ASPIRINE UPSA BUFFERED EFFERVESCENT 1000 mg Effervescent tablet 2Tube/10

Effervescent tablet.

Acetylsalicylic acid.............................................................................................................................1000 mg

For one effervescent tablet.

Excipients with known effect: one tablet contains 20 mg of aspartame (source of phenylalanine) (E951), 1,6 g of lactose, 460 mg of sodium, 20 mg of potassium benzoate (E212) and in the flavouring, 0,00075 mg of benzyl alcohol and 0,000075 mg of sulfur dioxide (E220).

Excipients:

• Symptomatic treatment of mild to moderate pain and/or febrile states.

• Symptomatic treatment of inflammatory rheumatism.

This presentation is RESERVED FOR ADULTS AND CHILDREN weighing more than 50 kg (from approximately 15 years of age).

Dosage

• Mild to moderate pain and/or febrile states :

For adults and children weighing more than 50 kg (from approximately 15 years of age):

The maximum recommended daily dose is 3 g of aspirin, i.e. 3 effervescent tablets per day.

The usual dose is 1 effervescent tablet at 1000 mg, to be repeated if needed after at least 4 hours, not exceeding 3 effervescent tablets per day.

• Inflammatory rheumatism :

3 to 6 g maximum per day, to be divided into 3 or 4 doses spaced at least 4 hours apart.

For elderly subjects : 

The dose will be reduced; the maximum recommended daily dose is 2 g of aspirin, i.e. 2 effervescent tablets per day.

The usual dose is 1 effervescent tablet at 1000 mg, to be repeated if needed after at least 4 hours, not exceeding 2 effervescent tablets per day.

Method of administration

Oral use.

Drink immediately after the effervescent tablet has completely dissolved in a large glass of water.

Frequency of administration

Systematic intakes prevent pain or fever fluctuations: they must be spaced at least 4 hours.

Duration of treatment

The patient must be informed not to use acetylsalicylic acid for more than 3 days in case of fever and for more than 5 days in case of pain without the advice of a doctor or dentist.

• Hypersensitivity to the active substance or to any of the excipients listed in section Composition.

• History of gastrointestinal bleeding or perforation during a previous treatment with a non-steroidal anti-inflammatory drug (NSAID).

• Active peptic ulcer, history of peptic ulcer or recurrent bleeding (2 or more distinct documented episodes of bleeding or ulceration).

• History of asthma triggered by the administration of salicylates or substances with similar activity, notably non-steroidal anti-inflammatory drugs.

• Any constitutional or acquired hemorrhagic disease.

• Bleeding risk.

• Severe hepatic impairment.

• Severe renal impairment.

• Severe heart failure.

• Pregnancy, from the beginning of the 6th month (24 weeks of amenorrhoea) for aspirin doses above 100 mg per day (see section Fertility, pregnancy and breastfeeding).

In combination with methotrexate used at doses greater than 20 mg/week (see section Interactions) for anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day), or for analgesic or antipyretic doses (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid.

In combination with oral anticoagulants for anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day), or for analgesic or antipyretic doses (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid and in a patient with a history of gastroduodenal ulcer (see section Interactions).

• Concomitant use of ASPIRIN UPSA EFFERVESCENT BUFFERED 1000 mg, effervescent tablet with other NSAIDs, including selective cyclooxygenase 2 inhibitors (cox-2), should be avoided.

• In case of combination with other medicinal products, to avoid a risk of overdose, check that other medicinal products do not contain acetylsalicylic acid.

• The occurrence of adverse effects can be minimized by using the lowest effective dose for the shortest duration of treatment necessary to relieve symptoms.

In case of long-term administration of high-dose analgesic medicines, the occurrence of headaches must not be treated with higher doses. Regular use of analgesics, in particular combinations of analgesics, may lead to persistent kidney damage with a risk of renal failure.

• Elderly patients : Elderly patients have an increased risk of adverse effects with NSAIDs, in particular gastrointestinal bleeding and potentially fatal perforations (see below). Renal, hepatic and cardiac functions must be closely monitored.

• Particular attention is required in patients with a history of hypertension and/or heart failure, as cases of fluid and sodium retention and oedema have been reported in association with NSAID treatment.

• In some cases of severe G6PD deficiency, high doses of acetylsalicylic acid have been able to cause haemolysis. Administration of acetylsalicylic acid in case of G6PD deficiency must be carried out under medical supervision.

