- Approval Id
- 51a5ac218a740c90
- Drug Approval Emc Name
- Paracetamol 500 mg Tablets PL43461/0006
- Drug Name
- Paracetamol 500 mg Tablets PL43461/0006
- Company Name
- Flamingo Pharma (UK) Ltd
- Company Address
- The BLOC, 38 Springfield Way, Kingston Upon Hull, HU10 6RJ, UK
- Company Website
- http://www.flamingopharma.co.uk
- Company Telephone
- +44 (0) 7784240228
- Company Medical Info Direct Line
- 00 800 890 13370
- Atc Code
- N02BE01
- Legal Category
- General Sales List
- Authorisation Holder
- Flamingo Pharma UK Ltd
1st Floor, Kirkland House,
11-15 Peterborough Road,
Harrow, Middlesex,
HA1 2AX,
United Kingdom
- Authorisation Number
- PL 43461/0006
- Authorisation Date
- 16th March 2011
Renewal: Pending
- Instruction Authorisation Holder
- Flamingo Pharma UK Ltd
1st Floor, Kirkland House,
11-15 Peterborough Road,
Harrow, Middlesex,
HA1 2AX,
United Kingdom
- Instruction Authorisation Number
- PL 43461/0006
- Instruction Authorisation Date
- 16th March 2011
Renewal: Pending
- Instruction Composition
- Each tablet contains 500 mg of paracetamol. Each tablet also contains sodium metabisulphite 0.56 mg.
For a list of excipients, see section 6.1.
- Instruction Dosage Form
- Tablet
White to off white, circular flat bevelled edge tablet with breakline on one side and plain on other.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
Paracetamol Tablets is a mild analgesic and antipyretic, and is recommended for the treatment of most painful and febrile conditions, for example, 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 up to four times daily as required.
\*\*Children:\*\*
Aged 10 - 15 years: One tablet up to four times daily as required.
\*\*Not suitable for children under 10 years of age.\*\*
Children should not be given Paracetamol Tablets for more than 3 days without consulting a doctor.
\*\*Dosage instruction:\*\*
Do not take more frequently than every 4 hours. Not more than 4 doses should be administered in any 24 hour period.
Oral administration only.4.3 Contraindications
Hypersensitivity to paracetamol or any other ingredients. Alcoholics could be at risk in taking paracetamol.4.4 Special warnings and precautions for use
Contains paracetamol. Do not use with any other paracetamol-containing products.
Underlying liver disease increases the risk or paracetamol related liver damage. Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication.
Do not exceed the stated dose.
Patients should be advised to consult their doctor if their headaches become persistent.
Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day.
Caution should be exercised in patients with glutathione depleted states, as the use of paracetamol may increase the risk of metabolic acidosis (refer also to section 4.9).
Use with caution in patients with glutathione depletion due to metabolic deficiencies.
If symptoms, medical advice must be sought.
Keep out of the sight and reach of children.
\*\*\*\*Pack Label\*\*:\*\*
Talk to a doctor at once if you take too much of this medicine even if you feel well.
Do not take anything else containing paracetamol while taking this medicine.
\*\*\*\*Patient Information Leaflet\*\*:\*\*
\*\*If you take more Paracetamol than you should\*\*
Talk to a doctor at once if you take too much of this medicine even if you feel well, because too much paracetamol can cause delayed, serious liver damage.
If your symptoms continue or your headache becomes persistent, see your doctor.
\*\*Paracetamol Tablets contains Sodium Metabisulphite\*\*
Paracetamol Tablets contain sodium metabisulphite which may rarely cause severe hypersensitivity reactions and bronchospasm (breathing difficulties).
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.4.5 Interaction with other medicinal products and other forms of interaction
Chronic use of paracetamol enhances effect of warfarin and other coumarins with increased risk of bleeding; occasional doses have no significant effect. Cholestyramine reduces absorption of paracetamol. Metoclopramide and Domperidone accelerate absorption of paracetamol.4.6 Fertility, pregnancy and lactation
Paracetamol is excreted in breast milk but not in clinically significant quantities. Available published data do not contraindicate breast- feeding.
Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.4.7 Effects on ability to drive and use machines
None.4.8 Undesirable effects
Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class and frequency.
