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Acetaminophen

Class: Analgesics and Antipyretics, Miscellaneous
VA Class: CN103
CAS Number: 103-90-2
Brands: Acephen, FeverAll, Ofirmev, Tylenol

Acetaminophen is also contained as an ingredient in the following combinations:
Acetaminophen, Aspirin, and Caffeine
Acetaminophen and Codeine Phosphate
Acetaminophen and Diphenhydramine Citrate
Oxycodone and Acetaminophen

Medically reviewed by Drugs.com on Jan 22, 2021. Written by ASHP.

Warning

    Hepatotoxicity
  • Acute liver failure, sometimes resulting in liver transplantation and death, can occur. Liver injury usually is associated with doses that exceed the maximum recommended daily dosage and often involves use of more than one acetaminophen-containing preparation.

    Medication Errors with IV Acetaminophen
  • Use caution when prescribing, preparing, and administering IV acetaminophen to avoid dosing errors that could result in accidental overdosage and death.

  • Ensure that the dose (in mg) and the volume (in mL) are not confused, the dose for patients weighing <50 kg is based on body weight, the infusion pump is programmed correctly, and the total daily dosage of acetaminophen from all sources does not exceed the maximum recommended daily dosage.

Introduction

Synthetic nonopiate derivative of p-aminophenol; produces analgesia and antipyresis.

Uses for Acetaminophen

Pain

Symptomatic relief of mild to moderate pain.

Recommended by many experts as initial analgesic for many patients; however, consider risk of inadvertent overdosage and resultant acute liver failure. (See Hepatic Effects and also see Pediatric Use under Cautions.)

Self-medication in children ≥6 years of age and adults for the temporary relief of minor aches and pain associated with headache, muscular aches, backache, minor arthritis pain, common cold, toothache, and menstrual cramps. Self-medication in infants and children for the temporary relief of minor aches and pain associated with the common cold, flu, headache, sore throat, immunizations, toothache, muscle aches, sprains, and overexertion.

Self-medication in fixed combination with aspirin and caffeine for the temporary relief of mild to moderate pain associated with migraine headache. This combination also can be used for the treatment of severe migraine headache if previous attacks have responded to similar nonopiate analgesics or NSAIAs.

Symptomatic treatment of pain associated with osteoarthritis; considered an initial drug of choice for pain management in osteoarthritis patients.

Used in fixed combination with other agents (e.g., chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, phenylephrine, pseudoephedrine) for short-term relief of minor aches and pain, headache, fever, and/or other symptoms (e.g., rhinorrhea, sneezing, lacrimation, itching eyes, oronasopharyngeal itching, nasal congestion, cough) associated with seasonal allergic rhinitis (e.g., hay fever), other upper respiratory allergies, or the common cold.

Treatment of pain in various combinations with aspirin, caffeine, opiates, and/or other agents. Oral use in combination with an opiate (e.g., codeine, oxycodone) produces greater analgesic effect than that produced by either acetaminophen or higher doses of the opiate alone.

IV use in patients with moderate to severe postoperative pain reduces pain intensity and rescue opiate requirements compared with placebo, but clinical benefits of the lower opiate dosages (e.g., reduction in opiate-related adverse effects) not established.

Fever

Reduction of fever.

Self-medication to reduce fever in infants, children, and adults.

Acetaminophen Dosage and Administration

Administration

Usually administered orally; may be administered rectally as suppositories in patients who cannot tolerate oral therapy. Also may be administered IV.

Oral Administration

Swallow extended-release tablets whole; do not crush, chew, or dissolve in liquid.

Because combinations and dosage strengths vary for fixed-combination preparations, consult manufacturer’s product labeling for appropriate dosage of the specific preparation.

Pediatric Administration

For liquid preparations (e.g., solution, suspension), use the calibrated dosing device provided by the manufacturer for measurement of the dose.

80-mg orally disintegrating tablets may be used in children ≥2 years of age.

160-mg orally disintegrating tablets or 325-mg conventional tablets commonly used in children ≥6 years of age.

Orally disintegrating tablets (e.g., Tylenol Meltaways) should be allowed to dissolve in the mouth or should be chewed before swallowing. Use caution to ensure that the correct number of tablets required for the intended dose is removed from the blister package.