• Monitoring of treatment must be reinforced in the following cases:

• history of gastroduodenal ulcer, digestive hemorrhage or gastritis,
• in patients with renal insufficiency, hepatic insufficiency or cardiovascular insufficiency, as acetylsalicylic acid may increase the risk of renal insufficiency and acute renal insufficiency,
• asthma: the occurrence of asthma attacks, in certain subjects, may be linked to an allergy to non-steroidal anti-inflammatory drugs or to acetylsalicylic acid. In this case, this medicinal product is contraindicated,
• metrorrhagia or menorrhagia (risk of increased intensity and duration of periods),
• use of an intrauterine device.

• Gastrointestinal hemorrhages, ulcerations and perforations: Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal events.

The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing dose in patients with a history of ulcer, particularly if complicated with bleeding or perforation (see section Contraindications) as well as in elderly subjects. In these patients, treatment must be started at the lowest possible dose. A combined mucosa-protective treatment (for example misoprostol or a proton pump inhibitor) must be considered for these patients, as for patients requiring combined treatment with low doses of acetylsalicylic acid or treated with other medicinal products likely to increase the gastrointestinal risk (see below and section Interactions).

Patients with a gastrointestinal history, particularly if they are elderly patients, must report any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially at the start of treatment.

Particular attention must be paid to patients receiving combined treatments that may increase the risk of ulceration or hemorrhage, such as oral corticosteroids, oral anticoagulants such as warfarin, selective serotonin reuptake inhibitors (SSRIs), platelet antiaggregants such as acetylsalicylic acid, anagrelide, cobimetinib, deferasirox, defibrotide, heparins, ibrutinib, mixed adrenergic-serotonergic medicinal products, nicorandil and thrombolytics (see section Interactions).

If hemorrhage or ulceration occurs in a patient receiving ASPIRIN UPSA BUFFERED EFFERVESCENT 1000 mg, effervescent tablet, treatment must be stopped.

NSAIDs should be administered with caution and under close supervision in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), due to the risk of exacerbation of the condition (see section Adverse effects).

• Serious skin reactions, some of which have been fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been very rarely reported during treatment with NSAIDs (see section Adverse effects). The incidence of these undesirable effects in patients appears greater at the start of treatment, with onset in most cases occurring during the first month of treatment. ASPIRIN UPSA BUFFERED EFFERVESCENT 1000 mg, effervescent tablet must be stopped at the first appearance of a skin rash, mucosal lesions or any other sign of hypersensitivity

• Given the platelet antiaggregant effect of acetylsalicylic acid, appearing from very low doses and persisting for several days, the patient should be warned of the risks of bleeding that may occur in the event of even minor surgical procedures (e.g. tooth extraction).

• Acetylsalicylic acid alters uricaemia (at analgesic doses acetylsalicylic acid increases uricaemia by inhibiting uric acid excretion; at the doses used in rheumatology, acetylsalicylic acid has a uricosuric effect).

• At the high doses used in rheumatology, monitoring for signs of overdose is recommended. If tinnitus, reduced hearing acuity and dizziness occur, the treatment regimen should be re-evaluated.

• Use of this medicine is not recommended during breastfeeding.

• This medicinal product contains 1,6 g of lactose per effervescent tablet. Patients with galactose intolerance, total lactase deficiency or glucose and/or galactose malabsorption syndrome (rare hereditary diseases) must not take this medicinal product.

• This medicinal product contains 460 mg of sodium per effervescent tablet, equivalent to 23 % of the maximum daily sodium intake recommended by the WHO. The maximum recommended daily dose of this product (3 effervescent tablets) is equivalent to 69 % of the maximum daily sodium intake recommended by the WHO. ASPIRIN UPSA BUFFERED EFFERVESCENT 1000 mg, effervescent tablet has a high sodium content. To be taken into account in people following a low-sodium diet.

• This medicinal product contains 20 mg of potassium benzoate (E212) per effervescent tablet.

• This medicinal product contains traces of benzyl alcohol per effervescent tablet. Benzyl alcohol may cause allergic reactions. Due to a risk of accumulation and toxicity (metabolic acidosis), precautions must be taken in pregnant and breastfeeding women, and in subjects with hepatic or renal insufficiency.

• This medicinal product contains traces of sulfur dioxide (E220) per effervescent tablet. May, in rare cases, cause severe hypersensitivity reactions and bronchospasm.

