Momodol XR

Paracetamol produces analgesia by peripheral blockage of pain impulse generation. It produces antipyresis by inhibiting the hypothalamic heat regulating centre. Its weak anti inflammatory activity is related to inhibition of prostaglandin (PG) synthesis in the CNS.

Paracetamol (acetaminophen) is thought to act primarily in the CNS, raising the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1 and COX-2, along with COX-3, enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, paracetamol does not inhibit cyclooxygenase in peripheral tissues, so it has no peripheral anti inflammatory effect. Aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site, but studies have found that paracetamol blocks COX indirectly, and that this blockade is ineffective in the presence of peroxides. This may explain why paracetamol is effective in the central nervous system and in endothelial cells but not in platelets and immune cells, which carry high levels of peroxides. Studies also suggest that paracetamol selectively blocks a variant of the COX enzyme distinct from the known COX-1 and COX-2 variants. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, and further research may offer more insight into how it works. The antipyretic properties of paracetamol are likely due to a direct effect on the heat regulating centre of the hypothalamus, resulting in peripheral vasodilation, sweating, and consequent heat loss.

Epidemiological studies during human pregnancy have not shown any harmful effects when Paracetamol is used at the recommended dose, though patients should still follow their doctor's advice about using it. Paracetamol does pass into breast milk, but only in amounts too small to be clinically significant, and the published data available do not point to any reason to avoid breastfeeding.

Pediatric use: Paracetamol IV can be used for acute pain and fever in children aged 2 years and older. This is backed by evidence from adequate and well-controlled studies of Paracetamol IV in adults.

Geriatric use: Elderly patients showed no overall difference in safety or effectiveness compared with younger patients. Other reported clinical experience has not found any difference in response between the two groups either.

Patients with hepatic impairment: Paracetamol must not be given to patients with severe hepatic impairment or severe active liver disease. In patients with hepatic impairment or active liver disease, use it with caution, and a reduced total daily dose of Paracetamol may be warranted.

Patients with renal impairment: In severe renal impairment (creatinine clearance below 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.

Keep in a dry place away from light and heat. Keep out of the reach of children.