- Approval Id
- a95d42299c8734a6
- Drug Approval Emc Name
- Paracetamol 500mg capsule shaped tablets
- Drug Name
- Paracetamol 500mg capsule shaped tablets
- Company Name
- Ipca Laboratories UK Ltd
- Company Address
- Silverbriar, Enterprise Park East, Sunderland,, Tyne and Wear, SR5 2TQ, UK
- Company Website
- http://www.ipca.com
- Company Telephone
- +44 (0)7546 801 411
- Company Medical Info Direct Line
- 08003685328
- Company Medical Info Email
- pharmacovigilance.mumbai@ipca.com
- Company Customer Care Direct Line
- 08003685328
- Company Stock Availability
- +44(0)7546 801 411
- Atc Code
- N02BE01
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Ipca Laboratories UK Ltd.
Unit 97-98, Silverbriar,
Sunderland Enterprise Park East,
Sunderland, SR5 2TQ, United Kingdom
- Authorisation Number
- PL 28278/0015
- Authorisation Date
- 04/07/2019
- Instruction Authorisation Holder
- Ipca Laboratories UK Ltd.
Unit 97-98, Silverbriar,
Sunderland Enterprise Park East,
Sunderland, SR5 2TQ, United Kingdom
- Instruction Authorisation Number
- PL 28278/0015
- Instruction Authorisation Date
- 04/07/2019
- Instruction Composition
- Each tablet contains Paracetamol 500 mg
For a full list of excipients, see section 6.1.
- Instruction Dosage Form
- Tablet
White to off white capsule shaped uncoated tablets with breakline on one side and plain on other side.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
Headache including migraine and tension headaches, toothache, backache, rheumatic and muscle pains, dysmenorrhoea, sore throat, and for relieving the fever, aches and pains of colds and flu. Also recommended for the symptomatic relief of pain due to non-serious arthritis.4.2 Posology and method of administration
Adults, the elderly, and children aged 16 years and over:
One or two tablets every 4-6 hours , if you need to. Do not take more than 8 tablets in any 24 hours.
Children:
Aged 10 - 15 years:
One tablet every 4-6 hours, if you need to. Do not take more than 4 tablets in any 24 hours.
Do not give children under 10 years of age.
Children should not be given Paracetmol 500mg tablets for more than 3 days without consulting a doctor.
These doses should not be repeated more frequently than every four hours nor should more than four doses be given in any 24 hour period.
Oral administration only.4.3 Contraindications
Hypersensitivity to paracetamol or any of the constituents.4.4 Special warnings and precautions for use
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.
Caution should be exercised in asthma patients who are sensitive to acetylsalicylic acid, since mild reactions of bronchospasm have been reported with paracetamol (cross-reaction).
In patients with glutathione-depleted conditions such as sepsis, the use of paracetamol may increase the risk of metabolic acidosis.
Caution in liver disease. Do not combine with other analgesic drugs containing paracetamol (eg combination medicine). Higher doses than recommended may result in very severe liver damage. Clinical signs of liver injury usually start after a couple of days and usually culminate in 4-6 days. Antidote should be given as early as possible. See also section 4.9 Overdose. In case of high fever, signs of secondary infection or if the symptoms last longer than 3 days, treatment should be reassessed.4.5 Interaction with other medicinal products and other forms of interaction
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)
Studies have shown that the effect of warfarin may be enhanced during treatment with paracetamol. The effect appears to increase with the dose of paracetamol but may occur at doses of 1.5-2.0 g of paracetamol per day for at least 5-7 days. Single doses of paracetamol in normal dosage are considered to have no effect.
Pharmacokinetic interactions
Enzyme-inducing drugs, such as certain antiepileptics (phenytoin, phenobarbital, carbamazepine) have been shown to decrease to approximately 60% of plasma AUC of paracetamol in pharmacokinetic studies. Other substances with enzyme inducing properties, eg rifampicin and St. John's Wort (Hypericum) are also suspected of lowering paracetamol concentrations. In addition, the risk may be greater for liver injury when treated with the maximum recommended dose of paracetamol in patients on enzyme inducing drugs.
Probenecid almost halves the clearance of paracetamol by inhibiting its conjugation with glucuronic acid. This would mean that the dose of paracetamol may be halved when co-administered with probenecid.
The absorption rate of paracetamol may be increased by metoclopramide, but the substances can be given in combination. The absorption of paracetamol is reduced by cholestyramine. Colestyramine should not be given within one hour if maximum analgesic effect is to be achieved.
