Acetaminophen

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

1. See Also
   1. Acetaminophen Overdose
   2. Intravenous Acetaminophen
2. Indications
   1. Mild to Moderate Pain
      1. Combined with other Analgesics for moderate to severe pain
   2. Fever
3. Contraindications
   1. Severe hepatic insufficiency
   2. Severe progressive liver disease
   3. Acetaminophen Hypersensitivity
4. Efficacy: Rheumatologic Conditions
   1. Scheduled dosing much more effective than prn
   2. Tylenol 1000 mg qid is as effective as Tylenol #3
5. 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)
6. 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)
7. 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)
8. Preparations
   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. Intravenous (Ofirmev)
      1. Available in generic formulation expected in 2022
   7. Combination agents with Opioids
      1. Vicodin or Lortab (Acetaminophen with Hydrocodone)
      2. Percocet (Acetaminophen with Oxycodone)
   8. Combination agents - miscellaneous
      1. Excedrin Migraine (Acetaminophen with Aspirin and Caffeine)
      2. Sudafed PE (Acetaminophen with Diphenhydramine and Phenylephrine)
9. 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
10. 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 (>6 weeks)
       1. However Acetaminophen association with ADHD is very weak, and without any evidence of causality (observational study)
       2. Cooper (2014) JAMA Pediatr 168(4):306-307 [PubMed]
    4. Untreated fever over 101 F is also associated with increased fetal risks in pregnancy (and NSAIDs present additional risks)
       1. Dreier (2014) Pediatrics 133(3): e674-88 [PubMed]
11. Precautions
    1. Dehydration predisposes to overdosage
    2. Never exceed maximum daily dosage (hepatotoxicity)
12. 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