Is there an interaction between dextropropoxyphene (Dexofen) and ethylmorphine hydrochloride (Cocil

Fråga: Is there an interaction between dextropropoxyphene (Dexofen) and ethylmorphine hydrochloride (Cocillana-Etyfin)? This question concerns a male patient who is currently being treated with Dexofen and Cocillana-Etyfin. The questioner wants to know if there is any information regarding an interaction between ethylmorphine hydrochloride and dextropropoxyphene.

Sammanfattning: Dextropropoxyphene and morphine, the active metabolite of ethylmorphine, share the same receptor profile. It is not clear whether ethylmorphine per se has pharmacological activity. For these reasons, the combination does not appear pharmacologically rational, and caution is advised as concomitant use could lead to an increased risk for CNS depression. There is also a risk for a pharmacokinetic interaction, but the clinical relevance of this is uncertain.

Svar: Cocillana-Etyfin is a cough suppressant, which contains the opioid analgesic ethylmorphine hydrochloride, and two expectorants (cocillana and senega root) (1). Dextropropoxyphene is a pure opioid agonist with high affinity for mu-receptors (2). Ethylmorphine is metabolised to morphine (1), which also is a pure opioid agonist (2). Whereas morphine has an antitussive effect (3), it seems unclear whether ethylmorphine (or the other metabolite, norethylmorphine) per se is pharmacologically active. The pharmacological rationality of combining dextropropoxyphene with ethylmorphine is questionable, since morphine and dextropropoxyphene share the same receptor profile. Thus, the combination of the two drugs could increase the risk of CNS depression.

Furthermore, there is a theoretical ground for a metabolic drug interaction between ethylmorphine and dextropropoxyphene. There are in vivo data suggesting that dextropropoxyphene is an inhibitor of CYP2D6 (4). Etylmorphine is metabolised to norethylmorphine via CYP3A4 and then to morphine via CYP2D6 (5). In one study, the urinary excretion of etylmorphine and its metabolites were examined in CYP2D6 poor metabolizers (PM) and CYP2D6 extensive metabolizers (EM). The EM excreted substantially more morphine than the PM (11 % vs. 3 % of the given dose, p<0.05) (6). Therefore, inhibition of CYP2D6 could cause less ethylmorphine to be transformed into morphine. This could lead to a lower antitussive effect, given that it is unknown to what extent ethylmorphine has any antitussive activity of its own.