There have been no drug interaction studies for Duodart. The following statements reflect the information available on the individual components.
Pharmacokinetic interactions: Interactions with CYP450 enzyme system: Dutasteride: Dutasteride is metabolized by CYP3A4. A reduction in clearance by concomitant administration of CYP3A4 inhibitors is regarded as clinically irrelevant in view of the wide therapeutic window. In vitro, dutasteride is not metabolised by CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP2C8, CYP2C9, CYP2C19 and CYP2B6. Under in vitro conditions dutasteride has no inhibitory effect on cytochrome P450 enzymes, and in animal studies in rats and dogs, it did not cause any induction of cytochrome P450 enzymes.
Tamsulosin: Concomitant administration of tamsulosin with CYP3A4 or CYP2D6 enzyme inhibitors may lead to increased tamsulosin exposure. Concomitant administration of ketoconazole (a potent CYP3A4 inhibitor) resulted in an increase of the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8 respectively.
Concomitant administration of paroxetine (a potent CYP2D6 inhibitor) caused an increase of the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6 respectively.
The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitors with tamsulosin have not been evaluated clinically, however there is a potential for significant increase in tamsulosin exposure.
Interactions with oral anticoagulants: Dutasteride: Dutasteride did not show any interaction with the plasma protein binding of warfarin, acenocoumarol or phenprocoumon in vitro.
Tamsulosin: No study has been conducted on interactions between tamsulosin hydrochloride and warfarin. Tamsulosin has no effect on the pharmacokinetics or efficacy of acenocoumarol in healthy subjects. The effect of acenocoumarol on the pharmacokinetics of tamsulosin has not been investigated. There are no interaction studies with phenprocoumon. The INR values of patients on oral anticoagulation therapy should be closely monitored for 2-3 months when starting or stopping treatment with Duodart.
Other pharmacokinetic interactions: Dutasteride: No clinically significant pharmacokinetic or pharmacodynamic interactions have been observed between dutasteride and tamsulosin, terazosin, warfarin, digoxin and cholestyramine.
In vitro, dutasteride did not displace diazepam or phenytoin from plasma protein binding and in turn was not displaced by them either.
Tamsulosin: Concomitant administration of tamsulosin hydrochloride and furosemide produced an 11-12% reduction in the Cmax and AUC of tamsulosin hydrochloride; however these changes are clinically irrelevant and no dose adjustment is necessary.
In clinical studies, tamsulosin had no effect on the pharmacokinetics of atenolol, digoxin, enalapril, nifedipine or theophylline.
Pharmacodynamic interactions: Tamsulosin: In three studies on hypertonic patients whose blood pressure was stable with atenolol, enalapril or nifedipine, tamsulosin did not have a relevant effect on blood pressure compared to placebo.