Acetaminophen

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Acetaminophen Quick Reference
Acetaminophen
IUPAC Name
N-(4-hydroxyphenyl)ethanamide
Chemical Information
Empirical Formula Acetaminophen: C8H9NO2
Molecular Weight 151.16
General Drug Information
Classification Analgesics
Schedule Over-the-counter
How Supplied Tablet,rectal suppository, chewable tablet, capsule, suspension or solution, drops, extended-release tablet, and orally disintegrating tablet .
Trade Names Tylenol (most common)
Pregnancy Category B
Breast Feeding Generally considered safe for the infant. Acetaminophen is secreted into breast milk
Generic Availability Generic Available
Patent Expiration Date Generic available
Administration Information
Route(s) Oral and rectal
Method(s) May take with or without food.

Oral tablets/capsules: swallow with a drink of water

Extended-release tablets: swallow whole, do not crush or chew

Orally disintegrating tablet: place tablet in mouth and allow to dissolve or chew before swallowing

Suspension and drops: Shake well and use the medication cup or dropper provided by the manufacturer. Place drops in the child’s inner cheek

Rectal suppository Take the wrapper off of the suppository. Rinse the suppository in water. Lie down on left side of body and bring knees to chest. Use finger to insert suppository and hold in place for a minute. Insert ½-1 inch in infants and children and 1 inch in adults. Stand up after 15 minutes and wash hands.

Pharmacokinetic Information
Absorption F = 80%
tmax = 0.25-2 hr
Distribution Vd = 1.5-3 L/kg
Protein binding = 0.9%
Metabolism hepatic conjugation with glucuronic acid (60%), sulfuric acid (35%), and cysteine (3%). Some of the drug may be hydroxylated and deacetylated. CYP2A6,CYP2E1
Excretion T1/2 = 1.5-3 hours
85% of oral dose appears in the urine most as the glucuronide conjugate


