Acetaminophen

U.S. BRAND NAMES — Acephen™ [OTC]; Apra Children's [OTC]; Aspirin Free Anacin® Maximum Strength [OTC]; Cetafen Extra® [OTC]; Cetafen® [OTC]; Comtrex® Sore Throat Maximum Strength [OTC]; FeverALL® [OTC]; Genapap™ Children [OTC]; Genapap™ Extra Strength [OTC]; Genapap™ Infant [OTC]; Genapap™ [OTC]; Genebs Extra Strength [OTC]; Genebs [OTC]; Infantaire [OTC]; Mapap Children's [OTC]; Mapap Extra Strength [OTC]; Mapap Infants [OTC]; Mapap [OTC]; Nortemp Children's [OTC]; Pain Eze [OTC]; Silapap® Children's [OTC]; Silapap® Infants [OTC]; Tycolene Maximum Strength [OTC]; Tycolene [OTC]; Tylenol® 8 Hour [OTC]; Tylenol® Arthritis Pain [OTC]; Tylenol® Children's with Flavor Creator [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infants [OTC]; Tylenol® Junior [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin [OTC]
CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
SYNONYMS — APAP; N-Acetyl-P-Aminophenol; Paracetamol
THERAPEUTIC CATEGORY Analgesic, Non-narcoticAntipyretic
DOSING
(For additional information see "Acetaminophen: Drug information")Neonates: Oral, rectal: 10-15 mg/kg/dose every 6-8 hours as needed International Evidence-Based Group for Neonatal Pain recommendations (Anand, 2001; Anand, 2002): Preterm infants 28-32 weeks: Oral: 10-12 mg/kg/dose every 6-8 hours; maximum daily dose: 40 mg/kg/day Rectal: 20 mg/kg/dose every 12 hours; maximum daily dose: 40 mg/kg/day Preterm infants 32-36 weeks and term infants <10 days: Oral: 10-15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 15 mg/kg/dose every 8 hours; maximum daily dose: 60 mg/kg/day Term infants 10 days: Oral: 10-15 mg/kg/dose every 4-6 hours; maximum daily dose: 90 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 20 mg/kg/dose every 6-8 hours; maximum daily dose: 90 mg/kg/day
Infants and Children: Oral: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours; alternatively, the following doses may be used.
Alternative Acetaminophen Dosing (Oral)1: 6-11 lbs: 0-3 months: 40 mg 12-17 lbs: 4-11 months: 80 mg 18-23 lbs: 1-2 years: 120 mg 24-35 lbs: 2-3 years: 160 mg 36-47 lbs: 4-5 years: 240 mg 48-59 lbs: 6-8 years: 320 mg 60-71 lbs: 9-10 years: 400 mg 72-95 lbs: 11 years: 480 mg 1Manufacturer's recommendations; use of weight to select dose is preferred; if weight is not available, then use age Rectal: 10-20 mg/kg/dose every 4-6 hours as needed. Note: Although the perioperative use of high-dose rectal acetaminophen (eg, 25-45 mg/kg/dose) has been investigated in several studies, its routine use remains controversial; optimal doses and dosing frequency to ensure efficacy and safety have not yet been established; further studies are needed (see Buck, 2001).