Rectal Administration

Dividing suppositories in an attempt to administer lower dosages may not provide a predictable dose.

Some experts state that rectal acetaminophen preparations should not be used for self-medication in children unless such use is specifically discussed with a clinician and parents or caregivers are instructed to adhere to dosage and administration recommendations.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.

Monitor the end of the infusion to prevent possibility of air embolism, especially when acetaminophen solution is the primary infusion.

Commercially available 10-mg/mL injection may be administered without further dilution. Each vial (1 g/100 mL) is for single use only; discard any unused portions.

Dose of 1 g: Administer by inserting a vented IV set through the septum of the 100-mL vial.

Dose of <1 g: Dose must be withdrawn from vial and placed in a separate container for IV infusion to avoid inadvertent administration of the total volume of the vial. Aseptically withdraw the appropriate dose from an intact sealed vial and transfer to an empty sterile container (e.g., glass bottle, plastic container, syringe); draw small-volume (up to 60 mL) pediatric doses into a syringe and administer via syringe pump.

Administer within 6 hours after penetration of the vacuum seal of the vial or transfer of vial contents to another container.

Do not admix with any other drugs.

Rate of Administration

Administer by IV infusion over 15 minutes.

Dosage

To minimize risk of inadvertent overdosage, FDA recommends that health care providers stop prescribing and dispensing prescription combination preparations containing >325 mg of acetaminophen per dosage unit; doses consisting of either 1 or 2 dosage units (i.e., 325 or 650 mg of acetaminophen per dose) may be prescribed as clinically appropriate for the patient and in consideration of the strengths of each component (generally acetaminophen and an opiate analgesic) of the fixed combination. (See Preparations.)

FDA recommends that pharmacists receiving prescriptions for fixed-combination preparations containing >325 mg of acetaminophen per dosage unit contact the prescriber to discuss use of a preparation containing ≤325 mg of the drug per dosage unit.

Take care to avoid dosing errors when prescribing, preparing, and administering IV acetaminophen. (See Boxed Warning.)

Pediatric Patients

Dosage in children should be guided by body weight. (See Pediatric Use under Cautions.)

Pain
Oral

Dose may be given every 4–6 hours as necessary (up to 5 times in 24 hours).

Dosage for Self-medication of Pain in Children up to 11 Years of Age207237279280

Age

Weight

Oral Dose

≤3 months

2.7–5 kg

40 mg

4–11 months

5–8 kg

80 mg

12–23 months

8–11 kg

120 mg

2–3 years

11–16 kg

160 mg

4–5 years

16–21 kg

240 mg

6–8 years

22–27 kg

320 mg

9–10 years

27–32 kg

400 mg

11 years

33–43 kg

480 mg

For self-medication in children ≥12 years of age, 650 mg every 4–6 hours or 1 g every 6 hours as necessary. (See Prescribing Limits under Dosage and Administration.)

Rectal

Dose may be given every 4–6 hours as necessary (up to 5 times in 24 hours).

Dosage for Self-medication of Pain in Children 2–12 Years of Age198

Age

Rectal Dose

2–4 years

160 mg

4–6 years

240 mg

6–9 years

320 mg

9–11 years

320–400 mg

11–12 years

320–480 mg

Individualize dosage in children <2 years of age.

For self-medication in children ≥12 years of age, 325–650 mg every 4 hours as necessary.

IV

Administer as single or repeated doses.

Children 2–12 years of age: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

Adolescents ≥13 years of age and weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

Adolescents ≥13 years of age and weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours. May switch between oral and IV acetaminophen without dosage adjustment.

Fever
Oral

Dose may be given every 4–6 hours as necessary (up to 5 times in 24 hours).

Dosage for Self-medication of Fever in Children up to 11 Years of Age207237279280

Age

Weight

Oral Dose

≤3 months

2.7–5 kg

40 mg

4–11 months

5–8 kg

80 mg

12–23 months

8–11 kg

120 mg

2–3 years

11–16 kg

160 mg

4–5 years

16–21 kg

240 mg

6–8 years

22–27 kg

320 mg

9–10 years

27–32 kg

400 mg

11 years

33–43 kg

480 mg

For self-medication in children ≥12 years of age, 650 mg every 4–6 hours or 1 g every 6 hours as necessary. (See Prescribing Limits under Dosage and Administration.)