Contents

Brand/Trade Names of Drug

Includes combination products containing acetaminophen

Acephen® Anacin® Aspirin Free Maximum Strength Tablets® Capital® and Codeine Endocet® Excedrin P.M.® Caplets® Excedrin P.M.® Geltabs® Excedrin P.M.® Tablets Excedrin® Extra-Strength Caplets® Excedrin® Extra-Strength Tablets Excedrin® Migraine Caplets® Excedrin® Migraine Geltabs Excedrin® Migraine Tablets FeverAll® Children's FeverAll® Infants' FeverAll® Junior Strength Gelpirin® Genapap® Genapap® Children's Genapap® Drops Infant's Genapap® Extra Strength Caplets® Genapap® Extra Strength Tablets Genapap® Gel-Coat Caplets® Genebs® Genebs® Extra Strength Caplets® Genebs® Extra Strength Tablets Goody's® Extra Strength Tablets Goody's® Fast Pain Relief Tablets Goody's® Headache Powders Liquiprin® Drops Roxicet® Supac® Tylenol® Tylenol® Arthritis Pain Extended Relief Caplets® Tylenol® Meltaways Children's Tylenol® Concentrated Drops Infant's Tylenol® Extra Strength Adult Tylenol® Extra Strength Caplets® Tylenol® Extra Strength Gelcaps® Tylenol® Extra Strength Geltabs® Tylenol® Extra Strength Tablets Tylenol® Meltaways Junior Strength Tylenol® Suspension Children's Tylenol® with Codeine Elixir Tylenol® with Codeine No. 3 Tylenol® with Codeine No. 4 Tylox® Vanquish® Caplets® Wygesic® Allerest® No Drowsiness containing Acetaminophen and Pseudoephedrine Hydrochloride Axocet® containing Acetaminophen and Butalbital Benadryl® Severe Allergy and Sinus Headache Maximum Strength Caplets® containing Acetaminophen, Diphenhydramine Hydrochloride, and Pseudoephedrine Hydrochloride Bupap® containing Acetaminophen and Butalbital Dristan® Cold No Drowsiness Formula Maximum Strength Caplets® containing Acetaminophen and Pseudoephedrine Hydrochloride Duradrin® containing Acetaminophen, Dichloralphenazone, and Isometheptene Mucate Excedrin® Aspirin-Free Caplets® containing Acetaminophen and Caffeine Excedrin® Aspirin-Free Geltabs® containing Acetaminophen and Caffeine Excedrin® Quicktabs® containing Acetaminophen and Caffeine I.D.A.® containing Acetaminophen, Dichloralphenazone, and Isometheptene Mucate Midol® Menstrual Formula Maximum Strength Caplets® containing Acetaminophen, Caffeine, and Pyrilamine Maleate Midol® Menstrual Formula Maximum Strength Gelcaps® containing Acetaminophen, Caffeine, and Pyrilamine Maleate Midol® PMS Maximum Strength Caplets® containing Acetaminophen, Pamabrom, and Pyrilamine Maleate Midol® PMS Maximum Strength Gelcaps® containing Acetaminophen, Pamabrom, and Pyrilamine Maleate Midol® Teen Menstrual Formula Caplets® containing Acetaminophen and Pamabrom Midrin® containing Acetaminophen, Dichloralphenazone, and Isometheptene Mucate Ornex® Caplets® containing Acetaminophen and Pseudoephedrine Hydrochloride Ornex® Maximum Strength Caplets® containing Acetaminophen and Pseudoephedrine Hydrochloride Pamprin® Maximum Pain Relief Caplets® containing Acetaminophen, Magnesium Salicylate, and Pamabrom Pamprin® Multi-Symptom containing Acetaminophen, Pamabrom, and Pyrilamine Maleate Percogesic® containing Acetaminophen and Phenyltoloxamine Citrate Percogesic® Extra Strength Caplets® containing Acetaminophen and Diphenhydramine Hydrochloride Phrenilin® containing Acetaminophen and Butalbital Phrenilin® Forte containing Acetaminophen and Butalbital Premsyn PMS® Caplets® containing Acetaminophen, Pamabrom, and Pyrilamine Maleate Sedapap® containing Acetaminophen and Butalbital Sinarest® No Drowsiness Tablets containing Acetaminophen and Pseudoephedrine Hydrochloride Sine-Off® Maximum Strength No Drowsiness Formula Caplets® containing Acetaminophen and Pseudoephedrine Hydrochloride Sinutab® containing Acetaminophen and Pseudoephedrine Hydrochloride Sinutab® Sinus Medication Maximum Strength Without Drowsiness Tablets containing Acetaminophen and Pseudoephedrine Hydrochloride Sominex® Pain Relief Formula containing Acetaminophen and Diphenhydramine Hydrochloride St. Joseph® Cold Tablets for Children containing Acetaminophen and Phenylpropanolamine Hydrochloride Sudafed® Sinus & Headache Caplets® containing Acetaminophen and Pseudoephedrine Hydrochloride Sudafed® Sinus & Headache Maximum Strength Tablets containing Acetaminophen and Pseudoephedrine Hydrochloride Tylenol® Allergy Sinus NightTime Maximum Strength Caplets® containing Acetaminophen, Diphenhydramine Hydrochloride, and Pseudoephedrine Hydrochloride Tylenol® Cold Decongestant and Fever Reducer Concentrated Drops Infant's containing Acetaminophen and Pseudoephedrine Hydrochloride Tylenol® Flu NightTime Maximum Strength Gelcaps® containing Acetaminophen, Diphenhydramine Hydrochloride, and Pseudoephedrine Hydrochloride Tylenol® PM Extra Strength Caplets® containing Acetaminophen and Diphenhydramine Hydrochloride Tylenol® PM Extra Strength Gelcaps® containing Acetaminophen and Diphenhydramine Hydrochloride Tylenol® PM Extra Strength Geltabs® containing Acetaminophen and Diphenhydramine Hydrochloride Tylenol® Sinus Geltabs® Maximum Strength Tablets containing Acetaminophen and Pseudoephedrine Hydrochloride Tylenol® Sinus Medication Maximum Strength Geltabs® containing Acetaminophen and Pseudoephedrine Hydrochloride Tylenol® Sinus Medication Maximum-Strength Caplets® containing Acetaminophen and Pseudoephedrine Hydrochloride Tylenol® Sinus Medication Maximum-Strength Gelcaps® containing Acetaminophen and Pseudoephedrine Hydrochloride Tylenol® Women's Caplets® containing Acetaminophen and Pamabrom Ultracet® containing Acetaminophen and Tramadol Hydrochloride Women's Tylenol® Menstrual Relief Caplets® containing Acetaminophen and Pamabrom

