Paracetamol 500mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Doans Tablets 500mg Paracetamol Tablets 500mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient: Paracetamol 500mg.
3 PHARMACEUTICAL FORM
Tablet.
White to off-white caplets plain on both sides. These tablets are for oral administration.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
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. Symptomatic relief of influenza, feverishness, feverish colds.
4.2 Posology and method of administration
Posology
Adults, the elderly and children 16 years and over: One or two tablets to be taken up to four times daily. Maximum dose of 8 tablets in 24 hours.
Children 10 to 15 years of age: One tablet to be taken for every 4-6 hours when necessary to a maximum of 4 doses in 24 hours.
Children under 10 years of age: Not recommended. Alternative presentations of paracetamol are recommended for paediatric usage in order to obtain suitable doses of less than 500mg.
Dosage instruction
Dose should not be repeated more frequently than 4 hour intervals.
- Not more than 4 doses should be administered in any 24 hour period.
- Dosage should not be continued for more than 3 days without consulting a doctor.
Method of Administration For oral administration.
4.3 Contraindications
Hypersensitivity to paracetamol or any other ingredients. Patients with impaired liver or kidney function and patients taking other drugs that affect the liver. Alcoholics could be at risk in taking paracetamol. The hazard of overdose is greater in those with non-cirrhotic liver disease.
4.4 Special warnings and precautions for use
(i) Do not exceed the stated dose. Where analgesics are used long-term (>3 months) with administration every two days or more frequently, headache may develop or worsen. Headache induced by overuse of analgesics (MOH medication-overuse headache) should not be treated by dose increase. In such cases, the use of analgesics should be discontinued in consultation with the doctor.
(ii) Consult a doctor if symptoms persist.
(iii) Ask the doctor or pharmacist about taking the tablets if they are already on a course of medication.
(iv) This product contains paracetamol.
(v) Do not take with other paracetamol- containing products.
(vi) Immediate medical advice should be sought in the event of an overdose even if you feel well, because of the risk of delayed serious liver damage.
(vii) Care is advised in the administration of paracetamol to patients with alcohol dependency (see section 4.9), severe renal or severe hepatic impairment. The hazards of1 overdose are greater in those with alcoholic liver disease.
(viii) Keep out of the sight and reach of children.
4.5 Interaction with other medicinal products and other forms of interaction
Alcohol reduces liver capacity to deal with paracetamol.
Anticoagulants - the 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.
Metoclopramide and domperidone - may increase speed of absorption of paracetamol.
Colestyramine - may reduce absorption if given within one hour of paracetamol.
Imatinib - restriction or avoidance of concomitant regular paracetamol use should be taken with imatinib.
May interact with chloramphenicol causing increased plasma levels.
4.6 Fertility, pregnancy and lactation
Pregnancy:
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol being used in the recommended dosage, paracetamol should be avoided in pregnancy unless considered essential by the physician
Breast-feeding:
Paracetamol is excreted in breast milk but not in clinically significant quantities. Available published data do not contraindicate breast-feeding.
4.7 Effects on ability to drive and use machines
None.
4.8 Undesirable effects
Allergic reactions and sensitivity are rare but may include skin rashes, drug fever and mucosal lesions. There have been reports of blood dyscrasias including thrombocytopenia, neutropenia, pancytopenia, leukopenia and agranulocytosis and/or acute pancreatitis, but these were not necessarily causally related to paracetamol. At the recommended dosages drowsiness, impairment of mental function and methaemoglobinaemia have been seen.
Very rare cases of serious skin reactions have been reported.
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; website: www.mhra.gov.uk/yellowcard
4.9 Overdose
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, coma 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.
Liver damage is likely in adults who have taken 10 g 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, phenobarbital, phenytoin, primidone, rifampicin, St John's Wort or other drugs than induce liver enzymes.
Or
B, Regularly consumes ethanol in excess of recommended amounts.
Or
C, Is likely to be glutathione depleted e.g. eating disorders, cystic fibrosis, HIV, starvation, cachexia.
It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are employed) become irreversibly bound to liver tissue.
Management:
Prompt treatment is essential in the management of paracetamol over dosage. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention.
Any patient who has ingested about 7.5 g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Specific therapy with an antidote such as acetylcysteine or methionine may be necessary.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour.
Acetylcysteine may be given either intravenously or by mouth or methionine may be given by mouth within 10 - 12 hours of ingestion of the overdose.
Cysteamine was also formerly used.
Generally, treatment is required if the blood-paracetamol concentration is higher than a line (the ‘200' line) drawn on semi-log/linear paper joining the points 200 mg per litre (1.32 mmol. per litre) at 4 hours and 30 mg per litre (0.20 mmol. per litre) at 15 hours.
The effectiveness of the antidote declines sharply after this time.
Determination of the concentration before 4 hours is not considered to give a reliable measurement and administration of acetylcysteine or methionine more than 15 hours after overdose is generally ineffective and may be associated with an exacerbation of any liver abnormality. 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 24h from ingestion should be discussed with the NPIS or a liver unit.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesic and Antipyretic, ATC code: N02BE01
Paracetamol is an effective analgesic and antipyretic agent but has only weak antiinflammatory properties.
Mechanism of action:
Its mechanism of action is not fully understood, as it is only a weak inhibitor of prostaglandin bio-synthesis, but it has been suggested that it is more effective against enzymes in the CNS than those in the periphery. The drug has no effect on the cardiovascular and respiratory systems, and it does not cause gastric irritation or bleeding like salicylates.
5.2 Pharmacokinetic properties
Absorption :
Paracetamol is readily absorbed from the gastro-intestinal tract.
Distribution:
Peak plasma concentrations occurring 30 minutes to 2 hours after ingestion. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentration
Metabolism:
It is metabolised in the liver. 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.
Elimination:
It is excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than
5 % is excreted as unchanged paracetamol. The elimination half life varies from about 1-4 hours.
5.3 Preclinical safety data
There is no pre-clinical data of relevance to a prescriber, which is additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize starch, Povidone K-30, Sodium metabisulphite, Sodium Starch Glycollate, Colloidal Anhydrous Silica, Magnesium stearate.
6.2 Incompatibilities
None stated.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a dry place. Do not store above 25°C.Store in original package- for blister pack.
6.5 Nature and contents of container
Child resistant blister packs of 4, 8, 16, 24, 32, 50, 60, 84, 96 and 100 tablets.
Tamper evident bottle 4, 8, 16, 100, 250, 500 and 1000 tablets.
Specification details of blister packs:
- PVC (white, rigid, opaque): 250 microns
- PVC/ Aluminium foil (hard tempered): 15/ 20 microns
- Primer (nitrocellulose): 1.5-2.5 gsm
- Heat seal lacquer: 6.5 - 8.5 gsm
6.6 Special precautions for disposal
No special precautions required.
7 MARKETING AUTHORISATION HOLDER
JCSH Pharma Ltd
47 Bloomfield Close, Knaphill, Woking, Surrey GU21 2BL United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL46447/0005
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
2nd February 2005
10 DATE OF REVISION OF THE TEXT