Ben-U-Ron

For the treatment of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, period pains, aches and pains, symptomatic relief of rheumatic aches and pains and of influenza, feverishness and feverish colds.

Adults, the elderly and young persons 16 years and over:

2 tablets every 4 hours to a maximum of 8 tablets in 24 hours.

Children 6 - 9 years:

½ tablet every 4 hours to a maximum of 4 doses in 24 hours.

Children 10 - 11 years:

1 tablet every 4 hours to a maximum of 4 doses in 24 hours

Adolescents 12 - 15 years:

1 to 1 ½ tablets every 4 hours to a maximum of 4 doses in 24 hours

Do not give to children aged under 6 years of age.

Hypersensitivity to Ben-U-Ron or any of the constituents.

Care is advised in the administration of Ben-U-Ron to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.

Contains Ben-U-Ron.

Do not take anything else containing Ben-U-Ron while taking this medicine.

Talk to your doctor at once if you take too much of this medicine, even if you feel well. This is because too much Ben-U-Ron can cause delayed, serious liver damage.

Patients should be advised that Ben-U-Ron may cause severe skin reactions. If a skin reaction such as skin reddening, blisters, or rash occurs, they should stop use and seek medical assistance right away.

None known.

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Liver damage is possible in adults who have taken 10g or more of Ben-U-Ron. Ingestion of 5g or more of Ben-U-Ron may lead to liver damage if the patient has risk factors (see below).

Risk Factors

If the patient

a) Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.

Or

b) Regularly consumes ethanol in excess of recommended amounts.

Or

c) Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of Ben-U-Ron overdosage 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.

Management

Immediate treatment is essential in the management of Ben-U-Ron 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, see BNF overdose section.

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma Ben-U-Ron 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 Ben-U-Ron however, the maximum protective effect is obtained up to 8 hours post ingestion.

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.

Mechanisms of Action/Effect

Analgesic - the mechanism of analgesic action has not been fully determined. Ben-U-Ron 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 sensitise pain receptors to mechanical or chemical stimulation.

Antipyretic - Ben-U-Ron probably produces antipyresis by acting centrally on the hypothalamic heat-regulation centre 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.

Absorption and Fate

Ben-U-Ron is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged Ben-U-Ron. The elimination half-life varies from about 1 to 4 hours. 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 Ben-U-Ron overdosage and cause liver damage.

None stated

None known.

Not applicable.