Skip to Content
Diagnosed with ankylosing spondylitis? Biologics can help >>

Acetaminophen

Pronunciation

Class: Analgesics and Antipyretics, Miscellaneous
VA Class: CN103
CAS Number: 103-90-2
Brands: Acephen, Alagesic, Bupap, Butapap, Capacet, Capital and Codeine, Endocet, Excedrin, FeverAll, Fioricet, Fioricet with Codeine, Goody’s, Lortab, Midol, Norco, Ofirmev, Pamprin, Percocet, Percogesic, Phrenilin, Premsyn , Primlev, Roxicet, Trezix, Tylenol, Tylenol with Codeine, Tylenol PM, Ultracet, Vanquish, Vicodin

Warning(s)

  • Hepatotoxicity
  • Acute liver failure, sometimes resulting in liver transplantation and death, can occur.300 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.300

  • 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.300

  • 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.300

Introduction

Synthetic nonopiate derivative of p-aminophenol; produces analgesia and antipyresis.198 207 222

Uses for Acetaminophen

Pain

Symptomatic relief of mild to moderate pain.198 207 222 300

Recommended by many experts as initial analgesic for many patients;197 199 200 201 263 however, consider risk of inadvertent overdosage and resultant acute liver failure.246 262 264 265 266 267 268 269 270 271 272 273 (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.222 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.207 235

Self-medication in fixed combination with aspirin and caffeine for the temporary relief of mild to moderate pain associated with migraine headache.212 213 214 This combination also can be used for the treatment of severe migraine headache if previous attacks have responded to similar nonopiate analgesics or NSAIAs.231

Symptomatic treatment of pain associated with osteoarthritis; considered an initial drug of choice for pain management in osteoarthritis patients.197 199 200 201

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.253 254 255 256 257 258 259

Treatment of pain in various combinations with aspirin, caffeine, opiates, and/or other agents.a 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.a

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.295 296 297 298 300

Fever

Reduction of fever.300 a

Self-medication to reduce fever in infants, children, and adults.207 222 235

Acetaminophen Dosage and Administration

Administration

Usually administered orally; may be administered rectally as suppositories in patients who cannot tolerate oral therapy.207 222 226 227 228 Also may be administered IV.300

Oral Administration

Swallow extended-release tablets whole; do not crush, chew, or dissolve in liquid.222

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.207 281

80-mg orally disintegrating tablets may be used in children ≥2 years of age.207 235

160-mg orally disintegrating tablets or 325-mg conventional tablets commonly used in children ≥6 years of age.207 222 235

Orally disintegrating tablets (e.g., Tylenol Meltaways) should be allowed to dissolve in the mouth or should be chewed before swallowing.237 Use caution to ensure that the correct number of tablets required for the intended dose is removed from the blister package.236 237

Rectal Administration

Dividing suppositories in an attempt to administer lower dosages may not provide a predictable dose.226

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.226 227 228

IV Administration

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

Administer by IV infusion.300

Monitor the end of the infusion to prevent possibility of air embolism, especially when acetaminophen solution is the primary infusion.300

Commercially available 10-mg/mL injection may be administered without further dilution.300 Each vial (1 g/100 mL) is for single use only; discard any unused portions.300

Dose of 1 g: Administer by inserting a vented IV set through the septum of the 100-mL vial.300

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.300 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.300

Administer within 6 hours after penetration of the vacuum seal of the vial or transfer of vial contents to another container.300

Do not admix with any other drugs.300

Rate of Administration

Administer by IV infusion over 15 minutes.300

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;286 287 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.286 (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.286 287

Take care to avoid dosing errors when prescribing, preparing, and administering IV acetaminophen.300 (See Boxed Warning.)

Pediatric Patients

Dosage in children should be guided by body weight.207 237 (See Pediatric Use under Cautions.)

Pain
Oral

Dose may be given every 4–6 hours as necessary (up to 5 times in 24 hours).198 207 237

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.222 278 (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).198

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.226 227 228

For self-medication in children ≥12 years of age, 325–650 mg every 4 hours as necessary.198

IV

Administer as single or repeated doses.300

Children 2–12 years of age: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.300

Adolescents ≥13 years of age and weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.300

Adolescents ≥13 years of age and weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours.300 May switch between oral and IV acetaminophen without dosage adjustment.300

Fever
Oral

Dose may be given every 4–6 hours as necessary (up to 5 times in 24 hours).198 207 237

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.222 278 (See Prescribing Limits under Dosage and Administration.)

Rectal

Dose may be given every 4 hours as necessary (up to 5 times in 24 hours).198

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.226 227 228

For self-medication in children ≥12 years of age, 325–650 mg every 4 hours as necessary.198

IV

Administer as single or repeated doses.300

Children 2–12 years of age: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.300

Adolescents ≥13 years of age and weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.300

Adolescents ≥13 years of age and weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours.300 May switch between oral and IV acetaminophen without dosage adjustment.300

Adults

Pain
Oral

For self-medication, 650 mg every 4–6 hours or 1 g every 6 hours as necessary.222 278 Alternatively, 1.3 g as extended-release tablets every 8 hours.222 (See Prescribing Limits under Dosage and Administration.)

Rectal

325–650 mg every 4 hours as necessary.198

IV

Administer as single or repeated doses.300

Adults weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours.300 May switch between oral and IV acetaminophen without dosage adjustment.300

Adults weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.300

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.212

Pain Associated with Osteoarthritis
Oral

1 g 4 times daily.149 a Alternatively, 1.3 g as extended-release tablets every 8 hours.199 200 201

Fever
Oral

For self-medication, 650 mg every 4–6 hours or 1 g every 6 hours as necessary.222 278 (See Prescribing Limits under Dosage and Administration.)

Rectal

325–650 mg every 4 hours as necessary.198

IV

Administer as single or repeated doses.300

Adults weighing ≥50 kg: 1 g every 6 hours or 650 mg every 4 hours.300 May switch between oral and IV acetaminophen without dosage adjustment.300

Adults weighing <50 kg: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours.300

Prescribing Limits

Pediatric Patients

Pain
Oral

Do not exceed recommended daily dosage.204 205 206 207 237 For self-medication in children ≥12 years of age, some manufacturers recommend a maximum dosage of 3 g daily.278 (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).207 278 279 280

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).300

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).300

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).300

Fever
Oral

Do not exceed recommended daily dosage.204 205 206 207 237 For self-medication in children ≥12 years of age, some manufacturers recommend a maximum dosage of 3 g daily.278 (See Prescribing Limits: Adults, under Dosage and Administration.)

