ACETAMINOPHEN

OVERVIEW

Paracetamol aka acetaminophen, to relieve pain and reduce fever. It is considered a safer alternative to nonsteroidal anti-inflammatory drugs (NSAIDs) and is available over the counter in a variety of formulations, including tablets, capsules, liquid suspensions, and suppositories.

DOSAGE

Adults

Standard Dose: 500 mg to 1000 mg every 4-6 hours as needed.
Maximum Daily Dose: Do not exceed 3000 mg to 4000 mg in 24 hours, depending on guidelines and individual health considerations.

Children

Standard Dose: 10-15 mg per kg of body weight, given every 4-6 hours as needed.
Maximum Daily Dose: Do not exceed 60 mg per kg in 24 hours.

Formulation: Available as liquid suspension, chewable tablet, or suppository. The dose should be calculated based on the child’s weight.

Paracetamol Dosage
Age	Dose	Frequency
Tablet
Over 16 years	Up to 1000 mg	Max 4 times in 24 hours
12 to 15 years	Up to 750 mg	Max 4 times in 24 hours
10 to 11 years	500 mg	Max 4 times in 24 hours
8 to 9 years	375 mg	Max 4 times in 24 hours
6 to 7 years	250 mg	Max 4 times in 24 hours
Six Plus Syrup
10 to 11 years	10 mL (500 mg)	Max 4 times in 24 hours
8 to 9 years	7.5 mL (375 mg)	Max 4 times in 24 hours
6 to 7 years	5 mL (250 mg)	Max 4 times in 24 hours
Infant Syrup
4 to 5 years	10 mL (240 mg)	Max 4 times in 24 hours
2 to 3 years	7.5 mL (180 mg)	Max 4 times in 24 hours
6 to 23 months	5 mL (120 mg)	Max 4 times in 24 hours
3 to 5 months	2.5 mL (60 mg)	Max 4 times in 24 hours

MECHANISM OF ACTION

Inhibition of prostaglandin synthesis

Paracetamol works primarily by inhibiting the enzyme cyclooxygenase (COX), which is responsible for converting arachidonic acid into prostaglandins. Prostaglandins are mediators of inflammation, pain and fever. This is thought to specifically inhibit COX-2 in the brain, which helps reduce pain and fever without having an anti-inflammatory effect.

Effects on the central nervous system

Paracetamol acts on the central nervous system, particularly the hypothalamus which regulates body temperature. This action contributes to its antipyretic effect.

Modulation of serotonin pathways

Some studies suggest that paracetamol may affect serotonergic pathways in the brain, which may enhance its analgesic (pain-relieving) effects.

Endocannabinoid System Interactions

There is emerging evidence that paracetamol may interact with the endocannabinoid system, which is involved in pain regulation. This interaction may enhance its analgesic properties.

ADVERSE DRUG REACTIONS

Common Adverse Reactions

Gastrointestinal Issues

• Nausea
• Vomiting
• Abdominal pain (rare)

Allergic Reactions

• Skin rashes
• Allergic reactions (e.g., urticaria, angioedema) are rare but occurs.

Serious Adverse Reactions

Liver Damage

• Jaundice (yellowing of the skin and eyes)
• Dark urine
• Pale stools
• Abdominal swelling
• Confusion or lethargy

Kidney Damage

Long-term high doses can contribute to kidney failure.

Hematological Effects

In rare cases, paracetamol can cause blood disorders such as thrombocytopenia (low number of platelets) or leukopenia (low number of white blood cells).

CONTRAINDICATION AND WARNING

Contraindications

Severe Liver Disease

Individuals with severe liver damage or active liver disease should avoid using paracetamol due to the risk of increasing liver damage.

Hypersensitivity

Known allergy to paracetamol or any of its ingredients. Allergic reactions may include skin rashes, urticaria or anaphylaxis.

Warnings

Liver Toxicity

Overdose can cause severe liver damage or acute liver failure. It is important to follow the recommended dosage and avoid combining paracetamol-containing products.

Chronic Alcohol Consumption

People who consume alcohol regularly or excessively have an increased risk of liver toxicity and should use paracetamol with caution.

Malnutrition or Dehydration

Individuals suffering from malnutrition or dehydration may have altered paracetamol metabolism and should use it with caution.

Drug Interactions

Take caution when using other medications that affect liver function or other over-the-counter products containing paracetamol.

Pregnancy and Breastfeeding

Although it is generally considered safe during pregnancy and breastfeeding, it is important to consult a healthcare provider for personalized advice.

Renal Impairment

Use with caution in individuals with renal disease, as metabolism and excretion may be affected.

DRUG-DRUG INTERACTIONS

Anticoagulants

Paracetamol may increase the anticoagulant effect of warfarin, increasing the risk of bleeding. Regular monitoring of INR (International Normalized Ratio) is recommended if both are used together.

Alcohol

Frequent consumption of alcohol with this can increase the risk of liver toxicity. It is advisable to limit alcohol consumption while using paracetamol.

Other Hepatotoxic Drugs

Medicines that can affect liver function (eg, some anticonvulsants such as phenytoin, rifampicin) may increase the risk of liver damage when taken with this.

Certain Antibiotics

Isoniazid may enhance the hepatotoxic effect of paracetamol which increases the risk of liver damage.

Barbiturates

Long-term use of barbiturates may increase the metabolism of paracetamol, increasing the risk of hepatotoxicity.

Probenecid

This medicine may increase the plasma concentration of paracetamol by inhibiting its metabolism and excretion, thereby increasing the risk of toxicity.