- Approval Id
- adff3346a5f0cdde
- Drug Approval Emc Name
- Panadol Extra Advance 500mg/65mg Tablets (P)
- Drug Name
- Panadol Extra Advance 500mg/65mg Tablets (P)
- Company Name
- Haleon UK Trading Limited
- Company Address
- The Heights, Weybridge, Surrey, KT13 0NY, UK
- Company Website
- https://www.haleon.com/
- Company Medical Info Direct Line
- 0800 783 8881
- Company Medical Info Email
- mystory.gb@haleon.com
- Company Customer Care Direct Line
- 0800 783 8881
- Atc Code
- N02BE51
- Legal Category
- Pharmacy
- Authorisation Holder
- Haleon UK Trading Limited
The Heights
Weybridge
Surrey
KT13 0NY
United Kingdom
- Authorisation Number
- PL 44673/0079
- Authorisation Date
- | | |
| --- | --- |
| First Authorisation: Last Renewal: | 26/02/2010 09/04/2009 |
- Instruction Authorisation Holder
- Haleon UK Trading Limited
The Heights
Weybridge
Surrey
KT13 0NY
United Kingdom
- Instruction Authorisation Number
- PL 44673/0079
- Instruction Authorisation Date
- | | |
| --- | --- |
| First Authorisation: Last Renewal: | 26/02/2010 09/04/2009 |
- Instruction Composition
- Each tablet contains Paracetamol 500 mg and Caffeine 65 mg.
For full list of excipients, see section 6.1.
- Instruction Dosage Form
- Tablet.
White to off-white, film coated, oval shaped tablets. “xPx” (with the P inside in a circle) debossed on one side, “- -” on the other side.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
A mild analgesic and antipyretic formulated to give extra pain relief. The tablets are recommended for the treatment of most painful and febrile conditions, for example, headache, including migraine, backache, toothache, rheumatic pain and dysmenorrhoea, and the relief of the symptoms of colds, influenza and sore throat.4.2 Posology and method of administration
Oral use.
Adults (including the elderly), and children aged 16 years and over:
Two tablets up to four times daily. The dose should not be repeated more frequently than every 4 hours. Do not exceed 8 tablets in 24 hours.
Children aged 12-15 years:
One tablet up to four times daily. The dose should not be repeated more frequently than every 4 hours. Do not exceed 4 tablets in 24 hours.
Not recommended for children under 12 years.4.3 Contraindications
Hypersensitivity to paracetamol, caffeine or any of the other constituents.4.4 Special warnings and precautions for use
Do not exceed stated dose.
Contains paracetamol. Do not use with any other paracetamol containing products. The concomitant use with other products containing paracetamol may lead to an overdose.
Paracetamol overdose may cause liver failure, which may require liver transplant or lead to death.
Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.
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.
Excessive intake of caffeine (e.g. coffee, tea and some canned drinks) should be avoided while taking this product.
If symptoms persist, 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:
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.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 colestyramine. 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.
Caffeine may increase clearance of lithium. Concomitant use is therefore not recommended.
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 Pregnancy and lactation
Paracetamol-caffeine is not recommended for use during pregnancy due to the possible increased risk of lower birth weight and spontaneous abortion associated with caffeine consumption.
Caffeine in breast milk may potentially have a stimulating effect on breast fed infants.
Due to the caffeine content of this product it should not be used if you are pregnant or breast feeding.4.7 Effects on ability to drive and use machines
None.4.8 Undesirable effects
Adverse events 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 MedDRA System Organ Class. Adverse reactions identified during post-marketing use are reported voluntarily from a population of uncertain size, the frequency of these reactions is unknown but likely to be very rare (<1/10,000).
\*\*Post marketing data\*\*
\*\*PARACETAMOL\*\*
| | |
| --- | --- |
| \*\*Body System\*\* | \*\*Undesirable effect\*\* |
| Blood and lymphatic system disorders | Thrombocytopenia Agranulocytosis |
| Immune system disorders | Very rare cases of serious skin reactions have been reported. Anaphylaxis Cutaneous hypersensitivity reactions including (amongst others) skin rashes and angioedema. |
| Metabolism and nutrition disorders | High anion gap metabolic acidosis (frequency not known – cannot be estimated from the available data) (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). |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm – more likely in patients sensitive to aspirin and other NSAIDs |
| Hepatobiliary disorders | Hepatic dysfunction |
\*\*CAFFEINE\*\*
When the recommended paracetamol-caffeine dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects.
| | |
| --- | --- |
| \*\*Body System\*\* | \*\*Undesirable effect\*\* |
| Central nervous system | Dizziness Headache |
| Cardiac disorders | Palpitation |
| Psychiatric disorders | Insomnia Restlessness Anxiety and irritability |
| Gastrointestinal disorders | Gastrointestinal disturbances |
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 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 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.