• This medicinal product contains 20 mg of aspartame (E951) per effervescent tablet. Aspartame contains a source of phenylalanine. May be harmful to people with phenylketonuria (PKU), a rare genetic disease characterised by the accumulation of phenylalanine that cannot be correctly eliminated.

• Concomitant use of this medicine is not recommended with:

• acetazolamide,
• anagrelide,
• oral anticoagulants, for analgesic or antipyretic doses (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid and in a patient with no history of gastroduodenal ulcer,
• oral anticoagulants, for antiplatelet doses of acetylsalicylic acid (from 50 mg to 375 mg per day) and in a patient with a history of gastroduodenal ulcer (see section Interactions),
• non-steroidal anti-inflammatory drugs at anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day), analgesic or antipyretic doses (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid,
• clopidogrel (outside the validated indications for this combination in acute coronary syndromes),
• glucocorticoids (except hydrocortisone) for anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) of acetylsalicylic acid (see section Interactions),
• heparins (curative doses and/or elderly subject) for anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) or analgesic or antipyretic doses (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid,
• nicorandil,
• pemetrexed in patients with mild to moderate renal impairment (see section Dosage and administration),
• probenecid,
• ticagrelor,
• ticlopidine (see section Interactions).

• Particularly close medical supervision is essential for the following drug combinations (see section Interactions) :

• Oral anticoagulants and low-dose aspirin,
• Other non-steroidal anti-inflammatory drugs and high-dose aspirin (greater than 3 g/day),
• Antiplatelet agents, cobimetinib, deferasirox, diuretics and high-dose aspirin (greater than 3 g/day), systemic glucocorticoids (except hydrocortisone used as replacement therapy in Addison's disease), parenteral heparins, ibrutinib, angiotensin-converting enzyme inhibitors and, by extrapolation, angiotensin II antagonists (for high-dose aspirin, greater than 3 g/day), methotrexate (at doses below 20 mg/week), pemetrexed and ticagrelor.

Risk related to antiplatelet effect

Several substances are involved in the interactions, due to their antiplatelet properties: abciximab, aspirin and NSAIDs, clopidogrel, epoprostenol, eptifibatide, iloprost and iloprost tromethamine, tirofiban and ticlopidine.

The use of several antiplatelet agents increases the risk of bleeding, as does their combination with heparin and related molecules, oral anticoagulants and thrombolytics, and this must be taken into account by maintaining regular clinical and biological monitoring.

Contraindicated combinations (see section Contraindications)

+ Oral anticoagulants

For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day), analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day) and in case of a history of gastroduodenal ulcer.

Increased risk of haemorrhage, particularly in cases of a history of gastroduodenal ulcer.

+ Methotrexate used at doses greater than 20 mg/week

For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) or for analgesic or antipyretic doses (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid.

Increased toxicity, particularly haematological, of methotrexate (decreased renal clearance of methotrexate by acetylsalicylic acid).

Combinations not recommended

+ Acetazolamide

Increased undesirable effects, particularly metabolic acidosis, of acetylsalicylic acid at high doses and of acetazolamide, due to decreased elimination of acetylsalicylic acid by acetazolamide.

+ Anagrelide

Increased haemorrhagic events.

+ Oral anticoagulants

For analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day) and in the absence of a history of gastroduodenal ulcer.

Increased bleeding risk.

+ Oral anticoagulants

For antiplatelet doses of acetylsalicylic acid (from 50 mg to 375 mg per day) and in case of a history of gastroduodenal ulcer.

Increased risk of bleeding. Need for monitoring where appropriate, in particular of bleeding time.

+ Non-steroidal anti-inflammatory drugs

For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day), or for analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid

Increased risk of ulcerogenic and digestive hemorrhage.

+ Clopidogrel (outside the validated indications for this combination in acute coronary syndromes)

Increased risk of bleeding due to the addition of platelet antiaggregant activities.

+ Defibrotide

Increased bleeding risk.

+ Glucocorticoids (except hydrocortisone)

For anti-inflammatory doses of acetylsalicylic acid (≥ 1 g per dose and/or ≥ 3 g per day).

Increased bleeding risk.

+ Heparins (therapeutic doses and/or elderly subject)

For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) or for analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day).

Increased bleeding risk (inhibition of platelet function) and damage to the gastroduodenal mucosa by acetylsalicylic acid.