Children 12 years and Adults: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 500 mg Cetafen Extra® Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Tycolene Maximum Strength, Tylenol® Extra Strength: 500 mg
Caplet, extended release: Tylenol® 8 Hour, Tylenol® Arthritis Pain: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) Apra Children's: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) [alcohol free; contains benzoic acid; cherry and grape flavors] Mapap Children's: 160 mg/5 mL (120 mL) [alcohol free; contains benzoic acid and sodium benzoate; cherry flavor]
Gelcap: Mapap Extra Strength, Tylenol® Extra Strength: 500 mg
Geltab: Tylenol® Extra Strength: 500 mg
Geltab, extended release: Tylenol® 8 Hour: 650 mg [DSC]
Liquid, oral: 500 mg/15 mL (240 mL) Comtrex® Sore Throat Maximum Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; honey lemon flavor] Genapap™ Children: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry and grape flavors] Silapap®: 160 mg/5 mL (120 mL, 240 mL, 480 mL) [sugar free; contains sodium benzoate; cherry flavor] Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; cherry flavor]
Solution, oral: 160 mg/5 mL (120 mL, 480 mL)
Solution, oral [drops]: 80 mg/0.8 mL (15 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)] Genapap™ Infant: 80 mg/0.8 mL (15 mL) [fruit flavor] Infantaire: 80 mg/0.8mL (15 mL, 30 mL) Silapap® Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor]
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen™: 120 mg, 325 mg, 650 mg FeverALL®: 80 mg, 120 mg, 325 mg, 650 mg Mapap: 125 mg, 650 mg
Suspension, oral: Mapap Children's: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry flavor] Nortemp Children's: 160 mg/5 mL (120 mL) [alcohol free; contains sodium benzoate; cotton candy flavor] Tylenol® Children's: 160 mg/5 mL (120 mL, 240 mL) [contains sodium benzoate; bubble gum yum, cherry blast, dye free cherry, grape splash, and very berry strawberry flavors] Tylenol® Children's with Flavor Creator: 160 mg/5 mL (120 mL) [contains sodium 2 mg/5 mL and sodium benzoate; cherry blast flavor; packaged with apple (4), bubblegum (8), chocolate (4), & strawberry (4) sugar free flavor packets]
Suspension, oral [drops]: Mapap Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor] Tylenol® Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry, dye free cherry, and grape flavors]
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Pain Eze, Tylenol® Extra Strength, Valorin Extra: 500 mg Cetafen®, Genapap™, Genebs, Mapap, Tycolene, Tylenol®, Valorin: 325 mg
Tablet, chewable: 80 mg Genapap™ Children: 80 mg [contains phenylalanine 6 mg/tablet; fruit and grape flavors] Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; bubble gum, fruit, and grape flavors] Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways: 80 mg [bubble gum, grape, and watermelon flavors] Tylenol® Junior Meltaways: 160 mg [bubble gum and grape flavors]
GENERIC AVAILABLE — Yes: Excludes extended release products
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use; do not crush or chew extended release products
USE — Treatment of mild to moderate pain and fever; does not have antirheumatic or systemic anti-inflammatory effects
ADVERSE REACTIONS Dermatologic: Rash
Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Hepatic necrosis with overdose
Renal: Renal injury with chronic use
Miscellaneous: Hypersensitivity reactions (rare)
CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component
PRECAUTIONS — Some products (eg, chewable tablets) contain aspartame which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — May cause severe hepatic toxicity with overdose. Use with caution in patients with alcoholic liver disease. Chronic daily dosing in adults of 5-8 g of acetaminophen over several weeks or 3-4 g/day for 1 year have resulted in liver damage. Do not exceed maximum daily doses; consider acetaminophen content of combination products when evaluating the dose of acetaminophen.
Some elixir preparations contain benzoic acid; liquid preparations (ie, elixir, liquid, suspension, and drops) may contain sodium benzoate (see Dosage Forms); benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP1A2 substrate (minor), CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A3/4 isoenzyme substrate
Enzyme inducers (barbiturates, carbamazepine, phenytoin, rifampin), carmustine (with high dose acetaminophen), isoniazid, alcohol (especially chronic use) can increase hepatotoxicity; rifampin may decrease acetaminophen's therapeutic effect; anticholinergic agents (scopolamine) may effect GI absorption; acetaminophen may increase the clearance of lamotrigine; acetaminophen may increase zidovudine concentration and toxicity
FOOD INTERACTIONS — Rate of absorption may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — B (show table)
REFERENCE RANGE — Acute ingestions: Toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion of overdose
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center
PHARMACOKINETICS Protein binding: 20% to 50%
Metabolism: At normal therapeutic dosages the parent compound is metabolized in the liver to sulfate and glucuronide metabolites, while a small amount is metabolized by microsomal mixed function oxidases to a highly reactive intermediate (N-acetyl-imidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g in a single day) glutathione can become depleted, and conjugation becomes insufficient to meet the metabolic demand causing an increase in N-acetyl-imidoquinone concentration, which is thought to cause hepatic cell necrosis.
Half-life: Neonates: 2-5 hours Adults: 1-3 hours
Time to peak serum concentration: 10-60 minutes after normal oral doses, but may be delayed in acute overdoses
PATIENT INFORMATION — Avoid alcohol; do not take longer than 10 days without physician's advice
(For additional information see "Acetaminophen: Patient drug information")
ADDITIONAL INFORMATION — Drops may contain saccharin.
Acetaminophen (15 mg/kg/dose given orally every 6 hours for 24 hours) did not relieve the intraoperative or the immediate postoperative pain associated with neonatal circumcision; some benefit was seen 6 hours after circumcision (see Howard, 1994).
There is currently no scientific evidence to support alternating acetaminophen with ibuprofen in the treatment of fever (see Mayoral, 2000).