Generic Name of Drug

Ex: acetaminophen (a set a mee' noe fen) Click Here

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Description

Acetaminophen has been used by patients for over 100 years and has been available over-the-counter for nearly 50 years. [1] Acetaminophen has very weak anti-inflammatory actions; however it is generally safer than anti-inflammatory agents like aspirin and NSAIDs.[2] Acetaminophen does not affect the bleeding time, cause stomach ulcers, or alter the acid-base status of the body. It is typically used for mild to moderate pain caused from muscle aches, headaches, menstrual periods, sore throats, toothaches, and to decrease fever. It is often prescribed as a first line agent for osteoarthritis.[3] Acetaminophen's effects are considered equal to those of aspirin in terms of analgesic and antipyretic properties. It does not have the risk of gastrointestinal bleeding that is associated with aspirin. [4]


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Mechanism of action

Acetaminophen is an analgesic whose exact mechanism of action is unknown. It seems to work peripherally. It is an antipyretic via its action on the hypothalamus. Acetaminophen inhibits prostaglandin synthesis. [5] It is the active metabolite of phenacetin. The maximum daily dose of acetaminophen is 4 grams per day. Acetaminophen lacks antiinflammatory properties because it only weakly inhibits cyclooxygenase. It works as an antipyretic via its inhibition of cyclooxygenase in the brain.

The most severe adverse effect occurs when excessive acetaminophen is administered. Overdosage can lead to fatal hepatic necrosis. The mechanism of hepatic injury occurs from metabolism with the cytochrome P450 system leading to the production of the metabolite, N-acetyl-para-benzoquinonimine. N-acetyl-para-benzoquinonimine is conjugated with glutathione and further metabolized to mercapturic acid and excreted in the urine. When too much acetaminophen is consumed, glutathione becomes in short supply. Thus N-acetyl-para-benzoquinonimine, which is very reactive, is free to cause oxidative injury to the liver. [2]


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Time Required for Therapeutic Response

  • Initial: 30 minutes [6]

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Pharmacokinetics

Absorption

Acetaminophen is almost completely absorbed from the gastrointestinal tract with peak plasma concentrations occurring in 30-60 minutes. [2]The bioavailability is around 80%[5]

Distribution

Acetaminophen is uniformly distributed throughout the body. The binding to plasma proteins is variable, however when over doses have occurred, approximately 20-50% of the drug is bound to plasma proteins. [2]An alernative source reports that the plasma protein binding is less than 20%. The volume of distribution is 0.9L/kg.[5]

Metabolism

Acetaminophen undergoes hepatic metabolism. It undergoes hepatic conjugation with glucuronic acid (60%), sulfuric acid (35%), and cysteine (3%). Some of the drug may be hydroxylated and deacetylated. A small amount of acetaminophen undergoes N-hydroxylation to form N-acetyl-benzoquinoneimine which is very reactive.[2] 3% of the dose is oxidized by CYP2A6 and CYP2E1. This forms two metabolites; 3-hydroxy-acetaminophen, which is nontoxic, and N-acetyl-p-benzoquinone imine (NAPQI) (Also called N-acetyl-benzoquinoneimine), which is toxic. NAPQI must be conjugated with glutathione to avoid hepatotoxicity. There are no active metabolites produced.[5]

Excretion

Acetaminophen is excreted in the urine approximately 90-100% after 24 hours, mostly as the metabolites of acetaminophen.[2] The clearance of acetaminophen is 0.144-0.14 L/hr*kg.[5] Less than 5% of acetaminophen is excreted as unmetabolized acetaminophen in the urine.[7] Acetaminophen undergoes first-order elimination.[8]

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Special Population Pharmacokinetics

  • Renal insufficiency- The absorption and disposition of acetaminophen does not appear to be altered. The AUC of the metabolites of acetaminophen seem to increase in patients with renal insufficiency leading to a build-up of conjugates.[9] In patients with moderate renal failure, plasma concentrations of acetaminophen glucuronide increased and the mean plasma half-live increased to 30.5 hours compared with about 3 hours in the healthy volunteers.[10]
  • Hepatic insufficiencyAcetaminophen appears to be elimintaed at a slower rate in patients with hepatic disease, though repeated administration does not lead to accumulation, when acetaminophen is taken at recommended dosages. [11] It is possible that chronic alcoholics may have an increased risk for acetaminophen toxicity, especially if they stop drinking abruptly and take acetaminophen.[12]
  • Hemodialysis- In patients on hemodialysis 2-3 times a week, the mean plasma concentration of acetaminophen was 6.8 mg x l-1 after the first 24 hours and did not change much during the following 10 days. The glucuronide conjugate had a steady state concentration of 60.0 mg x l-1 and the sulphate had a steady state concentration of 54.5 mg x l-1. The steady state concentration was acheived on day two and was maintained until the end of the study, day 10. Thus there was not a significant accumulation of the conjugates in hemodialysis patients.[13]
  • Geriatric- The rate and extent of absorption are not affected by age. Elderly patients may have a slower elimination of acetaminophen[14]