Paracetamol may affect the pharmacokinetics of chloramphenicol. Therefore, plasma-based chloramphenicol is recommended for combination therapy.4.6 Fertility, pregnancy and lactation
Pregnancy: No known risks during use during pregnancy. A large amount of data from pregnant women indicates neither malformations, fetal toxicity nor neonatal toxicity. Paracetamol may be used during pregnancy if clinically motivated, but it should be used with the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Lactation: Paracetamol passes into breast milk but the risk of affecting the child seems unlikely with therapeutic doses.4.7 Effects on ability to drive and use machines
Paracetamol has no or negligible effect on the ability to drive and use machines.4.8 Undesirable effects
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 causality related to paracetamol.
| | |
| --- | --- |
| Blood and lymphatic system disorders Very rare (<1/10 000) | Thrombocytopenia Agranulocytosis |
| Immune system disorders Very rare (<1/10 000) | Anaphylaxis |
| Respiratory, thoracic and mediastinal disorders Very rare (<1/10 000) | Bronchospasm |
| Kidney and urinary tract Very rare (<1/10 000) | renal effects |
| Skin and subcutaneous tissue Rare (> 1/10 000 to <1/1 000) Very rare (<1/10 000) | Exanthem, urticaria, angioedema Allergic dermatitis |
| Hepatobiliary disorders Rare (> 1/10 000 to <1/1 000) Very rare (<1/10 000) | Hepatic dysfunction Liver damage |
| Metabolism and nutrition disorders Not known (cannot be estimated from the available data) | High anion gap metabolic acidosis\\* |
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.
\\*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.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
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.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics, antipyretic, ATC code: N02BE01
Paracetamol is an anilide derivative with corresponding analgesic and antipyretic properties such as acetylsalicylic acid. However, paracetamol does not cause gastrointestinal irritation and is also well tolerated by patients with ulcer. Paracetamol does not affect platelet aggregation or bleeding time. Paracetamol is generally tolerated by patients with hypersensitivity to acetylsalicylic acid.
The antipyretic effect is obtained by the influence of heat regulating centers in the CNS, thereby increasing heat output.
The latency of the analgesic effect is about ½ hour, maximum power is reached within 1-2 hours and the duration is 4-5 hours. The progress of the antipyretic effect is somewhat slower: Thus, latency is about ½-1 hour, maximal fever reduction is noted after 2-3 hours and the effect duration is approx. 8 hours.5.2 Pharmacokinetic properties
Paracetamol is well absorbed by oral administration. Maximum plasma concentrations of paracetamol are achieved within ½-1 hour.
Plasma half-life is approximately 2 hours. Paracetamol is metabolised in the liver primarily by conjugation to glucuronide and sulphate. A minor proportion (in therapeutic dose about 3-10%) is oxidatively metabolized by cytochrome P450 and the resulting reactive intermediate metabolite is preferentially bound to the glutathione of the liver and excreted as cysteine and mercaptic acid conjugate. The secretion is via the kidneys. From a therapeutic dose, approximately 2-3% unchanged, approx. 80-90% as glucuronide and sulfate and a minor amount of cysteine and mercapturic acid derivatives.5.3 Preclinical safety data
There are no preclinical data relevant to the safety assessment beyond what has already been taken into account in the Summary of Product Characteristics.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
Tablet content: Pregelatinised maize starch, Magnesium stearate.6.2 Incompatibilities
Not applicable6.3 Shelf life
3 years6.4 Special precautions for storage
No special storage instructions.6.5 Nature and contents of container
Paracetamol 500mg tablets supplied in PVC-Aluminium blister with pack size 10 tablets, 16 tablets, 30 tablets, 32 tablets, 50 tablets, 100 tablets
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
No special instructions.
- Instruction Content
- ## Composition
Each tablet contains Paracetamol 500 mg
For a full list of excipients, see section 6.1.
## Pharmaceutical Form
Tablet
White to off white capsule shaped uncoated tablets with breakline on one side and plain on other side.
## Clinical Particulars
4.1 Therapeutic indications
Headache including migraine and tension headaches, toothache, backache, rheumatic and muscle pains, dysmenorrhoea, sore throat, and for relieving the fever, aches and pains of colds and flu. Also recommended for the symptomatic relief of pain due to non-serious arthritis.4.2 Posology and method of administration
Adults, the elderly, and children aged 16 years and over:
One or two tablets every 4-6 hours , if you need to. Do not take more than 8 tablets in any 24 hours.
Children:
Aged 10 - 15 years:
One tablet every 4-6 hours, if you need to. Do not take more than 4 tablets in any 24 hours.
Do not give children under 10 years of age.
Children should not be given Paracetmol 500mg tablets for more than 3 days without consulting a doctor.
These doses should not be repeated more frequently than every four hours nor should more than four doses be given in any 24 hour period.
Oral administration only.4.3 Contraindications
Hypersensitivity to paracetamol or any of the constituents.4.4 Special warnings and precautions for use
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.
Caution should be exercised in asthma patients who are sensitive to acetylsalicylic acid, since mild reactions of bronchospasm have been reported with paracetamol (cross-reaction).
In patients with glutathione-depleted conditions such as sepsis, the use of paracetamol may increase the risk of metabolic acidosis.
Caution in liver disease. Do not combine with other analgesic drugs containing paracetamol (eg combination medicine). Higher doses than recommended may result in very severe liver damage. Clinical signs of liver injury usually start after a couple of days and usually culminate in 4-6 days. Antidote should be given as early as possible. See also section 4.9 Overdose. In case of high fever, signs of secondary infection or if the symptoms last longer than 3 days, treatment should be reassessed.4.5 Interaction with other medicinal products and other forms of interaction
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)
Studies have shown that the effect of warfarin may be enhanced during treatment with paracetamol. The effect appears to increase with the dose of paracetamol but may occur at doses of 1.5-2.0 g of paracetamol per day for at least 5-7 days. Single doses of paracetamol in normal dosage are considered to have no effect.
