ACETYLSALICYLIC ACID PANPHARMA 1 g Powder/solvent for solution for injection 6Vial + 6Ampoule/5mL

Powder and solution for injectable preparation.

Lysine acetylsalicylate................................................................................................................................1,8 g

Corresponding quantity of acetylsalicylic acid..................................................................................1,0 g

For 2 g of powder.

Excipient with known effect : none

Excipients:

• Short-term treatment of intense pain.

• Treatment of inflammatory rheumatism.

• Symptomatic treatment of fever when administration by the oral route is not possible.

RESERVED FOR ADULTS.

Method of administration

Injectable route.

Extemporaneously dissolve the contents of the vial with 5 ml of water for injectable preparations.

Administration may be carried out either as deep I.M., or as direct I.V., or as I.V. infusion using a vehicle solution (sodium chloride, glucose or sorbitol solution).

It is recommended to avoid mixing this medicinal product with other injectable specialties in the same syringe.

Systematic intakes help avoid pain fluctuations. They should be spaced at least 4 hours apart.

Posologies

900 mg of DL-Lysine acetylsalicylate corresponds to 500 mg of acetylsalicylic acid (aspirin).

Injectable aspirin vials exist in two dosages, 500 mg and 1000 mg.

Intense pain and fever:

• Adult: the maximum daily dose is 3000 mg of aspirin.

For reference: 500 or 1000 mg of aspirin per administration, not to exceed 3000 mg per day.

• Elderly subject: the maximum daily dose is 2000 mg of aspirin.

For reference: 500 or 1000 mg of aspirin per administration, not to exceed 2000 mg per day.

Rheumatic conditions:

• Adult: 3000 to 6000 mg of aspirin maximum per day, to be divided into 3 or 4 doses spaced at least 4 hours apart.

• Elderly subject: The dose should be reduced.

This medicine is CONTRAINDICATED in the following situations:

• hypersensitivity to the active substances or to any of the excipients mentioned in section Composition or to other non-steroidal anti-inflammatory drugs (cross-reactivity),

• asthma or a history of asthma with or without nasal polyps induced by salicylates or substances of similar activity, in particular non-steroidal anti-inflammatory drugs,

• active gastroduodenal ulcer, history of gastric haemorrhage or perforation following treatment with acetylsalicylic acid or another non-steroidal anti-inflammatory drug,

• any constitutional or acquired haemorrhagic disease,

• haemorrhagic risk,

• severe hepatic impairment,

• severe renal impairment,

• uncontrolled severe heart failure,

• in combination with methotrexate used at doses above 20 mg/week (see section Interactions) and 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,

• in combination with oral anticoagulants at anti-inflammatory doses of acetylsalicylic acid (≥ 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) in a patient with a history of gastroduodenal ulcer (see section Interactions),

• patients with mastocytosis, in whom the use of acetylsalicylic acid may cause severe hypersensitivity reactions (including circulatory shock with vasomotor flushing, hypotension, tachycardia and vomiting).

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

This medicine contains acetylsalicylic acid. Other medicines also contain it. Do not combine them, so as not to exceed the recommended daily dose.

When combined with other medicines, to avoid the risk of overdose, check that the other medicines do not contain acetylsalicylic acid in their composition.

In patients receiving concomitant treatment with nicorandil and NSAIDs including acetylsalicylic acid, there is an increased risk of serious complications such as gastrointestinal ulcerations, perforations and haemorrhages. Thus, caution should be exercised if acetylsalicylic acid or NSAIDs are taken at the same time as nicorandil (see section Interactions).

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

Reye's syndrome, very rare but life-threatening conditions, have been observed in children and adolescents with signs of viral infections (in particular chickenpox and influenza-like episodes) and receiving acetylsalicylic acid. Consequently, acetylsalicylic acid should be administered to these children and adolescents 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 may have caused haemolysis. Administration of acetylsalicylic acid in cases of G6PD deficiency must be carried out under strict medical supervision.

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

Treatment monitoring should be reinforced in the following cases:

• history of gastroduodenal ulcer, gastrointestinal haemorrhage or gastritis,

• mild to moderate renal or hepatic insufficiency (acetylsalicylic acid being contraindicated in cases of severe renal or hepatic insufficiency, see section Contraindications),

• asthma: in some subjects, the occurrence of an asthma attack 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 magnitude and duration of periods).

