DETAILED DESCRIPTION : -

Anti-pyretic, Analgesic

Symptomatic treatment of mild to moderate pain including a headache, migraine, neuralgia, toothache, sore throat, menstrual pains, Joint pains (arthritis), pains associated with influenza, fever and feverish colds.

Mechanism of Action

Pharmacodynamics: Mechanism of Action: Analgesic: The mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent, through a peripheral action by blocking pain impulse generation.
The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation.

Antipyretic: Paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat-regulation center to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.

Pharmacokinetics: Absorption and Fate: Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations (C_max) occurring about 30 min to 2 hrs after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged Paracetamol. The elimination half-life (t ) varies from about 1-4 hrs. Plasma protein-binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.
A minor hydroxylated metabolite which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdosage and cause liver damage.

Dosage / Direction for Use

Maximum dose in 24 hours: 6 tablets

Do not exceed the stated dose.

Do not take more frequently than every 4 hours.

Do not take with any other product containing paracetamol.

Not suitable for children under the age of 12 years.

Do not take more than 3 days without medical advice.

Overdosage

Liver damage is possible in adults who have taken 10 g of paracetamol. Ingestion of 5 g of paracetamol may lead to liver damage if the patient has risk factors.
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.

Symptoms: Paracetamol overdosage in the first 24 hrs are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12-48 hrs 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.

Management: Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hr. Plasma paracetamol concentration should be measured at 4 hrs or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hrs after ingestion of paracetamol; however, the maximum protective effect is obtained up to 8 hrs post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetyl cysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside the hospital.

Contraindications

Hypersensitivity to paracetamol or any of the constituents of Paracetamol-650.

Special Precautions

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with the non-cirrhotic alcoholic liver disease.
Do not take more medicine than the label instructed. If the patient did not get better, talk to the physician.
Do not take anything else containing paracetamol while taking Paracetamol-650.
Inform the physician at once if the patient takes too much of Paracetamol-650, even if the patient feels well. This is because too much paracetamol can cause delayed, serious liver damage.
Patients should be advised that paracetamol may cause severe skin reactions. If a skin reaction eg, skin reddening, blisters or rash occur, they should stop use and seek medical assistance right away.

Use In Pregnancy & Lactation

Use in pregnancy & lactation: Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of the physician regarding its use. Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breastfeeding.

Adverse Reactions

Adverse effects of paracetamol are rare. Very rare cases of serious skin reactions have been reported. There have been reports of blood dyscrasias including thrombocytopenia purpura, methemoglobinaemia, and agranulocytosis, but these were not necessarily causality related to paracetamol.

Interactions

Cholestyramine: The speed of absorption of paracetamol is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within 1 hr if maximal analgesia is required.
Metoclopramide and Domperidone: The absorption of paracetamol is increased by metoclopramide and domperidone. However, concurrent use need not be avoided.
Warfarin: The anticoagulant effect of warfarin and other coumarins may be enhanced by the prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Chloramphenicol: Increased plasma concentration of chloramphenicol.

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1^sttrimester (and there is no evidence of a risk in later trimesters).

Storage

Store below 30 C. Protect from light.