Aspirin 300mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Aspirin Tablets BP 300 mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Aspirin 300 mg
For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Tablet.
4.1 Therapeutic indications
As an analgesic, antpyretic and anti-inflammatory: for indications including rheumatoid arthritis, osteoarthritis, sciatica, lumbago, fibrositis, muscular aches and pains and acute and chronic rheumatic conditions.
Symptomatic relief of influenza and feverish colds.
Mild to moderate pain including headache, toothache, sore throat, dysmenorrhoea, migraine and neuralgia.
Aspirin also has an antithrombotic action, mediated through inhibition of platelet activation, which has been shown to be useful in secondary prophylaxis following myocardial infarction, and in patients with unstable angina and cerebral transient ischaemic attacks.
4.2 Posology and method of administration
Adults and children over 16 years: one to three tablets.
This dose may be taken if necessary up to 4 times a day at intervals of not less than 4 hours.
Maximum daily dose 3600mg in divided doses.
Do not give to children under 16 years, unless specifically indicated (e.g. Kawasaki’s disease).
Elderly: There is no need for dosage reduction in the elderly.
Antithrombotic action: For its antithrombotic effect following myocardial infarction, transient ischaemic attack, or in patients with unstable angina, the recommended dose is 300mg daily.
For oral administration.
Aspirin should be taken with food to help avoid gastrointestinal problems.
4.3 Contraindications
Aspirin should not be taken by patients with the following conditions:
• Hypersensitivity to aspirin or to any of the excipients listed in section 6.1. Aspirin is contraindicated in patients with a history of hypersensitivity reactions to aspirin or other NSAIDs, which include those in whom attacks of asthma, angioedema, urticaria or rhinitis, have been precipitated by such drugs.
• Haemophilia or other haemorrhagic disorders as there is an increased risk of bleeding
• Active peptic ulceration or a past history of ulceration or dyspepsia
• Severe cardiac failure
• Severe renal or hepatic impairment
• Nasal polyps associated with asthma
• Concurrent coagulant therapy
• Children under 16, unless specifically indicated e.g. Kawasaki’s disease (See section 4.4)
• Pregnancy, particularly during the 3rd trimester, or breast feeding
4.4 Special warnings and precautions for use
Caution should be exercised in patients with asthma, allergic disease, anaemia, cardiac failure, thyrotoxicosis, systemic lupus erythematosus and other connective tissue disorders, impairment of hepatic or renal function (avoid if severe) and dehydration. Aspirin and other NSAID’s may cause salt and water retention and renal failure especially in patients with pre-existing renal impairment (see also section 4.8).
Do not exceed the stated dose
If symptoms persist for more than 3 days consult your doctor.
Keep out of the reach of children.
Do not give to children under 16 years of age unless on the advice of your doctor. There is a possible association between Aspirin and Reye’s syndrome when given to children. Reye’s syndrome is a very rare disease which affects the brain and liver and can be fatal. For this reason it should not be given to children under 16, unless specifically indicated (e.g. Kawasaki’s disease).
Aspirin decreases platelet adhesiveness and increases bleeding time. Haematological and haemorrhagic effects can occur, and may be severe. Patients should report any unusual bleeding symptoms to their physician. Aspirin should be stopped several days before surgery.
Long term use of aspirin can lead to slight ongoing blood loss from gastrointestinal bleeding which may cause iron-deficiency anaemia, particularly in the elderly. Avoid prolonged use in the elderly, who are particularly prone to the adverse effects of aspirin.
Aspirin may be given with H2 antagonists, proton pump inhibitors or misoprostol where patients are at risk of peptic ulcer or gastritis.
Patients with glucose-6-phosphate dehydrogenase deficiency (G-6-PD) are at increased risk of haemolysis.
Aspirin can interfere with insulin and glucagon control in diabetics.
Aspirin can interfere with thyroid function tests.
Symptoms of chronic aspirin overdose (salicylism) can occur where higher doses are taken for long periods and include dizziness, tinnitus, deafness, sweating, nausea, and vomiting, headache, and confusion, and may be controlled by reducing the dosage.
Aspirin can cause an elevation in uric acid levels - this can precipitate or exacerbate an attack of gout
Before commencing long-term therapy for the management of cardiovascular or cerebrovascular disease patients should consult their doctor who can advise on the relative benefits versus the risks for the individual patient.
Vaccine recipients should avoid use of salicylates for 6 weeks after varicella vaccination (see section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).
