Take care when prescribing, preparing, and administering acetaminophen injection to avoid dosing errors that could result in accidental overdose and death. In particular, be careful to ensure the following: the dose in milligrams and milliliters is not confused; the dosing is based on weight for patients less than 50 kg; infusion pumps are properly programmed; and the total daily dose of acetaminophen from all sources does not exceed maximum daily limits.
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limits, and often involve more than 1 acetaminophen-containing product.
Note: Safety: Acetaminophen-induced hepatotoxicity, which can be life threatening, has been associated with doses >4 g/day. Although doses up to 4 g/day are generally well tolerated (Dart 2007; Krenzelok 2012; Larson 2007; Temple 2006; Whitcomb 1994), hepatotoxicity has been reported rarely at this dose limit (Amar 2007). Due to this risk, some experts recommend a lower maximum dose of 3 g/day in adults with normal liver function, particularly when used for longer durations (eg, >7 days) for pain (Chou 2021). Heavy alcohol use, malnutrition, fasting, low body weight, advanced age, febrile illness, select liver disease, and use of drugs that interact with acetaminophen metabolism may increase risk of hepatotoxicity; a lower total daily dose (eg, 2 g/day) or avoidance may be preferred (Hamilton 2019b; Hayward 2016; Larson 2007). When calculating total daily dose, confirm that all sources (eg, prescription, OTCs, combinations) are included.
Pain (mild to moderate) and/or fever (monotherapy or as an adjunct):
Oral: 325 to 650 mg every 4 to 6 hours as needed or 1 g every 6 hours as needed; maximum dose: 4 g/day (Amar 2007; APS 2016). See "Note: Safety" above regarding maximum dose.
OTC labeling (patient-guided therapy): Note: Dosage recommendations, including maximum doses, vary among OTC manufacturers.
Immediate release:
Regular strength (325 mg/tablet): 2 tablets (650 mg) every 4 to 6 hours as needed; maximum daily dose: 10 tablets/day (3.25 g/day).
Extra strength (500 mg/tablet): 2 tablets (1 g) every 6 hours as needed; maximum daily dose: 6 tablets/day (3 g/day).
Extended release (650 mg/tablet): 2 tablets (1.3 g) every 8 hours as needed; maximum daily dose: 6 tablets/day (3.9 g/day).
IV:
≥50 kg: 650 mg every 4 hours or 1 g every 6 hours; maximum single dose: 1 g/dose; maximum daily dose: 4 g/day.
<50 kg: 12.5 mg/kg every 4 hours or 15 mg/kg every 6 hours; maximum single dose: 15 mg/kg/dose (≤750 mg/dose); maximum daily dose: 75 mg/kg/day (≤3.75 g/day). Note: Some experts recommend this reduced dosing if used in patients with chronic alcoholism, malnutrition, or dehydration regardless of weight (Mariano 2019).
Rectal: 325 to 650 mg every 4 to 6 hours as needed (Pandharipande 2019); maximum daily dose: 3.9 g/day. Note: Absorption is irregular; bioavailability may be reduced by ~10% to 20% relative to oral administration (Bannwarth 2003).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
IV, Oral, Rectal:
Mild to severe impairment: No dosage adjustment likely to be necessary. The manufacturer's labeling for IV acetaminophen states that longer dosing intervals and a reduced total daily dose may be warranted in patients with severe kidney impairment (CrCl ≤30 mL/minute); however, acetaminophen concentrations and half-life are increased but similar to those in patients with normal renal function (Berg 1990; Forrest 1982; Martin 1991; Prescott 1989). Glucuronide and sulfate conjugate metabolites accumulate in renal impairment, but the clinical effects are unknown (Martin 1991).
Hemodialysis, intermittent (thrice weekly): Acetaminophen and its conjugates are readily dialyzable (Øie 1975): No dosage adjustment necessary (Davison 2014; Martin 1993).
Peritoneal dialysis: Not dialyzed (Lee 1996): No dosage adjustment necessary (Davison 2014).
CRRT: Dialyzed (Scoville 2018): No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Böhler 1999, expert opinion).
Oral: Use with caution and consider dosage adjustment or avoiding use, depending on degree of hepatic impairment and other patient-specific factors. Although limited data exist, low-dose therapy (maximum: ≤2 to 3 g/day) is usually well tolerated in patients with chronic liver disease or cirrhosis, provided patients are not actively drinking alcohol; however, the presence of other factors increasing the risk of acetaminophen-induced hepatoxicity (eg, malnutrition, fasting, low body weight, advanced age, febrile illness, concurrent use of drugs that interact with acetaminophen metabolism) must also be taken into consideration (Bosilkovska 2012; Chandok 2010; Dwyer 2014; Hayward 2016; Imani 2014). Some experts would limit the maximum dose to ≤2 g/day in any patient with advanced chronic liver disease or cirrhosis (provided the patient is not actively drinking alcohol) and would avoid use in any patient with severe alcoholic hepatitis or acute liver injury. Avoiding use is also recommended by some experts in patients with advanced chronic liver disease or cirrhosis who are actively drinking alcohol, malnourished, not eating, or receiving a concomitant interacting medication. For short-term or one-time use, a maximum of ≤4 g/day may be considered in lower risk patients with chronic liver disease or early-stage compensated cirrhosis who are not actively drinking alcohol (Hamilton 2019b).
IV:
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; a reduced total daily dosage may be warranted.
Severe impairment: Use is contraindicated.
(For additional information see "Acetaminophen (paracetamol): Pediatric drug information")
Note: Oral liquids are available in multiple concentrations (eg, 160 mg/5 mL, 500 mg/5 mL, 500 mg/15 mL); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as "mg."
Pain (mild to moderate) or fever: Note: All sources of acetaminophen (eg, prescription, OTC, combination products) should be considered when evaluating a patient's maximum daily dose. To lower the risk for hepatotoxicity, limit daily dose to ≤75 mg/kg/day (maximum of 5 daily doses), not to exceed 4,000 mg/day; while recommended doses are generally considered safe, hepatotoxicity has been reported (rarely) even with doses below recommendations (AAP [Sullivan 2011]; Heard 2014; Lavonas 2010).
Oral:
Weight-directed dosing: Infants, Children, and Adolescents: 10 to 15 mg/kg/dose every 4 to 6 hours as needed (American Pain Society 2008; Kliegman 2011; AAP [Sullivan 2011]); do not exceed 5 doses in 24 hours; maximum daily dose: 75 mg/kg/day not to exceed 4,000 mg/day.
