received acetaminophen dosages exceeding those recommended202 203 204 205 206 (10–15 mg/kg per dose with a maximum of 5 doses per day) for children.202 204 Contributing factors include improper interpretation of dosing information or failure to read such information, use of adult-strength preparations, use of excessive dosing because of the perception that desired therapeutic effects had not been achieved, and lack of knowledge about the potential toxicity of acetaminophen in excessive dosage.203 204 205 206

Inadvertent overdosage, possibly resulting in hepatic failure and death, reported following confusion over different concentrations of acetaminophen (e.g., 80 mg/0.8 mL, 80 mg/mL, 160 mg/5 mL) contained in various pediatric preparations.275 276 277 To minimize dosing confusion, FDA recommended that only one concentration of liquid acetaminophen be available for OTC use in all pediatric patients.275 Some manufacturers voluntarily changed the concentration of the infants' formulation to be the same as that of the children's formulation (i.e., from 80 mg/0.8 mL or 80 mg/mL to 160 mg/5 mL).275 276 277 However, older, more-concentrated infants' preparations (80 mg/0.8 mL or 80 mg/mL) may remain available.275 276 To avoid confusion and potential for dosing errors, advise patients to carefully read the product labeling to identify the concentration of acetaminophen (in mg/mL), dosage, and directions for use.275 (See Advice to Patients.)

Risk of overdosage and toxicity (including death) in children <2 years of age receiving preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.247 248 Limited evidence of efficacy for these cold and cough preparations in this age group; appropriate dosages not established.247 FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns.

Use of IV acetaminophen for analgesia or antipyresis in pediatric patients ≥2 years of age supported by controlled studies in adults and additional safety and pharmacokinetic data from 355 pediatric patients (age range: premature neonates to adolescents).300 Efficacy of IV acetaminophen for analgesia and antipyresis not established in children <2 years of age.300

Geriatric Use

In studies of IV acetaminophen, no substantial differences in safety or efficacy relative to younger patients, but increased sensitivity cannot be ruled out.300

Hepatic Impairment

Use with caution in patients with hepatic impairment or active liver disease; dosage reduction may be warranted.300 (See Hepatic Impairment under Dosage and Administration.) Contraindicated in those with severe hepatic impairment or severe active liver disease.300

Renal Impairment

Use with caution in patients with severe renal impairment (Clcr ≤30 mL/minute); dosage reduction may be warranted.300 (See Renal Impairment under Dosage and Administration.)

ALERT U.S. Boxed Warning

Risk of medication errors and hepatotoxicity (injection):

Take care when prescribing, preparing, and administering acetaminophen injection to avoid dosing errors that could result in accidental overdose and death. In particular, be careful to ensure the following: the dose in milligrams and milliliters is not confused; the dosing is based on weight for patients less than 50 kg; infusion pumps are properly programmed; and the total daily dose of acetaminophen from all sources does not exceed maximum daily limits.

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limits, and often involve more than 1 acetaminophen-containing product.

Monitoring Parameters

Serum acetaminophen levels: Where acute overdose suspected and with long-term use in patients with hepatic disease; relief of pain or fever

Inform MD

Before taking acetaminophen, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to acetaminophen or to any of its ingredients
  • have liver problems
  • have kidney problems
  • drink alcoholic beverages
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Acetaminophen Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight
  • your age

The recommended adult dose of acetaminophen for the treatment of pain and/or fever reduction is 1000 mg every 6 hours or 650 mg every 4 hours. The maximum daily dose for adults for all forms of acetaminophen is 4000 mg.

The recommended dose of acetaminophen for children for the treatment of pain and/or fever reduction is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours. The maximum daily dose for children for all forms of acetaminophen is 75 mg/kg.

What is acetaminophen?

Acetaminophen is a pain reliever and a fever reducer.

Acetaminophen is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers.

Acetaminophen may also be used for purposes not listed in this medication guide.

Before taking this medicine

You should not take acetaminophen if you are allergic to it, or if you have severe liver disease.

Do not take this medicine without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take acetaminophen.

Your doctor will determine whether acetaminophen is safe for you to use during pregnancy. Do not use this medicine without the advice of your doctor if you are pregnant.

Acetaminophen can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give this medicine to a child younger than 2 years old without the advice of a doctor.

What other drugs will affect acetaminophen?

Other drugs may interact with acetaminophen, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

For the Consumer

Applies to acetaminophen: capsule, capsule liquid filled, elixir, liquid, powder, powder for solution, solution, suppository, suspension, syrup, tablet, tablet chewable, tablet disintegrating, tablet effervescent, tablet extended release

Other dosage forms:

  • intravenous solution

Along with its needed effects, acetaminophen may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking acetaminophen:

Rare
  • Bloody or black, tarry stools
  • bloody or cloudy urine
  • fever with or without chills (not present before treatment and not caused by the condition being treated)
  • pain in the lower back and/or side (severe and/or sharp)
  • pinpoint red spots on the skin
  • skin rash, hives, or itching
  • sore throat (not present before treatment and not caused by the condition being treated)
  • sores, ulcers, or white spots on the lips or in the mouth
  • sudden decrease in the amount of urine
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking acetaminophen:

Symptoms of overdose
  • Diarrhea
  • increased sweating
  • loss of appetite
  • nausea or vomiting
  • stomach cramps or pain
  • swelling, pain, or tenderness in the upper abdomen or stomach area

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