Source: Health Products Regulatory Authority (IE) Publisher: UNI-PHARMA KLEON TSETIS PHARMACEUTICAL LABORATORIES S.A., 14th km National Road 1, GR-145 64 Kifissia, Greece
Pharmacotherapeutic group: Mucolytics
ATC code: R05CB01
The mechanisms of action of NAC in these respiratory indications include mucolytic effects. The mucolytic action is mediated by a reduction in the viscosity of bronchial mucus. This is explained by the depolymerisation with the disulfide bridges between the macromolecules in the mucus being opened.
After oral administration acetylcysteine is rapidly and almost completely absorbed.
The oral bioavailability of acetylcysteine is very low (between 6 and 10%) due to high first pass effect. In humans maximum plasma concentration is reached in 1 to 3 hours after an oral dose.
Approximately 50% of acetylcysteine is protein bound after oral administration. There is no information available on the behaviour of acetylcysteine at the blood-brain barrier in humans.
Acetylcysteine is metabolized by rapid hepatic biotransformation. The metabolites occur in three different forms: in free form into cysteine the active metabolite, bound to protein via labile disulfide bonds and as integral amino acids into diacetylcystine and cystine.
Excretion of inactive metabolites (inorganic sulfates, diacetylcystine) is via the kidneys. The elimination half-life after oral administration is 6.25 hours.
There is evidence that clearance of acetylcysteine can be significantly reduced up to 90% in the subjects with end-stage renal disease. This could result in a dramatically longer half-life and a marked increase in systemic exposure to acetylcysteine in patients with end-stage renal disease. It is not known to what extent the results can be extrapolated to the less severe forms of renal impairment that are more likely to be encountered during routine use of the proposed product.
Restricted liver function causes the plasma half-life to increase up to 8 hours, based in one study of patients with chronic liver disease. The total clearance of acetylcysteine was found to be significantly reduced following an intravenous dose of 600 mg over three minutes in nine subjects with hepatic cirrhosis. See also section 4.2.
Limited data in patients over 65 years of age is available.
No evidence of teratogenicity was identified in non-standard embryo toxicity studies in rabbits and rats. Acetylcysteine crosses the placenta in rats and can be detected in amniotic fluid.
There are no non-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
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