  • Gender- The PK is not altered based on gender[15]


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Indications

FDA Approved Indications


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Non-FDA Approved Indications


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Dosage

  • Mild pain: 325-1000mg by mouth or per rectum every 4-6 hours.
    • Maximum daily dose: 4 grams/day
  • Fever: 325-1000mg by mouth or per rectum every 4-6 hours. [32]
    • Maximum daily dose: 4 grams/day
    • Maximum dose: 1 gram/dose[32]


  • Maximum Dosage Limits
    • Adults: 4 grams/day[32]
    • Elderly:
    • Adolescents and children >=10 years:
    • Children < 10 years:
  • Dosage Adjustment
    • Renal insufficiency: CrCl: 10-50mL/min give every 6 hours[32]
      • CrCl<10: give every 8 hours
    • Hepatic insufficiency: Consider decreasing dose[32]
    • Hemodialysis: no supplement needed[32]
    • Geriatric:
    • Pediatric:
      • Neonates: 10-15mg/kg by mouth or per rectum every 6-8 hours as needed
      • Infants or children: 10-15 mg/kg by mouth or per rectum every 4-6 hours as needed
      • Children greater than 12 years: 325-650 mg by mouth or per rectum every 4-6 hours with a maximum daily dose of 4 grams per day[32]
    • Gender: No dosage adjustment needed

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Administration

  • Tablets/Capsules
    • Swallow whole with drink of water or other liquid. May take with or without food.
  • Oral: Extended-release tablets:
    • Swallow whole, do not crush or chew.[3]
  • Oral: Orally disintegrating tablet:
    • Place tablet in mouth and allow to dissolve or chew before swallowing.
  • Oral: Suspension and drops
    • Shake well and use the medication cup or dropper provided by the manufacturer
    • Place drops in the child’s inner cheek
  • Rectal suppository
    • Take the wrapper off of the suppository
    • Rinse the suppository in water
    • Lie down on left side of body and bring knees to chest
    • Use finger to insert suppository and hold in place for a minute
    • Insert ½-1 inch in infants and children and 1 inch in adults
    • Stand up after 15 minutes and wash hands.[3]


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Monitoring Parameters

  • LFTs with chronic use

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Contraindications/Precautions

Contraindications

  • Hypersensitivity to acetaminophen, or a component of acetaminophen
  • Chronic alcohol users


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Precautions

  • G6PD deficiency: especially at high doses, may be at an increased risk for drug-induced hemolysis[32]
  • Phenylketonuria: certain products (chewable tablets) contain NutraSweet which should be avoided in these patients.[32]
  • Impaired renal function: avoid chronic use of acetaminophen to avoid buildup of metabolites[32]


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Pregnancy indications

  • Pregnancy category: B


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Breast-feeding indications

  • Secretion into breast milk: Acetaminophen is found in the breast milk of mothers who take acetaminophen. It does not seem to impact the infant in any adverse way, thus acetaminophen is generally considered safe for mothers to take when they are breast feeding.[33]

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Drug-Drug Interactions

Acetaminophen Drug/Drug Interaction Chart
Severity Level Click here to see Severity Level Legend Increased Effect/Toxicity Decreased Effect
4 None. None.
3 Acetaminophen[34] increase risk of overdosage. Busulfan[35] increases the risk of hepatotoxicity. Ethanol [2][36] increased risk of hepatotoxicity, especially in chronic or heavy users of alcohol. Imatinib[37][38] increases the risk of hepatotoxicity. Isoniazid[39][40][41] increases the risk of hepatotoxicity. None.
2 Diflunisal[42] increased risk of hepatotoxicity because diflunisal increases the concentrations of acetaminophen. Lamotrigine [43] increase risk of hepatotoxicity. Rifampin and rifabutin [44][45][46] increased liver toxicity and decreased analgesic effects of acetaminophen.Warfarin[47] increase risk of overdosage. Salicylates[48] increased the INR. Cholestyramine [49][50] decreases the intestinal adsorption of acetaminophen. Lamotrigine[43] decreases the AUC of lamotrigine by 20% when given with acetaminophen. Rifampin and rifabutin[44][45][46] increased liver toxicity and decreased analgesic effects of acetaminophen.
1 Carbamazepine, Oxcarbazepine, barbiturates and phenytoin or Fosphenytoin[51] increase the risk of hepatotoxicity because these drugs induce CYP2E1 and CYP1A2. None.