Rectal

Dose may be given every 4 hours as necessary (up to 5 times in 24 hours).

Dosage for Self-medication of Fever in Children 2–12 Years of Age198

Age

Rectal Dose

2–4 years

160 mg

4–6 years

240 mg

6–9 years

320 mg

9–11 years

320–400 mg

11–12 years

320–480 mg

Individualize dosage in children <2 years of age.

For self-medication in children ≥12 years of age, 325–650 mg every 4 hours as necessary.

IV

Administer as single or repeated doses.

Children 2–12 years of age: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

Adolescents ≥13 years of age and weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

Adolescents ≥13 years of age and weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours. May switch between oral and IV acetaminophen without dosage adjustment.

Adults

Pain
Oral

For self-medication, 650 mg every 4–6 hours or 1 g every 6 hours as necessary. Alternatively, 1.3 g as extended-release tablets every 8 hours. (See Prescribing Limits under Dosage and Administration.)

Rectal

325–650 mg every 4 hours as necessary.

IV

Administer as single or repeated doses.

Adults weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours. May switch between oral and IV acetaminophen without dosage adjustment.

Adults weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

Pain Associated with Migraine Headache
Oral

Acetaminophen, aspirin, and caffeine for self-medication: 2 tablets (each containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg) as a single dose.

Pain Associated with Osteoarthritis
Oral

1 g 4 times daily. Alternatively, 1.3 g as extended-release tablets every 8 hours.

Fever
Oral

For self-medication, 650 mg every 4–6 hours or 1 g every 6 hours as necessary. (See Prescribing Limits under Dosage and Administration.)

Rectal

325–650 mg every 4 hours as necessary.

IV

Administer as single or repeated doses.

Adults weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours. May switch between oral and IV acetaminophen without dosage adjustment.

Adults weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.

Prescribing Limits

Pediatric Patients

Pain
Oral

Do not exceed recommended daily dosage. For self-medication in children ≥12 years of age, some manufacturers recommend a maximum dosage of 3 g daily. (See Prescribing Limits: Adults, under Dosage and Administration.)

Self-medication should not exceed 5 days (in children 2–11 years of age) or 10 days (in children ≥12 years of age).

IV

Children 2–12 years of age: Maximum single dose is 15 mg/kg, minimum dosing interval is 4 hours, and maximum daily dosage is 75 mg/kg per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Adolescents ≥13 years of age and weighing <50 kg: Maximum single dose is 15 mg/kg, minimum dosing interval is 4 hours, and maximum daily dosage is 75 mg/kg per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Adolescents ≥13 years of age and weighing ≥50 kg: Maximum single dose is 1 g, minimum dosing interval is 4 hours, and maximum daily dosage is 4 g per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Fever
Oral

Do not exceed recommended daily dosage. For self-medication in children ≥12 years of age, some manufacturers recommend a maximum dosage of 3 g daily. (See Prescribing Limits: Adults, under Dosage and Administration.)

Self-medication should not exceed 3 days.

IV

Children 2–12 years of age: Maximum single dose is 15 mg/kg, minimum dosing interval is 4 hours, and maximum daily dosage is 75 mg/kg per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Adolescents ≥13 years of age and weighing <50 kg: Maximum single dose is 15 mg/kg, minimum dosing interval is 4 hours, and maximum daily dosage is 75 mg/kg per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Adolescents ≥13 years of age and weighing ≥50 kg: Maximum single dose is 1 g, minimum dosing interval is 4 hours, and maximum daily dosage is 4 g per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Adults

Current limit is 4 g daily. Some experts recommend a maximum dosage of 3 g daily when used for long-term therapy (e.g., ≥2 weeks). FDA is evaluating whether data exist to support establishing a lower (i.e., <4 g daily) maximum daily dosage for certain patients (e.g., those who chronically ingest alcohol). Some manufacturers (e.g., McNeil, Tylenol) voluntarily revised their labeling and currently recommend a maximum dosage of 3 g daily.

Pain
Oral or Rectal

Maximum 4 g daily. Some manufacturers recommend a maximum oral dosage of 3 g daily. (See Prescribing Limits: Adults, under Dosage and Administration.)

Self-medication should not exceed 10 days.

