Paracetamol 500mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Paracetamol 500mg Tablets Paracetamol 500mg Caplets Boots Paracetamol 500mg Caplets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Paracetamol 500 mg.
Excipient with known effect: Also contains 0.56mg of Sodium metabisulfite.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
White, capsule shaped tablet with a break-line on one face.
The break line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of most painful and febrile conditions for example headache including migraine and tension headaches neuralgia, toothache, sore throat, period pains, aches and pains. .Also recommended for symptomatic relief of rheumatic aches and pains and the fever, aches and pains of cold and flu.
4.2 Posology and method of administration
For oral administration.
Adults, the elderly and children over 12 years:
2 tablets up to four times daily as required
Children 6 to 12 years of age:
Half to one tablet three or four times daily as required..
Children under 6 years of age:
Do not give to children aged under 6 years of age.
The dose should not be repeated more frequently than every 4 hours, and not more than 4 doses should be taken in any 24 hour period.
Children should not be given Paracetamol for more than 3 days without consulting a doctor.
4.3. Contra-indications
Hypersensitivity to paracetamol or to any of the excipients listed in section 6.1
4.4 Special warnings and special precautions for use
Prolonged or frequent use is discouraged. Patients should be advised not to take other Paracetamol containing products concurrently. Taking multiple daily doses in one administration can severely damage the liver; in such case unconsciousness does not occur. However, medical assistance should be sought immediately. Prolonged use except under medical supervision may be harmful. In adolescents treated with 60mg/kg daily of Paracetamol, the combination with another antipyretic is not justified except in the case of ineffectiveness.
Caution is advised in the administration of Paracetamol to patients with moderate and severe renal insufficiency, mild to moderate hepatic insufficiency (including Gilbert's syndrome), severe hepatic insufficiency (child-pugh>9), acute hepatitis, concomitant treatment with medicinal products affecting hepatic functions, glucose-6-phosphatedehydrogenase deficiency, hemolytic anemia, alcohol abuse dehydration and chronic malnutrition (see section 4.2).
The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease. Caution should be exercised in cases of chronic alcoholism. The daily dose should not exceed 2 grams in such case. Alcohol should not be used during the treatment with Paracetamol.
Caution is advised in asthmatic patients sensitive to aspirin, because light reaction bronchospasm with paracetamol (cross-reaction) has been reported in less than 5% of the patients tested.
In the case of high fever, or signs of secondary infection or persistence of symptoms a doctor should be consulted.
Do not exceed the stated dose.
Patients should be advised to consult their doctor if their headaches become persistent.
Patients should be advised not to take other paracetamol-containing products concurrently.
Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day.
If symptoms persist consult your doctor.
Keep out of the reach and sight of children.
Pack Label:
These words must appear in a prominent position.
“Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor”. This must appear adjacent to either the directions for use or the recommended dosage.
“Do not take anything else containing paracetamol while taking this medicine”.
Patient. Information Leaflet:
Talk to a 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”.
Important information regarding the ingredients of this medicine
This medicinal product contains sodium metabisulfite which may rarely cause severe hypersensitivity reactions and bronchospasm.
4.5 Interaction with other medicinal products and other forms of interaction
Hepatotoxic substances may increase the possibility of Paracetamol accumulation and overdose. The risk of hepatotoxicity of paracetamol may be increased by drugs which induce liver microsomal enzymes such as barbiturates, tricyclic antidepressants, and alcohol.
Probenecid causes an almost 2-fold reduction in clearance of Paracetamol by inhibiting its conjugation with glucuronid acid. A reduction of the Paracetamol dose should be considered for concomitant treatment with probenecid.
Salicylamide may prolong the elimination t1/2 of Paracetamol
Colestyramine: The speed of absorption of paracetamol is reduced by colestyramine..
Metoclopramide and Domperidone: The speed of absorption of paracetamol is increased by metoclopramide and domperidone
Warfarin and other anticoagulants: Concomitant use of Paracetamol (4 g per day for at least 4 days) with oral anticoagulants may lead to slight variations of INR values. In this case, increased monitoring of INR values should be done during the duration of the combination and after its discontinuation. 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.
Isoniazid: Reduction of paracetamol clearance, with possible potentiation of its action and/or toxicity, by inhibiting its metabolism in the liver.
Lamotrigine: Decrease in the bioavailability of lamotrigine, with possible reduction of its effect, due to possible induction of its metabolism in the liver.
Interference with laboratory tests: Paracetamol may affect uric acid tests by wolframatop phosphoric acid, and blood sugar tests by glucose-oxydase-peroxydase.
4.6 Fertility, pregnancy and lactation
Pregnancy:
Epidemiological data on the oral administration of therapeutic doses of Paracetamol indicate no adverse effects on pregnancy or on the health of the fetus/newborn child. Prospective data on overdose during pregnancy showed no increased risk of malformations. Reproduction studies investigating oral administration did not indicate any signs of malformation or fetotoxicity (see section 5.3).
Paracetamol is considered to be safe in normal therapeutic doses for short-term use as a minor analgesic/antipyretic in pregnancy.
Lactation:
Following oral administration, Paracetamol is excreted into breast milk in small quantities. To date, no adverse reactions or undesirable effects are known in association with lactation. Therapeutic doses of Paracetamol can be administered during breast-feeding.
4.7. Effects on Ability to Drive and Use Machines
Paracetamol has no influence on the ability to drive and use machines.
