Paracetamol 500 mg Effervescent Tablets (PL43870/0012)

For the relief of mild to moderate pain including headache, migraine, neuralgia, toothache, period pain and pain caused by rheumatism.

It is also used to relieve the symptoms of colds, flu and sore throats.

Adults and children over 15 years:

One or two tablets to be taken every four to six hours if necessary. Do not exceed 8 tablets in 24 hours.

Children 12 to 15 years:

Children under 12 years.

Not to be given to children under 12 years.

Elderly patients:

Normal adult dose unless there is impaired kidney or liver function.

Directions:

The tablets must be dissolved in a glass of water. The tablets dissolve more quickly in warm water if stirred.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

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

Contains Paracetamol.

Do not take anything else containing paracetamol 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 paracetamol can cause delayed, serious liver damage.

Patients should be advised that paracetamol 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.

Each tablet contains approximately 315 mg of sodium. This sodium should be taken into account when prescribing for patients on a sodium restricted diet.

Each tablet contains approximately 102mg of lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Caution is advised if paracetamol is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as those using maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.

Cholestyramine: The speed of absorption of paracetamol is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour 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 prolonged regular use of paracetamol with increased risk of bleeding.; occasional doses have no significant effect.

Chloramphenicol: Increased plasma concentration of chloramphenicol.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risks factors (see section 4.4)

Pregnancy

A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.

Breast-feeding

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast-feeding.

None known

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, methaemoglobenaemia and agranulocytosis, but these were not necessarily causally related to Paracetamol.

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 paracetamol. Ingestion of 5g or more of paracetamol 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 paracetamol 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 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, see BNF overdose section.

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.

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.

Pharmacotherapeutic group: Analides, Other Analgesics and Antipyretics. ATC Code: N02B E01

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 sensitise pain receptors to mechanical or chemical stimulation.

Antipyretic – paracetamol 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

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring 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 paracetamol. 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 paracetamol overdosage and cause liver damage.

Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.

Citric acid

Lactose monohydrate

Sodium hydrogen carbonate

Povidone

Simethicone emulsion

Saccharin sodium

Lemon flavour, containing citral, citric acid, ethyl alcohol, lemon oil, lime oil, alpha-tocopherol, triacetine, maltodextrin, gum arabic and sucrose

Sodium content approximately 315 mg per tablet

Not applicable.

3 years.

Polypropylene tube:

Do not store above 25° C. Keep the container tightly closed.

Strip Pack:

Store in the original package in order to protect from moisture.

Polypropylene tube:

Polypropylene tube with polyethylene stopper containing silica gel as desiccant. The tubes are packed into an outer carton.

Pack sizes: 16 / 32 / 60 / 100.

Strip Pack:

4 ply Laminate of Paper / PE Extrusion I Aluminum Foil/I PE Extrusion on both sides of strip.

or

Plain unprinted 4-layer Laminate of Paper/PE/Aluminium Foil/ Surlyn and Aluminium foil, soft dull side laminated to paper and bright side Surlyn Coated

Pack sizes: 32, 60, 100 tablets.

Not all pack sizes may be marketed

None.