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Drug-Food-Herb Interactions

Acetaminophen Drug/Food/Herb Interaction Chart
Severity Level Click here to see Severity Level Legend Increased Effect/Toxicity Decreased Effect
4 None. None.
3 None. None.
2 Tobacco[51] smoking induces CYP1A2, thus increasing the possibility of development of hepatotoxicity from acetaminophen. None.
1 St John's Wort[52] increased risk of hepatotoxicity . Echinacea and kava kava[53] increased risk of hepatotoxicity. Ginkgo[53] increased risk of bleeding. None.

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Adverse Reactions/Side Effects

Acetaminophen is typically very well tolerated with few side effects when taken at the normal recommended doses[3]


Acetaminophen Adverse Reactions Chart
Incidence Body System Adverse Reactions
> 10 % CNS None.
2-10% CNS None.
CV None.
Dermatologic None.
GI None.
GU None.
Neuromuscular & skeletal None.
Respiratory None.
Misc None.
< 2% All rash, hives, itching, swelling of the body, hoarseness, difficulty breathing or swallowing Report these to a doctor right away


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Overdosage Measures

Symptoms and signs of acetaminophen toxicity: Initially present with nausea, vomiting and sweating and then may cause hepatic necrosis which may be fatal. It may take 2-3 days before the hepatic involvement is realized. Other signs include renal tubular necrosis, and hypoglycemic coma and thrombocytopenia.[5] The typical toxic dose is greater than 10 grams. Hepatic enzymes should be monitored throughout treatment of overdose.[5]

If hypoprothrombinemia occurs, vitamin K should be administered.[5]

If the dose of acetaminophen has exceeded 140mg/kg, then acetylcysteine should be given. [5]

Methylene blue should be administered IV (slowly) if methemoglobinemia is greater than 30%.[5]


Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management.


The fatility rate of acetaminophen toxicity is 0.4%[34]

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Product Information and Distribution

Acetaminophen Product Availability Information
Name Manufacturer Dosage Form Strength Quantity NDC Storage
Acetaminophen [54] Watson Oral Tablets 325 mg 1000 00536-3222-10 20-25°C (68-77°F)
100 00536-3222-01
500mg 1000 00536-3231-10
100 00536-3231-01
Acetaminophen Product Availability Information
Name Manufacturer Dosage Form Strength Quantity NDC Storage
Acetaminophen [54] Watson Captabs 325 mg 1000 00536-3218-10 20-25°C (68-77°F)
100 00536-3218-01


Acetaminophen Product Availability Information
Name Manufacturer Dosage Form Strength Quantity NDC Storage
Acetaminophen [54] Watson Childs fruit-chew 80 mg 30 00536-3233-07 20-25°C (68-77°F)
Acetaminophen Product Availability Information
Name Manufacturer Dosage Form Strength Quantity NDC Storage
Acetaminophen [54] Watson Infant Drops Suspension 80 mg/0.8 mL 15 mL 00536-1936-72 20-25°C (68-77°F)
Acetaminophen Product Availability Information
Name Manufacturer Dosage Form Strength Quantity NDC Storage
Acetaminophen[54] Watson Suppositories 120mg 12 00536-1255-12 20-25°C (68-77°F)
325mg 12 00536-1320-12
650 mg 12 00536-1260-12


  • Manufacturers/Distributors
    • Watson
    • G and W Laboratories Inc
    • Rugby Laboratories Division of Watson Pharmaceuticals
    • Ivax Corporation a Division of Teva USA
    • Mutual/United Research Laboratories
    • Leiner Health Products
    • Alpharma USPD Inc
    • Major Pharmaceuticals Inc
    • Leader Brand Products
    • McNeil Consumer Healthcare Div Mcneil Ppc Inc

List may not be all inclusive

  • Inactive ingredients- Inactive Inredients may vary between manufacturer. The following is an example of some of the active ingredients which may be present in a tablet. Please check with the manufacturer to obtain the most complete list of inactive ingredients

Crospovidone, Magnesium stearate, Microcrystalline cellulose, Providone, Pregelatinized starch, Silicon dioxide, Stearic acid