Gastrointestinal haemorrhages or ulcers/perforations may occur at any time during treatment without necessarily any prior symptoms or history. The relative risk increases with dose, in elderly subjects, subjects with low body weight, subjects with a history of gastric ulcers, particularly in cases of complications such as haemorrhage or perforation, and patients undergoing anticoagulant or antiplatelet treatment (see section Interactions). In case of gastrointestinal haemorrhage, stop treatment immediately.

Given the antiplatelet effect of acetylsalicylic acid, which appears even at very low doses and persists for several days, the patient should be warned of the risk of bleeding that may occur during even minor surgical procedures (e.g. dental extraction). Discontinuation of treatment before a surgical intervention must be determined on a case-by-case basis.

Acetylsalicylic acid alters uric acid levels (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 (anti-inflammatory doses), it is recommended to monitor for signs of overdose. If tinnitus, reduced hearing acuity and dizziness occur, treatment arrangements should be reassessed.

Concomitant treatment with levothyroxine and salicylates should be avoided. Salicylates may inhibit the binding of thyroid hormones to transport proteins and thus produce an initial temporary increase in free thyroid hormones, followed by an overall reduction in total thyroid hormone levels. Therefore, in case of concomitant intake of levothyroxine and salicylates, thyroid hormone levels should be monitored (see section Interactions).

In children, it is recommended to monitor salicylaemia, particularly when starting treatment.

The use of this medicine is not recommended during breastfeeding (see section Fertility, pregnancy and breastfeeding).

It has been shown that medicines that inhibit the activity of cyclo-oxygenase involved in prostaglandin synthesis may impair female fertility by acting on ovulation. This is reversible upon discontinuation of treatment.

Concomitant use of acetylsalicylic acid is not recommended with (see section Interactions) :

• acetazolamide,

• 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,

• non-steroidal anti-inflammatory drugs for 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 indications validated for this combination in acute coronary syndrome),

• glucocorticoids (except hydrocortisone as replacement therapy) for anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) of acetylsalicylic acid (see section Interactions),

• heparins at curative doses and/or in elderly subjects, and 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 (creatinine clearance between 45 ml/min and 80 ml/min),

• ticagrelor outside the indications validated for this combination in acute coronary syndromes,

• ticlopidine,

• probenecid,

• anagrelide,

• levothyroxine.

Injectable aspirin vials are reserved for adults.

Alcohol intake may increase the risk of gastrointestinal lesions and prolong bleeding time when acetylsalicylic acid is taken together with alcohol. Caution is therefore recommended in case of concomitant administration within the 36 hours that follow (see section Interactions).

Risk related to antiplatelet effect

Several substances are involved in interactions due to their antiplatelet properties: abciximab, cangrelor, cilostazol, clopidogrel, epoprostenol, eptifibatide, iloprost and iloprost trometamol, recombinant activated protein C, human protein C, tirofiban, ticlopidine and prasugrel.

The use of several antiplatelet agents increases the risk of bleeding, as does their combination with any other medicinal product increasing bleeding risk through additive effect (heparin and related molecules, oral anticoagulants and other thrombolytics…). These combinations must be taken into account while 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 (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid 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 above 20 mg/week

For anti-inflammatory doses of acetylsalicylic acid (≥ 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).

Combinations not recommended (See section Warnings and precautions)

+ Acetazolamide

Increased undesirable effects (notably metabolic acidosis) of high-dose acetylsalicylic acid and of acetazolamide, due to decreased elimination of acetylsalicylic acid by acetazolamide.

Increased risk of toxicity of acetylsalicylic acid (vomiting, tachycardia, hyperpnoea, mental confusion) or of acetazolamide (fatigue, lethargy, drowsiness, confusion, hyperchloraemic metabolic acidosis).

+ Anagrelide

Increased haemorrhagic events.

+ Oral anticoagulants

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

Need for monitoring, 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 (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid.

Increased risk of ulcerogenic and digestive hemorrhage.

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

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 (≥ 500 mg per dose and/or < 3 g per day) of acetylsalicylic acid.

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.

+ Levothyroxine

Salicylates, particularly at doses above 2 g/day, may inhibit the binding of thyroid hormones to carrier proteins and thus cause an initial transient increase in free thyroid hormones, followed by an overall decrease in total thyroid hormone levels. Therefore, thyroid hormone levels should be monitored (see section Warnings and precautions).

+ Nicorandil

Increased risk of severe gastrointestinal complications (ulceration, perforation, haemorrhage).