Fixed dosing:
Oral suspension, chewable tablets: Infants and Children <12 years: Consult specific product formulations for appropriate age groups. See table; use of weight to select dose is preferred; if weight is not available, then use age; doses may be repeated every 4 hours; maximum: 5 doses/day.
|
Weight (preferred)A |
Age |
Dosage (mg) | |
|---|---|---|---|
|
kg |
lbs | ||
|
AManufacturer’s recommendations are based on weight in pounds (OTC labeling); weight in kg listed here is derived from pounds and rounded; kg weight listed also is adjusted to allow for continuous weight ranges in kg. OTC labeling instructs consumer to consult with physician for dosing instructions in infants and children under 2 years of age. | |||
|
2.7 to 5.3 |
6 to 11 |
0 to 3 mo |
40 |
|
5.4 to 8.1 |
12 to 17 |
4 to 11 mo |
80 |
|
8.2 to 10.8 |
18 to 23 |
1 to 2 y |
120 |
|
10.9 to 16.3 |
24 to 35 |
2 to 3 y |
160 |
|
16.4 to 21.7 |
36 to 47 |
4 to 5 y |
240 |
|
21.8 to 27.2 |
48 to 59 |
6 to 8 y |
320 to 325 |
|
27.3 to 32.6 |
60 to 71 |
9 to 10 y |
325 to 400 |
|
32.7 to 43.2 |
72 to 95 |
11 y |
480 to 500 |
Immediate-release solid dosage formulations: Note: Actual OTC dosing recommendations may vary by product and/or manufacturer:
Children 6 to 11 years: 325 mg every 4 to 6 hours; maximum daily dose: 1,625 mg/day; Note: Do not use more than 5 days unless directed by a physician.
Children ≥12 years and Adolescents:
Regular strength: 650 mg every 4 to 6 hours; maximum daily dose: 3,250 mg/day unless directed by a physician; under physician supervision daily doses ≤4,000 mg may be used.
Extra strength: 1,000 mg every 6 hours; maximum daily dose: 3,000 mg/day unless directed by a physician; under physician supervision daily doses ≤4,000 mg may be used.
Extended release: Children ≥12 years and Adolescents: 1,300 mg every 8 hours; maximum daily dose: 3,900 mg/day.
IV:
Infants and Children <2 years:
Manufacturer’s labeling: Fever: 15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day.
Alternate dosing: Limited data available: Pain and fever: 7.5 to 15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day (Wilson-Smith 2009).
Children ≥2 years (Shastri 2015; Zuppa 2011):
<50 kg: 15 mg/kg/dose every 6 hours or 12.5 mg/kg/dose every 4 hours; maximum single dose: 15 mg/kg up to 750 mg; maximum daily dose: 75 mg/kg/day not to exceed 3,750 mg/day.
≥50 kg: 15 mg/kg/dose every 6 hours or 12.5 mg/kg/dose every 4 hours; maximum single dose: 15 mg/kg up to 1,000 mg; maximum daily dose: 75 mg/kg/day not to exceed 4,000 mg/day.
Adolescents:
<50 kg: 15 mg/kg/dose every 6 hours or 12.5 mg/kg/dose every 4 hours; maximum single dose: 15 mg/kg up to 750 mg; maximum daily dose: 75 mg/kg/day not to exceed 3,750 mg/day.
≥50 kg: 1,000 mg every 6 hours or 650 mg every 4 hours; maximum single dose: 1,000 mg; maximum daily dose: 4,000 mg/day.
Rectal:
Weight-directed dosing: Limited data available: Infants and Children <12 years: 10 to 20 mg/kg/dose every 4 to 6 hours as needed; do not exceed 5 doses in 24 hours (Kliegman 2011; Vernon 1979); maximum daily dose: 75 mg/kg/day not to exceed 1,625 mg/day.
Fixed dosing:
Infants 6 to 11 months: 80 mg every 6 hours; maximum daily dose: 320 mg/day.
Infants and Children 12 to 36 months: 80 mg every 4 to 6 hours; maximum daily dose: 400 mg/day.
Children >3 to 6 years: 120 mg every 4 to 6 hours; maximum daily dose: 600 mg/day.
Children >6 up to 12 years: 325 mg every 4 to 6 hours; maximum daily dose: 1,625 mg/day.
Children ≥12 years and Adolescents: 650 mg every 4 to 6 hours; maximum daily dose: 3,900 mg/day.
Pain; peri-/postoperative management; adjunct to opioid therapy:
IV:
Infants and Children <2 years: Limited data available: 7.5 to 15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day (Wilson-Smith 2009).
Children ≥2 years (Shastri 2015; Zuppa 2011):
<50 kg: 15 mg/kg/dose every 6 hours or 12.5 mg/kg/dose every 4 hours; maximum single dose: 15 mg/kg up to 750 mg; maximum daily dose: 75 mg/kg/day not to exceed 3,750 mg/day.
≥50 kg: 15 mg/kg/dose every 6 hours or 12.5 mg/kg/dose every 4 hours; maximum single dose: 15 mg/kg up to 1,000 mg; maximum daily dose: 75 mg/kg/day not to exceed 4,000 mg/day.
Adolescents:
<50 kg: 15 mg/kg/dose every 6 hours or 12.5 mg/kg/dose every 4 hours; maximum single dose: 15 mg/kg up to 750 mg; maximum daily dose: 75 mg/kg/day not to exceed 3,750 mg/day.
≥50 kg: 1,000 mg every 6 hours or 650 mg every 4 hours; maximum single dose: 1,000 mg; maximum daily dose: 4,000 mg/day.
Rectal: Limited data available: Children:
Loading dose: 40 mg/kg for 1 dose, in most trials, the dose was administered postoperatively (Birmingham 2001; Capici 2008; Hahn 2000; Mireskandari 2011; Prins 2008; Riad 2007; Viitanen 2003); a maximum dose of 1,000 mg was most frequently reported. However, in one trial evaluating 24 older pediatric patients (all patients ≥25 kg; mean age: ~13 years), the data suggested that a dose of 1,000 mg does not produce therapeutic serum concentrations (target for study: >10 mcg/mL) compared to a 40 mg/kg dose (up to ~2,000 mg); the resultant Cmax was: 7.8 mcg/mL (1,000 mg dose group) vs 15.9 mcg/mL (40 mg/kg dose group). Note: Therapeutic serum concentrations for analgesia have not been well-established (Howell 2003).
Maintenance dose: 20 to 25 mg/kg/dose every 6 hours as needed for 2 to 3 days has been suggested if further pain control is needed postoperatively; maximum daily dose: 100 mg/kg/day not to exceed 4,000 mg/day; therapy longer than 5 days has not been evaluated (Birmingham 2001; Hahn 2000; Prins 2008).
