- Approval Id
- bcfd6cf383a65320
- Drug Approval Emc Name
- Paracetamol 500mg Tablets
- Drug Name
- Paracetamol 500mg Tablets
- Company Address
- First Floor, Andrews House, College Road, Guildford, Surrey, GU1 4QB, UK
- Company Website
- https://www.zentiva.co.uk/contact/mi-form
- Company Medical Info Direct Line
- +44 (0)800 090 2408
- Company Medical Info Email
- UKMedInfo@zentiva.com
- Company Customer Care Direct Line
- +44 (0)844 8793 188
- Atc Code
- N02BE01
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Zentiva Pharma UK Limited
12 New Fetter Lane
London
EC4A 1JP
United Kingdom
- Authorisation Number
- PL 17780/0069
- Authorisation Date
- 13 November 2001
- Instruction Authorisation Holder
- Zentiva Pharma UK Limited
12 New Fetter Lane
London
EC4A 1JP
United Kingdom
- Instruction Authorisation Number
- PL 17780/0069
- Instruction Authorisation Date
- 13 November 2001
- Instruction Composition
- Each tablet contains 500 mg of paracetamol.
For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- Tablet.
White capsule shaped tablet with flat edges
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
Paracetamol is a mild analgesic and antipyretic, and is recommended for the treatment of most painful and febrile conditions, for example, headache including migraine, toothache, neuralgia, colds and influenza, sore throat, backache, rheumatic pain and dysmenorrhoea.4.2 Posology and method of administration
\*\*Posology\*\*
Adults, Elderly and Children over 16 years:
Two tablets every four hours as required. Not more than eight tablets in 24 hours Do not take for more than 3 days without consulting your doctor.
These doses should not be given more frequently than every four hours nor should more than four doses be given in any 24 hour period.
\*\*Paediatric population\*\*
Not recommended for children under 10 years of age.
Children aged 10 to 15 years:
One tablet every four to six hours when necessary to a maximum of four doses in 24 hours. Do not take for more than 3 days without consulting your doctor.
These doses should not be repeated more frequently than every four to six hours nor should more than four doses be given in any 24 hour period.
\*\*Method of administration\*\*
For oral administration4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.14.4 Special warnings and precautions for use
\*\*Paediatric population\*\*
Not recommended for children under the age of 10 years.
Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.
Do not exceed the recommended dose.
Do not take for more than 3 days without consulting a doctor.
Do not take with any other paracetamol-containing products.
If symptoms persist consult your doctor.
Keep out of the reach of children.
Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.
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.4.5 Interaction with other medicinal products and other forms of interaction
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see section 4.4).4.6 Fertility, pregnancy and lactation
Pregnancy
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 their doctor regarding its use. 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 if clinically needed however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Breastfeeding
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
Paracetamol has no influence on the ability to drive and use machines.4.8 Undesirable effects
The information below lists reported adverse reactions, ranked using the following frequency classification:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Immune system disorders
Hypersensitivity including skin rash may occur.
Not known: anaphylactic shock; angioedema
Blood and lymphatic system disorders
Not known: blood dyscrasias including thrombocytopenia and agranulocytosis
Skin and subcutaneous disorders
Very rare cases of serious skin reactions have been reported.
Metabolism and nutrition disorders
Not known: high anion gap metabolic acidosis.
Description of selected adverse reactions
\*High anion gap metabolic acidosis\*
Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.
\*\*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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
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:
• is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John's Wort or other drugs that induce liver enzymes, or
• regularly consumes ethanol in excess of recommended amounts, or
• 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, disseminated intravascular coagulation, haemorrhage, hypoglycaemia, cerebral oedema, gastrointestinal bleeding 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. The effectiveness of the antidote declines sharply after this time. 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 24h from ingestion should be discussed with the NPIS or a liver unit.
Further measures will depend on the severity, nature and course of clinical symptoms of paracetamol intoxication and should follow standard intensive care protocols.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
ATC code: N02B E01, Other analgesics and antipyretics
Paracetamol is an effective analgesic and antipyretic agent, but has only weak anti-inflammatory properties. Its mechanism of action is not fully understood. It has been suggested that it may act predominantly by inhibiting prostaglandin synthesis in the 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. Paracetamol probably produces an antipyretic action by a central effect on the hypothalamic heat-regulating 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. The drug has no effect on the cardiovascular and respiratory systems, and unlike salicylates it does not cause gastric irritation or bleeding.5.2 Pharmacokinetic properties
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver (90-95%) and 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 to 4 hours. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.
A minor hydroxylated metabolite (N-acetyl-p-benzoquinoneimine) 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. The time to peak plasma concentration of paracetamol is 0.5 to 2 hours, the time to peak effect 1 to 3 hours and the duration of action 3 to 4 hours.5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
Maize starch
Purified talc
Stearic acid
Povidone
Soluble starch.6.2 Incompatibilities
Not applicable6.3 Shelf life
36 months.6.4 Special precautions for storage
Store in the original package6.5 Nature and contents of container
Polypropylene containers
Pack sizes: 500, 1000, 2500, 5000, 10000
Polyethylene bag contained in cardboard cartons
Pack sizes: 500, 1000, 2500, 5000, 10000
Amber glass bottles or polypropylene bottles
Pack sizes: 50, 100
Blister strips: 35gsm Glassine (pergamin) paper/9 micron soft temper Aluminium foil/250 micron PVC contained in cardboard cartons.