Self-medication should not exceed 3 days.207 278 279 280

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).300

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).300

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).300

Adults

Current limit is 4 g daily.197 198 222 Some experts recommend a maximum dosage of 3 g daily when used for long-term therapy (e.g., ≥2 weeks).243 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).245 246 Some manufacturers (e.g., McNeil, Tylenol) voluntarily revised their labeling and currently recommend a maximum dosage of 3 g daily.272 278

Pain
Oral or Rectal

Maximum 4 g daily.198 222 Some manufacturers recommend a maximum oral dosage of 3 g daily.278 (See Prescribing Limits: Adults, under Dosage and Administration.)

Self-medication should not exceed 10 days.222

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).300

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).300

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.212

Pain Associated with Osteoarthritis
Oral

Maximum 4 g daily.197

Fever
Oral or Rectal

Maximum 4 g daily.198 222 Some manufacturers recommend maximum oral dosage of 3 g daily.278 (See Prescribing Limits: Adults, under Dosage and Administration.)

Self-medication should not exceed 3 days.222

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).300

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).300

Special Populations

Hepatic Impairment

Reduction of total daily dosage may be warranted in patients with hepatic impairment or active liver disease.300 (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).300

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.)

Interactions for Acetaminophen

Drugs Affecting Hepatic Microsomal Enzymes

Drugs that induce or regulate CYP2E1 may alter metabolism of acetaminophen and increase its hepatotoxic potential.300 (See Metabolism under Pharmacokinetics.) Clinical importance not established.300

Specific Drugs

Drug

Interaction

Comments

Alcohol

Increased risk of acetaminophen-induced hepatotoxicity101 102 103 104 105 107 108 109 110 111 112 113 115 116 117 120 122 123 124 125 126 127 128 129 130 131 132

Complex effects on acetaminophen pharmacokinetics; excessive alcohol use can induce hepatic cytochromes, but alcohol also competitively inhibits acetaminophen metabolism300

Avoid regular or excessive use of acetaminophen; alternatively, avoid chronic ingestion of alcohol128 129 147 222 (see Prescribing Limits: Adults, under Dosage and Administration)

Anticonvulsants (barbiturates, carbamazepine, phenytoin)

Increased conversion of acetaminophen to hepatotoxic metabolites; increased risk of hepatotoxicity152 157 160 162 163 164 165

Limit acetaminophen self-medication;165 dosage adjustment not required162 163 164

Anticoagulants, oral

Possible increased PT168 176

Effects of IV acetaminophen not established300

Clinical importance questioned;a monitor anticoagulant activity if large doses of acetaminophen used168 169

Manufacturer of acetaminophen injection states more frequent INR monitoring also may be appropriate during short-term concomitant IV acetaminophen use300

Aspirin

No inhibition of antiplatelet effect of aspirin144

Isoniazid

Possible increased risk of hepatotoxicity166

Limit acetaminophen self-medication166

Phenothiazines

Possible increased risk of severe hypothermiaa

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).a

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.226 227 228

Pharmacokinetics of IV acetaminophen are dose proportional at doses of 0.5–1 g.300

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.300

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.300 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.300

Food

Food may delay absorption following administration as extended-release tablets.148

Distribution

Extent

Rapidly distributed to most body tissues except fat.300 a Crosses placenta198 293 and is distributed into breast milk in small quantities.198 293 300

Plasma Protein Binding

10–25%.300 a

Elimination

Metabolism

Metabolized principally by sulfate and glucuronide conjugation; 226 small amounts (5–10%) oxidized by CYP-dependent pathways (mainly CYP2E1) to a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI).226 300 NAPQI is detoxified by glutathione and eliminated; any remaining toxic metabolite may bind to hepatocytes and cause cellular necrosis.121 226

Elimination Route

Mainly excreted in urine as conjugates.300 a

Half-life

Reportedly 1.25–3 hours.a

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.300

Special Populations

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

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

Stability

Storage

Oral

Tablets

Room temperature.222 Protect orally disintegrating tablets (Tylenol Meltaways) from high humidity.235 Protect grape-flavored orally disintegrating tablets from light.235

Suspension/Solution

Room temperature.207

Parenteral

Injection

20–25°C; do not refrigerate or freeze.300 Use within 6 hours after penetration of vacuum seal of vial or transfer of vial contents to another container.300

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

Compatible301

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 sodium301

Chlorpromazine HCl300 301

Diazepam300 301

Actions

  • Exhibits analgesic and antipyretic activity.207 222 300

  • Weak, reversible, isoform-nonspecific cyclooxygenase inhibitor at dosages of 1 g daily.144 Inhibitory effect on cyclooxygenase-1 is limited; does not inhibit platelet function.144

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.245 246

  • When used for self-medication, importance of reading the product labeling.222 Importance of not exceeding the recommended daily dosage204 205 206 207 235 238 245 246 and of not using other acetaminophen-containing products (e.g., some cold and cough products) concomitantly.204 207 235 238 245 246 262 264 265 266 267 268 269 270 271 272 273

  • When used for self-medication in pediatric patients, importance of basing the dose on the child’s weight;205 207 importance of not exceeding the recommended daily dosage.204 205 206 207 235

  • Importance of advising parents and caregivers about the appropriate dose, frequency, duration of therapy, and specific strength and formulation for an individual pediatric patient.226 275 Advise of the danger of substituting alternative dosage forms, particularly adult for pediatric formulations.226

  • 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.275

  • 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).205 207 226 236 275 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.275

  • Importance of discontinuing therapy and seeking immediate medical attention if rash or other manifestations of dermatologic or hypersensitivity reactions occur.282 Advise individuals with a history of such reactions not to take any acetaminophen-containing preparations.282

  • Importance of seeking quick medical attention if ingested dosage exceeds recommended dosage.207 222 235