IV

Adults weighing ≥50 kg: Maximum single dose is 1 g, minimum dosing interval is 4 hours, and maximum daily dosage is 4 g per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Adults weighing <50 kg: Maximum single dose is 15 mg/kg, minimum dosing interval is 4 hours, and maximum daily dosage is 75 mg/kg per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Pain Associated with Migraine Headache
Oral

Acetaminophen, aspirin, and caffeine: Maximum for self-medication is 2 tablets (each containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg) in 24 hours unless otherwise directed by a clinician.

Pain Associated with Osteoarthritis
Oral

Maximum 4 g daily.

Fever
Oral or Rectal

Maximum 4 g daily. Some manufacturers recommend maximum oral dosage of 3 g daily. (See Prescribing Limits: Adults, under Dosage and Administration.)

Self-medication should not exceed 3 days.

IV

Adults weighing ≥50 kg: Maximum single dose is 1 g, minimum dosing interval is 4 hours, and maximum daily dosage is 4 g per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Adults weighing <50 kg: Maximum single dose is 15 mg/kg, minimum dosing interval is 4 hours, and maximum daily dosage is 75 mg/kg per 24-hour period (including all routes of administration and all acetaminophen-containing preparations, including fixed combinations).

Special Populations

Hepatic Impairment

Reduction of total daily dosage may be warranted in patients with hepatic impairment or active liver disease. (See Hepatic Impairment under Cautions.)

Renal Impairment

Longer dosing intervals and reduced total daily dosage may be warranted in patients with severe renal impairment (Clcr ≤30 mL/minute).

Cautions for Acetaminophen

Contraindications

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

  • Severe hepatic impairment or severe active liver disease.

Warnings/Precautions

Warnings

Hepatic Effects

Ingestion of a single toxic dose or multiple excessive doses can result in hepatotoxicity. (See Boxed Warning.) About 50% of cases of acute liver failure in the US result from inadvertent overdosage. (See Advice to Patients.) Following suspected overdosage, evaluate necessity of antidote (acetylcysteine) therapy.

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

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). Contraindicated in those with severe hepatic impairment or severe active liver disease.

Sensitivity Reactions

Hypersensitivity Reactions

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

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.

Other Warnings/Precautions

Dermatologic Reactions

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

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

Use of Multiple Acetaminophen-containing Preparations

Do not use multiple acetaminophen-containing preparations concomitantly. (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).

Because many OTC and prescription preparations contain acetaminophen, concomitant use of more than one acetaminophen-containing preparation can result in adverse consequences (e.g., acetaminophen overdosage). Avoid such concomitant use. (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. 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. FDA recommends that health care providers stop prescribing and dispensing prescription combination preparations containing >325 mg of acetaminophen per dosage unit. (See Preparations and also see Dosage under Dosage and Administration.)

Masking of Fever

Antipyretic effects may mask the presence of fever.

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.

Commonly used during all stages of pregnancy for analgesia and antipyresis. 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. 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. Some experts state that as with all drug use during pregnancy, avoid routine acetaminophen use.

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.

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

Lactation

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

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

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

Pediatric Use

Severe hepatotoxicity and death reported in children who apparently received acetaminophen dosages exceeding those recommended (10–15 mg/kg per dose with a maximum of 5 doses per day) for children. 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.

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. To minimize dosing confusion, FDA recommended that only one concentration of liquid acetaminophen be available for OTC use in all pediatric patients. 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). However, older, more-concentrated infants' preparations (80 mg/0.8 mL or 80 mg/mL) may remain available. 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. (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. Limited evidence of efficacy for these cold and cough preparations in this age group; appropriate dosages not established. 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). Efficacy of IV acetaminophen for analgesia and antipyresis not established in children <2 years of age.

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.

Hepatic Impairment

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

Renal Impairment

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

Interactions for Acetaminophen

Drugs Affecting Hepatic Microsomal Enzymes

Drugs that induce or regulate CYP2E1 may alter metabolism of acetaminophen and increase its hepatotoxic potential. (See Metabolism under Pharmacokinetics.) Clinical importance not established.