Note: In the majority of trials, suppositories were not divided due to unequal distribution of drug within suppository; doses were rounded to the nearest mg amount using 1 or 2 suppositories of available product strengths.
Altered kidney function:
Infants, Children, and Adolescents:
Oral, rectal: Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; based on adult pharmacokinetic studies, dosage adjustment may not be necessary for short courses. In adult pharmacokinetic studies, plasma concentrations of acetaminophen did not differ in renal impairment patients when compared to healthy patients for short courses of treatment (ie, 3 days); however, accumulation of the glucuronide and sulfate conjugate metabolites in renal impairment has been described following a single dose of acetaminophen up to repeat dosing for 10 days; the clinical significance of this finding is unknown (Berg 1990; Martin 1991; Prescott 1989).
IV:
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Severe impairment (CrCl <30 mL/minute): The manufacturer's labeling for IV acetaminophen states that longer dosing intervals and a reduced total daily dose may be warranted in patients with severe kidney impairment; use with caution.
Hemodialysis, intermittent: Acetaminophen and its conjugates are readily dialyzable (Davison 2014; Øie 1975): No dosage adjustment necessary when used for mild to moderate pain (Davison 2014).
Peritoneal dialysis: Not dialyzed (Davison 2014; Lee 1996): No dosage adjustment necessary when used for mild to moderate pain (Davison 2014).
Use with caution. Limited, low-dose therapy is usually well-tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4,000 mg/day have been reported. Avoid chronic use in hepatic impairment.
Pain (acute) or fever: Oral, IV: Refer to adult dosing.
Persistent pain (off-label): Adults ≥75 years: Oral:
Initial: 325 to 500 mg every 4 hours or 500 to 1,000 mg every 6 hours
Maximum: ≤4,000 mg/day. In older adults with hepatic impairment or history of alcohol abuse being treated for persistent pain, do not exceed a maximum of 2,000 to 3,000 mg/day (AGS 2009)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Mapap: 500 mg [aspirin free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Tylenol: 325 mg [aspirin free; contains fd&c red #40, soybeans (glycine max)]
Elixir, Oral:
Apra: 160 mg/5 mL (120 mL, 240 mL, 480 mL, 3840 mL) [contains alcohol, usp]
Pain Relief Childrens: 160 mg/5 mL (118 mL [DSC], 237 mL [DSC], 473 mL) [alcohol free, aspirin free; contains fd&c red #40, polyethylene glycol, saccharin sodium, sodium benzoate, sorbitol]
Generic: 160 mg/5 mL (473 mL [DSC])
Gel, Oral:
ElixSure Fever/Pain: 160 mg/5 mL (120 mL) [alcohol free, aspirin free; contains butylparaben, carbomer 934p, polyethylene glycol; bubble-gum flavor]
ElixSure Fever/Pain: 160 mg/5 mL (120 mL) [alcohol free, aspirin free; contains butylparaben, carbomer 934p, polyethylene glycol; cherry flavor]
ElixSure Fever/Pain: 160 mg/5 mL (120 mL) [alcohol free, aspirin free; contains butylparaben, carbomer 934p, polyethylene glycol; grape flavor]
Liquid, Oral:
Acetaminophen Extra Strength: 500 mg/15 mL (237 mL [DSC]) [alcohol free, aspirin free; contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), polyethylene glycol, saccharin sodium, sodium benzoate]
Childrens Silapap: 160 mg/5 mL (118 mL, 237 mL, 473 mL) [alcohol free, sugar free; contains fd&c red #40, methylparaben, propylene glycol, saccharin sodium, sodium benzoate; cherry flavor]
Ed-APAP: 160 mg/5 mL (236 mL) [alcohol free; contains fd&c red #40, saccharin sodium, sodium benzoate; cherry flavor]
Liquid Pain Relief: 160 mg/5 mL (473 mL [DSC]) [contains fd&c red #40, polyethylene glycol, saccharin sodium, sodium benzoate; cherry flavor]
Liquid Pain Relief: 160 mg/5 mL (473 mL) [alcohol free, aspirin free; contains fd&c red #40, methylparaben, polyethylene glycol, propylene glycol, propylparaben]
M-PAP: 160 mg/5 mL (120 mL, 473 mL) [alcohol free, aspirin free, sugar free; contains fd&c red #40, polyethylene glycol, saccharin sodium, sodium benzoate; cherry flavor]
Mapap: 160 mg/5 mL (118 mL [DSC], 473 mL [DSC]) [alcohol free, aspirin free; contains benzoic acid, fd&c red #40, polyethylene glycol, propylene glycol, sodium benzoate; cherry flavor]
Mapap Acetaminophen Extra Str: 500 mg/15 mL (237 mL) [contains fd&c red #40, polyethylene glycol, propylene glycol, saccharin sodium, sodium benzoate; cherry flavor]
Pain Relief: 500 mg/15 mL (237 mL) [alcohol free, aspirin free; contains fd&c red #40, methylparaben, polyethylene glycol, propylene glycol, propylparaben]
Generic: 160 mg/5 mL (118 mL, 473 mL)
Packet, Oral:
Tylenol Childrens Pain + Fever: 160 mg (18 ea, 30 ea) [aspirin free, ibuprofen free; wild berry flavor]
Tylenol Dissolve Packs: 500 mg (12 ea, 32 ea) [berry flavor]
Solution, Intravenous:
Generic: 10 mg/mL (50 mL, 100 mL); 1000 mg/100 mL (100 mL)
Solution, Intravenous [preservative free]:
Ofirmev: 10 mg/mL (100 mL)
Generic: 10 mg/mL (100 mL)
Solution, Oral:
Pain & Fever Childrens: 160 mg/5 mL (118 mL [DSC], 473 mL [DSC]) [alcohol free, aspirin free, sugar free; contains fd&c red #40, polyethylene glycol, propylene glycol, sodium benzoate; cherry flavor]
Generic: 160 mg/5 mL (5 mL, 10.15 mL, 20.3 mL, 118 mL, 473 mL); 325 mg/10.15 mL (10.15 mL); 650 mg/20.3 mL (20.3 mL)
Suppository, Rectal:
FeverAll Adults: 650 mg (50 ea) [contains polysorbate 80]
FeverAll Childrens: 120 mg (6 ea, 50 ea) [contains polysorbate 80]
FeverAll Infants: 80 mg (1 ea, 6 ea, 50 ea) [contains polysorbate 80]
FeverAll Junior Strength: 325 mg (6 ea, 50 ea) [contains polysorbate 80]
Suspension, Oral:
