Acetilcisteina Hexal AG

Mucolytic adjuvant in the therapy of respiratory disorders associated with thick, viscous, mucus hypersecretion.

Posology

Adults and adolescents over the age of 12 years

200 mg (1 sachet) 3 times a day. Maximum recommended daily dose 600 mg/day.

The duration of therapy is dependent on the nature and severity of the illness, and should be decided by the doctor treating the patient for adults and adolescents.

Abundant fluid intake supports the mucolytic effect of Acetilcisteina Hexal AG.

Method of administration

Dissolve the contents of one sachet completely in a glass containing a little water just before use, stirring as needed with a teaspoon.

Acetilcisteina Hexal AG 200 mg Powder for Oral Solution must not be used when:

- Phenylketonuria is present, as the product contains aspartame.

Patients with bronchial asthma should be closely monitored during therapy; if' bronchospasm occurs, treatment with Acetilcisteina Hexal AG 200 mg Powder for Oral Solution should be discontinued immediately.

Administration of Acetilcisteina Hexal AG, especially at the beginning of treatment, may liquefy bronchial secretions and, at the same time, increase their volume. If the patient is unable to expectorate efficiently, to avoid retention of secretions postural drainage and tracheal suction should be used.

There are no studies on the efficacy and safety of Acetilcisteina Hexal AG 200 mg three times daily in adolescent population. However, mild to severe adverse reactions have been reported with the use of IV Acetilcisteina Hexal AG in adults and adolescents.

This medicine contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicine contains aspartame, which is a source phenylalanine. This may be harmful to people with phenylketonuria.

This medicine contains a colouring agent called sunset yellow (Ell0), which may cause allergic reactions.

Acetilcisteina Hexal AG can cause interference with the colorimetric assay method for the determination of salicylates.

Acetilcisteina Hexal AG can interfere with tests for ketones in urine.

Upon opening the sachet the powder may smell of sulphur (rotten egg smell). This is a normal characteristic of the active substance. Upon addition of water the solution will have a citrus odour.

No studies on the effects on the ability to drive or use machines have been performed. Acetilcisteina Hexal AG 200 mg Powder for Oral Solution has no known effect on the ability to drive and use machines.

Adverse reactions are listed below, by system organ class and frequency.

The occurrence of serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in temporal association with the use of Acetilcisteina Hexal AG. In most of these cases reported at least one other drug was administered at the same time, which may have possibly enhanced the described mucocutaneous effects.

In case of the recurrence of skin and mucosal lesions, medical advice should be sought at once and the use of Acetilcisteina Hexal AG terminated immediately.

In case of recurrence skin and mucosal lesions, medical advice should be sought at once and the use of Acetilcisteina Hexal AG terminated immediately.

A decreased blood platelet aggregation in the presence of Acetilcisteina Hexal AG has been confirmed by various studies. The clinical relevance has not yet been clarified to date.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

An acute overdose of Acetilcisteina Hexal AG can cause gastrointestinal symptoms such as nausea, vomiting and diarrhoea.

Treatment of Overdose

Treatment of overdose is to be symptomatic and supportive treatment as indicated by the patient's clinical condition.

Pharmacotherapeutic group: Mycolytics, ATC code: R05CB01

N-acetyl-L-cysteine (NAC), the active ingredient in Acetilcisteina Hexal AG 200 mg Powder for Oral Solution exerts an intense mucolytic-fluidizing action on mucous and mucopurulent secretions by depolymerizing the mucoproteic complexes and the nucleic acids which confer viscosity to the vitreous and purulent component of the sputum and other secretions.

Furthermore, Acetilcisteina Hexal AG exerts a direct antioxidant action, having a free thiol (- SH) nucleophilic group that is able to interact directly with electrophilic groups of oxidant radicals. Of particular interest is the recent finding that Acetilcisteina Hexal AG protects α1-antitrypsin enzyme inhibiting elastase from inactivation by hypochlorous acid (HOCl), a powerful oxidant agent produced by the myeloperoxidase enzyme of activated phagocytes. Due to its molecular structure, Acetilcisteina Hexal AG can readily cross cell membranes. Inside the cell, NAC is deacetylated to L-cysteine, an amino acid essential for glutathione synthesis (GSH).

GSH is a highly reactive tripeptide found ubiquitously in the various tissues of animals and is essential for the maintenance of functional capacity as well as cellular morphological integrity. It is the most important protective intracellular mechanism against oxidant radicals, both exogenous and endogenous, as well as toward numerous cytotoxic substances.

These features make Acetilcisteina Hexal AG 200 mg Powder for Oral Solution particularly suitable for the treatment of acute and chronic affections of the respiratory system, characterised by thick, viscous mucous and mucopurulent secretions.

There is no evidence on the efficacy and safety of mucolytic s including Acetilcisteina Hexal AG in acute bronchitis.

Absorption

Following oral administration, Acetilcisteina Hexal AG is rapidly and almost completely absorbed and metabolised in the liver to cysteine (the pharmacologically active metabolite), diAcetilcisteina Hexal AG, cysteine and further mixed disulphides.

Distribution

Due to the high first-pass effect, the bioavailability of orally administered Acetilcisteina Hexal AG is very low (approximately 10%). In humans, maximum plasma concentrations are achieved after 1-3 hours with the maximum plasma concentration of the metabolite cysteine in the range of approximately 2µmol/l. The protein binding of Acetilcisteina Hexal AG was determined to be about 50%.

Biotransformation

Acetilcisteina Hexal AG and its metabolites occur in three different forms in the organism: partially in free form, partially bound to proteins via labile disulphide bonds and partially as incorporated amino acid. Acetilcisteina Hexal AG is excreted almost exclusively in the form of inactive metabolites (inorganic sulphates, diAcetilcisteina Hexal AG) via the kidneys. The plasma half-life of Acetilcisteina Hexal AG is approximately 1 hour and is mainly determined by the rapid hepatic biotransformation. Impaired hepatic function therefore leads to prolonged plasma half-lives of up to 8 hours.

Elimination

Pharmacokinetic studies with intravenous administration of Acetilcisteina Hexal AG revealed a distribution volume of 0.47 1/kg (in total) or 0.59 I/kg (reduced Acetilcisteina Hexal AG); the plasma clearance was determined to be 0.11 l/h/kg (in total) and 0.84 l/h/kg (reduced Acetilcisteina Hexal AG), respectively. The elimination half-life after intravenous administration is 30-40 minutes while excretion follows three-phase kinetics (alpha, beta and terminal gamma phase).

Acetilcisteina Hexal AG crosses the placenta and is detected in cord blood. No information is available regarding excretion in breast milk.

No knowledge is available concerning the behaviour of Acetilcisteina Hexal AG at the blood- brain barrier in humans

Acute toxicity studies in rats and mice, by oral, intraperitoneal and intravenous administration showed Acetilcisteina Hexal AG to be of low toxicity. LD50 values greater than 7 g / kg in mice and 6 g / kg in rats have been reported. Chronic toxicity studies with Acetilcisteina Hexal AG in rats at doses up to 2000 mg/ kg/ day and dogs at doses up to 300 mg/ kg / day for periods up to 52 weeks demonstrate that Acetilcisteina Hexal AG is well tolerated, even at higher doses. In reproductive toxicity studies in rats and rabbits, the oral administration of doses up to 2000 mg / kg / day did not show changes in reproductive capacity, teratogenic effects or peri/postnatal toxicity.

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

No special requirements for disposal. Any unused product should be disposed of in accordance with local requirements.