Use another anti-inflammatory or another analgesic or antipyretic.

+ Nicorandil

Increased risk of ulcerogenic and digestive hemorrhage.

+ Pemetrexed

In patients with weak to moderate renal function (see section Dosage and administration), risk of increased toxicity of pemetrexed (decrease in its renal clearance by acetylsalicylic acid at anti-inflammatory doses, i.e. ≥ 1 g per dose and/or ≥ 3 g per day).

+ Probenecid

Reduction of the uricosuric effect through competition for uric acid elimination at the renal tubules.

+ Ticagrelor (outside the indications validated for this combination in acute coronary syndromes)

Increased risk of bleeding due to the addition of platelet antiaggregant activities.

+ Ticlopidine

Increased risk of bleeding due to the addition of platelet antiaggregant activities.

If the combination cannot be avoided, close clinical monitoring.

Associations requiring precautions for use

+ Angiotensin II receptor antagonists, Angiotensin-converting enzyme inhibitors

For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) or for analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day).

Acute renal failure in at-risk patients (elderly, dehydrated, on diuretics, with impaired renal function), due to decreased glomerular filtration secondary to decreased synthesis of renal prostaglandins. Furthermore, reduced antihypertensive effect.

Hydrate the patient and monitor renal function at the start of treatment and regularly during the combination.

+ Clopidogrel (within the approved indications for this combination in acute coronary syndromes)

Increased risk of bleeding due to additive antiplatelet activities. Clinical monitoring.

+ Cobimetinib

Increased risk of bleeding.

Clinical monitoring.

+ Diuretics

 For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) or for analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day).

Acute renal failure in patients at risk (elderly, dehydrated, with impaired renal function), due to decreased glomerular filtration secondary to decreased synthesis of renal prostaglandins. Furthermore, reduction of the antihypertensive effect.

Hydrate the patient and monitor renal function at the start of treatment and regularly during the combination.

+ Ibrutinib

Increased risk of bleeding.

Clinical monitoring.

+ Methotrexate used at doses less than or equal to 20 mg/week

For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) or for analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day).

Increased toxicity, particularly haematological, of methotrexate (decreased renal clearance of methotrexate by acetylsalicylic acid).

Weekly monitoring of the blood count during the first weeks of the combination. Increased monitoring in case of impairment (even slight) of renal function, as well as in elderly subjects.

+ Methotrexate used at doses greater than 20 mg/week

For antiplatelet doses of acetylsalicylic acid (50 to 375 mg per day).

Increased toxicity, particularly haematological, of methotrexate (decreased renal clearance of methotrexate by acetylsalicylic acid).

Weekly monitoring of the blood count during the first weeks of the combination. Increased monitoring in case of impairment (even slight) of renal function, as well as in elderly subjects.

+ Pemetrexed

In patients with normal renal function, risk of increased toxicity of pemetrexed (decreased renal clearance of pemetrexed by acetylsalicylic acid at anti-inflammatory doses).

Biological monitoring of renal function.

+ Ticagrelor (within the validated indications for this combination in acute coronary syndromes)

Increased risk of bleeding due to the addition of platelet antiaggregant activities.

Clinical monitoring.

+ Gastrointestinal topicals, antacids and adsorbents

Decreased absorption of acetylsalicylic acid.

As a precaution, these gastrointestinal topicals or antacids and adsorbents should be taken at a distance from acetylsalicylic acid (more than 2 hours, if possible).

Associations to be taken into account

+ Oral anticoagulants

For antiplatelet doses of acetylsalicylic acid (from 50 mg to 375 mg per day).

Increased risk of haemorrhage, particularly in cases of a history of gastroduodenal ulcer.

+ Non-steroidal anti-inflammatory drugs

For antiplatelet doses of acetylsalicylic acid (from 50 mg to 375 mg per day in 1 or more intakes).

Increased risk of ulcerogenic and digestive hemorrhage.

+ Deferasirox

For anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) or for analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per dose and/or < 3 g per day).

Increased risk of ulcerogenic and digestive hemorrhage.

+ Glucocorticoids (except hydrocortisone)

For analgesic or antipyretic doses of acetylsalicylic acid (≥ 500 mg per intake and/or < 3 g per day).

Increased risk of gastrointestinal bleeding.

+ Heparins (therapeutic doses and/or elderly subject)

For antiplatelet doses of acetylsalicylic acid (from 50 mg to 375 mg/day).

