Therapeutic use of levocloperastine as an antitussive agent - An overview of preclinical data and clinical trials in adults and children

Cough associated with acute and chronic respiratory conditions is common in patients of all ages. Levocloperastine is a novel antitussive with a pharmacological profile distinct from that of the racemic DL-cloperastine. Levocloperastine with its dual mechanism of action acts on both the central bulbar cough Centre and on peripheral receptors in the tracheobronchial tree, In preclinical studies. levocloperastine demonstrated antitussive effects similar to those observed with codeine. In acute and repeated-dose toxicity studies, levocloperastine was well tolerated in rodents and dogs, with no clinically significant cardiovascular or gastrointestinal adverse events, The pharmacokinetic behaviour of levocloperastine. best described by a two-compartmental model with absorption phase. is similar to that of the racemic compound DL-cloperastine. In clinical trials, levocloperastine had a faster onset of action and produced greater reductions in the intensity and frequency of cough compared with DL-cloperastine, codeine and levodropropizine. The antitussive effects (reduction in intensity and frequency of cough) of levocloperastine were observed after the first day of treatment in patients of all ages. In children, levocloperastine reduced night-time awakenings and irritability; in adults, it was also effective in treating ACE-inhibitor cough. Levocloperastine was generally well tolerated. There was no evidence of clinically significant central adverse events, whereas drowsiness, dry mouth and nausea were reported with comparator agents (levodropropizine, codeine, DL-cloperastine). Levocloperastine represents an effective alternative to currently used antitussive agents with the added advantage of faster onset of action and improved tolerability in all patient groups.