uspected. Therapy with telotristat should not be resumed unless the liver injury can be explained by another cause.
Constipation
Telotristat reduces bowel movement (BM) frequency. Constipation was reported in patients using a higher dose (500 mg). Patients should be monitored for signs and symptoms of constipation. If constipation develops, the use of telotristat and other concomitant therapies affecting bowel motility should be re-eva luated.
Depressive disorders
Depression, depressed mood and decreased interest have been reported in clinical trials in some patients treated with telotristat or placebo. A causal relationship between depressive disorders and telotristat has not been established. Patients should be advised to report any symptoms of depression, depressed mood and decreased interest to their physicians.
Lactose intolerance
Xermelo contains anhydrous lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
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 (CES) inhibitors
Loperamide caused a <30% decrease in the formation of telotristat (active metabolite) in vitro (see section 5.2). In phase 3 clinical trials, 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.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
Women of childbearing potential should be advised to use adequate contraception during treatment with telotristat.
Pregnancy
There are no data from the use of telotristat in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). Xermelo is not recommended during pregnancy and in women of childbearing potential not using contraception.
Breast-feeding
It is unknown whether telotristat ethyl and its metabolite are excreted in human breast milk. A risk to newborns/infants cannot be excluded. Patients should not breast-feed during telotristat treatment.
Fertility
No studies on the effect of telotristat on human fertility have been conducted. Telotristat had no effect on fertility in animal studies (see section 5.3).
4.7 Effects on ability to drive and use machin |