Pharmacokinetic interactions
Enzyme-inducing drugs, such as certain antiepileptics (phenytoin, phenobarbital, carbamazepine) have been shown to decrease to approximately 60% of plasma AUC of paracetamol in pharmacokinetic studies. Other substances with enzyme inducing properties, eg rifampicin and St. John's Wort (Hypericum) are also suspected of lowering paracetamol concentrations. In addition, the risk may be greater for liver injury when treated with the maximum recommended dose of paracetamol in patients on enzyme inducing drugs.
Probenecid almost halves the clearance of paracetamol by inhibiting its conjugation with glucuronic acid. This would mean that the dose of paracetamol may be halved when co-administered with probenecid.
The absorption rate of paracetamol may be increased by metoclopramide, but the substances can be given in combination. The absorption of paracetamol is reduced by cholestyramine. Colestyramine should not be given within one hour if maximum analgesic effect is to be achieved.
Paracetamol may affect the pharmacokinetics of chloramphenicol. Therefore, plasma-based chloramphenicol is recommended for combination therapy.4.6 Fertility, pregnancy and lactation
Pregnancy: No known risks during use during pregnancy. A large amount of data from pregnant women indicates neither malformations, fetal toxicity nor neonatal toxicity. Paracetamol may be used during pregnancy if clinically motivated, but it should be used with the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Lactation: Paracetamol passes into breast milk but the risk of affecting the child seems unlikely with therapeutic doses.4.7 Effects on ability to drive and use machines
Paracetamol has no or negligible effect on the ability to drive and use machines.4.8 Undesirable effects
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 causality related to paracetamol.
| | |
| --- | --- |
| Blood and lymphatic system disorders Very rare (<1/10 000) | Thrombocytopenia Agranulocytosis |
| Immune system disorders Very rare (<1/10 000) | Anaphylaxis |
| Respiratory, thoracic and mediastinal disorders Very rare (<1/10 000) | Bronchospasm |
| Kidney and urinary tract Very rare (<1/10 000) | renal effects |
| Skin and subcutaneous tissue Rare (> 1/10 000 to <1/1 000) Very rare (<1/10 000) | Exanthem, urticaria, angioedema Allergic dermatitis |
| Hepatobiliary disorders Rare (> 1/10 000 to <1/1 000) Very rare (<1/10 000) | Hepatic dysfunction Liver damage |
| Metabolism and nutrition disorders Not known (cannot be estimated from the available data) | High anion gap metabolic acidosis\\* |
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.
\\*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.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
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.
## Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics, antipyretic, ATC code: N02BE01
Paracetamol is an anilide derivative with corresponding analgesic and antipyretic properties such as acetylsalicylic acid. However, paracetamol does not cause gastrointestinal irritation and is also well tolerated by patients with ulcer. Paracetamol does not affect platelet aggregation or bleeding time. Paracetamol is generally tolerated by patients with hypersensitivity to acetylsalicylic acid.
The antipyretic effect is obtained by the influence of heat regulating centers in the CNS, thereby increasing heat output.
The latency of the analgesic effect is about ½ hour, maximum power is reached within 1-2 hours and the duration is 4-5 hours. The progress of the antipyretic effect is somewhat slower: Thus, latency is about ½-1 hour, maximal fever reduction is noted after 2-3 hours and the effect duration is approx. 8 hours.5.2 Pharmacokinetic properties
Paracetamol is well absorbed by oral administration. Maximum plasma concentrations of paracetamol are achieved within ½-1 hour.
Plasma half-life is approximately 2 hours. Paracetamol is metabolised in the liver primarily by conjugation to glucuronide and sulphate. A minor proportion (in therapeutic dose about 3-10%) is oxidatively metabolized by cytochrome P450 and the resulting reactive intermediate metabolite is preferentially bound to the glutathione of the liver and excreted as cysteine and mercaptic acid conjugate. The secretion is via the kidneys. From a therapeutic dose, approximately 2-3% unchanged, approx. 80-90% as glucuronide and sulfate and a minor amount of cysteine and mercapturic acid derivatives.5.3 Preclinical safety data
There are no preclinical data relevant to the safety assessment beyond what has already been taken into account in the Summary of Product Characteristics.
## Pharmaceutical Particulars
6.1 List of excipients
Tablet content: Pregelatinised maize starch, Magnesium stearate.6.2 Incompatibilities
Not applicable6.3 Shelf life
3 years6.4 Special precautions for storage
No special storage instructions.6.5 Nature and contents of container
Paracetamol 500mg tablets supplied in PVC-Aluminium blister with pack size 10 tablets, 16 tablets, 30 tablets, 32 tablets, 50 tablets, 100 tablets
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
No special instructions.