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Pharmacogenomic information

Acetaminophen Pharmacogenomic Information

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Patient Information

  • If symptoms worsen, stop taking this medication
  • If pain persists for more than 10 days contact your health-care professional
  • Contact your healthcare professional if fever persists greater than three days
  • If a body part becomes painful or swollen call your health care professional
  • Report the following side effects to your health care professional right away: rash, hives, itching, swelling of the body, hoarseness, difficulty breathing or swallowing.[3]

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References

  1. ↑ Prescott LF. Paracetamol: past, present, and future. American journal of therapeutics. 2000 Mar;7(2):143-7.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Hardman JG L, LE, editor. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 American society of Health-System Pharmacists Inc. Acetaminophen. The MedMaster™ Patient Drug Information database from Medline Plus; 2006.
  4. ↑ Koch-Weser J. Drug therapy. Acetaminophen. The New England journal of medicine. 1976 Dec 2;295 23:1297-300.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 Mallinckrodt Inc. Hydrocodone Bitartrate and Acetaminophen Tablets USP. St. Louis, Missouri: Mallinckrodt.
  6. ↑ Olson NZ, Otero AM, Marrero I, Tirado S, Cooper S, Doyle G, et al. Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain. J Clin Pharmacol. 2001 Nov;41(11):1238-47.
  7. ↑ Forrest JA, Clements JA, Prescott LF. Clinical pharmacokinetics of paracetamol. Clin Pharmacokinet. 1982 Mar-Apr;7(2):93-107.
  8. ↑ Slattery JT, Levy G. Pharmacokinetic model of acetaminophen elimination. American journal of hospital pharmacy. 1979 Apr;36 4:440.
  9. ↑ Chan MT, Anderson PJ, Chan JC, Lau GS, Critchley JA. Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment. European journal of clinical pharmacology. 1997;52(4):285-8.
  10. ↑ Prescott LF, Speirs GC, Critchley JA, Temple RM, Winney RJ. Paracetamol disposition and metabolite kinetics in patients with chronic renal failure. European journal of clinical pharmacology. 1989;36(3):291-7.
  11. ↑ Benson GD, Koff RS, Tolman KG. The therapeutic use of acetaminophen in patients with liver disease. American journal of therapeutics. 2005 Mar-Apr;12(2):133-41.
  12. ↑ Prescott LF. Paracetamol, alcohol and the liver. Br J Clin Pharmacol. 2000 Apr;49(4):291-301.
  13. ↑ Martin U, Temple RM, Winney RJ, Prescott LF. The disposition of paracetamol and its conjugates during multiple dosing in patients with end-stage renal failure maintained on haemodialysis. European journal of clinical pharmacology. 1993;45(2):141-5.
  14. ↑ Divoll M, Abernethy DR, Ameer B, Greenblatt DJ. Acetaminophen kinetics in the elderly. Clinical pharmacology and therapeutics. 1982 Feb;31(2):151-6.
  15. ↑ Abernethy DR, Divoll M, Greenblatt DJ, Ameer B. Obesity, sex, and acetaminophen disposition. Clinical pharmacology and therapeutics. 1982 Jun;31(6):783-90.
  16. ↑ Dalton JD, Jr., Schweinle JE. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med. 2006 Nov;48(5):615-23.
  17. ↑ Battisti WP, Katz NP, Weaver AL, Matsumoto AK, Kivitz AJ, Polis AB, et al. Pain management in osteoarthritis: a focus on onset of efficacy--a comparison of rofecoxib, celecoxib, acetaminophen, and nabumetone across four clinical trials. J Pain. 2004 Nov;5(9):511-20.
  18. ↑ Kubitzek F, Ziegler G, Gold MS, Liu JM, Ionescu E. Analgesic efficacy of low-dose diclofenac versus paracetamol and placebo in postoperative dental pain. Journal of orofacial pain. 2003 Summer;17(3):237-44.
  19. ↑ Macleod AG, Ashford B, Voltz M, Williams B, Cramond T, Gorta L, et al. Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: a randomized, double-blind, prospective trial. Australian dental journal. 2002 Jun;47(2):147-51.
  20. ↑ Dawood MY, Khan-Dawood FS. Clinical efficacy and differential inhibition of menstrual fluid prostaglandin F2alpha in a randomized, double-blind, crossover treatment with placebo, acetaminophen, and ibuprofen in primary dysmenorrhea. American journal of obstetrics and gynecology. 2007 Jan;196(1):35 e1-5.
  21. ↑ Akin M, Price W, Rodriguez G, Jr., Erasala G, Hurley G, Smith RP. Continuous, low-level, topical heat wrap therapy as compared to acetaminophen for primary dysmenorrhea. The Journal of reproductive medicine. 2004 Sep;49(9):739-45.
  22. ↑ Dlugosz CK, Chater RW, Engle JP. Appropriate use of nonprescription analgesics in pediatric patients. J Pediatr Health Care. 2006 Sep-Oct;20(5):316-25; quiz 26-8.
  23. ↑ Nabulsi MM, Tamim H, Mahfoud Z, Itani M, Sabra R, Chamseddine F, et al. Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study [ISRCTN30487061]. BMC medicine. 2006;4:4.
  24. ↑ Mehlisch DR, Weaver M, Fladung B. Ketoprofen, acetaminophen, and placebo in the treatment of tension headache. Headache. 1998 Sep;38(8):579-89.
