Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Colonis Pharma Limited, Quantum House, Hobson Industrial Estate, Burnopfield County Durham, NE16 6EA, United Kingdom
Pharmacotherapeutic group: Mycolytics
ATC code: R05CB01
N-acetyl-L-cysteine (NAC), the active ingredient in Acetylcysteine 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, acetylcysteine 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 acetylcysteine protects ฮฑ1-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, acetylcysteine 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 Acetylcysteine 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 mucolytics including acetylcysteine in acute bronchitis.
Following oral administration, acetylcysteine is rapidly and almost completely absorbed and metabolised in the liver to cysteine (the pharmacologically active metabolite), diacetylcysteine, cysteine and further mixed disulphides.
Due to the high first-pass effect, the bioavailability of orally administered acetylcysteine 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 2ยตmol/l. The protein binding of Acetylcysteine was determined to be about 50%.
Acetylcysteine 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. Acetylcysteine is excreted almost exclusively in the form of inactive metabolites (inorganic sulphates, diacetylcysteine) via the kidneys. The plasma half-life of Acetylcysteine 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.
Pharmacokinetic studies with intravenous administration of acetylcysteine revealed a distribution volume of 0.47 l/kg (in total) or 0.59 l/kg (reduced acetylcysteine); the plasma clearance was determined to be 0.11 l/h/kg (in total) and 0.84 l/h/kg (reduced acetylcysteine), respectively. The elimination half-life after intravenous administration is 30-40 minutes while excretion follows three-phase kinetics (alpha, beta and terminal gamma phase).
Acetylcysteine 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 acetylcysteine at the blood-brain barrier in humans.
Acute toxicity studies in rats and mice, by oral, intraperitoneal and intravenous administration showed acetylcysteine 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 acetylcysteine 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 acetylcysteine 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.
ยฉ All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
