An acute overdose of Exomuc 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.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Adverse reactions are listed below, by system organ class and frequency.
| System Organ Class | Frequency/ Adverse Reactions | |||
| Uncommon (> 1/1,000, < 1/100) | Rare ((>1/10,000, < 1/1,000) | Very rare (< 1/10,000) | Not known | |
| Immune system disorders | Hypersensitivity | Anaphylactic shock, anaphylactic/ anaphylactoid reaction | ||
| Nervous system disorders | Headache | |||
| Ear and labyrinth disorders | Tinnitus | |||
| Cardiac disorders | Tachycardia | |||
| Vascular disorders | Hypotension | Haemorrhage | ||
| Respiratory, thoracic and mediastinal disorders | Bronchospasm, dyspnoea | |||
| Gastrointestinal disorders | Vomiting, diarrhoea, stomatitis, abdominal pain, nausea | Dyspepsia | ||
| Skin and subcutaneous tissue disorders | Urticaria, rash, angioedema, pruritus | |||
| General disorders and administration site conditions | Fever | Oedema of the face | ||
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 Exomuc. 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 Exomuc terminated immediately.
In case of recurrence skin and mucosal lesions, medical advice should be sought at once and the use of Exomuc terminated immediately.
A decreased blood platelet aggregation in the presence of Exomuc 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.
Acute toxicity studies in rats and mice, by oral, intraperitoneal and intravenous administration showed Exomuc 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 Exomuc 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 Exomuc 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.
Pharmacotherapeutic group: Mycolytics, ATC code: R05CB01
N-acetyl-L-cysteine (NAC), the active ingredient in Exomuc 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, Exomuc 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 Exomuc 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, Exomuc 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 Exomuc 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 Exomuc in acute bronchitis.
Absorption
Following oral administration, Exomuc is rapidly and almost completely absorbed and metabolised in the liver to cysteine (the pharmacologically active metabolite), diExomuc, cysteine and further mixed disulphides.
Distribution
Due to the high first-pass effect, the bioavailability of orally administered Exomuc 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 Exomuc was determined to be about 50%.
Biotransformation
Exomuc 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. Exomuc is excreted almost exclusively in the form of inactive metabolites (inorganic sulphates, diExomuc) via the kidneys. The plasma half-life of Exomuc 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 Exomuc revealed a distribution volume of 0.47 1/kg (in total) or 0.59 I/kg (reduced Exomuc); the plasma clearance was determined to be 0.11 l/h/kg (in total) and 0.84 l/h/kg (reduced Exomuc), respectively. The elimination half-life after intravenous administration is 30-40 minutes while excretion follows three-phase kinetics (alpha, beta and terminal gamma phase).
Exomuc 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 Exomuc at the blood- brain barrier in humans
No special requirements for disposal. Any unused product should be disposed of in accordance with local requirements.