  25. ↑ Smalbrugge M, Jongenelis LK, Pot AM, Beekman AT, Eefsting JA. Pain among nursing home patients in the Netherlands: prevalence, course, clinical correlates, recognition and analgesic treatment--an observational cohort study. BMC geriatrics. 2007;7:3.
  26. ↑ Rio J, Nos C, Bonaventura I, Arroyo R, Genis D, Sureda B, et al. Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-1a flu symptoms in MS: a randomized trial. Neurology. 2004 Aug 10;63(3):525-8.
  27. ↑ Temple AR, Benson GD, Zinsenheim JR, Schweinle JE. Multicenter, randomized, double-blind, active-controlled, parallel-group trial of the long-term (6-12 months) safety of acetaminophen in adult patients with osteoarthritis. Clin Ther. 2006 Feb;28(2):222-35.
  28. ↑ Sarzi-Puttini P, Cimmino MA, Scarpa R, Caporali R, Parazzini F, Zaninelli A, et al. Osteoarthritis: an overview of the disease and its treatment strategies. Seminars in arthritis and rheumatism. 2005 Aug;35(1 Suppl 1):1-10.
  29. ↑ Wenzel RG, Sarvis CA, Krause ML. Over-the-counter drugs for acute migraine attacks: literature review and recommendations. Pharmacotherapy. 2003 Apr;23(4):494-505.
  30. ↑ Burk CT, Gilderman A, Salas J, Berenbeim D, Nichol MB. The impact of an over-the-counter migraine medication program on quality of life. Headache. 2003 Mar;43(3):191-201.
  31. ↑ Diener HC, Limmroth V. Analgesics. Current medical research and opinion. 2001;17 Suppl 1:s13-6.
  32. ↑ 32.0 32.1 32.2 32.3 32.4 32.5 32.6 32.7 32.8 32.9 Epocrates Online. Acetaminophen. Epocrates Online; 2006.
  33. ↑ American Academy of Pediatrics (AAP)Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108:776-89.
  34. ↑ 34.0 34.1 Jones A. Over-the-counter analgesics: a toxicology perspective. American journal of therapeutics. 2002 May-Jun;9(3):245-57.
  35. ↑ Wishart DS et al., DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006 1;34
  36. ↑ Smilkstein MJ, Bronstein AC, Linden C, Augenstein WL, Kulig KW, Rumack BH. Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. Ann Emerg Med. 1991 Oct;20(10):1058-63.
  37. ↑ Systemic Therapy Update. BC Cancer Agency 2006;9(5). [cited 14 March 2007].Available from: http://www.bccancer.bc.ca/NR/rdonlyres/4478D9DB-662B-43C2-8839-6D3C374D3FAE/19815/UpdateMay2006final_28Apr06.pdf
  38. ↑ Imatinib mesylate. Am J Health Syst Pharm 2001;58(23):2241-2.
  39. ↑ Nolan CM, Sandblom RE, Thummel KE, Slattery JT, Nelson SD. Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. Chest. 1994 Feb;105(2):408-11.
  40. ↑ Zand R, Nelson SD, Slattery JT, Thummel KE, Kalhorn TF, Adams SP, et al. Inhibition and induction of cytochrome P4502E1-catalyzed oxidation by isoniazid in humans. Clinical pharmacology and therapeutics. 1993 Aug;54(2):142-9.
  41. ↑ Epstein MM, Nelson SD, Slattery JT, Kalhorn TF, Wall RA, Wright JM. Inhibition of the metabolism of paracetamol by isoniazid. Br J Clin Pharmacol. 1991 Feb;31(2):139-42.
  42. ↑ Kiang TK, Ensom MH, Chang TK. UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacology & therapeutics. 2005 Apr;106(1):97-132.
  43. ↑ 43.0 43.1 Depot M, Powell JR, Messenheimer JA, Jr., Cloutier G, Dalton MJ. Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine. Clinical pharmacology and therapeutics. 1990 Oct;48(4):346-55.
  44. ↑ 44.0 44.1 Stephenson I, Qualie M, Wiselka MJ. Hepatic failure and encephalopathy attributed to an interaction between acetaminophen and rifampicin. The American journal of gastroenterology. 2001 Apr;96(4):1310-1.
  45. ↑ 45.0 45.1 Huang R, Okuno H, Takasu M, Takeda S, Kano H, Shiozaki Y, et al. Effects of rifampin on the glutathione depletion and cytochrome c reduction by acetaminophen reactive metabolites in an in vitro P450 enzyme system. Japanese journal of pharmacology. 2000 Jul;83(3):182-90.
  46. ↑ 46.0 46.1 Dimova S, Stoytchev T. Influence of rifampicin on the toxicity and the analgesic effect of acetaminophen. European journal of drug metabolism and pharmacokinetics. 1994 Oct-Dec;19(4):311-7.
  47. ↑ Mahe I, Bertrand N, Drouet L, Bal Dit Sollier C, Simoneau G, Mazoyer E, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006 Dec;91(12):1621-7.
  48. ↑ Dipiro J, Talbert R, Yee G, Matzke G, Wells B, Posey L, editors. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York; 2002.
  49. ↑ Siegers CP, Moller-Hartmann W. Cholestyramine as an antidote against paracetamol-induced hepato- and nephrotoxicity in the rat. Toxicology letters. 1989 May;47(2):179-84.
  50. ↑ Par Pharmaceutical Inc. Questran® and Questran® Light (cholestyramine) package insert. Spring Valley, NY; 2002.
  51. ↑ 51.0 51.1 Burton M, Shaw L, Schentag J, Evans W, editors. Applied Pharmacokinetics and Pharmacodynamics: Principles of therapeutic drug monitoring. 4th ed. Baltimore: Lippincott Williams and Wilkins; 2006.
  52. ↑ Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic & clinical pharmacology & toxicology. 2007 Jan;100(1):23-30.
  53. ↑ 53.0 53.1 Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. Journal of clinical pharmacy and therapeutics. 2002 Dec;27(6):391-401.
  54. ↑ 54.0 54.1 54.2 54.3 54.4 Watson. Product Database. 2007.http://www.watsonpharm.com/products/search_results_products.asp?group=alpha&c=A

