ALKA SELTZER 324 mg Effervescent tablet Box/20

Effervescent tablet

Acetylsalicylic acid................................................................................................................................324 mg

For one effervescent tablet.

Excipient with known effect : sodium

Excipients:

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

Dosage

This presentation is reserved for adults and children from 20 kg (approximately from 6 years).

In children under 12 years, medical advice is required before taking acetylsalicylic acid.

In children under 18 years, medical advice is required in case of signs of viral infections when other measures have not proved conclusive.

In children, it is imperative to follow the dosages defined according to the child's weight and choose a suitable presentation. Approximate ages according to weight are given for information only.

In general, the recommended daily dose of acetylsalicylic acid in children is approximately 60 mg/kg per day, 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 unit per dose, to be repeated if necessary after 6 hours, not exceeding 4 units per day.

For children weighing 27 to 36 kg (approximately 8 to 12 years), the dosage is 1 unit per dose, to be repeated if necessary after 4 hours, not exceeding 6 units per day.

For children weighing 37 to 50 kg (approximately 11 to 15 years), the dosage is 2 units per dose, to be repeated if necessary after 6 hours, without exceeding 8 units per day.

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. 9 units per day.

The usual dose is 2 units of 324 mg, to be repeated if needed after a minimum of 4 hours, without exceeding 9 units per day.

For Elderly subjects:

The maximum recommended daily dose is 2 g of aspirin, i.e. 6 units per day. The usual dose is 1 unit of 324 mg, to be repeated if needed after a minimum of 4 hours, not exceeding 6 units per day.

Subjects with hepatic impairment

Acetylsalicylic acid should be used with caution in patients with mild to moderate hepatic impairment (see sections Contraindications and Warnings and precautions).

Subjects with renal impairment

Acetylsalicylic acid should be used with caution in patients with mild to moderate renal impairment (see sections Contraindications and Warnings and precautions).

Method of administration

Oral use.

Drink immediately after the effervescent tablet has completely dissolved in a large glass of water, preferably during or just after a meal.

Frequency of administration

Systematic dosing helps avoid fluctuations in pain or fever:

Doses should be regularly spaced, including at night, of preferably 6 hours, and at least 4 hours: follow the dosage specified above.

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 acetylsalicylic acid or to any of the excipients listed in section Composition.

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

• Active gastroduodenal ulcer,

• Any constitutional or acquired bleeding disorder,

• Bleeding risk,

• Severe hepatic impairment,

• Severe renal impairment,

• Severe uncontrolled heart failure,

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

• Combination with oral anticoagulants for anti-inflammatory doses of acetylsalicylic acid (≥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) in a patient with a history of gastroduodenal ulcer (see section Interactions).

• 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)

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

• 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, may lead to persistent kidney damage with a risk of renal failure.

• 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,
• renal or hepatic impairment
• asthma: the occurrence of asthma attacks, in some subjects, may be linked to an allergy to non-steroidal anti-inflammatory drugs or to acetylsalicylic acid. In this case, this medicine is contraindicated.
• Rare cases of acute myocardial ischaemia with or without myocardial infarction have been reported in the context of a hypersensitivity reaction (Kounis syndrome) in patients treated with acetylsalicylic acid. In case of confirmed Kounis syndrome due to acetylsalicylic acid, ALKA SELTZER 324 mg, effervescent tablet must be stopped immediately.
• metrorrhagia or menorrhagia (risk of increased heaviness and duration of periods).

• Gastrointestinal haemorrhages or ulcers/perforations may occur at any time during treatment without necessarily having prior symptoms or history. The relative risk increases in frail elderly subjects, subjects of low body weight, patients on anticoagulant or antiplatelet treatment (see section Interactions).

In case of gastrointestinal haemorrhage, stop treatment immediately.

• Effervescent tablets at 324 mg are not suitable for children under 20 kg for whom better-suited dosages exist.

• 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).

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

• Use of this medicine is not recommended during breastfeeding.

• Concomitant use of this medicine is not recommended with:

• 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 (see section Interactions),
•  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 the acute phase of coronary syndrome),
• glucocorticoids (except hydrocortisone for replacement therapy) at anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day) of acetylsalicylic acid (see section Interactions),
• Low molecular weight heparins (and related drugs) and unfractionated heparins: curative doses and/or elderly subject and at 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,
• Pemetrexed in patients with mild to moderate renal impairment (creatinine clearance between 45 ml/min and 80 ml/min),
• ticlopidine,
• uricosurics (see section Interactions).

Information on excipients:

• This medicine contains 477 mg of sodium per tablet, which is equivalent to 23,85 % of the maximum recommended daily dietary intake of sodium by the WHO of 2 g of sodium per adult.

