FLUIMUCIL 200 mg Granules for oral solution sachet sweetened with sorbitol and aspartame 30 sachet

Granules for oral solution.
Sachet. Box of 30.

For one sachet:

Acetylcysteine: 200,00 mg

Excipients with known effect: aspartame (E951), sorbitol (E420), glucose, lactose.

Treatment of disorders of bronchial secretion, particularly during acute bronchial conditions: acute bronchitis and acute episode of chronic bronchopneumopathies.

Dosage

The duration of treatment will not exceed 8 to 10 days without medical advice.

Adults and children over 7 years : 600 mg per day, in 3 doses, i.e. 1 sachet 3 times per day.

Children aged 2 to 7 years : 400 mg per day divided into 2 doses, i.e. 1 sachet 2 times per day.

Method of administration

Oral use.

Dissolve the contents of the sachet in a little water.

No interaction with food has been reported; there is no indication concerning administration of the medicine before or after meals.

• Hypersensitivity to the active substance or to any of the excipients listed in section Composition.
• Infant (under 2 years) (see section Warnings and precautions).
• Due to the presence of aspartame, this medicine is contraindicated in cases of phenylketonuria.

Productive coughs, which are a fundamental element of bronchopulmonary defence, should be preserved.

The combination of a mucolytic with an antitussive and/or with a secretion-drying substance (antimuscarinic) is irrational.

Mucolytics may induce bronchial overload in infants. Indeed, their capacity to drain bronchial mucus is limited, due to the physiological characteristics of their respiratory tree. They should therefore not be used in infants (see section Contraindications and Adverse effects).

Caution is recommended when the product is used in patients with gastroduodenal ulcer or a history of this condition, particularly in case of concomitant administration of other medicines with a known irritant effect on the gastric mucosa.

Patients suffering from bronchial asthma must be closely monitored during treatment. In case of bronchospasm, acetylcysteine must be stopped immediately and appropriate treatment must be initiated.

Administration of acetylcysteine, mainly at the start of treatment, may liquefy bronchial secretions and increase their volume. If the patient is not able to expectorate effectively, postural drainage and bronchial suction must be performed.

Acetylcysteine may moderately influence histamine metabolism; therefore, caution is required when administering the medicine as long-term treatment to patients with histamine intolerance, due to the possible occurrence of intolerance symptoms (headache, vasomotor rhinitis, pruritus).

A slight smell of sulphur does not indicate an alteration of the product but comes from the specific nature of the active ingredient.

This medicine contains 25 mg of aspartame per sachet. Aspartame is a source of phenylalanine. It may be harmful for people with phenylketonuria (PKU), a rare genetic disease characterised by the accumulation of phenylalanine that cannot be properly eliminated.

This medicine contains glucose and lactose in the orange flavouring. Patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases) must not take this medicine.

This medicine contains 675 mg of sorbitol per sachet. Sorbitol is a source of fructose. Patients with hereditary fructose intolerance (HFI) must not take this medicine.

The treatment should be re-evaluated in case of persistence or worsening of the symptoms or of the condition.

Antitussive medicines and mucolytic agents such as acetylcysteine must not be administered concomitantly, as the reduction of the cough reflex could lead to an accumulation of bronchial secretions.

Activated charcoal may reduce the effect of acetylcysteine.

Dissolving acetylcysteine formulations simultaneously with other medicines is not recommended.

Reports of inactivation of antibiotics resulting from acetylcysteine are so far based only on trials in vitro in which the substances concerned have been mixed directly. Nevertheless, when oral administration of antibiotics or other medicines is necessary, it is advised to administer them at 2 hours apart from the intake of acetylcysteine. This does not apply to loracarbef.

Concomitant administration of nitrate derivatives and acetylcysteine has been shown to result in significant hypotension and an increase in vasodilation of the temporal artery. If concomitant treatment with a nitrate derivative and acetylcysteine is necessary, patients must be monitored for any hypotension that may be severe. They must also be warned of the possible occurrence of headaches.

Concomitant administration of acetylcysteine and carbamazepine may lead to sub-therapeutic carbamazepine concentrations.

Paediatric population

Interaction studies have only been carried out in adults.

Changes to laboratory tests

Acetylcysteine may cause interference with the colorimetric analytical method used for salicylate assay. Acetylcysteine may interfere with the assay of ketonuria.

Pregnancy

There are limited data on the use of acetylcysteine in pregnant women. Animal studies have not shown direct or indirect harmful effects on reproduction (see section Preclinical safety).