Specific Drugs

Drug

Interaction

Comments

Alcohol

Increased risk of acetaminophen-induced hepatotoxicity

Complex effects on acetaminophen pharmacokinetics; excessive alcohol use can induce hepatic cytochromes, but alcohol also competitively inhibits acetaminophen metabolism

Avoid regular or excessive use of acetaminophen; alternatively, avoid chronic ingestion of alcohol (see Prescribing Limits: Adults, under Dosage and Administration)

Anticonvulsants (barbiturates, carbamazepine, phenytoin)

Increased conversion of acetaminophen to hepatotoxic metabolites; increased risk of hepatotoxicity

Limit acetaminophen self-medication; dosage adjustment not required

Anticoagulants, oral

Possible increased PT

Effects of IV acetaminophen not established

Clinical importance questioned; monitor anticoagulant activity if large doses of acetaminophen used

Manufacturer of acetaminophen injection states more frequent INR monitoring also may be appropriate during short-term concomitant IV acetaminophen use

Aspirin

No inhibition of antiplatelet effect of aspirin

Isoniazid

Possible increased risk of hepatotoxicity

Limit acetaminophen self-medication

Phenothiazines

Possible increased risk of severe hypothermia

Acetaminophen Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentration attained within 10–60 minutes (immediate-release preparations) or 60–120 minutes (extended-release preparations).

Poor or variable absorption following rectal administration; considerable variation in peak plasma concentrations attained; time to reach peak plasma concentration is substantially longer than after oral administration.

Pharmacokinetics of IV acetaminophen are dose proportional at doses of 0.5–1 g.

Systemic exposure is similar following IV or oral administration, but peak plasma concentration at end of 15-minute IV infusion is up to 70% higher than peak concentration following oral administration of same dose.

Following single-dose IV administration in pediatric patients (15-mg/kg dose) or adults (1-g dose), systemic exposure in children and adolescents is similar to that in adults, but exposure is higher in neonates and infants. Simulations suggest that dose reductions of 33% in infants 1 month to <2 years of age and 50% in neonates up to 28 days of age, with a minimum dosing interval of 6 hours, would result in systemic exposures similar to those observed in children ≥2 years of age.

Food

Food may delay absorption following administration as extended-release tablets.

Distribution

Extent

Rapidly distributed to most body tissues except fat. Crosses placenta and is distributed into breast milk in small quantities.

Plasma Protein Binding

10–25%.

Elimination

Metabolism

Metabolized principally by sulfate and glucuronide conjugation; small amounts (5–10%) oxidized by CYP-dependent pathways (mainly CYP2E1) to a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI is detoxified by glutathione and eliminated; any remaining toxic metabolite may bind to hepatocytes and cause cellular necrosis.

Elimination Route

Mainly excreted in urine as conjugates.

Half-life

Reportedly 1.25–3 hours.

Following IV administration, 2.4 hours in adults, 2.9–3 hours in children and adolescents, 4.2 hours in infants, and 7 hours in neonates.

Special Populations

Following toxic doses or in patients with liver damage, plasma half-life may be prolonged.

In patients with moderate to severe renal impairment, acetaminophen conjugates may accumulate.

Stability

Storage

Oral

Tablets

Room temperature. Protect orally disintegrating tablets (Tylenol Meltaways) from high humidity. Protect grape-flavored orally disintegrating tablets from light.

Suspension/Solution

Room temperature.

Parenteral

Injection

20–25°C; do not refrigerate or freeze. Use within 6 hours after penetration of vacuum seal of vial or transfer of vial contents to another container.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility301

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility
Admixture Compatibility301

Compatible

Ketamine HCl

Y-Site Compatibility

Compatible

Buprenorphine HCl

Butorphanol tartrate

Cefoxitin sodium

Ceftriaxone sodium

Clindamycin phosphate

Dexamethasone sodium phosphate

Diphenhydramine HCl

Dolasetron mesylate

Droperidol

Fentanyl citrate

Granisetron HCl

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Ketorolac tromethamine

Lidocaine HCl

Lorazepam

Mannitol

Meperidine HCl

Methylprednisolone sodium succinate

Metoclopramide HCl

Midazolam HCl

Morphine sulfate

Nalbuphine HCl

Ondansetron HCl

Piperacillin sodium-tazobactam sodium

Potassium chloride

Prochlorperazine edisylate

Ranitidine HCl

Sufentanil citrate

Vancomycin HCl

Incompatible

Acyclovir sodium

Chlorpromazine HCl

Diazepam

Actions

  • Exhibits analgesic and antipyretic activity.

