Paracetamol 500 Mg Effervescent Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Paracetamol 500 mg Effervescent Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each effervescent tablet contains:
Paracetamol 500mg
For excipients, see 6.1
3 PHARMACEUTICAL FORM
Effervescent Tablets
Round, biplane, white or off-white tablets with facets on both sides.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
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.
4.2 Posology and method of administration
Adults and children over 12 years:
One or two tablets to be taken every four to six hours if necessary. Do not exceed 8 tablets in 24 hours.
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.
4.3 Contraindications
Caution should be taken in patients with impaired kidney or liver function, or previous hypersensitivity to paracetamol or other ingredients.
4.4 Special warnings and precautions for use
Warnings:
The patient must not exceed the stated dose.
This product contains paracetamol.
Precautions for use:
If symptoms persist for more than three days the patient should consult a doctor.
If the patient is pregnant she should consult her doctor before taking this preparation.
Care is advised in the administration of paracetamol-containing products 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.
Patients should be advised not to take other paracetamol-containing products concurrently.
Keep out of the reach of children.
Each tablet contains approximately 392 mg of sodium. This sodium should be taken into account when prescribing for patients on a sodium restricted diet.
Immediate medical advise should be sought in the event of an overdose, even if the patient feels well, because of the risk of delayed, serious liver damage.
Interaction with other medicinal products and other forms of interaction
4.5
Alcohol, barbiturates, anticonvulsants and tricyclic antidepressants may increase the hepatotoxicity of paracetamol, particularly after an overdose.
Chloramphenicol - paracetamol may increase the half-life of Chloramphenicol.
Cholestyramine - may reduce absorption of paracetamol.
Metoclopramide - may potentiate the effect of paracetamol.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding.
4.6 Fertility, Pregnancy and 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 doctor regarding its use.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast-feeding.
4.7 Effects on ability to drive and use machines
No special comment-unlikely to produce an effect.
4.8 Undesirable effects
Paracetamol has been widely used and, when taken at the usual recommended dosage, side effects are mild and infrequent and reports of adverse reactions are rare. Skin rash and other allergic reactions occur rarely.
Most reports of adverse reactions to paracetamol relate to overdosage with the drug.
Isolated cases of thrombocytic purpura, haemolytic anaemia and agranulocytosis have been reported.
Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year and liver damage has been reported after daily ingestion of excessive amounts for shorter periods. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol nor was the control of the disease improved after paracetamol withdrawal.
Nephrotoxic effects following therapeutic doses of paracetamol are uncommon. Papillary necrosis has been reported after prolonged administration.
4.9 Overdose
Symptoms of overdosage:
Pallor, anorexia, nausea, vomiting and abdominal pain are frequent early symptoms of paracetamol overdosage.
Hepatic necrosis is a dose-related complication of paracetamol overdose. Hepatic enzymes may become elevated and prothrombin time prolonged within 12 to 48 hours but clinical symptoms may not be apparent for 1 to 6 days after ingestion. Toxicity is likely in subjects who have taken single doses of 10 g (150 mg/kg) or more. It is considered that excess quantities of toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested) become irreversibly bound to liver tissue.
Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
In paracetamol overdosage with liver cell damage, paracetamol half-life is often prolonged from around 2 hours in normal adults to 4 hours or longer. However liver cell damage has been found in patients with a paracetamol half life less than 4 hours. Diminution of 14CO2 excretion after 14C-aminopyrine has been reported to correlate better with liver cell damage in paracetamol overdosage than do either plasma paracetamol concentration or half-life, or conventional liver function test measurements. Renal failure due to acute tubular necrosis may follow paracetamol-induced fulminant hepatic failure. The incidence of this is, however, no more frequent in these patients than in others with fulminant hepatic failure from other causes.
Therapeutic measures in overdosage:
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 and any patient who had ingested around 7.5 g or more of paracetamol in the preceding 4 hours should undergo gastric lavage.
Administration of oral methionine or intravenous N-acetylcysteine which may have beneficial effect up to at least 48 hours after overdose, may be required. General supportive measures must be available.
5.1 Pharmacodynamic properties
Paracetamol has analgesic and antipyretic effects similar to those of aspirin and is useful in the treatment of mild to moderate pain. It has weak anti-inflammatory effects.
5.2 Pharmacokinetic properties
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 30-90 minutes post dose and the plasma halflife is in the range of 1 to 3 hours after therapeutic doses. Drug is widely distributed throughout most body fluids. Following therapeutic doses 90-100% of the drug is recovered in the urine within 24 hours almost entirely following hepatic conjugation with glucuronic acid (about 60%), sulphuric acid (about 35%) or cysteine (about 3%). Small amounts of hydroxylated and deacetylated metabolites have been detected. Children have less capacity for glucuronidation of the drug than do adults. In overdosage there is increased N-hydroxylation followed by glutathione conjugation. When the latter is exhausted, reaction with hepatic proteins is increased leading to necrosis.
5.3 Preclinical safety data
Acute toxicity
Paracetamol hepatotoxicity is directly dependent on the plasma concentration related to time. Plasma concentrations above 1.2 mmol/l at 4 hours, 0.6 mmol/l at 8 hours and 0.3 mmol/l at 12 hours are criteria for treatment with acetylcysteine to prevent irreversible liver damage.
Chronic toxicity
In animal experiments the subchronic and chronic toxicity of paracetamol occurred in rats and mice as lesions in the gastro-intestinal tract, blood-count changes, degeneration and even necrosis of the hepatic and renal parenchyma. The metabolites that are assumed to have the toxic effects and the organic changes associated with them have been proven in humans as well.
Therefore, paracetamol should not be taken for a long period of time and in excessive doses. Oral daily doses with clearly hepatotoxic effects are around 5.8 g for nonalcoholics, symptoms of intoxication can occur as soon as 3 weeks after administration.
Mutagenic and tumorigenic potential
In mammalian cell cultures paracetamol induces chromosome mutations depending on its concentration. In-vivo tests show negative as well as slightly positive results. Due to the insufficient relevance of the most part of the in-vivo tests no final evaluation is possible at this time.
Long-term studies in rats and mice have yielded no indications of a carcinogenic effect.
Reproductive toxicology
Paracetamol passes the placental barrier. Animal studies and experience to date in humans reveal no evidence of embryotoxicity.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
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 Macrogol 6000
Sodium content approximately 315 mg per tablet.
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
Do not store above 25°C. Keep the container tightly closed.
Nature and contents of container
6.5
Polypropylene tube with polyethylene stopper containing silica gel as desiccant. The tubes are packed into an outer carton.
Pack sizes: 16 / 24 / 32 / 60 / 100.
6.6 Special precautions for disposal
Dissolve tablets in a glass of water prior to intake.
7 MARKETING AUTHORISATION HOLDER
Medley Pharma Limited Unit 2A,
Olympic Way Sefton Business Park Liverpool L30 1RD UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 43870/0010
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
26 February 2002
10 DATE OF REVISION OF THE TEXT
05/01/2015