\*\*Caffeine\*\*
\*\*Symptoms\*\*
Overdose of caffeine may result in epigastric pain, vomitting, diuresis, tachycardia or cardia arrhythmia, CNS stimulation (insomnia, restlessness, excitement, agitation, jitteriness, tremors and convulsions).
It must be noted that for clinically significant symptoms of caffeine overdose to occur with this product, the amount ingested would be associated with serious paracetamol-related toxicity.
\*\*Management\*\*
Patients should receive general supportive care (e.g. hydration and maintenance of vital signs). The administration of activated charcoal may be beneficial when performed within one hour of the overdose, but can be considered for up to four hours after the overdose. The CNS effects of overdose may be treated with intravenous sedatives.
\*\*Summary\*\*
Treatment of overdose requires assessment of plasma paracetamol levels for antidote treatment, with signs and symptoms of caffeine toxicity being managed symptomatically.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
ATC code: N02B E51
The combination of paracetamol and caffeine is a well established analgesic combination.5.2 Pharmacokinetic properties
Paracetamol is rapidly and almost completely absorbed from the gastro-intestinal tract. It is relatively uniformly distributed throughout most body fluids and exhibits variable protein binding. Excretion is almost exclusively renal, in the form of conjugated metabolites. Caffeine is absorbed readily after oral administration. Maximal plasma concentrations are achieved within one hour and the plasma half-life is about 3.5 hours. 65 - 80% of administered caffeine is excreted in the urine as 1-methyluric acid and 1-methylxanthine.
Panadol Extra Advance 500 mg/65 mg Tablets contain a disintegrant system which accelerates tablet dissolution compared to standard parcetamol and caffeine tablets.
Human pharmacokinetic data demonstrate that the time taken to reach plasma paracetamol threshold (4-7 mcg/ml) is at least 44% faster with Panadol Extra Advance 500 mg/65 mg Tablets compared with standard paracetamol and caffeine tablets.
Total extent of absorption of paracetamol and caffeine from Panadol Extra Advance 500 mg/65 mg Tablets is equivalent to that from standard paracetamol and caffeine tablets.5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
Tablet core:
Starch pregelatinised,
Povidone k-25,
Calcium carbonate,
Crospovidone,
Alginic acid,
Magnesium stearate,
Microcrystalline cellulose.
Film coat and polish:
Titanium dioxide (E 171),
Hypromellose,
Macrogol,
Polysorbate 80,
Carnauba wax6.2 Incompatibilities
None.6.3 Shelf life
24 months.6.4 Special precautions for storage
Store below 25°C.6.5 Nature and contents of container
Tablets are in:
• PVC 250 µm or 300 µm aluminium foil 30 µm blister packs in an outer cardboard carton.
• Child resistant PVC / aluminium foil / polyethylene terephthalate blister packs in an outer cardboard carton.
These are available in packs of 24, 30 or 32 tablets.6.6 Special precautions for disposal and other handling
None.
- Instruction Content
- ## Composition
Each tablet contains Paracetamol 500 mg and Caffeine 65 mg.
For full list of excipients, see section 6.1.
## Pharmaceutical Form
Tablet.
White to off-white, film coated, oval shaped tablets. “xPx” (with the P inside in a circle) debossed on one side, “- -” on the other side.
## Clinical Particulars
4.1 Therapeutic indications
A mild analgesic and antipyretic formulated to give extra pain relief. The tablets are recommended for the treatment of most painful and febrile conditions, for example, headache, including migraine, backache, toothache, rheumatic pain and dysmenorrhoea, and the relief of the symptoms of colds, influenza and sore throat.4.2 Posology and method of administration
Oral use.
Adults (including the elderly), and children aged 16 years and over:
Two tablets up to four times daily. The dose should not be repeated more frequently than every 4 hours. Do not exceed 8 tablets in 24 hours.
Children aged 12-15 years:
One tablet up to four times daily. The dose should not be repeated more frequently than every 4 hours. Do not exceed 4 tablets in 24 hours.
Not recommended for children under 12 years.4.3 Contraindications
Hypersensitivity to paracetamol, caffeine or any of the other constituents.4.4 Special warnings and precautions for use
Do not exceed stated dose.
Contains paracetamol. Do not use with any other paracetamol containing products. The concomitant use with other products containing paracetamol may lead to an overdose.
Paracetamol overdose may cause liver failure, which may require liver transplant or lead to death.
Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.
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.
Excessive intake of caffeine (e.g. coffee, tea and some canned drinks) should be avoided while taking this product.
If symptoms persist, 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:
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.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 colestyramine. 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.
Caffeine may increase clearance of lithium. Concomitant use is therefore not recommended.