Aurophen Childrens: 160 mg/5 mL (118 mL) [alcohol free, aspirin free, gluten free, ibuprofen free; contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate; cherry flavor]
BetaTemp Childrens: 160 mg/5 mL (118 mL) [contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate]
Childrens Acetaminophen: 160 mg/5 mL (5 mL) [alcohol free, aspirin free; contains butylparaben, fd&c red #40, polysorbate 80, propylene glycol, sodium benzoate]
Childrens Acetaminophen: 160 mg/5 mL (5 mL) [alcohol free, aspirin free; contains butylparaben, fd&c red #40, polysorbate 80, propylene glycol, sodium benzoate; strawberry flavor]
Childrens Non-Aspirin: 160 mg/5 mL (118 mL)
GoodSense Pain & Fever Child: 160 mg/5 mL (118 mL) [alcohol free, aspirin free, dye free, gluten free, ibuprofen free; contains propylene glycol, propylparaben, sodium benzoate, sorbitol]
GoodSense Pain & Fever Child: 160 mg/5 mL (118 mL) [alcohol free, aspirin free, gluten free, ibuprofen free; contains brilliant blue fcf (fd&c blue #1), butylparaben, propylene glycol, sodium benzoate, sorbitol; grape flavor]
GoodSense Pain & Fever Child: 160 mg/5 mL (118 mL) [alcohol free, aspirin free, gluten free, ibuprofen free; contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate, sorbitol]
GoodSense Pain & Fever Child: 160 mg/5 mL (118 mL) [alcohol free, aspirin free, gluten free, ibuprofen free; contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate, sorbitol; cherry flavor]
GoodSense Pain & Fever Infants: 160 mg/5 mL (30 mL) [alcohol free, aspirin free, gluten free, ibuprofen free; contains brilliant blue fcf (fd&c blue #1), butylparaben, propylene glycol, sodium benzoate, sorbitol]
GoodSense Pain & Fever Infants: 160 mg/5 mL (30 mL) [alcohol free, aspirin free, gluten free, ibuprofen free; contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate, sorbitol]
Mapap Childrens: 160 mg/5 mL (118 mL [DSC]) [contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate]
Nortemp: 160 mg/5 mL (118 mL [DSC]) [alcohol free, aspirin free; contains butylparaben, fd&c red #40, polysorbate 80, propylene glycol, sodium benzoate; cotton candy flavor]
Nortemp Infants: 80 mg/0.8 mL (30 mL [DSC]) [alcohol free, aspirin free, sugar free; contains fd&c yellow #6 (sunset yellow), methylparaben, propylene glycol, saccharin sodium, sodium benzoate]
Pain & Fever Childrens: 160 mg/5 mL (118 mL) [alcohol free, aspirin free, dye free, gluten free, ibuprofen free; contains butylparaben, propylene glycol, sodium benzoate; cherry flavor]
Pain & Fever Infants: 160 mg/5 mL (59 mL [DSC]) [alcohol free, aspirin free, ibuprofen free; contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate, sorbitol]
Pain Relief Childrens: 160 mg/5 mL (118 mL) [cherry flavor]
Panadol Childrens: 160 mg/5 mL (118 mL) [aspirin free, ibuprofen free; contains benzoic acid, fd&c red #40, polyethylene glycol, propylene glycol, saccharin sodium; raspberry flavor]
Panadol Infants: 160 mg/5 mL (54.7 mL) [aspirin free, ibuprofen free; contains benzoic acid, fd&c red #40, polyethylene glycol, propylene glycol, saccharin sodium; raspberry flavor]
Tylenol Childrens: 160 mg/5 mL (120 mL) [alcohol free; cherry flavor]
Tylenol Childrens: 160 mg/5 mL (120 mL) [alcohol free, aspirin free, dye free, ibuprofen free]
Tylenol Childrens: 160 mg/5 mL (120 mL, 240 mL) [alcohol free, aspirin free, dye free, ibuprofen free; cherry flavor]
Tylenol Childrens: 160 mg/5 mL (120 mL) [alcohol free, aspirin free, ibuprofen free; bubble-gum flavor]
Tylenol Childrens: 160 mg/5 mL (120 mL) [alcohol free, aspirin free, ibuprofen free; contains brilliant blue fcf (fd&c blue #1), sodium benzoate; grape flavor]
Tylenol Childrens: 160 mg/5 mL (120 mL) [alcohol free, aspirin free, ibuprofen free; contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate; strawberry flavor]
Tylenol Childrens: 160 mg/5 mL (120 mL) [alcohol free, aspirin free, ibuprofen free; contains fd&c red #40, sodium benzoate]
Tylenol Childrens: 160 mg/5 mL (120 mL) [alcohol free, aspirin free, ibuprofen free; contains sodium benzoate, sorbitol; grape flavor]
Tylenol for Children + Adults: 160 mg/5 mL (240 mL) [alcohol free, aspirin free, dye free, ibuprofen free, paraben free; cherry flavor]
Tylenol Infants: 160 mg/5 mL (60 mL) [alcohol free, aspirin free, ibuprofen free; contains butylparaben, fd&c red #40, propylene glycol, sodium benzoate, sorbitol; cherry flavor]
Tylenol Infants Pain+Fever: 160 mg/5 mL (60 mL) [alcohol free, aspirin free, dye free, ibuprofen free]
Tylenol Infants Pain+Fever: 160 mg/5 mL (30 mL) [alcohol free, aspirin free, dye free, ibuprofen free; cherry flavor]
Tylenol Infants Pain+Fever: 160 mg/5 mL (60 mL) [alcohol free, aspirin free, ibuprofen free; contains brilliant blue fcf (fd&c blue #1), butylparaben, propylene glycol, sodium benzoate, sorbitol]
Tylenol Infants Pain+Fever: 160 mg/5 mL (30 mL) [alcohol free, aspirin free, ibuprofen free; contains brilliant blue fcf (fd&c blue #1), butylparaben, propylene glycol, sodium benzoate, sorbitol; grape flavor]
Generic: 160 mg/5 mL (5 mL, 10.15 mL, 20.3 mL, 59 mL, 118 mL); 650 mg/20.3 mL (20.3 mL)
Syrup, Oral:
Triaminic Fever Reducer: 160 mg/5 mL (59 mL, 118 mL) [alcohol free, aspirin free, ibuprofen free; contains benzoic acid, edetate (edta) disodium, fd&c red #40, polyethylene glycol; bubble-gum flavor]
Triaminic Fever Reducer: 160 mg/5 mL (59 mL, 118 mL) [alcohol free, aspirin free, ibuprofen free; contains brilliant blue fcf (fd&c blue #1), edetate (edta) disodium, fd&c red #40, polyethylene glycol, sodium benzoate; grape flavor]
Tablet, Oral:
Acetaminophen Extra Strength: 500 mg
Acetaminophen Extra Strength: 500 mg [scored]
