ASPIRINE UPSA VITAMIN C Buffered effervescent tablet 2Tube/10

Effervescent tablet.

Acetylsalicylic acid................................................................................................................................330 mg

Ascorbic acid.........................................................................................................................................200 mg

For one effervescent tablet.

Excipients with known effect: one tablet contains 485 mg of sodium and 48 mg of sodium benzoate (E211).

Excipients:

This medicine contains aspirin and vitamin C.

This presentation is RESERVED FOR ADULTS AND CHILDREN from 20 kg (approximately from 6 years of age) in the symptomatic treatment of mild to moderate pain and/or febrile conditions.

Dosage

Paediatric population

Mild to moderate pain and/or febrile states :

• In children, it is imperative to observe the dosages defined according to weight of the child and to choose an appropriate presentation. The approximate ages according to weight are given for information only.

The recommended total daily dose of acetylsalicylic acid is approximately 60 mg/kg, to be divided into 4 or 6 doses, i.e. approximately 15 mg/kg every 6 hours or 10 mg/kg every 4 hours.

• For children weighing 20 to 26 kg (approximately 6 to 10 years), the dosage is 1 effervescent tablet per dose, to be repeated if necessary after 6 hours, not to exceed 4 effervescent tablets per day.
• For children weighing 27 to 36 kg (approximately 8 to 12 years), the dosage is 1 effervescent tablet per dose, to be repeated if necessary after 4 hours, not to exceed 6 effervescent tablets per day.
• For children weighing 37 to 50 kg (approximately 11 to 15 years), the dosage is 2 effervescent tablets per dose, to be repeated if needed after 6 hours, not exceeding 8 effervescent tablets per day.

• For adults and children weighing more than 50 kg (from approximately 15 years): the maximum recommended daily dose is 3 g of aspirin, i.e. 9 effervescent tablets per day.

The usual dosage is 2 effervescent tablets at 330 mg, to be repeated if needed after at least 4 hours, not exceeding 9 effervescent tablets per day.

• For elderly subjects :

The maximum recommended daily dose is 2 g of aspirin, i.e. 6 effervescent tablets per day.

The usual dosage is 1 effervescent tablet at 330 mg, to be repeated if needed after at least 4 hours. In case of more intense pain or fever, 2 effervescent tablets at 330 mg, to be repeated if needed after at least 4 hours, not to exceed 6 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 dosing helps avoid fluctuations in pain or fever:

In children, they must be regularly spaced, including at night, of preferably 6 hours, and at least 4 hours: follow the dosage specified above.

In adults, they must be spaced at least 4 hours apart.

Duration of treatment

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

• Hypersensitivity to the active substances 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)

Oxalo-calcium renal lithiasis (urinary tract stones) for doses above 1 g/day.

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

In combination with oral anticoagulants at anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day), or at 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).

• The concomitant use of ASPIRINE UPSA VITAMINEE C TAMPONNEE EFFERVESCENTE, effervescent tablet with other NSAIDs, including selective cyclooxygenase 2 (COX-2) inhibitors, should be avoided.

• When combined with other medicines, to avoid a risk of overdose, check that other medicines do not contain acetylsalicylic acid and ascorbic acid.

• The occurrence of undesirable effects can be minimised 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 analgesics, the occurrence of headache should not be treated with higher doses.

Regular use of analgesics, particularly the combination of analgesics, can lead to persistent kidney damage with a risk of renal failure.

• Elderly patients : Elderly subjects have an increased risk of undesirable effects with NSAIDs, in particular gastrointestinal haemorrhage and perforations that may be fatal (see below). Renal, hepatic and cardiac functions should be closely monitored.

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

• Tablets at 330 mg are not suitable for children weighing less than 20 kg, for whom more suitable dosages exist.

• Reye's syndrome, very rare but life-threatening conditions, has been observed in children with signs of viral infections (in particular chickenpox and influenza-like episodes) receiving acetylsalicylic acid.

Consequently, acetylsalicylic acid should be administered to these children only on medical advice, when other measures have failed.

If persistent vomiting, impaired consciousness or abnormal behaviour occurs, treatment with acetylsalicylic acid must be stopped.

• 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.

• In children under 1 month, administration of acetylsalicylic acid is only justified in certain situations under medical prescription.

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

• history of gastroduodenal ulcer, digestive haemorrhage or gastritis,
• in patients with renal impairment, hepatic impairment or cardiovascular insufficiency, as acetylsalicylic acid may increase the risk of renal failure and acute renal failure,,
• 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 medicine is contraindicated,
• metrorrhagia or menorrhagia (risk of increased heaviness 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 bleeding or ulceration occurs in a patient receiving ASPIRINE UPSA VITAMINEE C TAMPONNEE EFFERVESCENTE, 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 adverse effects in patients appears to be greater at the start of treatment, the onset period being, in most cases, during the first month of treatment. ASPIRINE UPSA VITAMINEE C TAMPONNEE EFFERVESCENTE, effervescent tablet must be stopped as soon as a skin rash, mucous membrane lesions or any other sign of hypersensitivity appears.

• Given the antiplatelet effect of acetylsalicylic acid, appearing from very low doses and persisting for several days, the patient should be warned of the bleeding risks 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, it is recommended to monitor for signs of overdose. If tinnitus, decreased hearing acuity and dizziness occur, the treatment modalities should be re-evaluated. In children, it is recommended to monitor salicylemia, particularly when starting treatment.

• Use of this medicine is not recommended during breastfeeding.

• Vitamin C should be used with caution in patients suffering from disorders of iron metabolism, predisposed to the formation of urinary or renal stones, and in subjects deficient in Glucose-6 Phosphate Dehydrogenase.