4.8 Undesirable effects
The frequency using the following convention: very common (> 1/10); common (>1/100 to < 1/10); uncommon (>1/1000 to < 1/100); rare (>1/10000 to < 1/1000); very rare (< 1/10000), including isolated reports; not known: frequency cannot be estimated from the available data. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
|
Frequency |
System |
Symptoms |
|
Rare |
Blood and lymphatic system |
Platelet disorders, stem cell |
|
>1/10000 - < 1/1000 |
disorders |
disorders. |
|
Immune system disorders |
Allergies (excluding angioedema). | |
|
Psychiatric disorders |
Depression NOS, confusion, hallucinations. | |
|
Nervous system disorders |
Tremor NOS, headache NOS. | |
|
Eye disorders |
Abnormal vision. | |
|
Cardiac disorders |
Oedema. | |
|
Gastrointestinal disorders |
Haemorrhage NOS, abdominal pain NOS, diarrhoea NOS, nausea, vomiting. | |
|
Hepato-biliary disorders |
Hepatic function abnormal, hepatic failure, hepatic necrosis, jaundice. | |
|
Skin and subcutaneous tissue |
Pruritus, rash, sweating, purpura, | |
|
disorders |
angioedema, urticaria. Very rare cases of serious skin reactions have been reported. | |
|
General disorders and |
Dizziness (excluding vertigo), | |
|
administration site conditions |
malaise, pyrexia, sedation, drug interaction NOS. | |
|
Injury, poisoning and procedural complications |
Overdose and poisoning | |
|
Very Rare |
Hepato-biliary disorders |
hepatotoxicity |
|
(< 10 000) |
General disorders and |
hypersensitivity reaction (requiring |
|
administration site conditions |
discontinuation of treatment) | |
|
Blood and lymphatic system |
thrombocytopenia | |
|
disorders |
leukopenia neutropenia hemolytic anemia agranulocytosis | |
|
Metabolism and nutrition disorders |
Hypoglycaemia |
|
Renal and urinary disorders |
Sterile pyuria (cloudy urine) and renal side effects | |
|
Not known: Some cases of edema of the larynx, anap |
lylactic shock, anaemia, | |
bronchospasm*, liver alteration and hepatitis, renal alteration (severe renal impairment, nephrite interstitial, haematuria, anuresis), gastrointestinal effects and vertigo have been reported.
* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
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.
4.9 Overdose
There is a risk of poisoning, particularly in elderly subjects, in young adolescents, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition. Overdosing may be fatal.
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 hrs 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 hr. 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 hrs after ingestion of paracetamol however, the maximum protective effect is obtained upto 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.
5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties
ATC Code: N02B E01
Pharmacotherapeutic Group: Antipyretic analgesic
Mechanism of Action/ Effect
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 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.
5.2. Pharmacokinetic Properties
Absorption
The absorption of paracetamol by the oral route is rapid and complete. Maximum plasma concentrations are reached 30 to 60 minutes following ingestion.
Distribution
Paracetamol is distributed rapidly throughout all tissues. Concentrations are comparable in blood, saliva and plasma. Protein binding is low.
Metabolism
Paracetamol is metabolized mainly in the liver following two major metabolic pathways: glucuronic acid and sulphuric acid conjugates. The latter route is rapidly saturated at doses higher than the therapeutic dose. A minor route, catalyzed by the cytochrome P450, results in the formation of an intermediate reagent (N-acetyl-p-benzoquinoneimine) which under normal conditions of use is rapidly detoxified by glutathione and eliminated in the urine, after conjugation with cystein and mercaptopuric acid. Conversely, when massive intoxication occurs, the quantity of this toxic metabolite is increased.
Elimination
Elimination is essentially through the urine. 90% of the ingested dose is eliminated via the kidneys within 24 hours, principally as glucuronide (60 to 80%) and sulphate conjugates (20 to 30%). Less than 5% is eliminated in unchanged form.
Elimination half life is about 2 hours.
Renal Insufficiency: In cases of severe renal insufficiency (creatinine clearance lower than 10 ml/min) the elimination of paracetamol and its metabolites is delayed.
Elderly Subjects-The capacity for conjugation is not modified.
5.3. Preclinical Safety Data
No data of relevance which is additional to that already included in other sections of the SPC.
6. PHARMACEUTICAL PARTICULARS 6.1. List of excipients
Pregelatinised Maize Starch Sodium Metabisulfite Magnesium Stearate
6.2 Incompatibilities
Not applicable.
6.3. Shelf life
5 years.
6.4 Special precautions for storage
Blisters: Do not store above 25°C. Store in the original package in order to
protect from moisture.
Containers: Do not store above 25°C. Keep the container tightly closed in order
to protect from moisture.
6.5 Nature and contents of container
Al/PVC child resistant blisters enclosed in an outer carton.
Pack sizes: 8, 12, 16, 24, 30, 32, 100 tablets HDPE tablet containers.
OR
Child resistant and adult accessible PP container with HDPE lid
Pack sizes: 16, 1000 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7. MARKETING AUTHORISATION HOLDER
Bristol Laboratories Ltd Unit 3, Canalside, Northbridge Road, Berkhamsted, Hertfordshire HP4 1EG
United Kingdom
PL 17907/0001
9
10
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
02/12/2008
DATE OF REVISION OF THE TEXT
24/03/2016