Acetaminophen Extra Strength: 500 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Acetaminophen Extra Strength: 500 mg [contains corn starch]
Acetaminophen Extra Strength: 500 mg [contains fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]
Acetaminophen Extra Strength: 500 mg [aspirin free]
Acetaminophen Extra Strength: 500 mg [scored; aspirin free]
Acetaminophen Extra Strength: 500 mg [aspirin free; contains corn starch]
Acetaminophen Extra Strength: 500 mg [aspirin free, sodium free]
Aminofen: 500 mg [DSC]
Aminofen: 325 mg [DSC] [antihistamine free, caffeine free, salt free, sugar free]
GoodSense Pain Relief Extra St: 500 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #6 (sunset yellow)]
GoodSense Pain Relief Extra St: 500 mg [DSC] [gluten free; contains corn starch, edetate (edta) disodium, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake]
GoodSense Pain Relief Extra St: 500 mg [gluten free; contains fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]
Healthy Mama Shake That Ache: 500 mg
Mapap: 325 mg [DSC], 500 mg [DSC]
Mapap Extra Strength: 500 mg [DSC] [aspirin free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Maxapap Maximum Strength: 500 mg [DSC]
Maxapap Regular Strength: 325 mg [DSC]
Non-Aspirin: 325 mg
Non-Aspirin: 325 mg, 500 mg [contains corn starch]
Non-Aspirin Extra Strength: 500 mg
Non-Aspirin Pain Reliever: 325 mg [DSC] [contains methylparaben, propylparaben]
Pain & Fever: 325 mg [DSC]
Pain & Fever Extra Strength: 500 mg [DSC]
Pain & Fever Extra Strength: 500 mg [DSC] [scored]
Pain Relief Extra Strength: 500 mg
Pain Relief Extra Strength: 500 mg [contains methylparaben, propylparaben]
Pain Relief Extra Strength: 500 mg [aspirin free]
Pain Relief Extra Strength: 500 mg [aspirin free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Pain Relief Regular Strength: 325 mg [contains methylparaben, propylparaben]
Panadol Extra Strength: 500 mg [contains fd&c blue #1 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake]
Pharbetol: 325 mg
Pharbetol Extra Strength: 500 mg [aspirin free]
Tactinal: 325 mg [DSC] [scored/varied; aspirin free]
Tactinal Extra Strength: 500 mg [DSC] [aspirin free]
Tylenol: 325 mg [scored]
Tylenol: 325 mg [contains corn starch, fd&c red #40 aluminum lake]
Tylenol: 325 mg [contains fd&c red #40 aluminum lake]
Tylenol Extra Strength: 500 mg
Tylenol Extra Strength: 500 mg [contains brilliant blue fcf (fd&c blue #1), butylparaben, edetate (edta) calcium disodium, fd&c red #40, fd&c yellow #10 (quinoline yellow), methylparaben, polysorbate 80, propylparaben]
Tylenol Extra Strength: 500 mg [contains corn starch, fd&c red #40 aluminum lake]
Tylenol Extra Strength: 500 mg [contains fd&c red #40 aluminum lake]
Tylenol Extra Strength: 500 mg [contains fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]
Generic: 325 mg, 500 mg
Tablet Chewable, Oral:
Childrens APAP: 80 mg [scored; contains aspartame, fd&c yellow #6 aluminum lake; fruit flavor]
Childrens Non-Aspirin: 80 mg
Childrens Tactinal: 80 mg [DSC] [aspirin free, ibuprofen free]
Mapap: 80 mg [DSC]
Mapap Childrens: 80 mg [aspirin free, ibuprofen free; contains fd&c blue #1 aluminum lake; grape flavor]
Mapap Childrens: 160 mg [scored; aspirin free, ibuprofen free; bubble-gum flavor]
Pain & Fever Childrens: 80 mg [DSC] [aspirin free; contains aspartame]
7T Gummy ES: 500 mg [DSC] [aspirin free, ibuprofen free]
Tylenol Childrens Chewables: 160 mg [aspirin free, ibuprofen free]
Tylenol Childrens Chewables: 160 mg [aspirin free, ibuprofen free; contains brilliant blue fcf (fd&c blue #1)]
Generic: 80 mg [DSC], 160 mg, 325 mg
Tablet Extended Release, Oral:
8 Hour Pain Reliever: 650 mg
Acetaminophen 8 Hour: 650 mg [aspirin free; contains corn starch]
Arthritis Pain Relief: 650 mg
GoodSense Pain Relief: 650 mg [DSC] [contains fd&c red #40 aluminum lake]
Mapap Arthritis Pain: 650 mg [gluten free]
Tylenol 8 Hour: 650 mg
Tylenol 8 Hour Arthritis Pain: 650 mg
Generic: 650 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 10 mg/mL (100 mL)
Oral: May administer without regard to food; may administer with food to decrease possible GI upset; shake drops and suspension well before use; do not crush or chew ER products.
Bariatric surgery: Caplet and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation (tablet or adult strength liquid). Avoid children's liquid formulation due to sugar content and volume needed to achieve adult doses.
Injection: For IV infusion only. Administer undiluted over 15 minutes. Attach an administration set in accordance with the manufacturer’s recommendations; may vary by product. If dose to be administered (eg, 650 mg) is not equivalent to an available formulation (eg, 500 mg per 50 mL or 1,000 mg per 100 mL) then withdraw appropriate dose and place into separate empty, sterile container (eg, glass bottle, plastic IV container, syringe) for administration.
Rectal: Remove wrapper; insert suppository well up into the rectum.
Oral: Administer with food to decrease GI upset; shake drops and suspension well before use; do not crush or chew extended release products
Parenteral: For IV infusion only. May administer undiluted over 15 minutes. Use within 6 hours of opening vial or transferring to another container. Discard any unused portion; single-use vials only.
Rectal: Remove wrapper; insert suppository well up into the rectum.
Fever: Temporary reduction of fever.
Pain:
Injection: Management of mild to moderate pain in patients ≥2 years of age; management of moderate to severe pain when combined with opioid analgesia in patients ≥2 years.
Oral, Rectal: Temporary relief of minor aches, pains, and headache.