  • Importance of limiting alcohol intake.128 129 147 222

  • Advise patients that paracetamol and APAP are other names for acetaminophen.260 261

  • 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.275 Some manufacturers have voluntarily changed the concentration of the infants' formulation to be the same as that of the children's formulation.275 276 277 (See Pediatric Use under Cautions.) However, older, more-concentrated infants' preparations may remain available.275 276

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.268 FDA no longer considers prescription combination preparations containing >325 mg of acetaminophen to be safe.287 As of March 26, 2014, all manufacturers of such preparations had discontinued marketing of the preparations, but some had not withdrawn the drug applications.288 FDA intends to withdraw approval of those applications if they are not voluntarily withdrawn.288 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.289 Pharmacists are encouraged to return any prescription combination preparations containing >325 mg of acetaminophen per dosage unit to the wholesaler or manufacturer.287 FDA intends to address OTC acetaminophen-containing preparations in a separate regulatory action.286

* 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, 2004-2016, Selected Revisions February 1, 2016. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

13. Antlitz AM, Awalt LF. A double blind study of acetaminophen used in conjunction with oral anticoagulant therapy. Curr Ther Res. 1969; 11:360-1. [PubMed 4979983]

14. Hartshorn EA. Drug interactions: miscellaneous analgesics. Drug Intell Clin Pharm. 1972; 6:50-4.

20. Prescott LF, Roscoe P, Wright N et al. Plasma paracetamol half-life and hepatic necrosis in patients with paracetamol overdosage. Lancet. 1971; 1:519-22. [PubMed 4100436]

101. Barker JD Jr, de Carle DJ, Anuras S. Chronic excessive acetaminophen use and liver damage. Ann Intern Med. 1977; 87:299-301. [PubMed 900673]

102. Black M, Raucy J. Acetaminophen, alcohol, and cytochrome P-450. Ann Intern Med. 1986; 104:427-8. [IDIS 211795] [PubMed 3946982]

103. Dietz AJ Jr, Wahbe Khalil SK, Nygard G et al. Acetaminophen kinetics in the alcoholic. Clin Pharmacol Ther. 1982; 31:218.

104. Dietz AJ Jr, Carlson JD, Wahba Khalil SK et al. Effects of alcoholism on acetaminophen pharmacokinetics in man. J Clin Pharmacol. 1984; 24:205-8. [IDIS 186035] [PubMed 6725622]

105. Emby DJ, Fraser BN. Hepatotoxicity of paracetamol enhanced by ingestion of alcohol: report of two cases. South African Med J. 1977; 51:208-9.

106. Hall AH, Kulig KW, Rumack BH. Acetaminophen hepatotoxicity. JAMA. 1986; 256:1893-4. [IDIS 221268] [PubMed 3761493]

107. Kartsonis A, Reddy KR, Schiff ER. Alcohol, acetaminophen, and hepatic necrosis. Ann Intern Med. 1986; 105:138-9. [IDIS 217856] [PubMed 3717790]

108. Lesser PB, Vietti MM, Clark WD. Lethal enhancement of therapeutic doses of acetaminophen by alcohol. Digest Dis Sci. 1986; 31:103-5. [IDIS 210930] [PubMed 3940815]

109. Licht H, Seeff LB, Zimmerman HJ. Apparent potentiation of acetaminophen hepatotoxicity by alcohol. Ann Intern Med. 1980; 92:511. [IDIS 111999] [PubMed 7362155]

110. McClain CJ, Kromhout JP, Peterson FJ et al. Potentiation of acetaminophen hepatotoxicity by alcohol. JAMA. 1980; 244:251-3. [IDIS 127070] [PubMed 7382090]

111. Mitchell JR. Acetaminophen toxicity. N Engl J Med. 1988; 319:1601-2. [IDIS 248652] [PubMed 3200269]

112. O’Dell JR, Zetterman RK, Burnett DA. Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic. JAMA. 1986; 255:2636-7. [IDIS 215195] [PubMed 3701979]

113. Peterson FJ, Holloway DE, Erickson RR et al. Ethanol induction of acetaminophen toxicity and metabolism. Life Sci. 1980; 27:1705-11. [PubMed 7442469]

114. Rumack BH. Acetaminophen overdose in young children: treatment and effects of alcohol and other additional ingestants in 417 cases. Am J Dis Child. 1984; 138:428-33. [IDIS 184911] [PubMed 6711498]

115. Seeff LB, Cuccherini BA, Zimmerman HJ et al. Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Ann Intern Med. 1986; 104:399-404. [IDIS 211792] [PubMed 3511825]

116. Wright N, Prescott LF. Potentiation by previous drug therapy of hepatotoxicity following paracetamol overdosage. Scott Med J. 1973; 18:56-8. [PubMed 4699828]

117. Lauterburg BH, Velez ME. Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut. 1988; 29:1153-7. [IDIS 245985] [PubMed 3197987]

118. Benson GD. Hepatotoxicity following the therapeutic use of antipyretic analgesics. Am J Med. 1983; 75(Suppl 5A):85-93. [IDIS 180821] [PubMed 6359871]

119. Rumack BH. Acetaminophen overdose. Am J Med. 1983; 75(Suppl 5A):104-12. [IDIS 180824] [PubMed 6359859]

120. Prescott LF, Critchley JA. Drug interactions affecting analgesic toxicity. Am J Med. 1983; 75(Suppl 5A):113-6. [IDIS 180825] [PubMed 6359860]

121. Rumack BH, Peterson RC, Koch GG et al. Acetaminophen overdose: 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med. 1981; 141(Suppl 3):380-5. [IDIS 142752] [PubMed 7469629]

122. Johnson MW, Friedman PA, Mitch WE. Alcoholism, nonprescription drug and hepatotoxicity: the risk from unknown acetaminophen ingestion. Am J Gastroenterol. 1981; 76:530-3. [IDIS 165295] [PubMed 7331985]

123. Lyons L, Studdiford JS, Sommaripa AM. Treatment of acetaminophen overdosage with N-acetylcysteine. N Engl J Med. 1977; 296:174. [IDIS 116244] [PubMed 831082]

124. Leist MH, Gluskin LE, Payne JA. Enhanced toxicity of acetaminophen in alcoholics: report of three cases. J Clin Gastroenterol. 1985; 7:55-9. [PubMed 3980965]