  • Weak, reversible, isoform-nonspecific cyclooxygenase inhibitor at dosages of 1 g daily. Inhibitory effect on cyclooxygenase-1 is limited; does not inhibit platelet function.

Advice to Patients

  • Risk of severe hepatic damage with use of excessive dosages, with concomitant use of multiple acetaminophen-containing preparations, and in those consuming substantial amounts of alcohol (e.g., ≥3 alcohol-containing drinks per day) concomitantly.

  • When used for self-medication, importance of reading the product labeling. Importance of not exceeding the recommended daily dosage and of not using other acetaminophen-containing products (e.g., some cold and cough products) concomitantly.

  • When used for self-medication in pediatric patients, importance of basing the dose on the child’s weight; importance of not exceeding the recommended daily dosage.

  • Importance of advising parents and caregivers about the appropriate dose, frequency, duration of therapy, and specific strength and formulation for an individual pediatric patient. Advise of the danger of substituting alternative dosage forms, particularly adult for pediatric formulations.

  • Importance of informing parents and caregivers that multiple concentrations of liquid acetaminophen may be available and of advising them to carefully read the product labeling to identify the concentration of acetaminophen (in mg/mL), dosage, and directions for use.

  • Importance of ensuring that the correct amount of medication required for the intended dose is administered (e.g., importance of using only the calibrated measuring device provided with the particular formulation for measuring the dose, importance of ensuring that the strength and number of dosage units correspond to the intended dose). Importance of contacting a clinician if use of measuring device seems confusing or if there is any uncertainty in the proper use of the device.

  • Importance of discontinuing therapy and seeking immediate medical attention if rash or other manifestations of dermatologic or hypersensitivity reactions occur. Advise individuals with a history of such reactions not to take any acetaminophen-containing preparations.

  • Importance of seeking quick medical attention if ingested dosage exceeds recommended dosage.

  • Importance of limiting alcohol intake.

  • Advise patients that paracetamol and APAP are other names for acetaminophen.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., cough/cold preparations) as well as any concomitant illnesses.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

To minimize the risk of inadvertent acetaminophen overdosage in pediatric patients, FDA has recommended that only one concentration of liquid acetaminophen be available for OTC use in all pediatric patients. Some manufacturers have voluntarily changed the concentration of the infants' formulation to be the same as that of the children's formulation. (See Pediatric Use under Cautions.) However, older, more-concentrated infants' preparations may remain available.

To minimize the risk of inadvertent acetaminophen overdosage, FDA has requested manufacturers to reformulate prescription combination preparations containing the drug to limit the acetaminophen amount to ≤325 mg per dosage unit. FDA no longer considers prescription combination preparations containing >325 mg of acetaminophen to be safe. As of March 26, 2014, all manufacturers of such preparations had discontinued marketing of the preparations, but some had not withdrawn the drug applications. FDA intends to withdraw approval of those applications if they are not voluntarily withdrawn. Therefore, availability of combination preparations with higher concentrations of acetaminophen per dose will diminish over time. Some prescription combination preparations that previously contained >325 mg of acetaminophen per dosage unit may have been reformulated to contain smaller amount of acetaminophen. Pharmacists are encouraged to return any prescription combination preparations containing >325 mg of acetaminophen per dosage unit to the wholesaler or manufacturer. FDA intends to address OTC acetaminophen-containing preparations in a separate regulatory action.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Acetaminophen

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, gel-coated

500 mg*

Acetaminophen Extra Strength Gel-coated Capsules

Solution

167 mg/5 mL*

Tylenol Extra-Strength Adult

McNeil

Suspension

160 mg/5 mL*

Tylenol Oral Suspension Children’s

McNeil

Tylenol Oral Suspension Infant's

McNeil

Tablets

325 mg*

Tylenol Regular Strength (scored)

McNeil

Tablets, extended-release, film-coated

650 mg*

Tylenol Arthritis Pain Extended-Release Caplets

McNeil

Tylenol 8 HR Extended-Release Caplets

McNeil

Tablets, film-coated

500 mg*

Tylenol Extra Strength Caplets

McNeil

Tablets, orally disintegrating

80 mg*

Tylenol Meltaways Children’s

McNeil

160 mg*

Tylenol Meltaways Junior Strength

McNeil

Parenteral

Injection, for IV infusion

10 mg/mL (1 g)