• This medicine contains 485 mg of sodium per effervescent tablet, equivalent to 24,3 % of the maximum daily sodium intake recommended by the WHO. The maximum recommended daily dose of this product (9 effervescent tablets) is equivalent to 218,7 % of the maximum daily sodium intake recommended by the WHO. ASPIRINE UPSA VITAMINEE C TAMPONNEE EFFERVESCENTE, effervescent tablet has a high sodium content. To be taken into account in people following a low-sodium diet.

• This medicine contains 48 mg of sodium benzoate (E211) per effervescent tablet.

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 without a 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),
• defibrotide,
• glucocorticoids (except hydrocortisone) at 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 low to moderate renal function (see section Dosage and administration),
• probenecid,
• ticagrelor,
• ticlopidine (see section Interactions).

Particularly rigorous medical monitoring 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),
• Platelet aggregation inhibitors, ciclosporin, cobimetinib, deferasirox, deferiprone, diuretics and aspirin at high doses (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 aspirin at high doses, greater than 3 g/day), methotrexate (at doses less than 20 mg/week), pemetrexed and ticagrelor.

Interactions with aspirin:

Risk related to antiplatelet effect

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

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

Contraindicated combinations (see section Contraindications)

+ Oral anticoagulants

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) and in case of a history of gastroduodenal ulcer.

Increased risk of haemorrhage, particularly in case 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 (see section Warnings and precautions)

+ 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).

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 risk of bleeding (inhibition of platelet function and irritation of 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 the addition of platelet antiaggregant 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 pemetrexed toxicity (reduction of its renal clearance by acetylsalicylic acid at anti-inflammatory doses, i.e. ≥ 1 g per dose and/or ≥ 3 g per day).

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 topicals or antacids 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 case 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 bleeding risk.

+ Heparins (therapeutic doses and/or elderly subject)

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

Increased risk of bleeding (inhibition of platelet function and irritation of 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.

Interactions with vitamin C:

At doses above 2 g/day of vitamin C, ascorbic acid may interfere with the following laboratory tests: blood and urine creatinine and glucose assays (diabetes monitoring by glucose-oxidase test strips).

Associations requiring precautions for use

+ Deferiprone

By extrapolation from the interaction with deferoxamine: with high-dose intravenous ascorbic acid: abnormalities of cardiac function, even acute heart failure (generally reversible upon discontinuation of vitamin C).

+ Deferoxamine

With high-dose intravenous ascorbic acid: abnormalities of cardiac function, even acute heart failure (generally reversible upon discontinuation of vitamin C).

In cases of hemochromatosis, give vitamin C only after deferoxamine treatment has been started. Monitor cardiac function in case of combination.

Associations to be taken into account

+ Ciclosporin

Risk of decreased blood concentrations of ciclosporin, particularly in case of combination with vitamin E.

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 VITAMIN C BUFFERED EFFERVESCENT, 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 VITAMINED C BUFFERED EFFERVESCENT, 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 VITAMINED C BUFFERED EFFERVESCENT, 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 and, in the absence of data on the passage of vitamin C into breast milk, the use of this medicine should be avoided 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 in women wishing to conceive a child. In women experiencing difficulties conceiving or undergoing fertility tests, discontinuation of treatment should be considered.

ASPIRINE UPSA VITAMINEE C TAMPONNEE EFFERVESCENTE, effervescent tablet has no effect on the ability to drive vehicles and use machines.

RELATED TO ASPIRIN

Infections and infestations

• Reye's syndrome (see section Warnings and precautions).

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 haemorrhagic risk in the event of surgical intervention.

• Cerebral haemorrhage and intracranial haemorrhage

Immune system disorders

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

Nervous system disorders

• Headache, dizziness,

• sensation of decreased hearing acuity,

• tinnitus,

which are usually the sign of an overdose.

Cardiac disorders and vascular disorders

• Edema, 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 haemorrhages, sometimes fatal, may occur, particularly in elderly subjects (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).

RELATED TO VITAMIN C

Blood and lymphatic system disorders

At doses above 3 g/day of vitamin C, risk of haemolysis in subjects deficient in G6PD.

Nervous system disorders

• Vertigo.

Gastrointestinal disorders

• At doses above 1 g/day of vitamin C, possibility of digestive disorders (gastric burning, diarrhoea, abdominal pain).

Skin and subcutaneous tissue disorders

• Urticaria,

• rashes

Renal and urinary disorders

• Chromaturia,

• At doses above 1 g/day of vitamin C, possibility of urinary disorders (oxalic, cystinic and/or uric lithiases).

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/.

RELATED TO ASPIRIN

Intoxication is to be feared in elderly subjects and especially in young children (therapeutic overdose or frequent accidental intoxication) 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.

LINKED TO VITAMIN C

At doses above 1 g/day of vitamin C, possible: digestive disorders (gastric burning, diarrhoea, abdominal pain), urinary disorders (oxalic, cystinic and/or uric lithiasis).

At doses above 2 g/day of vitamin C, ascorbic acid may interfere with the following laboratory tests: blood and urine creatinine and glucose assays (diabetes monitoring by glucose-oxidase test strips).

At doses above 3 g/day of vitamin C, risk of haemolysis in subjects deficient in G6PD.

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.

Vitamin C is a water-soluble vitamin that takes part in various cellular oxidation-reduction reactions.

LINKED TO ASPIRIN

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.

LINKED TO VITAMIN C

The digestive absorption of vitamin C is good. In case of intake above requirements, the excess is eliminated via the urinary route.

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.

2 years.

To be stored at a temperature not exceeding + 25°C.

Keep the tube tightly closed, protected from moisture.

No special requirements.

Marketing authorisation (AMM)

CIP 3400930076811 (2T/10).

Not reimbursed by Social Security.