125. Sato C, Lieber CS. Mechanism of the preventive effect of ethanol on acetaminophen-induced hepatotoxicity. J Pharmacol Exp Ther. 1981; 218:811-5. [PubMed 7264963]

126. Sato C, Nakano M, Lieber CS. Prevention of acetaminophen-induced hepatotoxicity by acute ethanol administration in the rat: comparison with carbon tetrachloride-induced hepatotoxicity. J Pharmacol Exp Ther. 1981; 218:805- 10. [PubMed 7264962]

127. Sato C, Matsuda Y, Lieber CS. Increased hepatotoxicity of acetaminophen after chronic ethanol consumption in the rat. Gastroenterology. 1981; 80:140-8. [PubMed 7192662]

128. Acetaminophen/Ethanol. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1990(April):5.

129. Ethanol (ethyl alcohol) interactions: acetaminophen (Tylenol). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:525-6.

130. Whitcomb DC, Block GD. Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA. 1994; 272:1845-50. [IDIS 339694] [PubMed 7990219]

131. Strom BL. Adverse reactions to over-the-counter analgesics taken for therapeutic purposes. JAMA. 1994; 272:1866-7. [IDIS 339695] [PubMed 7990222]

132. Bonkovsky HL. Acetaminophen hepatotoxicity, fasting, and ethanol. JAMA. 1995; 274:301. [IDIS 349937] [PubMed 7609254]

133. Nelson EB, Temple AR. Acetaminophen hepatotoxicity, fasting, and ethanol. JAMA. 1995; 274:301. [IDIS 349938] [PubMed 7609255]

134. Cheung L, Potts RG, Meyer KC. Acetaminophen treatment nomogram. N Engl J Med. 1994; 330:1907-8. [IDIS 331248] [PubMed 8196743]

135. Smilkstein MJ, Douglas DR, Daya MR. Acetaminophen poisoning and liver function. N Engl J Med. 1994; 331:1310-1. [IDIS 338110] [PubMed 7935694]

136. Davie A. Acetaminophen poisoning and liver function. N Engl J Med. 1994; 331:1311. [IDIS 338111] [PubMed 7935695]

137. Whitcomb DC. Acetaminophen poisoning and liver function. N Engl J Med. 1994; 331:1311. [IDIS 338112] [PubMed 7695697]

138. Cheung L, Meyer KC. Acetaminophen poisoning and liver function. N Engl J Med. 1994; 331:1311-2.

139. Rose SR. Subtleties of managing acetaminophen poisoning. Am J Hosp Pharm. 1994; 51:3065-8. [PubMed 7856628]

140. Harrison PM, Keays R, Bray GP et al. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet. 1990; 335:1572-3. [IDIS 268192] [PubMed 1972496]

141. Keays R, Harrison PM, Wendon JA et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ. 1991; 303:1026-9. [IDIS 287456] [PubMed 1954453]

142. Harrison PM, Wendon JA, Gimson AES et al. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991; 324:1852-7. [IDIS 282299] [PubMed 1904133]

143. Graudins A, Aaron CK, Linden CH. Overdose of extended-release acetaminophen. N Engl J Med. 1995; 333:196. [IDIS 349625] [PubMed 7791835]

144. Catella-Lawson F, Reilly MP, Kapoor SC et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001; 345:1809-17

145. McNeil, Springhouse, PA: Personal communication.

146. McClements BM, Hyland M, Callender ME. Management of paracetamol poisoning complicated by enzyme induction due to alcohol or drugs. Lancet. 1990; 335:1526. [IDIS 267547] [PubMed 1972451]

147. Seeff LB, Cuccherini BA, Zimmerman HJ et al. Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Ann Intern Med. 1986; 104:399-404. [IDIS 211792] [PubMed 3511825]

148. Temple AR. Dear doctor letter regarding management of acetaminophen overdose. Fort Washington, PA: McNeil; 1995 Feb.

149. Reviewers’ comments (personal observations).

150. McNeil. Fort Washington, PA: Personal communication.

151. McNeil. Management of acetaminophen overdose. Fort Washington, PA; 1991 Aug.

152. Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet. 1995; 346:547-52. [IDIS 353263] [PubMed 7658783]

153. Douidar SM, Al-Khalil I, Habersang RW. Severe hepatotoxicity, acute renal failure, and pancytopenia in a young child after repeated acetaminophen overdosing. Clin Pediatr. 1994; 33:42-5.

154. Smilkstein MJ, Knapp GL, Kulig KW et al. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose: analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988; 319:1557-62. [IDIS 248647] [PubMed 3059186]

155. Harrison PM, Keays R, Bray GP et al. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet. 1990; 335:1572-3. [IDIS 268192] [PubMed 1972496]

156. Bray GP, Mowat C, Muir DF et al. The effect of chronic alcohol intake on prognosis and outcome in paracetamol overdose. Hum Exp Toxicol. 1991; 10:435-8. [PubMed 1687856]

157. Minton NA, Henry JA, Frankel RJ. Fatal paracetamol poisoning in an epileptic. Hum Toxicol. 1988; 7:33-4. [PubMed 3346037]

158. Murphy R, Swartz R, Watkins PB. Severe acetaminophen toxicity in a patient receiving isoniazid. Ann Intern Med. 1990; 113:799-800. [IDIS 273481] [PubMed 2240884]

159. Moulding TS, Redeker AG, Kanel GC. Acetaminophen, isoniazid, and hepatic toxicity. Ann Intern Med. 1991; 114:431. [IDIS 278529] [PubMed 1992890]

160. Bray GP, Harrison PM, O’Grady JG et al. Long-term anticonvulsant therapy worsens outcome in paracetamol-induced fulminant hepatic failure. Hum Exp Toxicol. 1992; 11:265-70. [PubMed 1354974]

161. Crippin JS. Acetaminophen hepatotoxicity: potentiation by isoniazid. Am J Gastroenterol. 1993; 88:590-2. [IDIS 313350] [PubMed 8470644]

162. Acetaminophen/carbamazepine. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1990(Jan):3.

163. Acetaminophen/hydantoins. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1990(Apr):6.

164. Acetaminophen/barbiturates. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1990(Apr):2.

165. Phenytoin (Dilantin) interactions: acetaminophen (Tylenol). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:346.