Ofirmev

Mallinckrodt

Rectal

Suppositories

80 mg

FeverAll Infants’

Taro

120 mg*

Acephen

G&W

FeverAll Children’s

Taro

325 mg

Acephen

G&W

FeverAll Junior Strength

Taro

650 mg*

Acephen

G&W

Acetaminophen and Aspirin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For solution

325 mg/packet Acetaminophen and Aspirin 500 mg/packet

Goody's Back & Body Pain Powder

Prestige

Tablets, film-coated

250 mg Acetaminophen, Aspirin 250 mg, and buffer

Excedrin Back and Body Caplets

Novartis

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Acetaminophen, Aspirin, and Caffeine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, gel-coated

250 mg Acetaminophen, Aspirin 250 mg, and Caffeine 65 mg*

Excedrin Menstrual Complete Gelcaps

Novartis

For solution

260 mg/packet Acetaminophen, Aspirin 520 mg/packet, and Caffeine 32.5 mg/packet

Goody’s Extra Strength Headache Powder

Prestige

325 mg/packet Acetaminophen, Aspirin 500 mg/packet, and Caffeine 65 mg/packet

Goody’s Cool Orange Extra Strength Powder

Prestige

Tablets, film-coated

194 mg Acetaminophen, Aspirin 227 mg, Caffeine 33 mg, and buffers

Vanquish Caplets

Moberg

250 mg Acetaminophen, Aspirin 250 mg, and Caffeine 65 mg

Excedrin Extra Strength Caplets

Novartis

Excedrin Migraine Caplets

Novartis

Goody's Extra Strength Caplets

Prestige

Pamprin Max

Chattem

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Acetaminophen and Codeine Phosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

120 mg/5 mL Acetaminophen and Codeine Phosphate 12 mg/5 mL*

Acetaminophen and Codeine Phosphate Oral Solution (C-V)

Suspension

120 mg/5 mL Acetaminophen and Codeine Phosphate 12 mg/5 mL

Capital and Codeine (C-V)

Valeant

Tablets

300 mg Acetaminophen and Codeine Phosphate 15 mg*

Acetaminophen and Codeine Phosphate Tablets (C-III)

300 mg Acetaminophen and Codeine Phosphate 30 mg*

Tylenol with Codeine No. 3 (C-III)

Janssen

300 mg Acetaminophen and Codeine Phosphate 60 mg*

Tylenol with Codeine No. 4 (C-III)

Janssen

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Acetaminophen and Diphenhydramine Citrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For solution

500 mg/packet Acetaminophen and Diphenhydramine Citrate 38 mg/packet

Goody's PM Powder

Prestige

Tablets, film-coated

500 mg Acetaminophen and Diphenhydramine Citrate 38 mg*

Excedrin PM Caplets

Novartis

Excedrin PM Geltabs

Novartis

Midol PM Caplets

Bayer

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Oxycodone and Acetaminophen

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

5 mg/5 mL Oxycodone Hydrochloride and Acetaminophen 325 mg/5 mL

Roxicet (C-II)

Roxane

Tablets

2.5 mg Oxycodone Hydrochloride and Acetaminophen 300 mg*

Oxycodone Hydrochloride and Acetaminophen Tablets (C-II)

2.5 mg Oxycodone Hydrochloride and Acetaminophen 325 mg*

Percocet (C-II)

Endo

5 mg Oxycodone Hydrochloride and Acetaminophen 300 mg*

Primlev (C-II)

Akrimax

5 mg Oxycodone Hydrochloride and Acetaminophen 325 mg*

Endocet (C-II; scored)

Qualitest

Percocet (C-II; scored)

Endo

7.5 mg Oxycodone Hydrochloride and Acetaminophen 300 mg*

Primlev (C-II)

Akrimax

7.5 mg Oxycodone Hydrochloride and Acetaminophen 325 mg*

Endocet (C-II)

Qualitest

Percocet (C-II)

Endo

10 mg Oxycodone Hydrochloride and Acetaminophen 300 mg*

Primlev (C-II)

Akrimax

10 mg Oxycodone Hydrochloride and Acetaminophen 325 mg*

Endocet (C-II)

Qualitest

Percocet (C-II)

