Paracetamol 500 Mg Effervescent Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Paracetamol 500 mg Effervescent Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each effervescent tablet contains 500 mg of Paracetamol.
Excipients: Sodium content approximately 503 mg/tablet. Also contains sorbitol (E420) 131 mg /tablet. For full list of excipients see section 6.1
3 PHARMACEUTICAL FORM
Effervescent Tablet
White to off white round, flat, beveled edged plain on both side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of mild to moderate pain and/or fever.
4.2 Posology and method of administration
This presentation is reserved for use only in adults and in adolescents aged 12 years and above.
Doses depend on body weight and age; a single dose ranges from 10 to 15 mg/kg body weight (= b.w.) to a maximum of 60 mg/kg b.w. for total daily dose.
Pediatric Patients:
• Children below 12 years of age: Paracetamol effervescent Tablet is not recommended in children aged less than 12 years.
• Adolescents of 12 to 15 years and weighing 41 to 50 kg the posology is one tablet per dose, repeated if necessary 6-4 hours later, without exceeding 4 tablets daily.
• Adolescents of 16 to 18 years and weighing more than 50 kg: as adults.
Adults:
The usual adults dose is one to two tablets of 500mg, repeated if necessary 4 hours later, without exceeding 3g of Paracetamol a day (i.e. 6 tablets).
Maximum daily dose:
• The maximum daily dose of Paracetamol must not exceed 3g.
• Maximum single dose is 1g (2 effervescent tablets)
Paracetamol 500 mg Effervescent Tablets are for oral administration. The tablets should be placed in a full tumbler of water and allowed to dissolve completely before swallowing.
Frequency of administration:
The specific dose interval depends on the symptoms and the maximum daily dose. Systematic administration enables to avoid pain or fever oscillation. Depending on the reoccurrence of symptoms (fever and/or pain), repeated administration is allowed. It should, however, preferably never fall below 6 hours and in no case fall below 4 hours. In adolescents administration should be regularly spaced, including nighttime, preferably at 6 hour intervals, otherwise at intervals of a minimum of 4 hours. If the pain persists for more than 5 days or the fever lasts for more than 3 days, or gets worse or other symptoms appear, you should stop the treatment and consult a doctor.
Renal Insufficiency:
In case of renal insufficiency the dose should be reduced:
|
Glomerular filtration |
Dose |
|
10 - 50 ml/min |
500 mg every 6 hours |
|
< 10 ml/min |
500 mg every 8 hours |
Impaired liver function:
In patients with impaired hepatic function or Gilbert’s syndrome, the dose must be reduced or the dosing interval prolonged.
The daily effective dose should not exceed 60 mg/kg/day (upto maximum 2g/day) in the following situations :
• adults weighing less than 50 kg
• mild to moderate hepatic insufficiency, Gilberts’s syndrome (familial non-haemolytic jaundice
• dehydration
• chronic malnutrition
• chronic alcoholism
Intake of paracetamol with food and drink does not affect the efficacy of the medicinal product.
4.3 Contraindications
Hypersensitivity to Paracetamol or any of the excipients.
4.4 Special warnings and precautions for use
Prolonged or frequent use is discouraged. Patients should be advised not to take other Paracetamol containing products concurrently. Taking multiple daily doses in one administration can severely damage the liver; in such case unconsciousness does not occur. However, medical assistance should be sought immediately. Prolonged use except under medical supervision may be harmful. In adolescents treated with 60mg/kg daily of Paracetamol, the combination with another antipyretic is not justified except in the case of ineffectiveness.
Caution is advised in the administration of Paracetamol to patients with moderate and severe renal insufficiency, mild to moderate hepatic insufficiency (including Gilbert’s syndrome), severe hepatic insufficiency (child-pugh>9), acute hepatitis, concomitant treatment with medicinal products affecting hepatic functions, glucose-6-phosphatedehydrogenase deficiency, hemolytic anemia, alcohol abuse dehydration and chronic malnutrition (see section 4.2).
The hazards of overdose are greater in those with non- cirrhotic alcoholic liver disease. Caution should be exercised in cases of chronic alcoholism. The daily dose should not exceed 2 grams in such case. Alcohol should not be used during the treatment with Paracetamol.
Caution is advised in asthmatic patients sensitive to aspirin, because light reaction bronchospasm with paracetamol (cross-reaction) has been reported in less than 5% of the patients tested.
This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
This medicinal product contains 503 mg of sodium per effervescent tablet. To be taken into consideration by patients on a controlled sodium diet.
In the case of high fever, or signs of secondary infection or persistence of symptoms a doctor should be consulted.