Plasma salicylate concentrations may be reduced by concurrent use of corticosteroids, and salicylate toxicity may occur following withdrawal of the corticosteroids. The risk of gastrointestinal ulceration and bleeding may be increased when aspirin and corticosteroids are co-administered. Alcohol and corticosteroids may enhance the effects of aspirin on the gastrointestinal tract.
Concurrent use of aspirin and other NSAIDs (including topical formulations) should be avoided. Use of two or more NSAID preparations increases the risk of serious gastrointestinal haemorrhage.
Alcohol may enhance the gastro-intestinal side effects of aspirin.
May enhance the effects of coumarin anticoagulants, antiplatelet agents and fibrinolytics leading to increased risk of bleeding.
May enhance the effects of oral hypoglycaemic agents of the sulphonylurea type.
May enhance the effects of phenytoin and sodium valproate.
Dipyridamole - increase in peak concentration.
Diuretics - frusemide and acetazolamide (risk of toxic effects), spironolactone (antagonized diuretic action).
The activity of methotrexate may be markedly enhanced and its toxicity increased.
May inhibit action of uricosurics (e.g. probenecid, sulfinpyrazone).
May increase the toxicity of sulphonamides.
Concurrent administration of carbonic anhydrase inhibitors such as acetazolamide and salicylates may result in severe acidosis and increased central nervous system toxicity.
Antacids and citrates may increase the excretion of aspirin.
May reduce the efficacy of antihypertensive drugs
Metoclopramide and domperidone may increase the rate of absorption of aspirin.
Aspirin should be avoided until 8-12 days after mifepristone.
Ototoxic medicine (eg vancomycin) may increase the potential for ototoxicity. Hearing loss may occur and may progress to deafness even after discontinuation of the medication. Effects may be reversible but are usually permanent.
There is an increased risk of bleeding when aspirin is given with SSRI’s and Venlafaxine.
There is an increased risk of bleeding when taken with Sibutramine.
Aspirin increases the plasma concentration of Zafirlukast.
Calcium-channel blockers - reduced hypotensive effects, increased antiplatelet effect which rarely results in pro-longed bleeding time.
Varicella vaccine - Vaccine recipients should avoid use of salicylates for 6 weeks after vaccination with varicella vaccine as Reye's syndrome has been reported following use of salicylates during wild-type varicella infection (see section 4.4).
There is a possible risk of bleeding when taken with ginkgo biloba.
Laboratory investigations - aspirin may interfere with some laboratory tests such as urine 5-hydroxyindoleacetic acid determinations and copper sulphate urine sugar tests.
Aspirin may lead to a reduced hypotensive effect, increased risk of renal impairment and hypokalaemia when taken with ACE inhibitors. Monitoring of renal function may be required
4.6 Fertility, pregnancy and lactation
Pregnancy
Inhibition of prostaglandin sysnthesis may adversely affect the pregnancy and/or the embryo/fetal development. Data from epidemiology studies suggest an increased risk of miscarriage and of cardiac malformation after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%.
Studies in animals have shown that salicylates can cause birth defects including fissure of the spine and skull, facial clefts and malformations of the CNS, viscera and skeleton, pre and post implantation loss and embryo-fetal lethality. During the first and second trimester aspirin should not be given unless necessary.
Regular or high dose use of salicylates late in pregnancy may result in:
- constriction or premature closing of the fetal ductus arteriosus
- increased risk of still birth or neonatal death
- decreased birth weight
- prolonged labour
- complicated deliveries and increased risk of maternal or fetal haemorrhage
- possibly persistent pulmonary hypertension of newborn
- kernicterus in jaundiced neonates
- renal dysfunction, which may progress to renal failure with oligo-hydramniosis
Administration is contraindicated in the last trimester of pregnancy and should be avoided during the late stages of labour and during the delivery of a premature infant.
Fertility
Aspirin should not be given to women wishing to become pregnant, since it is thought that prostaglandin synthesis inhibitors can reduce fertility. The effect on fertility is reversible.
Breastfeeding
Use in children under 16 years old is contraindicated due to possible risk of Reye's syndrome. Since aspirin is distributed into breast milk, breast fed infants may also be at risk. Aspirin should be avoided while breastfeeding.
4.7 Effects on ability to drive and use machines
Aspirin does not usually affect the ability to drive or operate machinery.
4.8 Undesirable effects
Adverse effects of aspirin treatment which have been reported include:
Blood and lymphatic system disorders - anaemia, haemolytic anaemia, hypoprothrombinaemia, thrombocytopenia, aplastic anaemia, pancytopenia, prolonged bleeding time, occult blood loss, elevated transaminase levels, agranulocytosis.