166. Isoniazid (INH) interactions: acetaminophen (Tylenol). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:231.

167. Cruzan S (US Department of Health and Human Services). FDA proposes alcohol warning for all OTC pain relievers. Rockville, MD; 1997 Nov 14. Press release No. P97-37.

168. Hylek EM, Heiman H, Skates SJ et al. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA. 1998; 279:657-62. [IDIS 407658] [PubMed 9496982]

169. Bell WR. Acetaminophen and warfarin: undesirable synergy. JAMA. 1998; 279:702-3. [IDIS 407661] [PubMed 9496990]

170. Temple AR. Dear doctor letter regarding use of acetaminophen in patients receiving warfarin. Fort Washington, PA: McNeil; 1998.

171. Temple AR. Dear pharmacist letter regarding use of acetaminophen in patients receiving warfarin. Fort Washington, PA: McNeil; 1998.

172. Koch-Weser J, Sellers EM. Drug interactions with coumarin anticoagulants. Part 2. New Engl J Med. 1971; 285:547-558. [PubMed 4397794]

173. Udall JA. Drug interference with warfarin therapy. Clin Med. 1970; 77:20-25.

174. Boeijinga JJ, Boerstra EE, Ris P. Interaction between paracetamol and coumarin anticoagulants. Lancet. 1982; 1:506. [IDIS 145340] [PubMed 6121161]

175. Rubin RN, Mentzer RL, Budzynski AZ. Potentiation of anticoagulant effect of warfarin by acetaminophen (Tylenol). Clin Res. 1984; 32:698a.

176. Bartle WR, Blakely JA. Potentiation of warfarin anticoagulation by acetaminophen. JAMA. 1991; 265:1260. [IDIS 278749] [PubMed 1995971]

177. Anticoagulants/acetaminophen. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1994 (October):39.

178. Acetaminophen (Tylenol) interactions: warfarin (Coumadin). In: Hansten PD, Horn JR. Drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997:7.

179. Kwan D, Bartle WR, Walker SE. The effects of acute and chronic acetaminophen dosing on the pharmacodynamics and pharmacokinetics of (R)- and (S)-warfarin. Clin Pharmacol Ther. 1995; 57:212.

180. Antlitz AM, Mead JA, Tolentino MA. Potentiation of oral anticoagulant therapy by acetaminophen. Curr Ther Res. 1968; 10:501-507. [PubMed 4971464]

181. Anon. ASHP therapeutic position statement on the use of the International Normalized Ratio system to monitor oral anticoagulant therapy. Am J Health-Syst Pharm. 1995; 52:529-31. [PubMed 7606561]

182. Aspirin interactions: warfarin (Coumadin). In: Hansten PD, Horn JR. Drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997:74-5.

183. Oral anticoagulant drug interactions: oral anticoagulant interactions. In: Hansten PD, Horn JR. Drug interactions: clinical significance of drug-drug interactions. 6th ed. Philadelphia: Lea & Febiger; 1989:71,103-104.

184. Gray CD. Acetaminophen and risk factors for excess anticoagulation with warfarin. JAMA. 1998; 280:695. [IDIS 410656] [PubMed 9728629]

185. Amato MG, Bussey H, Farnett L et al. Acetaminophen and risk factors for excess anticoagulation with warfarin. JAMA. 1998; 280:695-6. [IDIS 410657] [PubMed 9728630]

186. Riser J, Gilroy C, Hudson P et al. Acetaminophen and risk factors for excess anticoagulation with warfarin. JAMA. 1998; 280:696. [IDIS 410658] [PubMed 9728631]

187. Hylek EM. Acetaminophen and risk factors for excess anticoagulation with warfarin. JAMA. 1998; 280:697. [IDIS 410661] [PubMed 9728634]

188. Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther. 1997; 73:67-74. [PubMed 9014207]

189. Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy. 1998; 18:84-112. [IDIS 398636] [PubMed 9469685]

190. Cropp JS, Bussey HI. A review of enzyme induction of warfarin metabolism with recommendations for patient management. Pharmacotherapy. 1997; 17:917-28. [IDIS 393876] [PubMed 9324181]

191. Coon WW. Some aspects of the pharmacology of oral anticoagulants. Clin Pharmacol Ther. 1970; 11:312-36. [PubMed 4192279]

192. Koch-Weser J, Sellers EM. Drug interactions with coumarin anticoagulants. Part 1. N Engl J Med. 1971; 285:487-98.

193. Prescott LF, Illingworth RN, Critchley JAJH et al. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. Br Med J. 1979; 2:1097-1100. [IDIS 104971] [PubMed 519312]

194. Bridger S, Henderson K, Glucksman E et al. Deaths from low dose paracetamol poisoning. BMJ. 1998; 316:1724-5. [IDIS 406855] [PubMed 9614027]

195. Jones AL. Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol. 1998; 36:277-85. [IDIS 412445] [PubMed 9711192]

196. Prescott LF. Paracetamol overdosage: pharmacological considerations and clinical management. Drugs. 1983; 25:290-314. [IDIS 169473] [PubMed 6343056]

197. Altman RD, Hochberg MC, Moskowitz RW et al. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum. 2000; 43:1905-15. [IDIS 453740] [PubMed 11014340]

198. USP DI: drug information for the health care professional. 27th ed. Greenwood Village, CO: Micromedex, Inc; 2007;1:15-21.

