ACETAMINOPHEN (Paracetamol, Tylenol): What is used for?

What is Acetaminophen?

 Acetaminophen is an active ingredient used for treatment of fever, pain of mild or moderate intensity.

The brand names of Acetaminophen in United States are: Tylenol, Paracetamol, Panadol, Mapap.

Acetaminophen Mechanism of Action (MOA)

Analgesic and antipyretic. Inhibits the synthesis of prostaglandins in the CNS and blocks the generation of the painful impulse at the peripheral level. It acts on the hypothalamic temperature regulating center.

Therapeutic Indications of Acetaminophen 

– Oral or rectal: fever; pain of any etiology of mild or moderate intensity.
– Intravenous: moderate pain and fever, in the short term, when there is an urgent need or other routes are not possible.

Acetaminophen Dosage

– Oral:
Adults: 1g/6-8 hours or adults and children > 12 years: 500-650 mg/4-6 hours; maximum 4 g/day.
Children from 0 months: 15 mg/kg/6 hours or 10 mg/kg/4 hours.
Kidney failure: Clcr < 10 ml/minute: minimum interval between doses, 8 hours; Clcr 10-15 ml/minute, 6 hours.
Elderly, reduce dose by 25%.

– Rectal: children: 15 mg/kg every 6 hours or 10 mg/kg every 4 hours.
Do not exceed 60 mg/kg for children with weight < 25 kg and 80 mg/kg with weight between 25-37 kg.

Adults and adolescents: 600-1,300 mg/6 hours, maximum 5g/day.

– Intravenous (IV) (15-minute perfusion): dose according to patient weight:

  1. Weight <= 10 kg dose of 7.5 mg/kg or 0.75 ml/kg.
  2. Weight > 10 kg and <= 33 kg dose of 15 mg/kg or 1.5 ml/kg.
  3. Patient weight > 33 kg and <= 50 kg dose of 15 mg/kg or 1.5 ml/kg.
  4. Weight > 50 kg dose of 1 g. or 100 ml.

To avoid dosage errors in newborns and children and confusion between milligrams (mg) and milliliters (ml), it is recommended to specify the desired volume for administration in milliliters.
In newborns and children, very small volumes will be required. With ‚ȧ 10 kg will not be perfused directly from the vial or bag. The volume of paracetamol to be administered should be diluted up to 1/10 in a solution of 0.9% ClNa or 5% glucose and should be administered in continuous perfusion for at least 15 minutes. The minimum interval between each administration of paracetamol IV should be at least 4 hours and no more than 4 doses should be administered in 24 hours. In severe renal insufficiency: minimum interval between doses, 6 hours. With ‚ȧ50 kg, dosage calculations will be made based on weight.

Method of administration of Acetaminophen (Paracetamol)

  • Oralispersible tablet: dissolve in the mouth before being swallowed.
  • Effervescent granules: dissolve in a glass of water, drink when bubbling stops.
  • Oral solution: can be taken diluted in water, milk or fruit juice or directly.
  • Powder for oral solution: take dissolved in water.
  • Granulate for oral solution: dissolve in 1/2 glass of cold water and drink immediately.
  • Suppository: introduce deeply into the rectum. If it is too soft to use, cool it in the refrigerator for 30 minutes or under cold running water before removing the wrap or, if necessary afterwards, to avoid softening. The entire suppository should be used. Do not fraction before administration.

Contraindications of Acetaminophen 

  • Hypersensitivity to acetaminophen (paracetamol), propacetamol hydrochloride (paracetamol prodrug).
  • Severe hepatocellular insufficiency.
  • Viral hepatitis.
  • Recent history of rectitis, anitis, or rectorrhagic (rectal form only).

Warnings and precautions with Acetaminophen

  • Liver failure.
  • Acute hepatitis.
  • Concomitant with substances that affect liver function.
  • Dehydration due to alcohol abuse and chronic malnutrition. Chronic alcoholism.
  • Renal insufficiency.
  • Severe heart failure.
  • Pulmonary diseases.
  • Anemia.
  • Asthmatics sensitive to AAS (cross-reaction).In alcoholics or in case of hepatic insufficiency: do not exceed 2 g paracetamol/day. Children < 3 years.
  • Risk of severe skin reactions such as generalized acute exanthematic pustulosis, Stevens-Johnson s., and toxic epidermal necrolysis, discontinue at the first sign of skin rash or any other sign of hypersensitivity.
  • Toxic pictures associated with paracetamol can be produced either by the ingestion of a single overdose or by several doses with excessive doses.
  • Intravenous use caution in chronic malnutrition and dehydration. To prevent cases of overdose with IV administration it is recommended to prescribe the dose of acetaminophen (paracetamol) in milliliters.
  • In perfusion solutions: fetal anomalies by overdose.