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 Pregnancy and lactation
Paracetamol-caffeine is not recommended for use during pregnancy due to the possible increased risk of lower birth weight and spontaneous abortion associated with caffeine consumption.
Caffeine in breast milk may potentially have a stimulating effect on breast fed infants.
Due to the caffeine content of this product it should not be used if you are pregnant or breast feeding.4.7 Effects on ability to drive and use machines
None.4.8 Undesirable effects
Adverse events 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 MedDRA System Organ Class. Adverse reactions identified during post-marketing use are reported voluntarily from a population of uncertain size, the frequency of these reactions is unknown but likely to be very rare (<1/10,000).
\*\*Post marketing data\*\*
\*\*PARACETAMOL\*\*
| | |
| --- | --- |
| \*\*Body System\*\* | \*\*Undesirable effect\*\* |
| Blood and lymphatic system disorders | Thrombocytopenia Agranulocytosis |
| Immune system disorders | Very rare cases of serious skin reactions have been reported. Anaphylaxis Cutaneous hypersensitivity reactions including (amongst others) skin rashes and angioedema. |
| Metabolism and nutrition disorders | High anion gap metabolic acidosis (frequency not known – cannot be estimated from the available data) (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). |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm – more likely in patients sensitive to aspirin and other NSAIDs |
| Hepatobiliary disorders | Hepatic dysfunction |
\*\*CAFFEINE\*\*
When the recommended paracetamol-caffeine dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects.
| | |
| --- | --- |
| \*\*Body System\*\* | \*\*Undesirable effect\*\* |
| Central nervous system | Dizziness Headache |
| Cardiac disorders | Palpitation |
| Psychiatric disorders | Insomnia Restlessness Anxiety and irritability |
| Gastrointestinal disorders | Gastrointestinal disturbances |
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 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 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.
\*\*Caffeine\*\*
\*\*Symptoms\*\*
Overdose of caffeine may result in epigastric pain, vomitting, diuresis, tachycardia or cardia arrhythmia, CNS stimulation (insomnia, restlessness, excitement, agitation, jitteriness, tremors and convulsions).
It must be noted that for clinically significant symptoms of caffeine overdose to occur with this product, the amount ingested would be associated with serious paracetamol-related toxicity.
\*\*Management\*\*
Patients should receive general supportive care (e.g. hydration and maintenance of vital signs). The administration of activated charcoal may be beneficial when performed within one hour of the overdose, but can be considered for up to four hours after the overdose. The CNS effects of overdose may be treated with intravenous sedatives.
\*\*Summary\*\*
Treatment of overdose requires assessment of plasma paracetamol levels for antidote treatment, with signs and symptoms of caffeine toxicity being managed symptomatically.
## Pharmacological Properties
5.1 Pharmacodynamic properties
ATC code: N02B E51
The combination of paracetamol and caffeine is a well established analgesic combination.5.2 Pharmacokinetic properties
Paracetamol is rapidly and almost completely absorbed from the gastro-intestinal tract. It is relatively uniformly distributed throughout most body fluids and exhibits variable protein binding. Excretion is almost exclusively renal, in the form of conjugated metabolites. Caffeine is absorbed readily after oral administration. Maximal plasma concentrations are achieved within one hour and the plasma half-life is about 3.5 hours. 65 - 80% of administered caffeine is excreted in the urine as 1-methyluric acid and 1-methylxanthine.
Panadol Extra Advance 500 mg/65 mg Tablets contain a disintegrant system which accelerates tablet dissolution compared to standard parcetamol and caffeine tablets.
Human pharmacokinetic data demonstrate that the time taken to reach plasma paracetamol threshold (4-7 mcg/ml) is at least 44% faster with Panadol Extra Advance 500 mg/65 mg Tablets compared with standard paracetamol and caffeine tablets.
Total extent of absorption of paracetamol and caffeine from Panadol Extra Advance 500 mg/65 mg Tablets is equivalent to that from standard paracetamol and caffeine tablets.5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
## Pharmaceutical Particulars
6.1 List of excipients
Tablet core:
Starch pregelatinised,
Povidone k-25,
Calcium carbonate,
Crospovidone,
Alginic acid,
Magnesium stearate,
Microcrystalline cellulose.
Film coat and polish:
Titanium dioxide (E 171),
Hypromellose,
Macrogol,
Polysorbate 80,
Carnauba wax6.2 Incompatibilities
None.6.3 Shelf life
24 months.6.4 Special precautions for storage
Store below 25°C.6.5 Nature and contents of container
Tablets are in:
• PVC 250 µm or 300 µm aluminium foil 30 µm blister packs in an outer cardboard carton.
• Child resistant PVC / aluminium foil / polyethylene terephthalate blister packs in an outer cardboard carton.
These are available in packs of 24, 30 or 32 tablets.6.6 Special precautions for disposal and other handling
None.