199. Oddis CV. New perspectives on osteoarthritis. Am J Med. 1996; 100:2A-10S-2A-15S.

200. Schnitzer TJ. Non-NSAID pharmacologic treatment options for the management of chronic pain. Am J Med. 1998; 105:45S-52S. [IDIS 412691] [PubMed 9715834]

201. Eccles M, Freemantle N, Mason J. North of England evidence based guideline development project: summary guideline for non-steroidal anti-inflammatory drugs versus basic analgesia in treating the pain of degenerative arthritis. BMJ. 1998; 317:526-30. [IDIS 420160] [PubMed 9712607]

202. Heubi JE, Barbacci MB, Zimmerman HJ. Therapeutic misadventures with acetaminophen: hepatotoxicity after multiple doses in children. J Pediatr. 1998; 132:22-27. [IDIS 401027] [PubMed 9469995]

203. Kearns GL, Leeder JS, Wasserman GS. Acetaminophen overdose with therapeutic intent. J Pediatr. 1998; 132:5-8. [IDIS 401026] [PubMed 9469992]

204. Heubi JE, Bien JP. Acetaminophen use in children: more is not better. J Pediatr. 1997; 130:175-7. [IDIS 382117] [PubMed 9042116]

205. Rivera-Penera T, Gugig R, Davis J et al. Outcome of acetaminophen overdose in pediatric patients and factors contributing to hepatotoxicity. J Pediatr. 1997; 130:300-4. [IDIS 382126] [PubMed 9042136]

206. Anderson BD, Shepherd JG, Klein-Schwartz W. Outcome of acetaminophen overdose. J Pediatr. 1998; 132:1080. [IDIS 408675] [PubMed 9627615]

207. McNeil Consumer. Infants’ Tylenol acetaminophen Concentrated Drops; Children’s Tylenol acetaminophen Suspension Liquid and Soft Chews Chewable Tablets; Junior Strength Tylenol acetaminophen Soft Chews Chewable Tablets . In: Physicians’ desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:2014-16

208. Committee on Infectious Diseases, American Academy of Pediatrics. Red book: 2006 report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

209. Anon. Alcohol warning on over-the-counter pain medications. WHO Drug Info. 1998; 12:16.

210. Cruzan SM (US Food and Drug Administration). FDA announces new alcohol warnings for pain relievers and fever reducers. Rockville, MD; 1998 Oct 21. Press release No. 98-31.

211. US Food and Drug Administration. Over-the-counter drug products containing analgesic/antipyretic active ingredients for internal use; required alcohol warning. 21 CFR Part 201. Final rule. [Docket No. 77N-094W] Fed Regist. 1998; 63:56789-802.

212. Bristol-Myers. Excedrin Migraine (acetaminophen, aspirin, and caffeine) tablets product information. In Physician’ desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002. 1070

213. Cruzan S. FDA approves first OTC drug for relief of migraine pain. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1998 Jan 14.

214. Bristol-Myers. Excedrin Migraine (acetaminophen, aspirin, and caffeine) tablets product monograph. Princeton, NJ; 1997.

215. Lipton RB, Stewart WF, Ryan RE et al. Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain. Arch Neurol. 1998; 55:210-7. [PubMed 9482363]

216. Migliardi JR, Armellino JJ, Friedman M et al. Caffeine as an analgesic adjuvant in tension headache. Clin Pharmacol Ther. 1994; 56:576-86. [IDIS 339350] [PubMed 7955822]

217. Bauman RJ for the American Academy of Pediatrics. Technical report: treatment of the child with simple febrile seizures. Pediatrics. 1999; 103(E6):1-57. [IDIS 427497] [PubMed 9917431]

218. Camfield PR, Camfield CS, Shapiro SH et al. The first febrile seizure: antipyretic instruction plus either phenobarbital or placebo to prevent recurrence. J Pediatr. 1980; 97:16-21. [IDIS 116331] [PubMed 7381637]

219. Uhari M, Rantala H, Vainionpaa L et al. Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures. J Pediatr. 1995; 126:991-5. [IDIS 348600] [PubMed 7776115]

220. Schnaiderman D, Lahat E, Sheefer T et al. Antipyretic effectiveness of acetaminophen in febrile seizures: ongoing prophylaxis versus sporadic use. Eur J Pediatr. 1993; 152:747-9. [PubMed 8223808]

221. US Headache Consortium. Evidence-based guidelines for migraine headache in the primary care setting. St. Paul, MN; 2001. From the American Academy of Neurology web site [pharmacologic management of acute attacks]).

222. McNeil. Regular Strength Tylenol acetaminophen Tablets; Extra Strength Tylenol acetaminophen Gelcaps, Geltabs, Caplets, Tablets; Extra Strength Tylenol acetaminophen Adult Liquid Pain Reliever; Tylenol acetaminophen Arthritis Pain Extended Relief Caplets. In Physicians’ desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:2009-10.

223. Acetaminophen (paracetamol). In: Ellenhorn MJ, Schonwald S, Ordog G et al., eds. Ellenhorn’s medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore, MD: Williams & Wilkens; 1997:180-95.

224. Zed PJ, Krenzelok EP. Treatment of acetaminophen overdose. Am J Health-Syst Pharm. 1999; 56:1081-93. [IDIS 426020] [PubMed 10385455]

225. Kozer E, Koren G. Management of paracetamol overdose: current controversies. Drug Saf. 2001; 204:513-12.

226. American Academy of Pediatrics Committee on Drugs. Acetaminophen toxicity in children. Pediatrics. 2001; 108:1020-4. [IDIS 470914] [PubMed 11581462]

227. van Lingen RA, Deinum HT, Quak CME et al. Multiple-dose pharmacokinetics of rectally administered acetaminophen in tern infants. Clin Pharmacol Ther. 1999; 66:509-15. [IDIS 436484] [PubMed 10579478]

228. Birmingham PK, Tobin MJ, Henthorn TK et al. Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations. Anesthesiology. 1997; 87:244-52. [IDIS 412407] [PubMed 9286887]

229. Poisindex Managements: Acetaminophen-Acute. 26 Jul 2002. From Micromedex web site.

230. Anon. FDA acetaminophen AER review highlights inadvertent overdosing in children. Health News Daily. 2002 Aug 26. From the Health News Daily web site.

231. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. St. Paul, MN; 2001. From the American Academy of Neurology web site.

232. Bristol-Myers Squibb. Excedrin QuickTabs (acetaminophen and caffeine) product information. New York, NY; 2002.

233. Cumberland Pharmaceuticals. Acetadote (acetylcysteine) injection prescribing information. Nashville, TN; 2006 Feb.

234. N-acetylcysteine. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al., eds. Goldfrank’s Toxicologic Emergencies. 7th ed. McGraw-Hill; 2002:502-6.

