PANADOL ADVANCE 500 MG TABLETS
Active substance: PARACETAMOL
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1.
Name of the Medicinal Product Panadol Advance 500 mg Tablets
2
QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains Paracetamol 500.0 mg For full list of excipients, see 6.1
3.
Pharmaceutical Form Film-coated tablet White to off-white film-coated capsule-shaped tablet with flat edges, debossed with a P within a circle on one face and with a breakline on one side.
4.1.
Therapeutic indications Panadol Advance 500 mg Tablets are a mild analgesic and antipyretic, and are 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: Two tablets up to four times daily as required. Children: 6 - 12 years: Half to one tablet three or four times daily as required. Not suitable for children under six years of age. Children should not be given Panadol Advance 500 mg 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.
Contra-indications Hypersensitivity to paracetamol or any of the other constituents.
4.4.
Special warnings and precautions for use Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazard of overdose is greater in those with noncirrhotic alcoholic liver disease. Do not exceed the stated dose. Patients should be advised to consult their doctor if their headaches become persistent. Patients should be advised not to take other paracetamol-containing products concurrently. Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day. Sodium methyl-, sodium ethyl- and sodium propyl- parahydroxybenzoates (E219, E215, E217) may cause allergic reactions (possibly delayed). If symptoms persist consult your doctor. Keep out of the reach and sight of children.
Pack Label: Immediate medical advice should be sought in the event of an overdose, even if you feel well. Do not take with any other paracetamol-containing products. Patient Information Leaflet: 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 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.
4.6.
Pregnancy and Lactation 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. 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 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. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare. Post marketing data Body System Blood and lymphatic system disorders Immune system disorders Undesirable effect Thrombocytopenia Agranulocytosis Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome/toxic epidermal necrolysis Bronchospasm*
Respiratory, thoracic and mediastinal disorders Hepatobiliary disorders
Hepatic dysfunction
* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
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 Johns 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.
5.
5.1.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties 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. Clinical Efficacy In two dental pain studies, pain relief was observed at a median time of 15 minutes following administration of the 1000 mg dose of Panadol Advance 500 mg tablets. Panadol Advance 500 mg tablets demonstrated superior pain relief at 1000 mg dose compared to placebo and to Panadol Advance 500 mg tablets at 500 mg dose. Panadol Advance 500 mg tablets at the 500 mg dose also demonstrated superior efficacy compared to placebo.
5.2.
Pharmacokinetic properties Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. The concentration in plasma reaches a peak in 30 to 60 minutes 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. Panadol Advance 500 mg Tablets contain a disintegrant system which accelerates tablet dissolution compared to standard paracetamol tablets. Human scintigraphy data demonstrate that Panadol Advance 500 mg Tablets generally start to disintegrate by 5 minutes post dose in the stomach. There is also less between-subject and less within- subject variability (p<0.0001) in early absorption of paracetamol from Panadol Advance 500 mg Tablets compared to standard paracetamol tablets. Human pharmacokinetic data demonstrate that the time taken to reach plasma paracetamol therapeutic threshold (4-7mcg/ml) is at least 37% faster with Panadol Advance 500 mg Tablets compared to standard paracetamol tablets (P<0.05). Total extent of absorption of paracetamol from Panadol Advance 500 mg Tablets is equivalent to that from standard paracetamol 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.
6.
6.1.
Pharmaceutical Particulars
List of excipients Tablet core: Pregelatinised starch Calcium carbonate Alginic acid
Crospovidone Povidone (K-25) Magnesium stearate Colloidal anhydrous silica Parahydroxybenzoates (sodium methyl parahydroxybenzoate (E219), sodium ethyl parahydroxybenzoate (E215) and sodium propyl parahydroxybenzoate (E217)) Film coat and polish: Opadry white (YS-1-7003) Carnauba wax Purified water 6.2. Incompatibilities Not applicable
6.3.
Shelf Life 36 months.
6.4.
Special Precautions for Storage None.
6.5.
Nature and contents of container Opaque PVC 250 m / aluminium foil 30 m blister packs in an outer cardboard carton containing 4, 6, 12, 16, 24, 30 or 32 tablets or PVC 300 m / aluminium foil 30 m blister packs in a cardboard / PVC wallet containing 16 tablets.
6.6.
Instruction for Use/Handling Not applicable.
7.
MARKETING AUTHORISATION HOLDER SmithKline Beecham (SWG) Limited, 980 Great West Road,
Brentford, Middlesex. TW8 9GS United Kingdom Trading as: GlaxoSmithKline Consumer Healthcare, Brentford, TW8 9GS, UK.
8.
