POM: Prescription only medicine
This information is intended for use by health professionals
PosologyAdults including elderly: 1-2 tablets (300-600mg) every 3-4 hours as required, to a maximum of 12 tablets (3.6g) daily in divided doses.Children: Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki's disease).Antithrombotic action: For its antithrombotic effect following myocardial infarction, transient ischaemic attack, or in patients with unstable angina, the recommended dose is 300mg daily.
Method of AdministrationFor oral administration.
Methotrexate (used at doses >15 mg/week):The combined drugs, methotrexate and acetylsalicylic acid, enhance haematological toxicity of methotrexate due to the decreased renal clearance of methotrexate by acetylsalicylic acid. Therefore, the concomitant use of methotrexate (at doses >15 mg/week) with acetylsalicylic acid is contraindicated (see section 4.3).
Not recommended combinations
Uricosuric agents, e.g. probenecidSalicylates reverse the effect of probenecid. The combination should be avoided.
Combinations requiring precautions for use or to be taken into account
Anticoagulants e.g. coumarin, heparin, warfarinIncreased risk of bleeding due to inhibited thrombocyte function, injury of the duodenal mucosa and displacement of oral anticoagulants from their plasma protein binding sites. The bleeding time should be monitored (see section 4.4).
Anti-platelet agents (e.g clopidogrel and dipyridamole) and selective serotonin reuptake inhibitors (SSRIs; such as sertraline or paroxetine)Increased risk of gastrointestinal bleeding (see section 4.4).
Antidiabetics, e.g. sulphonylureasSalicylics may increase the hypoglycaemic effect of sulphonylureas.
Digoxin and lithiumAcetylsalicylic acid impairs the renal excretion of digoxin and lithium, resulting in increased plasma concentrations. Monitoring of plasma concentrations of digoxin and lithium is recommended when initiating and terminating treatment with acetylsalicylic acid. Dose adjustment may be necessary
Diuretics and antihypertensivesNSAIDs may decrease the antihypertensive effects of diuretics and other antihypertensive agents. As for other NSAIDs concomitant administration with ACE-inhibitors increases the risk of acute renal insufficiency.Diuretics: Risk of acute renal failure due to the decreased glomerual filtration via decreased renal prostaglandin synthesis. Hydrating the patient and monitoring renal function at the start of the treatment is recommended.
Carbonic anhydrase inhibitors (acetazolamide)May result in severe acidosis and increased central nervous system toxicity
Systemic corticosteroidsThe risk of gastrointestinal ulceration and bleeding may be increased when acetylsalicylic acid and corticosteroids are co-administered (see section 4.4).
Methotrexate (used at doses <15 mg/week):The combined drugs, methotrexate and acetylsalicylic acid, may increase haematological toxicity of methotrexate due to decreased renal clearance of methotrexate by acetylsalicylic acid. Weekly blood count checks should be done during the first weeks of the combination. Enhanced monitoring should take place in the presence of even mildly impaired renal function, as well, as in elderly.
Other NSAIDsIncreased risk of ulcerations and gastrointestinal bleeding due to synergistic effects.
Ciclosporin, tacrolimusConcomitant use of NSAIDs and ciclospoin or tacrolimus may increase the nephrotoxic effect of ciclosporin and tacrolimus. The renal function should be monitored in case of concomitant use of these agents and acetylsalicylic acid.
ValproateAcetylsalicylic acid has been reported to decrease the binding of valproate to serum albumin, thereby increasing its free plasma concentrations at steady state.
PhenytoinSalicylate diminishes the binding of phenytoin to plasma albumin. This may lead to decreased total phenytoin levels in plasma, but increased free phenytoin fraction. The unbound concentration, and thereby the therapeutic effect, does not appear to be significantly altered.
AlcoholConcomitant administration of alcohol and acetylsalicylic acid increases the risk of gastrointestinal bleeding.
IbuprofenExperimental data suggest that ibuprofen may inhibit the effect of low dose acetylsalicylic acid 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).
Low doses (up to 100 mg/day)Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe. Doses of 100- 500 mg/day:There is insufficient clinical experience regarding the use of doses above 100 mg/day up to 500 mg/day. Therefore, the recommendations below for doses of 500 mg/day and above apply also for this dose range.
Doses of 500 mg/day and above:Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage, and of cardiac malformation and gastroschisis 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 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, acetylsalicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible. Regular or high dose use of salicylates late in pregnancy may result in:- kernicterus in jaundiced neonatesDuring the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;the mother and the neonate, at the end of pregnancy, to: - possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.- inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.