Immediate medical advice should be sought in the event of overdosage even if the patient feels well because of the risk of irreversible liver damage (see section 4.9).
4.5 Interactions with other medicinal products and other forms of interaction
Hepatotoxic substances may increase the possibility of Paracetamol accumulation and overdose. The risk of hepatotoxicity of paracetamol may be increased by drugs which induce liver microsomal enzymes such as barbiturates, tricyclic antidepressants, and alcohol.
Probenecid causes an almost 2-fold reduction in clearance of Paracetamol by inhibiting its conjugation with glucuronid acid. A reduction of the Paracetamol dose should be considered for concomitant treatment with probenecid.
• Salicylamide may prolong the elimination t1/2 of Paracetamol
• Metoclopramide and Domperidone: accelerate absorption of Paracetamol
• Cholestyramine: reduces absorption of Paracetamol
• Concomitant use of Paracetamol (4 g per day for at least 4 days) with oral anticoagulants may lead to slight variations of INR values. In this case, increased monitoring of INR values should be done during the duration of the combination and after its discontinuation. 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.
• Isoniazid: Reduction of paracetamol clearance, with possible potentiation of its action and/or toxicity, by inhibiting its metabolism in the liver.
• Lamotrigine: Decrease in the bioavailability of lamotrigine, with possible reduction of its effect, due to possible induction of its metabolism in the liver.
Interference with laboratory tests: Paracetamol may affect uric acid tests by wolframatop phosphoric acid, and blood sugar tests by glucose-oxydase-peroxydase.
4.6 Pregnancy and lactation Pregnancy:
Epidemiological data on the oral administration of therapeutic doses of Paracetamol indicate no adverse effects on pregnancy or on the health of the fetus/newborn child. Prospective data on overdose during pregnancy showed no increased risk of malformations. Reproduction studies investigating oral administration did not indicate any signs of malformation or fetotoxicity (see section 5.3).
Paracetamol is considered to be safe in normal therapeutic doses for short-term use as a minor analgesic/antipyretic in pregnancy.
Lactation:
Following oral administration, Paracetamol is excreted into breast milk in small quantities. To date, no adverse reactions or undesirable effects are known in association with lactation. Therapeutic doses of Paracetamol can be administered during breast-feeding.
4.7 Effects on ability to drive and use machines
Paracetamol has no influence on the ability to drive and use machines.
4.8 Undesirable effects
The frequency using the following convention: very common (> 1/10); common (>1/100 to < 1/10); uncommon (>1/1000 to < 1/100); rare (>1/10000 to < 1/1000); very rare (< 1/10000), including isolated reports; not known: frequency cannot be estimated from the available data. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
|
Frequency |
System |
Symptoms |
|
Rare >1/10000 - < 1/1000 |
Blood and lymphatic system disorders |
Platelet disorders, stem cell disorders. |
|
Immune system disorders |
Allergies (excluding angioedema). | |
|
Psychiatric disorders |
Depression NOS, confusion, hallucinations. | |
|
Nervous system disorders |
Tremor NOS, headache NOS. | |
|
Eye disorders |
Abnormal vision. | |
|
Cardiac disorders |
Oedema. | |
|
Gastrointestinal disorders |
Haemorrhage NOS, abdominal pain NOS, diarrhoea NOS, nausea, vomiting. | |
|
Hepato-biliary disorders |
Hepatic function abnormal, hepatic failure, hepatic necrosis, jaundice. | |
|
Skin and subcutaneous tissue disorders |
Pruritus, rash, sweating, purpura, angioedema, urticaria | |
|
General disorders and administration site conditions |
Dizziness (excluding vertigo), malaise, pyrexia, sedation, drug interaction NOS. | |
|
Injury, poisoning and procedural complications |
Overdose and poisoning | |
|
Very Rare (< 10 000) |
Hepato-biliary disorders |
hepatotoxicity |
|
General disorders and administration site conditions |
hypersensitivity reaction (requiring discontinuation of treatment) | |
|
Blood and lymphatic system disorders |
thrombocytopenia leukopenia neutropenia hemolytic anemia | |
|
Metabolism and nutrition disorders |
Hypoglycaemia |
|
Renal and urinary disorders |
Sterile pyuria (cloudy urine) and renal side effects |
|
Skin disorders |
Serious skin reactions have been reported. |
Not known: Some cases of toxic epidermal necrolysis, Stevens Johnson syndrome, erythema multiforme, edema of the larynx, anaphylactic shock, anaemia, bronchospasm*, liver alteration and hepatitis, renal alteration (severe renal impairment, nephrite interstitial, haematuria, anuresis), gastrointestinal effects and vertigo have been reported.
* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
4.9 Overdose
There is a risk of poisoning, particularly in elderly subjects, in young adolescents, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition. Overdosing may be fatal.
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. Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with increased prothrombin levels that may appear 12 to 48 hours after administration.
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.
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.
High doses of sodium bicarbonate may be expected to induce gastrointestinal symptoms including belching and nausea. In addition, high doses of sodium bicarbonate may cause hypernatraemia; electrolytes should be monitored and patients managed accordingly.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: other analgesics and antipyretics; anilides ATC code: N02BE01
5.2 Pharmacokinetic properties
Absorption
The absorption of paracetamol by the oral route is rapid and complete. Maximum plasma concentrations are reached 30 to 60 minutes following ingestion.
Distribution
Paracetamol is distributed rapidly throughout all tissues. Concentrations are comparable in blood, saliva and plasma. Protein binding is low.
Metabolism
Paracetamol is metabolized mainly in the liver following two major metabolic pathways: glucuronic acid and sulphuric acid conjugates. The latter route is rapidly saturated at doses higher than the therapeutic dose. A minor route catalyzed by the cytochrome P450, results in the formation of an intermediate reagent (N-acetyl-p-benzoquinoneimine) which under normal conditions of use is rapidly detoxified by glutathione and eliminated in the urine, after conjugation with cystein and mercaptopuric acid. Conversely, when massive intoxication occurs, the quantity of this toxic metabolite is increased.
Elimination
Elimination is essentially through the urine. 90% of the ingested dose is eliminated via the kidneys within 24 hours, principally as glucuronide (60 to 80%) and sulphate conjugates (20 to 30%). Less than 5% is eliminated in unchanged form.
Elimination half life is about 2 hours.
Physiopathological Variations
Renal Insufficiency: In cases of severe renal insufficiency (creatinine clearance lower than 10 ml/min) the elimination of paracetamol and its metabolites is delayed.
Elderly Subjects. The capacity for conjugation is not modified.
5.3 Preclinical safety data
In animal studies investigating the acute, sub chronic and chronic toxicity of paracetamol in the rat and mouse, gastrointestinal lesions, blood count changes, degeneration of the hepatic and renal parenchyma and necrosis were observed. These changes are, on the one hand, attributed to the mechanism of action and, on the other, to the metabolism of paracetamol. The metabolites that is probably responsible for the toxic effects and the corresponding organic changes have also been found in humans. Moreover, during long term use (i.e. 1 year) very rare cases of reversible chronic aggressive hepatitis have been described in the range of maximum therapeutic doses. At sub toxic doses, symptoms of intoxication can occur following a 3-week intake period. Paracetamol should therefore not be administered over a long period of time or at high doses.
Extensive investigations showed no evidence of any relevant genotoxic risk of paracetamol in the therapeutic, i.e. non-toxic, dose range.
Long-term studies in rats and mice yielded no evidence on relevant carcinogenic effects at non-hepatotoxic dosages of paracetamol.
Paracetamol crosses the placental barrier. Animal studies and clinical experience to date have not indicated any teratogenic potential.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Anhydrous citric acid Sodium hydrogen carbonate
Sorbitol E420
Sodium carbonate anydrous Povidone K 25 (E1201)
Simeticone Saccharin sodium
Lemon flavour (containing maize maltodextrin, acacia gum (E414) and alpha-tocopherol (E307))
Macrogol 6000
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Store below 30°C. Keep the polypropylene tube tightly closed. Store in the original container to protect from the moisture and light.
6.5 Nature and contents of container
White opaque plain polypropylene tube and white opaque tamper evident polyethylene cap with inbuilt desiccant. Contains 24 tablets, 20 tablets, 8 tablets or 10 tablets in a tube.
Pack size: 60 (3 x 20) tablets per carton.
20 (1 x 20) tablets per carton 10 (1 x 10) tablets per carton 16 (2 x 8) tablets per carton 30 (3 x 10) tablets per carton 24 (3 x 8) tablets per carton.
24 (1 x 24) tablets per carton 100 (5 x 20) tablets per carton
Pack size: 20 tablets in a tube per carton.
10 tablets in a tube per carton.
Alu-Alu strip pack: The strip packs are made of Aluminium - Aluminium foils.
Pack size(s) for Alu-Alu strip pack:
8’s tablets per carton 10’s tablets per carton
16 tablets per carton 20 tablets per carton 24 tablets per carton 30 tablets per carton 60 tablets per carton 100 tablets per carton
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Accord Healthcare Limited Sage House 319 Pinner Road North Harrow Middlesex, HA1 4HF United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20075/0083
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/11/2009
10 DATE OF REVISION OF THE TEXT
27/04/2015