Acephen may be confused with AcipHex
Acetaminophen may be confused with acetazolamide
FeverALL may be confused with Fiberall
Triaminic Children's Fever Reducer Pain Reliever may be confused with Triaminic cough and cold products
Tylenol may be confused with atenolol, timolol, Tylenol PM, Tylox
Infusion bottles of ropivacaine and IV acetaminophen look similar. Potentially fatal mix-ups have been reported in which a glass bottle of Naropin was mistaken for Ofirmev in perioperative areas.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
Infant concentration change: All children’s and infant acetaminophen products are available as 160 mg/5 mL. Some remaining infant concentrated solutions of 80 mg/0.8 mL and 100 mg/mL may still be available on pharmacy shelves or in patient homes. Check concentrations closely prior to administering or dispensing and verify concentration available to patients prior to recommending a dose (November 2011).
Injection: Reports of 10-fold overdose errors using the parenteral product have occurred in the U.S. and Europe; calculation of doses in "mg" and subsequent administration of the dose in "mL" using the commercially available concentration of 10 mg/mL contributed to these errors. Expressing doses as mg and mL, as well as pharmacy preparation of doses, may decrease error potential (Dart, 2012; ISMP, 2012).
Depon [Greece] may be confused with Depen brand name for penicillamine [US]; Depin brand name for nifedipine [India]; Dipen brand name for diltiazem [Greece]
Duorol [Spain] may be confused with Diuril brand name for chlorothiazide [US, Canada]
Paralen [Czech Republic] may be confused with Aralen brand name for chloroquine [US, Mexico]
Acute hepatotoxicity may result from intentional or unintentional overdose in adult and pediatric patients. In pediatric patients, unintentional overdose can be a result of accidental ingestion, supratherapeutic dosing, more frequent administration than recommended, and use of multiple acetaminophen-containing products; hepatotoxicity has also been rarely reported with recommended dosages (Ref).
Spontaneous resolution occurs with or without treatment in ~65% of cases, although some cases may progress to acute liver failure leading to liver transplantation or death (Ref); a mortality of ~0.4% has been reported (Ref). Acetaminophen is one of the most commonly reported products causing drug-induced liver injury (Ref), with ~50% of cases of acute hepatic failure in the US attributed to acetaminophen (Ref). Minor increased alanine aminotransferase (ALT) and increased aspartate aminotransferase (AST) may occur during chronic acetaminophen therapy that are rarely symptomatic; resolution generally occurs with discontinuation or dose reduction, but may also occur with continuation of the same dose (Ref).
Mechanism: Dose-related; direct toxic effect through formation of toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI) that binds to cellular proteins, including mitochondrial proteins. Toxic free radicals, including peroxynitrite, may also cause damage inside the mitochondria (Ref).
Onset: Rapid; usually starts 24 to 72 hours after ingestion with marked elevations in serum ALT and AST, followed at 48 to 96 hours by clinical symptoms (Ref).
Risk factors:
• Dose:
ο Pediatric: Toxicity is likely to occur with single ingestions >150 mg/kg or when the maximum daily acetaminophen dose is >75 mg/kg/day (maximum of 5 daily doses) up to 4,000 mg/day from all sources (Ref).
ο Adult: Toxicity is likely to occur with single ingestions >250 mg/kg or >12,000 mg over a 24-hour period (Ref). Asymptomatic elevation of ALT may occur following maximal therapeutic doses of acetaminophen (4,000 mg/day) for ≥4 days (Ref).
• Multiple acetaminophen-containing products: An unintentional overdose may occur in adult and pediatric patients who take multiple acetaminophen or acetaminophen-containing combination products (Ref).
• Chronic alcohol ingestion: Chronic alcoholics who take therapeutic doses of acetaminophen are NOT at an increased risk of hepatotoxicity (Ref). In contrast, chronic alcoholics who ingest repeated supratherapeutic doses of acetaminophen are at an increased risk for hepatotoxicity (Ref).
• Concomitant medications and herbal products: Although use of products that induce CYP2E1 enzymes (eg, carbamazepine, phenobarbital, phenytoin, isoniazid, rifampin) have been postulated to predispose to acetaminophen hepatotoxicity by enhanced production of NAPQI, there is little evidence, aside from case reports, that drug interactions increase the risk of liver injury (Ref).
• Nutritional status: Malnutrition and fasting may increase the risk (Ref)
• Age: Pediatric patients are less susceptible, whereas elderly patients are at a higher risk (Ref)
• Delay to treatment with N-acetylcysteine (NAC): Most patients with acetaminophen overdose who receive treatment with NAC within 8 hours of ingestion will not develop hepatotoxicity (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Oral, Rectal: Frequency not defined:
Dermatologic: Erythema of skin, skin blister, skin rash
Otic: Hearing loss
IV:
>10%: Gastrointestinal: Nausea (adults: 34%; neonates, infants, children, and adolescents: ≥5%), vomiting (adults: 15%; neonates, infants, children, and adolescents: ≥5%)
1% to 10%:
Cardiovascular: Hypertension, hypotension, peripheral edema (adults)
Dermatologic: Pruritus (neonates, infants, children, and adolescents: ≥5%)
Endocrine & metabolic: Hypoalbuminemia (neonates, infants, children, and adolescents), hypokalemia, hypomagnesemia (neonates, infants, children, and adolescents), hypophosphatemia (neonates, infants, children, and adolescents)
Gastrointestinal: Constipation (neonates, infants, children, and adolescents: ≥5%), diarrhea (neonates, infants, children, and adolescents)
Genitourinary: Oliguria (neonates, infants, children, and adolescents)
Hematologic & oncologic: Anemia
Hepatic: Increased serum aspartate aminotransferase (Watkins 2006)
Local: Infusion-site pain, pain at injection site
Nervous system: Agitation (neonates, infants, children, and adolescents), anxiety (adults), fatigue (adults), headache, insomnia (adults: 7%), trismus (adults)
Neuromuscular & skeletal: Muscle spasm (≥1%)
Respiratory: Abnormal breath sounds (adults), atelectasis (neonates, infants, children, and adolescents), dyspnea (adults), pleural effusion (neonates, infants, children, and adolescents), pulmonary edema (neonates, infants, children, and adolescents), stridor (adults), wheezing (adults)
Postmarketing (all formulations):
Dermatologic: Acute generalized exanthematous pustulosis (FDA 2016), Stevens-Johnson syndrome (FDA 2016), toxic epidermal necrolysis (Watanabe 2016; FDA 2016)
Hepatic: Acute hepatic failure, hepatotoxicity (Ramachandran 2019, Yoon 2016), increased serum alanine aminotransferase (Watkins 2006)
Hypersensitivity: Anaphylaxis (Ho 2008, Numata 2016), hypersensitivity reaction (Thomspon 2019)
Injection: Hypersensitivity to acetaminophen or any component of the formulation; severe hepatic impairment or severe active liver disease
OTC labeling: When used for self-medication, do not use with other drug products containing acetaminophen or if allergic to acetaminophen or any of the inactive ingredients
Disease-related concerns:
• G6PD deficiency: Use with caution in patients with known G6PD deficiency.