Increased bleeding risk (inhibition of platelet function) and damage to the gastroduodenal mucosa by acetylsalicylic acid.

+ Heparins (prophylactic doses)

Concomitant use of medicines acting at various levels of haemostasis increases the risk of bleeding. Thus, in subjects under 65 years of age, the combination of heparin at preventive doses, or related substances, with acetylsalicylic acid, whatever the dose, must be taken into account by maintaining clinical and possibly biological monitoring.

+ Selective serotonin reuptake inhibitors

Increased risk of bleeding.

+ Mixed adrenergic-serotonergic agents

Increased risk of bleeding.

+ Thrombolytics

Increased risk of bleeding.

Pregnancy

Low doses, less than or equal to 100 mg per day:

Clinical studies show that doses up to 100 mg/day appear to be safe in extremely limited obstetric uses requiring specialised monitoring.

Doses between 100 and 500 mg per day:

Clinical experience with the administration of doses between 100 mg and 500 mg per day is insufficient. Consequently, the recommendations below for doses above 500 mg per day apply to these doses.

Doses greater than or equal to 500 mg per day:

From the beginning of the 6th months of pregnancy (24 weeks of amenorrhoea): any intake of ASPIRIN UPSA SOLUBLE EFFERVESCENT 1000 mg, effervescent tablet, even a single one, is contraindicated. Even a single intake from 24 weeks of amenorrhoea justifies cardiac and renal ultrasound monitoring of the foetus and/or newborn. Unless absolutely necessary,, ASPIRIN UPSA BUFFERED EFFERVESCENT 1000 mg, effervescent tablet must not be prescribed to a woman who is planning a pregnancy or during the first 5 months of pregnancy (before 24 weeks of amenorrhoea). If so, the dose should be as low as possible and the duration of treatment as short as possible. Prolonged use is strongly discouraged. In case of intake from the 20th weeks of amenorrhea, cardiac and renal monitoring of the fetus may prove necessary. In case of oligohydramnios, or constriction of the ductus arteriosus, treatment with ASPIRIN UPSA BUFFERED EFFERVESCENT 1000 mg, effervescent tablet must be discontinued.

Inhibition of prostaglandin synthesis by NSAIDs may affect the course of pregnancy and/or the development of the embryo or foetus.

Risks associated with use during the 1st trimester

Epidemiological studies suggest that treatment with a prostaglandin synthesis inhibitor during the 1st trimester of pregnancy is associated with an increased risk of miscarriage.

For certain NSAIDs, an increased risk of cardiac malformations and abdominal wall defects (gastroschisis) is also described. The absolute risk of foetal cardiovascular malformation rose from less than 1% to approximately 1,5% with exposure during the 1er trimester. The risk appears to increase with dose and duration of treatment.

In animals, administration of a prostaglandin synthesis inhibitor during the organogenesis phase causes increased pre- and post-implantation loss, increased embryo-foetal lethality and a higher incidence of certain malformations, including cardiovascular ones.

Risks associated with use during the 2th and 3th trimester

• From the 12th week of amenorrhea

Maternal intake of an NSAID exposes the fetus to a risk of functional renal impairment:

• In utero (onset of fetal diuresis): oligoamnios may occur shortly after the start of treatment. This is generally reversible upon discontinuation of treatment. It may progress to anamnios, particularly with prolonged exposure to an NSAID.
• At birth: renal failure (reversible or not) may be observed, or may even persist, especially in cases of late and prolonged exposure, with a risk of delayed severe hyperkalaemia.

• From the 20th week of amenorrhea:

In addition to renal functional impairment (see above), maternal intake of an NSAID exposes the foetus to a risk  of constriction of the ductus arteriosus (most often reversible on discontinuation of treatment).

• From the 24th week of amenorrhea:

The risk of cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary arterial hypertension) becomes greater and may lead to foetal or neonatal right heart failure or even foetal death in utero. This risk is all the greater and less reversible the closer the intake is to term. This effect exists even with a single intake

In late pregnancy (close to term), NSAID intake also exposes the mother and the newborn to:

-          prolonged bleeding time due to an antiaggregant action, which may occur even after administration of very low doses of the medicinal product;

-          inhibition of uterine contractions resulting in delayed labour or prolonged delivery.

Breast-feeding

Acetylsalicylic acid passes into breast milk, so this medication is not recommended during breastfeeding.