Pack sizes: 4, 6, 12, 16, 24, 30, 32, 48, 50, 60, 96, 100
HDPE Duma containers
Pack size: 4
Not all pack sizes are marketed.6.6 Special precautions for disposal and other handling
Not applicable
- Instruction Content
- ## Composition
Each tablet contains 500 mg of paracetamol.
For the full list of excipients, see section 6.1.
## Pharmaceutical Form
Tablet.
White capsule shaped tablet with flat edges
## Clinical Particulars
4.1 Therapeutic indications
Paracetamol is a mild analgesic and antipyretic, and is recommended for the treatment of most painful and febrile conditions, for example, headache including migraine, toothache, neuralgia, colds and influenza, sore throat, backache, rheumatic pain and dysmenorrhoea.4.2 Posology and method of administration
\*\*Posology\*\*
Adults, Elderly and Children over 16 years:
Two tablets every four hours as required. Not more than eight tablets in 24 hours Do not take for more than 3 days without consulting your doctor.
These doses should not be given more frequently than every four hours nor should more than four doses be given in any 24 hour period.
\*\*Paediatric population\*\*
Not recommended for children under 10 years of age.
Children aged 10 to 15 years:
One tablet every four to six hours when necessary to a maximum of four doses in 24 hours. Do not take for more than 3 days without consulting your doctor.
These doses should not be repeated more frequently than every four to six hours nor should more than four doses be given in any 24 hour period.
\*\*Method of administration\*\*
For oral administration4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.14.4 Special warnings and precautions for use
\*\*Paediatric population\*\*
Not recommended for children under the age of 10 years.
Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.
Do not exceed the recommended dose.
Do not take for more than 3 days without consulting a doctor.
Do not take with any other paracetamol-containing products.
If symptoms persist consult your doctor.
Keep out of the reach of children.
Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.
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.4.5 Interaction with other medicinal products and other forms of interaction
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see section 4.4).4.6 Fertility, pregnancy and lactation
Pregnancy
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 their doctor regarding its use. 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 if clinically needed however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Breastfeeding
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
Paracetamol has no influence on the ability to drive and use machines.4.8 Undesirable effects
The information below lists reported adverse reactions, ranked using the following frequency classification:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Immune system disorders
Hypersensitivity including skin rash may occur.
Not known: anaphylactic shock; angioedema
Blood and lymphatic system disorders
Not known: blood dyscrasias including thrombocytopenia and agranulocytosis
Skin and subcutaneous disorders
Very rare cases of serious skin reactions have been reported.
Metabolism and nutrition disorders
Not known: high anion gap metabolic acidosis.
Description of selected adverse reactions
\*High anion gap metabolic acidosis\*
Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.
\*\*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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
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:
• is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John's Wort or other drugs that induce liver enzymes, or
• regularly consumes ethanol in excess of recommended amounts, or
• 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, disseminated intravascular coagulation, haemorrhage, hypoglycaemia, cerebral oedema, gastrointestinal bleeding 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. The effectiveness of the antidote declines sharply after this time. 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 24h from ingestion should be discussed with the NPIS or a liver unit.
Further measures will depend on the severity, nature and course of clinical symptoms of paracetamol intoxication and should follow standard intensive care protocols.
## Pharmacological Properties
5.1 Pharmacodynamic properties
ATC code: N02B E01, Other analgesics and antipyretics
Paracetamol is an effective analgesic and antipyretic agent, but has only weak anti-inflammatory properties. Its mechanism of action is not fully understood. It has been suggested that it may act predominantly by inhibiting prostaglandin synthesis in the 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. Paracetamol probably produces an antipyretic action by a central effect on the hypothalamic heat-regulating 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. The drug has no effect on the cardiovascular and respiratory systems, and unlike salicylates it does not cause gastric irritation or bleeding.5.2 Pharmacokinetic properties
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver (90-95%) and 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 to 4 hours. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.
A minor hydroxylated metabolite (N-acetyl-p-benzoquinoneimine) 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. The time to peak plasma concentration of paracetamol is 0.5 to 2 hours, the time to peak effect 1 to 3 hours and the duration of action 3 to 4 hours.5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.
## Pharmaceutical Particulars
6.1 List of excipients
Maize starch
Purified talc
Stearic acid
Povidone
Soluble starch.6.2 Incompatibilities
Not applicable6.3 Shelf life
36 months.6.4 Special precautions for storage
Store in the original package6.5 Nature and contents of container
Polypropylene containers
Pack sizes: 500, 1000, 2500, 5000, 10000
Polyethylene bag contained in cardboard cartons
Pack sizes: 500, 1000, 2500, 5000, 10000
Amber glass bottles or polypropylene bottles
Pack sizes: 50, 100
Blister strips: 35gsm Glassine (pergamin) paper/9 micron soft temper Aluminium foil/250 micron PVC contained in cardboard cartons.
Pack sizes: 4, 6, 12, 16, 24, 30, 32, 48, 50, 60, 96, 100
HDPE Duma containers
Pack size: 4
Not all pack sizes are marketed.6.6 Special precautions for disposal and other handling
Not applicable
- Company Detail Path
- /organization/sanofi-ilac-sanayi-ve-ticaret-anonim-sirketi
