Acetaminophen

Aka: Acetaminophen, Tylenol, Paracetamol, N-acetyl-p-aminophenol

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II. Indications

  1. Fever
  2. Mild to Moderate Pain
    1. Combined with other Analgesics for moderate to severe pain

III. Contraindications

  1. Severe hepatic insufficiency
  2. Severe progressive liver disease
  3. Acetaminophen Hypersensitivity

IV. Mechanism

  1. Acetaminophen is derived from Acetanilide, and Analgesic discovered in the 1880s
  2. Analgesic
    1. May inhibit the nitric oxide pathway, raising the pain threshold via the Neurotransmitters NMDA and substance P
  3. Antipyretic
    1. May modulate Prostaglandin synthesis and release
    2. May effect Temperature Regulation in the Anterior Hypothalamus
  4. No significant antiinflammatory effect
    1. Weak Prostaglandin synthesis inhibitor

V. Medications

  1. Acetaminophen
    1. Chewable: 80 mg
    2. Elixir: 160 per 5 ml
    3. Dropper: 80 mg per 0.8 ml
    4. Suppository: 120 mg, 325 mg, 650 mg
    5. Tablet
      1. Regular strength: 325 mg
      2. Extra-Strength: 500 mg
    6. Acetaminophen Intravenous (Ofirmev)
      1. Available in generic formulation expected in 2022
  2. Acetaminophen Combination agents with Opioids
    1. Vicodin or Lortab (Acetaminophen with Hydrocodone)
    2. Percocet (Acetaminophen with Oxycodone)
  3. Acetaminophen Combination agents - miscellaneous
    1. Excedrin Migraine (Acetaminophen with Aspirin and Caffeine)
    2. Sudafed PE (Acetaminophen with Diphenhydramine and Phenylephrine)

VI. Dosing: Children

  1. Avoid overdosage of the Acetaminophen component at all cost (err on the side of underdosage)
  2. Acetaminophen
    1. Well hydrated child: 15 mg/kg every 6 hours
    2. Dehydration risk: 10 mg/kg every 6 hours
    3. Dosing by age (use only for an isolated single dose)
      1. Use measured weight based dosing for any subsequent doses!
      2. Age >2 months (5 kg): 80 mg per dose
      3. Age >4 months (6.5 kg): 100 mg per dose
      4. Age >6 months (8 kg): 120 mg per dose
      5. Age >12 months (10 kg): 160 mg per dose
      6. Age >2 years (13 kg): 200 mg per dose
      7. Age >3 years (15 kg): 240 mg per dose
      8. Age >5 years (19 kg): 280 mg per dose
    4. Maximum
      1. Do not exceed 75 mg/kg/day (up to 4 grams per day)

VII. Dosing: Adults (weight >50 kg)

  1. Regular Dose: 650 mg orally every 4 to 6 hours prn
  2. Higher Dose (Osteoarthritis)
    1. Regular Strength Tablet (325 mg)
      1. Take 975 mg (3 tablets) orally every 6 hours
    2. Extra-Strength Tablet (500 mg)
      1. Take 1000 mg (2 tablets) orally every 6 hours
  3. Maximum: 4 grams per day
    1. Limit to 2 grams per day maximum in advanced liver disease or severe Alcohol Use Disorder
    2. Do not exceed 12 regular strength tablets (325 mg)
    3. Do not exceed 8 extra-strength tablets (500 mg)

VIII. Pharmacokinetics

  1. Similar potency and time-effect curve to Aspirin
  2. Duration: 4 hours
  3. Onset: 10 to 60 min (within 5-10 min for intravenous form)

IX. Adverse Effects: Hepatotoxicity

  1. See Acetaminophen Toxicity
  2. Drug-Induced Skin Reaction (Stevens Johnson Syndrome, Toxic Epidermal Necrolysis)
    1. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM363052.pdf

X. Safety: Pregancy

  1. FDA Pregnancy Category B
  2. As with all Medications in Pregnancy, use the lowest effective dose in concert with non-pharmacologic measures
    1. Acetaminophen continues to be the preferred Analgesic in pregnancy without major safety concerns
    2. (2021) Presc Lett 28(11): 63-4
  3. May be associated with increased risk of ADHD in children with prolonged regular use (>4 to 6 weeks, esp. third trimester)
    1. However Acetaminophen association with ADHD is without evidence of causality
    2. Cooper (2014) JAMA Pediatr 168(4):306-307 [PubMed]
    3. Gou (2019) Aust N Z J Psychiatry 53(3): 195-206 [PubMed]
    4. Matosich (2024) Am Fam Physician 109(1): 81-2 [PubMed]
    5. Sznajder (2022) PLoS One 17(9): e0272593 [PubMed]
  4. Untreated fever over 101 F (esp. first trimester) is also associated with increased fetal risks in pregnancy
    1. Dreier (2014) Pediatrics 133(3): e674-88 [PubMed]

XI. Efficacy: Rheumatologic Conditions

  1. Scheduled dosing much more effective than prn
  2. Tylenol 1000 mg four times daily is as effective as Tylenol #3

XII. Precautions

  1. Dehydration predisposes to overdosage
  2. Never exceed maximum daily dosage (hepatotoxicity)

XIII. Resources

  1. Acetaminophen Tablet
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2569383a-4a05-4ddb-852e-b37e487ffcde

XIV. References

  1. LoVecchio (2021) Crit Dec Emerg Med 35(12): 32
  2. (2000) Med Lett Drugs Ther 42(1085):73-8 [PubMed]
  3. (1996) Med Lett Drugs Ther 38:5 [PubMed]
  4. Katzung (1989) Basic and Clinical Pharmacology

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Related Studies

Cost: Medications

acetaminophen (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ACETAMINOPHEN 120 MG SUPPOS Generic OTC $0.30 each
ACETAMINOPHEN 160 MG/5 ML LIQ Generic OTC $0.01 per ml
ACETAMINOPHEN 160 MG/5 ML SOLN Generic OTC $0.02 per ml
ACETAMINOPHEN 325 MG GELCAP Generic OTC $0.02 each
ACETAMINOPHEN 325 MG TABLET Generic OTC $0.02 each
ACETAMINOPHEN 500 MG CAPLET Generic OTC $0.03 each
ACETAMINOPHEN 500 MG GELCAP Generic OTC $0.03 each
ACETAMINOPHEN 500 MG SOFTGEL Generic OTC $0.05 each
ACETAMINOPHEN 500 MG TABLET Generic OTC $0.03 each
ACETAMINOPHEN 650 MG SUPPOS Generic OTC $0.29 each
ACETAMINOPHEN ER 650 MG CAPLET Generic OTC $0.07 each
ACETAMINOPHEN ER 650 MG TABLET Generic OTC $0.07 each
ACETAMINOPHEN PM CAPLET Generic OTC $0.05 each
ACETAMINOPHEN-COD #2 TABLET Generic $0.16 each
ACETAMINOPHEN-COD #3 TABLET Generic $0.13 each
ACETAMINOPHEN-COD #4 TABLET Generic $0.31 each
ACETAMINOPHEN-CODEINE 120 MG-12 MG/5 ML SOLUTION Generic $0.02 per ml
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

Related Topics in Analgesic Medications

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