MARKETING AUTHORISATION NUMBER PL 0071/0441
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION 13 June 2001
10
DATE OF REVISION OF THE TEXT
01/08/2012
Name of the Medicinal Product Panadol Advance 500 mg Tablets
2
QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains Paracetamol 500.0 mg For full list of excipients, see 6.1
3.
Pharmaceutical Form Film-coated tablet White to off-white film-coated capsule-shaped tablet with flat edges, debossed with a P within a circle on one face and with a breakline on one side.
4.1.
Therapeutic indications Panadol Advance 500 mg Tablets are a mild analgesic and antipyretic, and are 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: Two tablets up to four times daily as required. Children: 6 - 12 years: Half to one tablet three or four times daily as required. Not suitable for children under six years of age. Children should not be given Panadol Advance 500 mg 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.
Contra-indications Hypersensitivity to paracetamol or any of the other constituents.
4.4.
Special warnings and precautions for use Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazard of overdose is greater in those with noncirrhotic alcoholic liver disease. Do not exceed the stated dose. Patients should be advised to consult their doctor if their headaches become persistent. Patients should be advised not to take other paracetamol-containing products concurrently. Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day. Sodium methyl-, sodium ethyl- and sodium propyl- parahydroxybenzoates (E219, E215, E217) may cause allergic reactions (possibly delayed). If symptoms persist consult your doctor. Keep out of the reach and sight of children.
Pack Label: Immediate medical advice should be sought in the event of an overdose, even if you feel well. Do not take with any other paracetamol-containing products. Patient Information Leaflet: 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 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.
4.6.
Pregnancy and Lactation 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. 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 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. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare. Post marketing data Body System Blood and lymphatic system disorders Immune system disorders Undesirable effect Thrombocytopenia Agranulocytosis Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome/toxic epidermal necrolysis Bronchospasm*
Respiratory, thoracic and mediastinal disorders Hepatobiliary disorders
Hepatic dysfunction
* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
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 Johns 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.
5.
5.1.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties 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. Clinical Efficacy In two dental pain studies, pain relief was observed at a median time of 15 minutes following administration of the 1000 mg dose of Panadol Advance 500 mg tablets. Panadol Advance 500 mg tablets demonstrated superior pain relief at 1000 mg dose compared to placebo and to Panadol Advance 500 mg tablets at 500 mg dose. Panadol Advance 500 mg tablets at the 500 mg dose also demonstrated superior efficacy compared to placebo.
5.2.
Pharmacokinetic properties Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. The concentration in plasma reaches a peak in 30 to 60 minutes 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. Panadol Advance 500 mg Tablets contain a disintegrant system which accelerates tablet dissolution compared to standard paracetamol tablets. Human scintigraphy data demonstrate that Panadol Advance 500 mg Tablets generally start to disintegrate by 5 minutes post dose in the stomach. There is also less between-subject and less within- subject variability (p<0.0001) in early absorption of paracetamol from Panadol Advance 500 mg Tablets compared to standard paracetamol tablets. Human pharmacokinetic data demonstrate that the time taken to reach plasma paracetamol therapeutic threshold (4-7mcg/ml) is at least 37% faster with Panadol Advance 500 mg Tablets compared to standard paracetamol tablets (P<0.05). Total extent of absorption of paracetamol from Panadol Advance 500 mg Tablets is equivalent to that from standard paracetamol 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.
6.
6.1.
Pharmaceutical Particulars
List of excipients Tablet core: Pregelatinised starch Calcium carbonate Alginic acid
Crospovidone Povidone (K-25) Magnesium stearate Colloidal anhydrous silica Parahydroxybenzoates (sodium methyl parahydroxybenzoate (E219), sodium ethyl parahydroxybenzoate (E215) and sodium propyl parahydroxybenzoate (E217)) Film coat and polish: Opadry white (YS-1-7003) Carnauba wax Purified water 6.2. Incompatibilities Not applicable
6.3.
Shelf Life 36 months.
6.4.
Special Precautions for Storage None.
6.5.
Nature and contents of container Opaque PVC 250 m / aluminium foil 30 m blister packs in an outer cardboard carton containing 4, 6, 12, 16, 24, 30 or 32 tablets or PVC 300 m / aluminium foil 30 m blister packs in a cardboard / PVC wallet containing 16 tablets.
6.6.
Instruction for Use/Handling Not applicable.
7.
MARKETING AUTHORISATION HOLDER SmithKline Beecham (SWG) Limited, 980 Great West Road,
Brentford, Middlesex. TW8 9GS United Kingdom Trading as: GlaxoSmithKline Consumer Healthcare, Brentford, TW8 9GS, UK.
8.
MARKETING AUTHORISATION NUMBER PL 0071/0441
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION 13 June 2001
10
DATE OF REVISION OF THE TEXT
01/08/2012
Source: Medicines and Healthcare Products Regulatory Agency
Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.