+ Pemetrexed, in case of mild to moderate renal impairment

In case of mild to moderate renal impairment (between 45 ml/min and 80 ml/min), risk of increased pemetrexed toxicity (decreased renal clearance of pemetrexed by acetylsalicylic acid at anti-inflammatory doses).

Close clinical monitoring of pemetrexed toxicity.

+ 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

+ Valproic acid

Decreased protein binding of valproic acid and inhibition of valproic acid metabolism resulting in increased serum levels of total and free valproic acid.

Close clinical monitoring of valproate levels.

+ Angiotensin II receptor antagonists

For anti-inflammatory doses of acetylsalicylic acid (≥ 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 dehydrated patients, 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.

+ Clopidogrel (within the indications validated for this combination in acute coronary syndrome)

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 of acetylsalicylic acid (≥ 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 dehydrated patients 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.

+ Ibrutinib

Increased risk of bleeding. Clinical monitoring.

+ Angiotensin-converting enzyme inhibitors

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: Acute renal failure in dehydrated patients, due to decreased glomerular filtration secondary to decreased synthesis of renal prostaglandins. In addition, reduction of the antihypertensive effect.

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

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

For anti-inflammatory doses of acetylsalicylic acid (≥ 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.

+ Tenofovir (tenofovir disoproxil fumarate)

Increased risk of renal failure, particularly in patients with risk factors for renal dysfunction.

Renal function should be adequately monitored.

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

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

+ Gastrointestinal topicals, antacids and adsorbents

Reduction of the digestive absorption of acetylsalicylic acid.

Take gastrointestinal topicals or antacids at a distance (more than 2 hours if possible) from acetylsalicylic acid.

Associations to be taken into account

+ Antidiabetics (in particular sulfonylureas) and insulin

Potentiation of the antidiabetic effect.

+ Deferasirox

With acetylsalicylic acid used 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).

Increased risk of ulcerogenic and digestive hemorrhage.

+ Glucocorticoids (except hydrocortisone as replacement therapy)

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

Increased bleeding risk: reduction of blood salicylate levels during corticosteroid treatment and risk of salicylate overdose after withdrawal.

+ 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 heparins at preventive doses, or of substances related to acetylsalicylic acid, whatever the dose, must be taken into account, maintaining clinical and possibly biological monitoring.

+ Selective serotonin reuptake inhibitors.

Increased bleeding risk.

+ Mixed adrenergic-serotonergic medicines (amitriptyline, clomipramine, duloxetine, imipramine, milnacipran, oxitriptan, venlafaxine)

Increased bleeding risk.

+ Metamizole

Reduction of the effect of acetylsalicylic acid on platelet aggregation.

To be used with caution in patients taking low doses of acetylsalicylic acid for cardiac protection.

+ Pentoxifylline

Increased bleeding risk.

+ 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 ACETYLSALICYLIC ACID PANPHARMA 1 g, powder and solvent for solution for injection, 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,, ACETYLSALICYLIC ACID PANPHARMA 1 g, powder and solvent for solution for injection 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 week of amenorrhoea, cardiac and renal monitoring of the foetus may prove necessary. In case of oligohydramnios, or constriction of the ductus arteriosus, treatment with ACETYLSALICYLIC ACID PANPHARMA 1 g, powder and solvent for solution for injection. must be interrupted.

 

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 amenorrhoea

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

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 amenorrhoea:

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 in women wishing to conceive a child. In women experiencing difficulties conceiving or undergoing fertility tests, discontinuation of treatment should be considered.

No effect on the ability to drive vehicles or use machines has been observed.

The frequency of undesirable effects cannot be estimated. For this reason, frequencies are referenced as undetermined.

Blood and lymphatic system disorders

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

• Intracranial and gastrointestinal haemorrhages may also occur,

• An intracranial haemorrhage may be fatal, particularly in elderly subjects,

• Thrombocytopenia,

• Haemolytic anaemia in patients with a deficiency in G6PD (see section Warnings and precautions),

• Pancytopenia, bicytopenia, aplastic anemia, bone marrow failure, agranulocytosis, neutropenia, leukopenia.

Immune system disorders

• Hypersensitivity reactions,

• Anaphylactic reactions,

• Asthma,

• Quincke's edema.

Nervous system disorders

• Headache, dizziness, sensation of decreased hearing acuity, tinnitus, which are usually the hallmark of an overdose (see section Overdose),

• Intracranial hemorrhages may also occur,

• An intracranial hemorrhage may be fatal, particularly in elderly subjects.

