Introduction: The aim of this study was to compare the efficacy and tolerability of pholcodine with that of dextromethorphan, one of the most used cough sedative products, in patients with acute, non-productive cough. Methods: 129 adults with a diagnosis of acute, frequent, non-productive cough participated in a randomized, double-blind, parallel-group, multicenter trial. Medications were in a syrup formulation and were taken orally three times daily for 3 days. The efficacy endpoints were the change from baseline in the daytime and night-time cough frequency on 5-point scales at day 3, and cough intensity. Results: A reduction of 1.4 and 1.3 points in the mean daytime cough frequency at day 3 was seen in the pholcodine and dextromethorphan groups, respectively, in the per-protocol population. The reduction in mean night-time cough was 1.3 for both groups. Cough intensity reduction was 0.7 for pholcodine and 0.8 for dextromethorphan. Conclusions: These findings indicate that the efficacy of a 3-day course of pholcodine is similar to that of dextromethorphan in the treatment of adult patients with acute, non-productive cough. Both medications were well tolerated.

Comparative efficacy and tolerability of pholcodine and dextromethorphan in the management of patients with acute, non-productive cough : a randomized, double-blind, multicenter study.

Pholcodine has antitussive activity similar to, or somewhat greater than, that of codeine in animal test systems. The drug, which has been formulated in many combination medications (45)—some rational and some quite irrational pharmacologically—also appears to be active in man, although the clear–cut demonstrations, unfortunately, are in artificially—induced cough models. Additional efficacy studies are needed. Preclinical toxicity studies demonstrate a generally safer profile for pholcodine than codeine, although pholcodine appears to have greater depressant effects on the respiratory and cardiovascular systems in animals. These effects have not been observed in man after administration of therapeutic doses. Pholcodine appears to be devoid of addiction liability in man. In contrast to codeine, pholcodine is not metabolised to morphine in man, a fact which may contribute to its more favourable toxicity profile, and it is metabolised and eliminated much more slowly than codeine.

Pholcodine

Resume La pholcodine est un derive morphinique largement employe depuis 1950 a travers le monde dans le traitement de la toux non productive chez l’enfant et l’adulte. Les resultats des etudes precliniques, bien qu’anciens, de meme que les donnees cliniques, plus recentes ont montre que l’efficacite antitussive de la pholcodine semblait plus elevee et plus durable que celle de la codeine, pour une tolerance egale ou superieure. En outre, elle n’induirait pas de pharmacodependance. Des craintes quant a une eventuelle sensibilisation croisee avec les curares soulevent cependant des interrogations, et ce malgre l’analyse recente des donnees disponibles par l’Agence europeenne des medicaments (EMA) aboutissant a la confirmation de la balance benefice-risque favorable de la pholcodine. Des investigations complementaires ont ete demandees pour conclure sur ce point.

C. E. Heffron

Papers

Preliminary evaluation of pholcodine, a new antitussive agent.