LactationLow quantities of salicylates and of their metabolites are excreted into the breast milk. Adverse effects for the infant have not been reported up to now. However, aspirin should be avoided during lactation because of the possible risk of Reye's syndrome. In cases of long-term use and/or administration of higher doses, breastfeeding should be discontinued. Regular use of high doses of aspirin could impair platelet function and produce hypoprothrombinaemia in the infant neonatal vitamin K stores are low.
|Blood and lymphatic system disorders||Common: Increased bleeding tendencies. Rare: Thrombocytopenia, agranulocytosis, aplastic anaemia. Not known: Cases of bleeding with prolonged bleeding time such as epistaxis, gingival bleeding. Symptoms may persist for a period of 48 days after acetylsalicylic acid discontinuation. As a result there may be an increased risk of bleeding during surgical procedures. Existing (haematemesis, melaena) or occult gastrointestinal bleeding, which may lead to iron deficiency anaemia (more common at higher doses). anaemia, haemolytic anaemia, hypoprothrombinaemia, pancytopenia, occult blood loss, elevated transaminase levels|
|Immune system disorders||Rare: Hypersensitivity reactions, angio-oedema, allergic oedema, anaphylactic reactions including shock.|
|Metabolism and digestive system disorders||Not known: Hyperuricemia.|
|Nervous system disorders||Rare: Intracranial haemorrhage Not known: Headache, vertigo.|
|Ear and labyrinth disorders||Not known: Reduced hearing ability; tinnitus.|
|Vascular disorders||Rare: Haemorrhagic vasculitis.|
|Respiratory, thoracic and mediastinal disorders||Uncommon: Rhinitis, dyspnoea. Rare: Bronchospasm, asthma attacks.|
|Reproductive systemand mammary disorders||Rare: Menorrhagia|
|Gastrointestinal disorders||Common: Dyspepsia. Rare: Severe gastrointestinal haemorrhage, nausea, vomiting. Not known: Gastric or duodenal ulcers and perforation which can occasionally be major (may develop bloody or black tarry stools, severe stomach pain and vomiting blood), gastrointestinal irritation (mild stomach pain), erosions, heartburn, Fatalities have occurred.|
|Hepatobiliary disorders||Not known: Hepatic insufficiency, hepatitis (particularly in patients with SLE or connective tissue disease)|
|Skin and subcutaneous tissue disorders||Uncommon: Urticaria. Rare: Steven-Johnsons syndrome, Lyells syndrome, purpura, erythema nodosum, erythema multiforme.|
|Renal and urinary tract disorders||Not known: Impaired renal function|
|Body as a whole general disorders||Not known: 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)|
ChildrenAspirin may be associated with the development of Reye's Syndrome (encephalopathy and hepatic failure) in children presenting with an acute febrile illness.
SymptomsCommon features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, 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 four years. In children aged four 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, thrombocytopaenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.Other symptoms may include: headache, nausea, or abdominal pain.Central nervous system features including confusion, restlessness, hallucinations, disorientation, coma, cardiovascular collapse, respiratory arrest and convulsions are less common in adults than in children.
ManagementIf a toxic dose has been ingested, hospital admission is requiredGive 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 ten years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.Other symptoms to be treated symptomatically.
Shelf-lifeThree years from the date of manufacture.
Shelf-life after dilution/reconstitutionNot applicable.
Shelf-life after first openingNot applicable.
OTC Packs:The product containers are polyethylene snap-safe vials (CRC) or, as an alternative, amber glass bottles with clic-loc caps both with integral seal, cotton wool or polyfoam wad headspace filler.
Dispensing Packs:The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers with polyfoam wad or polyethylene ullage filler and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps and polyfoam wad or cotton wool. An alternative closure for polyethylene containers is a polypropylene, twist on, push down and twist off child-resistant, tamper-evident lid.The product may also be supplied in blister packs in cartons:a) Carton: Printed carton manufactured from white folding box board.b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-6g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.c) Child Resistant Blister Pack: (i) 250µm white rigid PVC. (ii) 9µm soft aluminium / 35g/m2 glassine paper.Pack sizes: GSL: 7's, 8's, 10's, 14's, 16'sP: 20's, 21's, 25's, 28's, 30's, 32's,POM: 40's, 48's, 50's, 56's, 60's, 84's, 90's, 100's, 112's, 500's, 1000's.Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.Maximum size of bulk packs: 50,000.