235. McNeil Consumer. Infants’ Tylenol (acetaminophen) Concentrated Drops, Children’s Tylenol (acetaminophen) Suspension Liquid and Meltaways, and Junior Tylenol (acetaminophen) Meltaways product information. In: PDR.net [database online]. Montvale, NJ: Thomson Healthcare; 2005. Undated.Accessed 2005 Sept 30.

236. Institute for Safe Medication Practices. Unsafe Tylenol packaging. Medication safety alert! Community/ambulatory care edition. 2005; Apr. From ISMP website. Accessed 2005 May 12.

237. McNeil Consumer. Children’s Tylenol (acetaminophen) Dosing Chart. In: PDR.net [database online]. Montvale, NJ: Thomson Healthcare; 2005. Undated.Accessed 2005 Sept 30

238. US Food and Drug Administration Letter to State Boards of Pharmacy: Acetaminophen hepatotoxicity and nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal and renal toxicity. 2004 Jan 22. From FDA website.) Accessed 19 Oct 2006.

239. Watkins PB, Kaplowitz N, Slattery JT et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily; a randomized controlled trial. JAMA. 2006; 296: 87-93. [PubMed 16820551]

240. Nourjah P, Ahmad SR, Karwoski C et al. Estimates of acetaminophen (paracetamol)-associated overdoses in the United States. Pharmacoepidemiol Drug Saf. 2006; 15:398-405. [PubMed 16294364]

241. Larson AM, Polson J, Fontana RJ et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005; 42:1364-72. [PubMed 16317692]

243. American Liver Foundation. The American Liver Foundation issues warning on dangers of excess acetaminophen. 18 Jul 2006. From the American Liver Foundation website.

244. Daly FFS, O’Malley GF, Heard K et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med. 2004; 44:393-8. [PubMed 15459622]

245. US Food and Drug Administration. Questions and answers on proposed rule for labeling changes to over-the-counter pain relievers. 2006 Dec 19. From FDA website.) Accessed 28 Dec 2006.

246. US Food and Drug Administration. Internal analgesic, antipyretic, and antirheumatic drug products for over-the-ccounter human use; proposed amendment of the tentative final monograph; required warnings and other labeling. 21 CFR Parts 201 and 343. Proposed rule. [Docket No. 1977N-0094L]. Fed Regist. 2006; 71:77314-52.

247. Srinivasan A, Budnitz D, Shehab N et al. Infant deaths associated with cough and cold medications—two states, 2005. MMWR Morb Mortal Wkly Rep. 2007; 56:1-4. [PubMed 17218934]

248. US Food and Drug Administration. Cough and cold medications in children less than two years of age. Rockville, MD; 2007 Jan 12. From FDA website.

249. Anon. Makers pull cold medicines sold for infants. CNN News, 2007 Oct 11. From CNN.com website.

250. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001; 108:776-89.

253. McNeil-PPC. Sinutab Sinus (acetaminophen and phenylephrine hydrochloride) caplets patient information. From McNeil-PPC website. Accessed 2008 Feb 27.

254. BF Ascher & Company Inc. Ornex (acetaminophen and pseudoephedrine hydrochloride) caplets patient information. From BF Ascher website. Accessed 2008 Feb 28.

255. Novartis Consumer Health, Inc. Excedrin PM (acetaminophen and diphenhydramine citrate) caplets patient information. From Novartis Consumer Health website. Accessed 2008 Feb 28.

256. McNeil-PPC. Benadryl Severe Allergy & Sinus Headache (acetaminophen, diphenhydramine hydrochloride, and phenylephrine hydrochloride) caplets patient information. From McNeil-PPC website. Accessed 2008 Feb 28.

257. Bayer HealthCare. Alka-Seltzer Plus Day (acetaminophen, dextromethorphan hydrobromide, and phenylephrine hydrochloride) & Night (acetaminophen, dextromethorphan hydrobromide, doxylamine succinate, and phenylephrine hydrochloride) tablets patient information. From Bayer HealthCare website. Accessed 2008 Feb 28.

258. Bayer HealthCare. Alka-Seltzer Plus Cold & Cough Formula (acetaminophen, chlorpheniramine maleate, dextromethorphan hydrobromide, and phenylephrine hydrochloride) tablets patient information. From Bayer HealthCare website. Accessed 2008 Feb 28.

259. McNeil-PPC, Inc. Tylenol Sinus Severe Congestion Daytime (acetaminophen, guaifenesin, and pseudoephedrine hydrochloride) Cool Burst caplets patient information. From McNeil-PPC website. Accessed 2008 Feb 28.

260. O’Neil MJ, Smith A, Heckelman PE, eds. The Merck index. 13th ed. Whitehouse Station, NJ: Merck & Co, Inc; 2001:46.

261. American drug index. St. Louis, MO; Wolters Kluwer Health; 2008:6.

262. McNeil Consumer Healthcare. Tylenol professional product information. 2010. From Tylenol Professional website. Accessed 2011 Sep 23.

263. American Geriatrics Society Panel on the Pharmacologic Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. J Am Geriatrics Soc. 2009; 57:1331-46.

264. US Food and Drug Administration. Acetaminophen overdose and liver injury—background and options for reducing injury. Option paper prepared by Center for Drug Evaluation and Research for FDA’s Drug Safety and Risk Managment Committee. From FDA website. Accessed 2011 Sep 23.

265. Acetaminophen Hepatoxicity Working Group, Center for Drug Evaluation and Research, Food and Drug Administration. Recommendations for FDA interventions to deacrease the occurrence of acetaminophen hepatotoxicity. 2008 Feb 26. From FDA website. Accessed 2011 Sep 23.

266. National Council for Prescription Drug Programs, Work Group (WG 10) Professional Services, Acetaminophen Best Practices Task Group. NCPDP recommendations for improved prescription container labels for medicines containing acetaminophen. 2011 Jul. From NCPDP website. Accessed 2011 Sep 23.

267. Institute for Safe Medication Practices. Don’t hide the acetaminophen. Medication Safety Alert. 2006; 5(Mar):1-2.

268. US Food and Drug Administration. FDA drug safety communication: prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure. Rockville, MD; 2011 Jan 13. From FDA website. Accessed 2011 Mar 27.

