Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Effect of other medicinal products on Xermelo
Short acting octreotide
Concomitant administration of short-acting octreotide with Xermelo significantly decreased the systemic exposure of telotristat ethyl and telotristat, the active metabolite (see section 5.2). Short- acting octreotide should be administered at least 30 minutes after administration of Xermelo if treatment with short-acting octreotide is needed in combination with Xermelo.

Carboxylesterase 2 (CES2) inhibitors
The IC50 of the inhibition of loperamide on the metabolism of telotristat ethyl by CES2 was 5.2 µM (see section 5.2). In phase 3 clinical studies , telotristat was routinely combined with loperamide with no evidence of safety concerns.

Effect of Xermelo on other medicinal products
CYP2B6 substrates
Telotristat induced CYP2B6 in vitro (see section 5.2). Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP2B6 substrates (e.g. valproic acid, bupropion, sertraline) by decreasing their systemic exposure. Monitoring for suboptimal efficacy is recommended.

CYP3A4 substrates
Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP3A4 substrates (e.g. midazolam, everolimus, sunitinib, simvastatin, ethinyloestradiol, amlodipine, cyclosporine…) by decreasing their systemic exposure (see section 5.2). Monitoring for suboptimal efficacy is recommended.

Carboxylesterase 2 (CES2) substrates
Concomitant use of Xermelo may change the exposure of medicinal products that are CES2 substrates (e.g. prasugrel, irinotecan, capecitabine and flutamide) (see section 5.2). If co-administration is unavoidable, monitor for suboptimal efficacy and adverse reactions .