Urinary antimuscarinics; Tolterodine + Duloxetine - Drug Interactions

Duloxetine increased maximum levels of tolterodine by 64%,but this was not considered to be clinically significant

Clinical evidence,mechanism, importance and management

In a placebo-controlled,crossover study, 14 healthy subjects received duloxetine 40mg twice daily and tolterodine 2mg twice daily for 5 days. Duloxetine increased steady-state AUC of tolterodine by 71 % and its maximum level by 64%. However, duloxetine had no effect on pharmacokinetics of 5-hydroxymethyl-tolterodine active metabolite of tolterodine (See reference number 1).

Duloxetine is an inhibitor of cytochrome P450 isoenzyme CYP2D6, by which tolterodine is metabolised.

The increases in tolterodine levels were not considered to be clinically relevant,and no routine dosage adjustment of tolterodine dosage was considered necessary when given with duloxetine (See reference number 1). Consider also Urinary antimuscarinics; Tolterodine + Fluoxetine interaction.

1. Hua TC,Pan A, Chan C, Poo YK, Skinner MH, Knadler MP, Gonzales CR, Wise SD. Effect of duloxetine on tolterodine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol (2004) 57, 652–6.