269. US Food and Drug Administration. Organ-specific warnings; internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; final monograph. 21 CFR Part 201 [Docket No. FDA-1977-N0013 (formerly Docket No. 1977N-0094L)] Fed Regist. 2009; 74:19385-409.

270. Larson AM, Polson J, Fontana RJ et al for the Acute Liver Failure Study Group. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005; 42:1364-72. [PubMed 16317692]

271. Lee WM. Acetaminophen-related acute liver failure in the United States. Hepatol Res. 2008; 38(suppl 1):S3-8. [PubMed 19125949]

272. Kuffner ER. Dear healthcare professional letter on plans for new dosing instructions for Tylenol. Fort Washington, PA: McNeil Consumer Healthcare; 2011 Jul 28. From McNeil website. Accessed 2011 Sep 23.

273. Acetaminophen Awareness Coalition. Know your dose. What is acetaminophen: about the ingredient. From Know Your Dose website. Accessed 2011 Sep 23.

274. Shayiq RM, Roberts DW, Rothstein K et al. Repeat exposure to incremental doses of acetaminophen-induced lethality in mice: an explanation for high acetaminophen dosage in human without hepatic injury. Hepatology. 1999; 29:451-63. [PubMed 9918922]

275. US Food and Drug Administration. FDA drug safety communication: addition of another concentration of liquid acetaminophen marketed for infants. Rockville, MD; 2011 Dec 22. From FDA website.

276. US Food and Drug Administration. Know Concentration Before Giving Acetaminophen to Infants. Rockville, MD; 2011 Dec 22. From FDA website.

277. US Food and Drug Administration. Questions and Answers: Important change in concentration for over-the-counter (OTC) liquid acetaminophen marketed for infants. Rockville, MD; 2011 Dec 22. From FDA website.

278. McNeil-PPC. Tylenol Extra Strength (acetaminophen) caplets, rapid release gels, EZ tabs, and rapid blast liquid patient information. From McNeil-PPC website. Accessed 12 Feb 7.

279. McNeil-PPC. Infants' Tylenol (acetaminophen) oral suspension liquid patient information. From McNeil-PPC website. Accessed 12 Feb 8.

280. McNeil-PPC. Children's Tylenol (acetaminophen) oral suspension liquid patient information. From McNeil-PPC website. Accessed 12 Feb 8.

281. McNeil-PPC. Children’s Tylenol (acetaminophen) Dosing Chart. From PDR.net website. Accessed 2012 Apr 10.

282. US Food and Drug Administration. FDA drug safety communication: FDA warns of rare but serious skin reactions with the pain reliever/fever reducer acetaminophen. Rockville, MD; 2013 Aug 1. From FDA website. Accessed 2013 Aug 15.

283. Halevi A, Ben-Amitai D, Garty BZ. Toxic epidermal necrolysis associated with acetaminophen ingestion. Ann Pharmacother. 2000; 34:32-4. [PubMed 10669183]

284. Trujillo C, Gago C, Ramos S. Stevens-Jonhson syndrome after acetaminophen ingestion, confirmed by challenge test in an eleven-year-old patient. Allergol Immunopathol (Madr). 2010 Mar-Apr; 38:99-100.

285. Leger F, Machet L, Jan V et al. Acute generalized exanthematous pustulosis associated with paracetamol. Acta Derm Venereol. 1998; 78:222-3. [PubMed 9602233]

286. US Food and Drug Administration. FDA recommends health care professionals discontinue prescribing and dispensing prescription combination drug products with more than 325 mg of acetaminophen to protect consumers. Rockville, MD; 2014 Jan 14. From FDA website.

287. US Food and Drug Administration. FDA reminds health care professionals to stop dispensing prescription combination drug products with more than 325 mg of acetaminophen. Rockville, MD; 2014 Apr 28. From FDA website.

288. US Food and Drug Administration. All manufacturers of prescription combination drug products with more than 325 mg of acetaminophen have discontinued marketing. Rockville, MD; 2014 Mar 26.

289. US Food and Drug Administration. Prescription drug products containing acetaminophen; actions to reduce liver injury from unintentional overdose. Notice. [Docket No. FDA-2011-N-0021] Fed Regist. 2011; 76:2691-7.

290. McNeil Consumer Healthcare. Tylenol 8 HR Extended Release Caplets. From Tylenol Professional website. Accessed 2014 Oct 23.

291. McNeil Consumer Healthcare. Tylenol Arthritis Pain Extended Release Caplets. From Tylenol Professional website. Accessed 2014 Oct 23.

292. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 022450Orig1s000: Chemistry review(s). From FDA website.

293. Acetaminophen. In: Briggs GG, Freeman RK. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 10th ed. Philadelphia: Wolters Kluwer Health; 2015:8-12.

294. Sachs HC and American Academy of Pediatrics Committee on Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013: 132:e796-e809.

295. Sinatra RS, Jahr JS, Reynolds LW et al. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology. 2005; 102:822-31. [PubMed 15791113]

296. Sinatra RS, Jahr JS, Reynolds L et al. Intravenous acetaminophen for pain after major orthopedic surgery: an expanded analysis. Pain Pract. 2012; 12:357-65. [PubMed 22008309]

297. Wininger SJ, Miller H, Minkowitz HS et al. A randomized, double-blind, placebo-controlled, multicenter, repeat-dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic surgery. Clin Ther. 2010; 32:2348-69. [PubMed 21353105]

298. Tzortzopoulou A, McNicol ED, Cepeda MS et al. Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. Cochrane Database Syst Rev. 2011; :CD007126. [PubMed 21975764]

299. US Food and Drug Administration. FDA drug safety communication: FDA has reviewed possible risks of pain medicine use during pregnancy. Rockville, MD; 2015 Jan 9. From FDA website.

300. Mallinckrodt Pharmaceuticals. Ofirmev (acetaminophen) injection prescribing information. Hazelwood, MO; 2014 Dec.

301. ASHP’s interactive handbook on injectable drugs. McEvoy, GK, ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc; updated 2014 Sep 1. From HID website.

a. AHFS drug information 2003. McEvoy GK, ed. Acetaminophen. Bethesda, MD: American Society of Health-System Pharmacists; 2003:page 2077-85.

Hide