Risk related to antiplatelet effect

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

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

Contraindicated combinations

+ Methotrexate used at doses above 20 mg / week

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

Increased toxicity, particularly haematological, of methotrexate (reduced renal clearance by anti-inflammatory drugs).

+ Oral anticoagulants

For anti-inflammatory doses of acetylsalicylic acid (≥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) in a patient with a history of gastroduodenal ulcer: increased bleeding risk, particularly in case of a history of gastroduodenal ulcer.

Combinations not recommended

+ Oral anticoagulants

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

For antiplatelet doses of acetylsalicylic acid (from 50 mg to 375 mg per day) and in case of a history of gastroduodenal ulcer: increased bleeding risk, particularly in case of a history of gastroduodenal ulcer. Monitoring is necessary, in particular of bleeding time.

+ Non-steroidal anti-inflammatory drugs

For anti-inflammatory doses of acetylsalicylic acid (≥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): increased risk of ulcerogenic and digestive haemorrhage.

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

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

+ Glucocorticoids (except hydrocortisone as replacement therapy)

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

+ Low molecular weight heparins, related products and unfractionated heparins (therapeutic doses and/or the elderly subject)

For anti-inflammatory doses of acetylsalicylic acid (≥ 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): increased risk of bleeding (inhibition of platelet function and damage to the gastroduodenal mucosa by acetylsalicylic acid). Use another analgesic, antipyretic or anti-inflammatory agent.

+ Pemetrexed

In patients with mild to moderate renal impairment (creatinine clearance between 45 ml/min and 80 ml/min), 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).

+ Uricosurics (benzbromarone, probenecid)

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

+ 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

+ Diuretics, angiotensin-converting enzyme inhibitors, angiotensin II antagonists

For anti-inflammatory doses of acetylsalicylic acid (≥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): acute renal failure in dehydrated patients due to reduced glomerular filtration secondary to decreased renal prostaglandin synthesis. Furthermore, 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

With acetylsalicylic acid used at analgesic or antipyretic doses (≥ 500 mg per dose and/or < 3 g per day) or anti-inflammatory doses (≥ 1 g per dose and/or ≥ 3 g per day). Increased toxicity, particularly haematological, of methotrexate (reduction of renal clearance by anti-inflammatory agents).

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 (reduction of its renal clearance 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.

+ Gastrointestinal topicals, antacids and charcoal

Reduction of the digestive absorption of acetylsalicylic acid.

Take gastrointestinal topicals and antacids at a distance (2 hours) from acetylsalicylic acid.

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

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

Associations to be taken into account

+ Oral anticoagulants

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

Increased risk of bleeding, particularly in cases of gastroduodenal ulcer.

+ Non-steroidal anti-inflammatory drugs

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

Increased risk of ulcerogenic and digestive hemorrhage.

+ Deferasirox

With acetylsalicylic acid 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 gastrointestinal bleeding.

+ 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.

+ Low molecular weight heparins (and related products) and unfractionated heparins: curative 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.

+ Low molecular weight heparins (and related products) and unfractionated heparins: preventive doses

Concomitant use of medicinal products 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 (low molecular weight and related products or unfractionated heparins) with acetylsalicylic acid, regardless of the dose, should be taken into account, maintaining clinical and possibly biological monitoring.

+ Selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

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 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 ALKA SELTZER 324 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,, ALKA SELTZER 324 mg, effervescent tablet should 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 occurrence of oligohydramnios, or constriction of the ductus arteriosus, treatment with ALKA SELTZER 324 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 amenorrhoea

Maternal use 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

Like 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.

ALKA SELTZER 324 mg, effervescent tablet has no or negligible effect on the ability to drive vehicles and use machines.

• Gastrointestinal effects:

• abdominal pain,
• overt (hematemesis, melaena...) or occult digestive haemorrhages, responsible for iron-deficiency anaemia. These haemorrhages are all the more frequent the higher the dose,
•  gastric ulcers and perforations,
• Intestinal diaphragm-like stenosis (frequency unknown), especially with long-term treatment.

• Effects on the central nervous system:

• headache, dizziness,
• sensation of decreased hearing acuity,
• tinnitus

which are usually the sign of an overdose.

• Haematological effects:

• 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.

• Hypersensitivity reaction:

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

• Cardiac effects

Kounis syndrome (acute myocardial ischaemia with or without myocardial infarction in the context of a hypersensitivity reaction) with an indeterminate frequency (see section Warnings and precautions "Special warnings and precautions for use").

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

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 decreased hearing acuity, headache, dizziness are the sign of an overdose and can be controlled by reducing the dose.

• Severe intoxication:

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

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, ATC code: N02BA01. N: Nervous 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.

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 at a temperature not exceeding 25°C.

No special requirements.

Marketing authorisation (AMM)

CIP 3400932926879 (B/20). CIP 3400932911042 (B/40).

Not reimbursed by Social Security (B/20, B/40).