Liver failure

Contraindicated in severe hepatocellular insufficiency.
Caution in case of hepatic insufficiency do not exceed 2 g paracetamol/day and minimum interval between doses, 8 hours.
Acceptable occasional use, but prolonged administration of high doses increases the risk of adverse effects.

Kidney failure

Caution. Acceptable occasional use, but prolonged administration of high doses increases the risk of adverse kidney effects.
Kidney failure: Clcr < 10 ml/min: minimum interval between doses, 8 hours; Clcr 10-15 ml/minute, 6 hours.

Interactions 

  • Increases effect (at doses > 2 g/day) of: oral anticoagulants.
  • Hepatotoxicity enhanced by: alcohol, isoniazid.
  • Decreased bioavailability and potentiation of toxicity by: anticonvulsants.
  • Plasma levels decreased by: estrogens.
  • Decreases effect of: loop diuretics, lamotrigine, zidovudine.
  • Increased action of: probenecid, isoniazid, propranolol.
  • Decreased effect of: anticholinergics, cholestyramine.
  • Increased absorption by: metoclopramide, domperidone.
  • Increased clearance by: rifampicin.
  • May increase toxicity of: chloramphenicol.
  • Lab: blood: increase of glucose, theophylline and uric acid; reduction of glucose by oxidase-peroxidase method.
  • Urine: increases values of metadrenaline and uric acid; false + in determination of 5-hydroxindolacetic acid in tests with the reagent nitrosonaftol. Increases prothrombin time. Suspend 3 days before pancreatic function tests with bentiromide.

Pregnancy and Acetaminophen 

There have been no controlled studies, it has been shown that paracetamol crosses the placenta, so it is recommended not to administer paracetamol except in case of need.
Safety information: There is no evidence of prenatal use of acetaminophen and urogenital impact or neurodevelopmental alterations of the child exposed in utero.
In solutions for perfusion: fetal anomalies by overdose (possible fetal involvement in the context of maternal overdose of acetaminophen/paracetamol).

Breastfeeding

Compatible. Although it is excreted in milk in small amounts, it has not been detected in the urine of infants.
It can be used at therapeutic doses.

Adverse reactions and side effects of Acetaminophen 

Rare: malaise, increased transaminase level, hypotension, hepatotoxicity, rash, haematological alterations, hypoglycemia, sterile pyuria.

Acetaminophen overdose 

Liver failure can lead to death.
Antidote, N-acetylcysteine:

Adults: attack dose: 150 mg/kg IV slow, or diluted in 200 ml dextrose 5% for 15 minutes; maintenance: 50 mg/kg in 500 ml dextrose 5%, 4-hour slow infusion, followed by 100 mg/kg in 1,000 ml dextrose 5%, 16-hour slow infusion.

In children: adjust dextrose volume 5% according to age and weight to avoid pulmonary vascular congestion. Interrupt when blood levels of acetaminophen are < 200 mcg/ml.

Maximum effectiveness of the antidote within 4 hours of intoxication; ineffective from 15 hours.

– Oral: administer N-acetylcysteine within 10 hours. Adults, initial 140 mg/kg + 17 doses of 70 mg/kg, one every 4 hours. Dilute each dose to 5% in cola drink, orange juice or water.
In perfusion solutions: fetal anomalies by overdose (possible fetal involvement in the context of maternal overdose of acetaminophen/paracetamol).

‚≠ź‚≠ź‚≠ź‚≠ź‚≠ź VIDEO OF ACETAMINOPHEN/PARACETAMOL, TYLENOL (DRUG)

Source: The content of this active ingredient has been written taking into account the clinical and molecular information of all medicines authorised and marketed in the United States under the Unique Ingredient Identifier (UNII) by the Substance Registration System (SRS) of the Food and Drug Administration (FDA) and the United States Pharmacopeia (USP).

In order to know in detail the information authorized by the FDA for each drug, you should consult the corresponding medication guide authorized by the FDA.

Resources:

UNII: 362O9ITL9D
ChemIDplus
DrugPortal
PubChem CID: 1983
NCI Thesaurus: C198

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