Cardiac disorders

• Kounis syndrome in the context of a hypersensitivity reaction to acetylsalicylic acid.

Vascular disorders

• Vasculitis including Henoch-Schönlein purpura,

• Hemorrhages that may be fatal.

Respiratory, thoracic and mediastinal disorders

• Non-cardiogenic pulmonary edema with long-term use, which may also occur in the context of a hypersensitivity reaction related to acetylsalicylic acid,

• Bronchospasm and asthma.

Gastrointestinal disorders

• Abdominal pain,

• Dyspepsia,

• Overt (hematemesis, melena...) or occult gastrointestinal hemorrhages, responsible for iron-deficiency anemia. These hemorrhages are all the more frequent the higher the dose,

• Upper gastrointestinal disorders: esophagitis, erosive duodenitis, erosive gastritis, esophageal ulceration, perforation, gastric or duodenal ulcer,

• Lower gastrointestinal disorders: ulcers of the small intestine (jejunum, ileum) and large intestine (colon, rectum), colitis and intestinal perforation,

These reactions may or may not be associated with hemorrhage and may occur regardless of the dose of acetylsalicylic acid and in patients with or without warning signs or a history of serious gastrointestinal disorders,

• Acute pancreatitis in the context of a hypersensitivity reaction to acetylsalicylic acid.

Hepatobiliary disorders

• Increased liver enzymes, liver involvement mainly hepatocellular,

• Chronic hepatitis.

Skin and subcutaneous tissue disorders

• Urticaria,

• Skin reactions,

• Fixed pigmented erythema.

Renal and urinary disorders

• Renal failure.

Disorders of the reproductive organs and breast

• Haematospermia.

General disorders and administration site conditions

• Possibility of pain at the injection site and local reactions,

• Reye's syndrome (in particular in children and adolescents with signs of viral infections (in particular chickenpox and influenza-like episodes) - see section Warnings and precautions),

• Oedema has been reported with high doses (anti-inflammatory doses) of acetylsalicylic acid.

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 reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - 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 intoxication) where it may be fatal.

Symptoms

• Moderate poisoning: tinnitus, sensation of reduced hearing acuity, headache, dizziness are the hallmark of an overdose and can be controlled by reducing the dose.

• Severe poisoning :

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

Symptoms are: fever, hyperventilation, ketosis, respiratory alkalosis, metabolic acidosis, coma, cardiovascular collapse, respiratory failure, marked hypoglycaemia.

Emergency management

• Immediate transfer to a specialised hospital setting,

• Gastrointestinal decontamination and administration of activated charcoal,

• Monitoring of acid-base balance,

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

• Symptomatic treatment.

A non-cardiogenic pulmonary oedema threatening life may occur in cases of acute and chronic overdose with acetylsalicylic acid (see section Adverse effects Undesirable Effects). This undesirable effect may be fatal in cases of overdose.

Symptoms : respiratory distress with in particular dyspnoea, tachycardia.

Emergency management :

• Hospitalization in a specialized hospital setting,

• Appropriate treatment such as prone ventilation with positive end-expiratory pressure, hemodialysis and inhalation of nitric oxide.

Pharmacotherapeutic class: OTHER ANALGESICS, ANTIPYRETICS AND ANTI-INFLAMMATORY at high dose (N: central nervous system/M: locomotor system).

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.

Lysine acetylsalicylate splits into acetylsalicylic acid and lysine in the plasma.

Acetylsalicylic acid is rapidly absorbed and hydrolyzed to salicylic acid.

The latter is largely bound to plasma proteins. A quarter of an hour after intravenous injection of 1 g of aspirin, a salicylemia of 220 mg/L is obtained. By intramuscular route, a quarter of an hour after injection of 1 g of aspirin, a salicylemia of 110 mg/L is obtained.

Urinary elimination increases with urinary pH. The half-life of acetylsalicylic acid is approximately 30 minutes. The half-life of salicylic acid is 3 to 9 hours and increases with the dose administered.

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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

3 years.

After opening: the product must be used immediately.

Store at a temperature not exceeding 25°C.

For storage conditions of the medicinal product after reconstitution, see section Shelf life.

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Marketing authorisation (AMM)

CIP 3400932610204 (6 vial + 6 ampoule/5 ml).

Price:

7,38 euros (6 vial + 6 ampoule/5 ml).

Social Security reimbursement at 65%.
Collection.