The following convention has been utilised for the classification of the undesirable effects: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10,000 to <1/1000) and very rare (<1/10,000), not known (cannot be estimated from available data).
Adverse event frequencies have been estimated from spontaneous reports received through post-marketing data.
\*\*Post marketing data\*\*
| | | |
| --- | --- | --- |
| \*\*Body System\*\* | \*\*Undesirable effect\*\* | \*\*Frequency\*\* |
| Blood and lymphatic system disorders | Thrombocytopenia Agranulocytosis | Very rare |
| Immune system disorders | Anaphylaxis Cutaneous hypersensitivity reactions including, among others, skin rashes and angiodema. Very rare cases of serious skin reactions have been reported. | Very rare |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm\\* | Very rare |
| Hepatobiliary disorders | Hepatic dysfunction | Very rare |
\\* 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search MHRA Yellow Card in the Google Play or Apple App store.4.9 Overdose
Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g 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.
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.
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.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
\*\*ATC code:\*\* N02BE01, Other analgesics and antipyretics
Paracetamol is an antipyretic analgesic. The mechanism of action is probably similar to that of aspirin and dependant on the inhibition of prostaglandin synthesis. This inhibition appears, however, to be on a selective basis.5.2 Pharmacokinetic properties
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract with peak plasma concentrations occurring 30 minutes to 1 hour and the plasma half-life is 1 - 4 hours after therapeutic doses.
Paracetamol is relatively uniformly distributed throughout most body fluids.
Binding of the drug to plasma proteins is variable; 20 to 30 % may be bound at the concentrations encountered during acute intoxication. Following therapeutic doses 90 - 100% of the drug may be recovered in the urine within the first day. However, practically no paracetamol is excreted unchanged and the bulk is excreted after hepatic conjugation.5.3 Preclinical safety data
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
Pregelatinised starch (maize)
Sodium metabisulphite
Stearic acid (E570)
Magnesium stearate (E572)6.2 Incompatibilities
None stated.6.3 Shelf life
5 years.6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.6.5 Nature and contents of container
Paracetamol 500mg Tablets are available in child-resistant packs (Glassine paper foil/ Aluminium or PVC \*I\* Aluminium foil) of 4,6,12 and 16 tablets.
Specification details of blister packs:
PVC/Aluminium foil
- PVC (white, rigid, opaque): 250 microns
- PVC/Aluminium foil (hard tempered): 15/20 microns
- Primer (nitrocellulose): 1.5 to 2.5 gsm
- Heat seal lacquer: 6.5 to 8.5 gsm
PVC/Glassine paper – Aluminium foil
- PVC (white, rigid, opaque): 250 microns
- Glassine paper/Aluminium foil : 35± 3.50/25± 2.0 gsm6.6 Special precautions for disposal and other handling
No special precautions required.
- Instruction Content
- ## Composition
Each tablet contains 500 mg of paracetamol. Each tablet also contains sodium metabisulphite 0.56 mg.
For a list of excipients, see section 6.1.
## Pharmaceutical Form
Tablet
White to off white, circular flat bevelled edge tablet with breakline on one side and plain on other.
## Clinical Particulars
4.1 Therapeutic indications
Paracetamol Tablets is a mild analgesic and antipyretic, and is recommended for the treatment of most painful and febrile conditions, for example, 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 up to four times daily as required.
\*\*Children:\*\*
Aged 10 - 15 years: One tablet up to four times daily as required.
\*\*Not suitable for children under 10 years of age.\*\*
Children should not be given Paracetamol Tablets for more than 3 days without consulting a doctor.
\*\*Dosage instruction:\*\*
Do not take more frequently than every 4 hours. Not more than 4 doses should be administered in any 24 hour period.
Oral administration only.4.3 Contraindications
Hypersensitivity to paracetamol or any other ingredients. Alcoholics could be at risk in taking paracetamol.4.4 Special warnings and precautions for use
Contains paracetamol. Do not use with any other paracetamol-containing products.
Underlying liver disease increases the risk or paracetamol related liver damage. Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication.
Do not exceed the stated dose.
Patients should be advised to consult their doctor if their headaches become persistent.
Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day.
Caution should be exercised in patients with glutathione depleted states, as the use of paracetamol may increase the risk of metabolic acidosis (refer also to section 4.9).
Use with caution in patients with glutathione depletion due to metabolic deficiencies.