Fertility

As with all NSAIDs, use of this medicine may temporarily impair female fertility by acting on ovulation; it is therefore not recommended for women wishing to conceive. In women experiencing difficulties conceiving or undergoing fertility testing, discontinuation of treatment should be considered

ASPIRIN UPSA BUFFERED EFFERVESCENT 1000 mg, effervescent tablet has no effect on the ability to drive vehicles and use machines.

Blood and lymphatic system disorders

• Haemorrhagic syndromes (epistaxis, gingival bleeding, purpura,...) with increased bleeding time. This effect persists for 4 to 8 days after stopping acetylsalicylic acid. It may create a risk of haemorrhage in case of surgical intervention.
• Cerebral haemorrhage and intracranial haemorrhage.

Immune system disorders

• Urticaria, skin reactions, anaphylactic reactions, asthma, Quincke's oedema.

• Nervous system disorders

• Headache, dizziness,
• sensation of reduced hearing acuity,
• tinnitus, which are usually the sign of an overdose.

Cardiac disorders and vascular disorders

• Oedema, hypertension and heart failure have been reported in association with NSAID treatment.

Gastrointestinal disorders

• The most frequently observed adverse effects are gastrointestinal in nature. Peptic ulcers, perforations or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section Warnings and precautions). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis or Crohn's disease (see section Warnings and precautions) have been reported following administration of NSAIDs. Less frequently, gastritis has been observed.

Skin and subcutaneous tissue disorders

• Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/

Intoxication is to be feared in elderly subjects and especially in young children (therapeutic overdose or frequent accidental poisoning) where it may be fatal.

Symptoms:

• Moderate intoxication

Tinnitus, sensation of reduced hearing acuity, headache, dizziness are the hallmark of an overdose and may be controlled by reducing the dosage.

• Severe poisoning :

In children, overdose may be fatal from 100 mg/kg in a single dose.

The symptoms are: fever, hyperventilation, ketosis, respiratory alkalosis, metabolic acidosis, coma, cardiovascular collapse, respiratory failure, severe hypoglycaemia.

Emergency management:

• Immediate transfer to a specialised hospital setting,

• gastrointestinal decontamination and administration of activated charcoal,

• control of the acid-base balance,

• alkaline diuresis to obtain a urinary pH between 7,5 and 8, possibility of haemodialysis in severe poisoning,

• symptomatic treatment.

Pharmacotherapeutic class: OTHER ANALGESICS AND ANTIPYRETICS-ANILIDES, ATC code: N02BA01.

(N: Nervous system)

Mechanism of action

Acetylsalicylic acid belongs to the group of non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory properties. Its mechanism of action is based on the irreversible inhibition of the cyclo-oxygenase enzymes involved in the synthesis of prostaglandins.

Acetylsalicylic acid also inhibits platelet aggregation by blocking platelet synthesis of thromboxane A2.

Absorption

Acetylsalicylic acid is rapidly and almost completely absorbed orally. Peak plasma concentrations are reached in 15 to 40 minutes.

The bioavailability of acetylsalicylic acid varies according to dose: it is approximately 60% for doses below 500 mg and 90% for doses above 1 g due to saturation of hepatic hydrolysis.

Acetylsalicylic acid undergoes rapid hydrolysis giving salicylic acid (a metabolite that is also active).

Distribution

Acetylsalicylic acid and salicylic acid diffuse rapidly into all tissues. They cross the placental barrier and are found in breast milk.

Salicylic acid is largely bound to plasma proteins (at 90%).

The plasma half-life is 15 to 20 minutes for acetylsalicylic acid, and 2 to 4 h for salicylic acid.

Biotransformation - Elimination

Acetylsalicylic acid is extensively metabolised in the liver. It is excreted mainly in the urine as salicylic acid and glucuronide conjugate, as well as salicyluric acid and gentisic acid.

Mutagenic and carcinogenic potential.

Acetylsalicylic acid has been the subject of very numerous preclinical studies carried out in vitro and in vivo the overall results of which revealed no reason to suspect a mutagenic effect.

Long-term studies carried out in rats and mice showed no carcinogenic effect of acetylsalicylic acid.

3 years.

Store below 25°C and protect from moisture.

Replace the cap on the tube immediately after use.

No special requirements.

Marketing authorisation (AMM)

CIP 3400933531539 (2T/10).

Price:

2,44 euros (2T/10).

Social Security reimbursement at 65%.
Collection.