• Hepatic impairment: Use with caution in patients with hepatic impairment or active liver disease; use of the IV formulation is contraindicated in patients with severe hepatic impairment or severe active liver disease.
• Hypovolemia: Use the IV formulation with caution in patients with severe hypovolemia (eg, due to dehydration or blood loss).
Dosage form specific issues:
• Aspartame: Some products may contain aspartame, which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; 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 (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).
Other warnings/precautions:
• Dosage limit: Limit acetaminophen dose from all sources (prescription, OTC, combination products) and all routes of administration (IV, oral, rectal) to <4 g/day (adults).
• Self-medication (OTC use): When used for self-medication, patients should be instructed to contact health care provider if symptoms get worse or new symptoms appear, redness or swelling is present in the painful area, fever lasts >3 days (all ages), or pain (excluding sore throat) lasts longer than: Children ≥12 years, Adolescents, and Adults: 10 days; Infants and Children <12 years: 5 days. When treating children with sore throat, if sore throat is severe, persists for >2 days, or is followed by fever, rash, headache, nausea, or vomiting, consult health care provider immediately.
Prophylactic use of acetaminophen to reduce fever and discomfort associated with vaccination is not recommended by the Advisory Committee on Immunization Practices (ACIP). Additionally, the ACIP does not recommend prophylactic acetaminophen to reduce risk of febrile seizure in infants and children with or without a history of febrile seizures. Antipyretics have not been shown to prevent febrile seizures (NCIRD/ACIP 2011). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; in the trial evaluating 459 infants (including 226 who received acetaminophen), antibody geometric mean concentrations (GMCs) for targeted vaccine immune response markers were lower in significantly more infants in the acetaminophen group compared with control. Before the booster dose, children who received prophylactic acetaminophen had lower antibody GMCs for all vaccine serotypes than children in the control group; this effect persisted after boosting even in the absence of additional acetaminophen doses. The clinical significance of this reduction in immune response has not been established (Prymula 2009). Antipyretics may be used to treat fever or discomfort following vaccination (NCIRD/ACIP 2011).
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Substrate of CYP1A2 (minor), CYP2A6 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Alcohol (Ethyl): May enhance the hepatotoxic effect of Acetaminophen. Risk C: Monitor therapy
Busulfan: Acetaminophen may increase the serum concentration of Busulfan. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy
Dasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and dasatinib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider therapy modification
Flucloxacillin: May enhance the adverse/toxic effect of Acetaminophen. Specifically, the risk for high anion gap metabolic acidosis may be increased. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: May decrease the serum concentration of Acetaminophen. Specifically, serum concentrations of acetaminophen may be decreased (leading to decreased efficacy), but the formation of the toxic N-acetyl-p-benzoquinone imine (NAPQI) metabolite may be increased (leading to increased hepatotoxicity). Risk C: Monitor therapy
Imatinib: Acetaminophen may enhance the hepatotoxic effect of Imatinib. Risk C: Monitor therapy
Isoniazid: May enhance the hepatotoxic effect of Acetaminophen. Isoniazid may increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy
LamoTRIgine: Acetaminophen may decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Lorlatinib: May decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy
MetyraPONE: May increase the serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk C: Monitor therapy
Mipomersen: Acetaminophen may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
PHENobarbital: May increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy
Phenylephrine (Systemic): Acetaminophen may increase the serum concentration of Phenylephrine (Systemic). Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Primidone: May increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Management: Consider limiting acetaminophen use in combination with probenecid. Probenecid may reduce clearance of acetaminophen to one of its non-toxic metabolities, increasing the risk for acetaminophen toxicity, even a lower doses. Risk D: Consider therapy modification
RifAMPin: May enhance the hepatotoxic effect of Acetaminophen. RifAMPin may decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
SORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and sorafenib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider therapy modification
Vaccines: Acetaminophen may diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days. Risk C: Monitor therapy
Rate of absorption may be decreased when given with food. Management: Administer without regard to food.
Acetaminophen crosses the placenta (Naga Rani 1989).
Based on epidemiological data, an increased risk of major congenital malformations has not been observed following maternal use of acetaminophen during pregnancy. Although not considered a major birth defect, an association between maternal acetaminophen use and cryptorchidism (undescended testis) has been observed (Fisher 2016; Jensen 2010; Kristensen 2011; Snijder 2012). The use of acetaminophen in normal doses during pregnancy is not associated with an increased risk of miscarriage or still birth; however, an increase in fetal death or spontaneous abortion may be seen following maternal overdose if treatment is delayed (Li 2003; Rebordosa 2009; Riggs 1989). Prenatal constriction of the ductus arteriosus has been noted in case reports following maternal use during the third trimester (Allegaert 2019); although this association was not confirmed in a large observational study (Dathe 2019), acetaminophen has been evaluated for the treatment of a persistent patent ductus arteriosus in preterm neonates (Terrin 2016). Additional adverse events such as wheezing and asthma in early childhood and adverse neurodevelopmental effects such as ADHD following in utero acetaminophen exposure have been evaluated in multiple studies; outcome information is inconclusive, and a causal association has not been established (Cheelo 2014; Fan 2017; Lourido-Cebreiro 2017; Scialli 2010; SMFM 2017). It should be noted that maternal fever is also associated with adverse fetal outcomes, including neural tube defects, oral clefts, and congenital heart defects. Treatment of maternal fever with an antipyretic may reduce these risks (Drier 2014).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of acetaminophen may be altered. Dose adjustments are not recommended (Kulo 2014). Acetaminophen is considered appropriate for the treatment of pain and fever in pregnancy (SMFM 2017). Acetaminophen may be used as part of a multimodal approach to pain relief following cesarean delivery (ACOG 209 2019), for the treatment of acute migraine in pregnant patients (Burch 2019; Hamilton 2019a; Marmura 2015) and is recommended for the treatment of fever in pregnant women diagnosed with influenza (ACOG 753 2018). Acetaminophen is recommended to be used at the lowest effective dose for the shortest duration of time to effectively treat the mother and protect the health of the fetus (Kilcoyne 2017).
Acetaminophen is present in breast milk (Notarianni 1987).
The relative infant dose (RID) of acetaminophen is 3.98% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 60 mg/kg/day.