If symptoms, medical advice must be sought.
Keep out of the sight and reach of children.
\*\*\*\*Pack Label\*\*:\*\*
Talk to a doctor at once if you take too much of this medicine even if you feel well.
Do not take anything else containing paracetamol while taking this medicine.
\*\*\*\*Patient Information Leaflet\*\*:\*\*
\*\*If you take more Paracetamol than you should\*\*
Talk to a doctor at once if you take too much of this medicine even if you feel well, because too much paracetamol can cause delayed, serious liver damage.
If your symptoms continue or your headache becomes persistent, see your doctor.
\*\*Paracetamol Tablets contains Sodium Metabisulphite\*\*
Paracetamol Tablets contain sodium metabisulphite which may rarely cause severe hypersensitivity reactions and bronchospasm (breathing difficulties).
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.4.5 Interaction with other medicinal products and other forms of interaction
Chronic use of paracetamol enhances effect of warfarin and other coumarins with increased risk of bleeding; occasional doses have no significant effect. Cholestyramine reduces absorption of paracetamol. Metoclopramide and Domperidone accelerate absorption of paracetamol.4.6 Fertility, pregnancy and lactation
Paracetamol is excreted in breast milk but not in clinically significant quantities. Available published data do not contraindicate breast- feeding.
Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.4.7 Effects on ability to drive and use machines
None.4.8 Undesirable effects
Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class and frequency.
The following convention has been utilised for the classification of the undesirable effects: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10,000 to <1/1000) and very rare (<1/10,000), not known (cannot be estimated from available data).
Adverse event frequencies have been estimated from spontaneous reports received through post-marketing data.
\*\*Post marketing data\*\*
| | | |
| --- | --- | --- |
| \*\*Body System\*\* | \*\*Undesirable effect\*\* | \*\*Frequency\*\* |
| Blood and lymphatic system disorders | Thrombocytopenia Agranulocytosis | Very rare |
| Immune system disorders | Anaphylaxis Cutaneous hypersensitivity reactions including, among others, skin rashes and angiodema. Very rare cases of serious skin reactions have been reported. | Very rare |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm\\* | Very rare |
| Hepatobiliary disorders | Hepatic dysfunction | Very rare |
\\* 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search MHRA Yellow Card in the Google Play or Apple App store.4.9 Overdose
Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g 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.
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.
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.
## Pharmacological Properties
5.1 Pharmacodynamic properties
\*\*ATC code:\*\* N02BE01, Other analgesics and antipyretics
Paracetamol is an antipyretic analgesic. The mechanism of action is probably similar to that of aspirin and dependant on the inhibition of prostaglandin synthesis. This inhibition appears, however, to be on a selective basis.5.2 Pharmacokinetic properties
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract with peak plasma concentrations occurring 30 minutes to 1 hour and the plasma half-life is 1 - 4 hours after therapeutic doses.
Paracetamol is relatively uniformly distributed throughout most body fluids.
Binding of the drug to plasma proteins is variable; 20 to 30 % may be bound at the concentrations encountered during acute intoxication. Following therapeutic doses 90 - 100% of the drug may be recovered in the urine within the first day. However, practically no paracetamol is excreted unchanged and the bulk is excreted after hepatic conjugation.5.3 Preclinical safety data
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
Pregelatinised starch (maize)
Sodium metabisulphite
Stearic acid (E570)
Magnesium stearate (E572)6.2 Incompatibilities
None stated.6.3 Shelf life
5 years.6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.6.5 Nature and contents of container
Paracetamol 500mg Tablets are available in child-resistant packs (Glassine paper foil/ Aluminium or PVC \*I\* Aluminium foil) of 4,6,12 and 16 tablets.
Specification details of blister packs:
PVC/Aluminium foil
- PVC (white, rigid, opaque): 250 microns
- PVC/Aluminium foil (hard tempered): 15/20 microns
- Primer (nitrocellulose): 1.5 to 2.5 gsm
- Heat seal lacquer: 6.5 to 8.5 gsm
PVC/Glassine paper – Aluminium foil
- PVC (white, rigid, opaque): 250 microns
- Glassine paper/Aluminium foil : 35± 3.50/25± 2.0 gsm6.6 Special precautions for disposal and other handling
No special precautions required.