Endo

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Other Acetaminophen Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

300 mg with Butalbital 50 mg and Caffeine 40 mg*

Fioricet

Actavis

300 mg with Butalbital 50 mg, Caffeine 40 mg, and Codeine Phosphate 30 mg*

Fioricet with Codeine (C-III)

Actavis

320.5 mg with Caffeine 30 mg and Dihydrocodeine Bitartrate 16 mg

Trezix (C-III)

WraSer

325 mg with Butalbital 50 mg and Caffeine 40 mg*

Capacet

Magna

325 mg with Butalbital 50 mg, Caffeine 40 mg, and Codeine Phosphate 30 mg*

Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules (C-III)

Capsules, gel-coated

500 mg with Caffeine 60 mg and Pyrilamine Maleate 15 mg

Midol Complete Gelcaps

Bayer

500 mg with Caffeine 65 mg*

Acetaminophen with Caffeine Gelcaps

Solution

83 mg/5 mL with Caffeine 5.4 mg/5 mL

Goody's Headache Relief Shot

Prestige

100 mg/5 mL with Hydrocodone Bitartrate 3.3 mg/5 mL*

Lortab Elixir (C-II)

ECR

108 mg/5 mL with Butalbital 16.7 mg/5 mL and Caffeine 13.3 mg/5 mL*

Alagesic LQ

Poly Pharmaceuticals

108 mg/5 mL with Hydrocodone Bitartrate 2.5 mg/5 mL*

Hydrocodone Bitartrate and Acetaminophen Oral Solution (C-II)

108 mg/5 mL with Hydrocodone Bitartrate 3.3 mg/5 mL*

Hydrocodone Bitartrate and Acetaminophen Oral Solution (C-II)

Tablets

300 mg with Butalbital 50 mg

Bupap

ECR

300 mg with Hydrocodone Bitartrate 5 mg*

Vicodin (C-II; scored)

AbbVie

300 mg with Hydrocodone Bitartrate 7.5 mg

Vicodin ES (C-II; scored)

AbbVie

300 mg with Hydrocodone Bitartrate 10 mg

Vicodin HP (C-II; scored)

AbbVie

325 mg with Butalbital 50 mg

Butapap

Mikart

Phrenilin (scored)

Valeant

325 mg with Butalbital 50 mg and Caffeine 40 mg*

Butalbital, Acetaminophen, and Caffeine Tablets

325 mg with Hydrocodone Bitartrate 2.5 mg*

Hydrocodone and Acetaminophen Tablets (C-II)

325 mg with Hydrocodone Bitartrate 5 mg*

Lortab (C-II; scored)

UCB

Norco (C-II; scored)

Actavis

325 mg with Hydrocodone Bitartrate 7.5 mg*

Lortab (C-II; scored)

UCB

Norco (C-II; scored)

Actavis

325 mg with Hydrocodone Bitartrate 10 mg*

Lortab (C-II; scored)

UCB

Norco (C-II; scored)

Actavis

Tablets, film-coated

325 mg with Diphenhydramine Hydrochloride 12.5 mg*

Percogesic Original Strength

Prestige

325 mg with Tramadol Hydrochloride 37.5 mg*

Ultracet (C-IV)

Janssen

500 mg with Caffeine 60 mg and Pyrilamine Maleate 15 mg*

MidolComplete Caplets

Bayer

500 mg with Caffeine 65 mg*

Excedrin Tension Headache Caplets

Novartis

500 mg with Diphenhydramine Hydrochloride 12.5 mg

Percogesic Extra Strength Caplets

Prestige

500 mg with Diphenhydramine Hydrochloride 25 mg*

Tylenol PM Extra Strength Caplets

McNeil

Tylenol PM Extra Strength Geltabs

McNeil

500 mg with Pamabrom 25 mg

Midol Teen Caplets

Bayer

500 mg with Pamabrom 25 mg and Pyrilamine Maleate 15 mg

Pamprin Multi-Symptom Caplets

Chattem

Premsyn PMS Caplets

Chattem

Acetaminophen also is commercially available in combination with other drugs, including analgesics, antihistamines, antimuscarinics, antitussives, barbiturates, decongestants, and expectorants.

AHFS DI Essentials™. © Copyright 2022, Selected Revisions February 1, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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