Gastrointestinal disorders - gastrointestinal bleeding, erosions, perforations or ulceration which can occasionally be major (may develop bloody or black tarry stools, severe stomach pain and vomiting blood), gastrointestinal irritation (mild stomach pain, heartburn, vomiting and nausea). Fatalities have occurred.
Hepatic disorders - hepatitis (particularly in patients with SLE or connective tissue disease)
Renal and urinary disorders - disturbances of renal function Ear and labyrinth disorders - tinnitus.
Salicylism - mild chronic salicylate intoxication may occur after repeated administration of large doses, symptoms include dizziness, tinnitus, deafness, sweating, nausea, vomiting, headache and mental confusion, and may be controlled by reducing the dose.
General disorders and administration site conditions - Allergic reactions -rhinitis, urticaria, purpura, Stevens-Johnson syndrome, angioneurotic oedema, angio-oedema, asthma, worsening of asthma, bronchospasms.
Children
Aspirin may be associated with the development of Reye's Syndrome (encephalopathy and hepatic failure) in children presenting with an acute febrile illness.
4.9 Overdose
Salicylate poisoning is usually associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L
(5.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.
Symptoms
Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, headache, confusion, dizziness, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.
A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of 4 years.
In children aged 4 years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.
Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.
Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children.
Management
Give activated charcoal if an adult presents within one hour of ingestion of more than 250 mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalinisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous 8.4% sodium bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.
Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations >700 mg/L (5.1 mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under 10 years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics/Antipyretics: salicylic acid and other derivatives,
ATC code: N02BA
Aspirin is an analgesic and antipyretic with anti-inflammatory properties. Aspirin inhibits prostaglandin synthetase.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400 mg was taken within 8 hours before or within 30 minutes after immediate release aspirin (81 mg), a decreased effect of aspirin on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.
5.2 Pharmacokinetic properties
Absorption: Aspirin is rapidly absorbed after oral administration, with some hydrolysis to salicylate before absorption. Absorption is delayed by the presence of food and is impaired in patients suffering migraine attacks. Absorption is more rapid in patients with achlorhydria and also following administration of polysorbates and antacids. After absorption aspirin is rapidly converted to salicylate but during the first 20 minutes following oral administration, aspirin is the predominant form of the drug in the plasma. Aspirin is bound to plasma proteins and is widely distributed.
Blood Concentration: Peak plasma concentrations of approximately 45 mcg/ml are attained 1-2 hours after an oral dose of 640 mg, but stabilise at approximately 270 mcg/ml after oral doses of 3 g daily. After an oral dose of about 2 g, peak plasma concentrations of approximately 15 mcg/ml of aspirin are attained in about one hour and peak plasma concentrations of approximately 130 mcg/ml of salicylate are attained in 2 to 4 hours.
Half Life:
Plasma/Aspirin Approximately 17 minutes
Plasma/Salicylate Low doses 2-4 hours, High doses up to 19 hours
Distribution: Aspirin is found in the saliva, milk, plasma and synovial fluid at concentrations less than blood and crosses the placenta.
Salicylate/extensive protein building.
Aspirin/protein binding to a small extent.
Metabolism: In the blood, rapid hydrolysis to salicylate acid; glucuronic acid/glycine conjugation to form glucuronides and salicyluronic acid; oxidation of a small proportion.
Excretion: Excreted in the urine mainly as salicyluronic acid. Salicylate reabsorbed by renal tubules in acid urine, and alkaline diuresis will increase the rate of excretion; 85% of dose excreted as free salicylate.
Salicylate is mainly eliminated by hepatic metabolism - the metabolites including salicylic acid, salicyl phenolic glucuronide, salicylic acyl glucuronide, gentisic acid and gentisuric acid. As a result of zero order kinetics, plasma steady state salicylate concentrations increase disproportionately with dose. Salicylate is also excreted unchanged in the urine to an extent which depends on the dosage and urinary pH. Renal excretion involves glomerular filtration, active renal tubular secretion and passive tubular reabsorption.
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize Starch
6.2 Incompatibilities
Aspirin is pharmaceutically incompatible with iron salts and alkalis.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Do not store above 25 °C and protect from light.
6.5 Nature and contents of container
Blister packs (PVC) of 16, 24, 32, 100 tablets Tablet Containers: 16, 25, 32, 50, 100, 500, 1000 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
N/A
7 MARKETING AUTHORISATION HOLDER
Athlone Pharmaceuticals limited
Ballymurray
Roscommon
Country Roscommon
Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 30464/0005
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
17/08/2007
10
DATE OF REVISION OF THE TEXT
02/06/2014