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Therapeutic Class Comparison Trial Articles

  1. Dalton JD, Jr., Schweinle JE. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med. 2006 Nov;48(5):615-23.
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Pharmacokinetics Articles

  1. Benson GD, Koff RS, Tolman KG. The therapeutic use of acetaminophen in patients with liver disease. American journal of therapeutics. 2005 Mar-Apr;12(2):133-41.
  2. Chan MT, Anderson PJ, Chan JC, Lau GS, Critchley JA. Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment. European journal of clinical pharmacology. 1997;52(4):285-8.
  3. Prescott LF, Speirs GC, Critchley JA, Temple RM, Winney RJ. Paracetamol disposition and metabolite kinetics in patients with chronic renal failure. European journal of clinical pharmacology. 1989;36(3):291-7.
  4. Martin U, Temple RM, Winney RJ, Prescott LF. The disposition of paracetamol and its conjugates during multiple dosing in patients with end-stage renal failure maintained on haemodialysis. European journal of clinical pharmacology. 1993;45(2):141-5.



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Drug Interaction Articles

  1. Yang F, Beard DA. Thermodynamically based profiling of drug metabolism and drug-drug metabolic interactions: a case study of acetaminophen and ethanol toxic interaction. Biophysical chemistry. 2006 Mar 20;120(2):121-34.
  2. Kiang TK, Ensom MH, Chang TK. UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacology & therapeutics. 2005 Apr;106(1):97-132
  3. Depot M, Powell JR, Messenheimer JA, Jr., Cloutier G, Dalton MJ. Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine. Clinical pharmacology and therapeutics. 1990 Oct;48(4):346-55.
  4. Mahe I, Bertrand N, Drouet L, Bal Dit Sollier C, Simoneau G, Mazoyer E, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006 Dec;91(12):1621-7.
  5. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. Journal of clinical pharmacy and therapeutics. 2002 Dec;27(6):391-401.


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External Links


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