Paracetamol is used to relieve fever and symptoms of the common cold and influenza. It is also effective in managing various types of pain, including headache, toothache, earache, body aches, muscle pain (myalgia), nerve pain (neuralgia), menstrual pain (dysmenorrhoea), sprains, colic pain, back pain, post-operative pain, postpartum pain, inflammatory pain, and post vaccination pain in children. Additionally, it is indicated for reducing pain and joint stiffness associated with rheumatic conditions and osteoarthritis.

Paracetamol exerts its analgesic effect by blocking the generation of pain impulses at the peripheral level and by increasing the pain threshold through actions within the central nervous system (CNS). Its antipyretic effect results from inhibition of the hypothalamic heat-regulating center, leading to heat loss through vasodilation and sweating.

The drug primarily acts in the CNS by inhibiting cyclooxygenase (COX) enzymes—COX-1, COX-2, and possibly COX-3—involved in prostaglandin synthesis. Unlike nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol has minimal effect on peripheral COX enzymes and therefore exhibits weak anti-inflammatory activity. Evidence suggests that, rather than directly blocking the active site of COX like aspirin, paracetamol inhibits the enzyme indirectly, and this effect is reduced in the presence of high peroxide levels. This may explain its limited action in peripheral tissues such as platelets and immune cells, but effective activity in the CNS and endothelial cells. Some studies also indicate selective inhibition of a COX variant (COX-3), although its exact mechanism of action remains not fully understood and requires further research.

Tablet:

• Adult: 1-2 tablets every 4 to 6 hours up to a maximum of 4 gm (8 tablets) daily.
• Children (6-12 years): ½ to 1 tablet 3 to 4 times daily. For long term treatment it is wise not to exceed the dose beyond 2.6 gm/day.

Extended Release Tablet:

• Adults & Children over 12 years: Two tablets, swallowed whole, every 6 to 8 hours (maximum of 6 tablets in any 24 hours).The tablet must not be crushed.

Syrup/Suspension:

• Children under 3 months: 10 mg/kg body weight (reduce to 5 mg/kg if jaundiced) 3 to 4 times daily.
• 3 months to below 1 year: ½ to 1 teaspoonful 3 to 4 times daily.
• 1-5 years: 1-2 teaspoonful 3 to 4 times daily.
• 6-12 years: 2-4 teaspoonful 3 to 4 times daily.
• Adults: 4-8 teaspoonful 3 to 4 times daily.

Suppository:

• Children 3-12 months: 60-120 mg,4 times daily.
• Children 1-5 years: 125-250 mg 4 times daily.
• Children 6-12 years: 250-500 mg 4 times daily.
• Adults & children over 12 years: 0.5-1 gm 4 times daily.

Paediatric Drop:

• Children Upto 3 months: 0.5 ml (40 mg)
• 4 to 11 months: 1.0 ml (80 mg)
• 7 to 2 years: 1.5 ml (120 mg). Do not exceed more than 5 dose daily for a maximum of 5 days.

Tablet with actizorb technology: It dissolves up to five times faster than standard Paracetamol tablets. It is a fast acting and safe analgesic with marked antipyretic property. It is specially suitable for patients who, for any reason, can not tolerate aspirin or other analgesics.

• Adults and children (aged 12 years and over): Take 1 to 2 Tablets every four to six hours as needed. Do not take more than 8 caplets in 24 hours.
• Children (7 to 11 years): Take ½-1 Tablet every four to six hours as needed. Do not take more than 4 caplets in 24 hours. Not recommended in children under 7 years.

IV Infusion:

• Adults and adolescents weighing 50 kg and over: the recommended dosage of Paracetamol IV is 1000 mg every 6 hours or 650 mg every 4 hours, with a maximum single dose of Paracetamol IV of 1000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 4000 mg per day.
• Adults and adolescents weighing under 50 kg: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.
• Children >2 to 12 years of age: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.

Patients taking barbiturates, tricyclic antidepressants, or alcohol may have a reduced ability to metabolize large doses of paracetamol. Alcohol consumption can also increase the risk of liver toxicity, especially in cases of overdose. Additionally, chronic use of anticonvulsants or oral contraceptive steroids may induce liver enzymes, leading to increased metabolism and clearance of paracetamol, which can reduce its therapeutic effectiveness.

It is contraindicated in known hypersensitivity to Paracetamol.

Paracetamol is generally well tolerated, and its side effects are usually mild. However, rare haematological reactions such as thrombocytopenia, leucopenia, pancytopenia, neutropenia, and agranulocytosis have been reported. Occasional adverse effects may also include pancreatitis, skin rashes, and other allergic reactions.

Epidemiological studies in pregnant women have shown no harmful effects when paracetamol is used at recommended doses; however, its use should be guided by a physician’s advice. Paracetamol is excreted into breast milk in small amounts that are not clinically significant, and available evidence does not contraindicate its use during breastfeeding.

Paracetamol should be used with caution in patients with severe renal or hepatic impairment. The risk of overdose is higher in individuals with non-cirrhotic alcoholic liver disease. Patients should not exceed the recommended dose and should avoid taking other products containing paracetamol at the same time. This medication should be used only by the person for whom it is prescribed and only when clearly necessary.

Exceeding the recommended dose may lead to serious liver injury, including severe hepatotoxicity and possible death. Extra caution is advised in patients with hepatic impairment or active liver disease, chronic alcohol use, malnutrition, severe hypovolemia (such as from dehydration or blood loss), or significant renal impairment (creatinine clearance <30 ml/min). Although rare, serious hypersensitivity reactions, including life-threatening anaphylaxis, have been reported. If signs of an allergic reaction occur, paracetamol (especially intravenous forms) should be discontinued immediately, and it should not be used in patients with known hypersensitivity to the drug.

Pediatric Use: The safety and effectiveness of Paracetamol IV for the treatment of acute pain and fever in pediatric patients ages 2 years and older is supported by evidence from adequate and well-controlled studies of Paracetamol IV in adults.

Geriatric use: No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Patients with Hepatic Impairment: Paracetamol is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease. A reduced total daily dose of Paracetamol may be warranted.

Patients with Renal Impairment: In cases of severe renal impairment (creatinine clearance < 30 ml/min), longer dosing intervals and a reduced total daily dose of Paracetamol may be warranted.

Liver damage is possible in adults who have taken 10 g or more of Paracetamol. Ingestion of 5 g or more of Paracetamol may lead to liver damage if the patient has following risk factors: If the patient is on long term treatment with Carbamazepine, Phenobarbitone, Phenytoin, Primidone, Rifampicin, St John’s Wort or other drugs that induce liver enzymes, or regularly consumes Ethanol in excess of recommended amounts, or is likely to be Glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms: Symptoms of Paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported. Immediate treatment is essential in the management of Paracetamol overdose. Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma Paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of Paracetamol. However, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral Methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be discussed with the NPIS or a liver unit.

Non-Opioid Analgesics

Store in a dry place, protected from light and heat. Keep out of reach of children.