As a precautionary measure, it is preferable to avoid the use of FLUIMUCIL during pregnancy.

The benefit/risk ratio must be assessed before use during pregnancy.

Breast-feeding

Data on the excretion of acetylcysteine and its metabolites in human milk are not known.

A risk to the breastfed child cannot be excluded.

A decision must be made either to discontinue breastfeeding or to discontinue/abstain from treatment with FLUIMUCIL, taking into account the benefit of breastfeeding for the child against the benefit of the treatment for the woman.

Fertility

There are no data on the effect of acetylcysteine on human fertility. Animal studies have not shown harmful effects on human fertility at the recommended doses (see section Preclinical safety).

Acetylcysteine has no known effect on the ability to drive vehicles and use machines.

Summary of the safety profile

The most frequent adverse effects associated with oral administration of acetylcysteine are gastrointestinal in nature. Hypersensitivity reactions including anaphylactic shock, anaphylactic/anaphylactoid reactions, bronchospasm, angioedema, rash and pruritus have been reported less frequently.

Tabulated summary of adverse reactions

The table below presents the adverse effects listed by system organ class and by frequency: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1 000, < 1/100); rare (≥ 1/10 000, < 1/1 000); very rare (< 1/10 000); frequency not known (cannot be estimated from the available data).

Within each frequency group, the undesirable effects observed are presented in order of decreasing seriousness, following a decreasing order of severity.

There is also a risk of bronchial obstruction due to excess secretions, particularly in infants and in certain patients unable to expectorate effectively (see section Warnings and precautions).

Description of certain particular adverse effects

In very rare cases, severe adverse reactions such as Stevens-Johnson syndrome and Lyell's syndrome have been reported with a temporal link to the administration of acetylcysteine. In most cases, at least one other suspect medicine could be identified for which the probability of triggering the reported mucocutaneous syndrome is higher. If recent mucocutaneous reactions occur, medical advice should therefore be sought and treatment with acetylcysteine stopped immediately.

A decrease in platelet aggregation in the presence of acetylcysteine has been confirmed by various investigations. The clinical significance has not yet been established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and network of Regional Pharmacovigilance Centres - Website https://signalement.social-sante.gouv.fr/.

Healthy volunteers received 11,2 g of acetylcysteine per day orally for three months without experiencing serious adverse effects. Oral doses up to 500 mg of acetylcysteine/kg of body weight were well tolerated without any symptoms of toxicity.

Symptoms

Overdoses may cause gastrointestinal symptoms, such as nausea, vomiting and diarrhoea.

Treatment

There is no antidote to acetylcysteine and treatment is symptomatic.

Pharmacotherapeutic class: MUCOLYTIC, ATC code: R05CB01

(R: Respiratory system)

Acetylcysteine is a mucolytic-type mucomodifier. It acts on the gel phase of mucus, probably by breaking the disulfide bonds of glycoproteins, and thus promotes expectoration.

Acetylcysteine is rapidly absorbed; the peak plasma concentration is reached within one hour, after oral administration of 200 to 600 mg. Bioavailability is of the order of 4 to 10% of the administered dose, probably due to intraluminal metabolism and a significant hepatic first-pass effect. It is metabolised into several oxidised derivatives. Its half-life is 2 hours. Renal clearance accounts for approximately 30% of total clearance.

Non-clinical data from conventional safety pharmacology, repeated-dose toxicity, genotoxicity and reproductive and developmental toxicity studies did not reveal any particular risk for humans.

In acute toxicity studies, oral LD50 values were established at 8 g/kg and > 10 g/kg in mice and rats respectively.

With prolonged administration over 12 weeks, a dose of 1 g/kg/day orally was well tolerated in rats. In dogs, oral administration of 300 mg/kg/day over a period of one year did not result in toxic reactions.

Acetylcysteine has been considered not genotoxic based on the results of the assays in vitro and in vivo.

Reproduction studies were carried out in rats at oral doses up to 2 000 mg/kg per day and in rabbits at oral doses up to 1 000 mg/kg per day; they did not reveal any impairment of female fertility nor any harmful effects on the foetus due to acetylcysteine. Furthermore, treatment of male rats with acetylcysteine at an oral dose of 250 mg/kg per day for 15 weeks did not affect fertility or the general reproductive performance of the animals.

3 years.

Store at a temperature below 30 °C.

No special requirements.