In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
The RID of acetaminophen was calculated using a milk concentration of 15.9 mcg/mL providing an estimated daily infant dose via breast milk of 2.385 mg/kg/day. This milk concentration was obtained following a single maternal dose of oral acetaminophen 1,000 mg given to 11 women, 3 to 9 days' postpartum (Hurden 1980).
Following a single oral maternal dose of acetaminophen 650 mg, the half-life of acetaminophen is 1.35 to 3.5 hours in breast milk (Berlin 1980). Acetaminophen can be detected in the urine of breastfeeding infants (Notarianni 1987). Except for a single case report of a rash (Matheson 1985), adverse reactions have generally not been observed in breastfeeding infants (Ito 1993).
Nonopioid analgesics are preferred for breastfeeding females who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Sachs 2013). Acetaminophen is one of the preferred non-narcotic agents (Sachs 2013) and is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).
Some products may contain phenylalanine and/or sodium.
Serum acetaminophen levels: Where acute overdose suspected and with long-term use in patients with hepatic disease; relief of pain or fever
Although not fully elucidated, the analgesic effects are believed to be due to activation of descending serotonergic inhibitory pathways in the CNS. Interactions with other nociceptive systems may be involved as well (Smith 2009). Antipyresis is produced from inhibition of the hypothalamic heat-regulating center.
Note: With the exception of half-life, the pharmacokinetic profile in pediatric patients (0-18 years) is similar to adult patients.
Onset of action:
Oral: <1 hour
IV: Analgesia: 5 to 10 minutes; Antipyretic: Within 30 minutes
Peak effect: IV: Analgesic: 1 hour
Duration:
IV, Oral: Analgesia: 4 to 6 hours
IV: Antipyretic: ≥6 hours
Absorption: Primarily absorbed in small intestine (rate of absorption dependent upon gastric emptying); minimal absorption from stomach; varies by dosage form
Distribution: ~1 L/kg at therapeutic doses
Protein binding: 10% to 25% at therapeutic concentrations; 8% to 43% at toxic concentrations
Metabolism: At normal therapeutic dosages, primarily hepatic metabolism to sulfate and glucuronide conjugates, while a small amount is metabolized by CYP2E1 to a highly reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), which is conjugated rapidly with glutathione and inactivated to nontoxic cysteine and mercapturic acid conjugates. At toxic doses (as little as 4 g daily) glutathione conjugation becomes insufficient to meet the metabolic demand causing an increase in NAPQI concentrations, which may cause hepatic cell necrosis. Oral administration is subject to first pass metabolism.
Half-life elimination: Prolonged following toxic doses
Neonates: 7 hours (range: 4 to 10 hours)
Infants: ~4 hours (range: 1 to 7 hours)
Children: 3 hours (range: 2 to 5 hours)
Adolescents: ~3 hours (range: 2 to 4 hours)
Adults: ~2 hours (range: 2 to 3 hours); may be slightly prolonged in severe renal insufficiency (CrCl<30 mL/minute): 2 to 5.3 hours
Time to peak, serum: Oral: Immediate release: 10 to 60 minutes (may be delayed in acute overdoses); IV: 15 minutes
Excretion: Urine (<5% unchanged; 60% to 80% as glucuronide metabolites; 20% to 30% as sulphate metabolites; ~8% cysteine and mercapturic acid metabolites)
Hepatic function impairment: The half-life may increase 2-fold or more in patients with liver disease.
Capsules (Tylenol Oral)
325 mg (per each): $0.18
Chewable (Acetaminophen Oral)
160 mg (per each): $6.29
325 mg (per each): $6.79
Chewable (Mapap Childrens Oral)
80 mg (per each): $0.08
160 mg (per each): $0.09
Chewable (Tylenol Childrens Chewables Oral)
160 mg (per each): $0.26
Gel (ElixSure Fever/Pain Oral)
160 mg/5 mL (per mL): $0.04
Liquid (Acetaminophen Oral)
160 mg/5 mL (per mL): $0.06
Liquid (Mapap Acetaminophen Extra Str Oral)
500 mg/15 mL (per mL): $0.02
Pack (Tylenol Childrens Pain + Fever Oral)
160 mg (per each): $0.35
Pack (Tylenol Dissolve Packs Oral)
500 mg (per each): $0.33
Solution (Acetaminophen Childrens Oral)
160 mg/5 mL (per mL): $0.02
Solution (Acetaminophen Intravenous)
10 mg/mL (per mL): $0.11 - $0.45
Solution (Acetaminophen Oral)
160 mg/5 mL (per mL): $0.18 - $0.45
Solution (Ofirmev Intravenous)
10 mg/mL (per mL): $0.57
Suppository (FeverAll Adults Rectal)
650 mg (per each): $0.66
Suppository (FeverAll Childrens Rectal)
120 mg (per each): $0.80
Suppository (FeverAll Infants Rectal)
80 mg (per each): $0.80
Suppository (FeverAll Junior Strength Rectal)
325 mg (per each): $0.80
Suspension (Acetaminophen Oral)
160 mg/5 mL (per mL): $0.20
Suspension (Panadol Childrens Oral)
160 mg/5 mL (per mL): $0.05
Suspension (Panadol Infants Oral)
160 mg/5 mL (per mL): $0.08
Suspension (Tylenol Childrens Oral)
160 mg/5 mL (per mL): $0.05
Suspension (Tylenol for Children + Adults Oral)
160 mg/5 mL (per mL): $0.05
Suspension (Tylenol Infants Oral)
160 mg/5 mL (per mL): $0.15
Suspension (Tylenol Infants Pain+Fever Oral)
160 mg/5 mL (per mL): $0.18
Syrup (Triaminic Fever Reducer Oral)
160 mg/5 mL (per mL): $0.08
Tablet, controlled release (Acetaminophen ER Oral)
650 mg (per each): $0.07 - $0.10
Tablet, controlled release (Tylenol 8 Hour Arthritis Pain Oral)
650 mg (per each): $0.12
Tablet, controlled release (Tylenol 8 Hour Oral)
650 mg (per each): $0.17
Tablets (Acetaminophen Oral)
325 mg (per each): $0.01 - $0.15
500 mg (per each): $0.01 - $0.15
Tablets (Healthy Mama Shake That Ache Oral)
500 mg (per each): $0.06
Tablets (Panadol Extra Strength Oral)
500 mg (per each): $0.14
Tablets (Pharbetol Extra Strength Oral)
500 mg (per each): $0.03
Tablets (Pharbetol Oral)
325 mg (per each): $0.02
Tablets (Tylenol Extra Strength Oral)
500 mg (per each): $0.11
Tablets (Tylenol Oral)
325 mg (per each): $0.05
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
