Xermelo

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS  
 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xermelo 250 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains telotristat etiprate equivalent to 250 mg telotristat ethyl. 
 
Excipient with known effect 
 
Each tablet contains 168 mg of lactose (as anhydrous). 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
White to off-white film-coated oval tablets (approximately 17 mm long by 7.5 mm wide) with ‘T-E’ 
debossed on one side and ‘250’ debossed on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Xermelo is indicated for the treatment of carcinoid syndrome diarrhoea in combination with 
somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy. 
 
4.2 Posology and method of administration 
 
Posology 
The recommended dose is 250 mg three times daily (tid).  
 
Available data suggest that clinical response is usually achieved within 12 weeks of treatment.  
It is recommended to reassess the benefit of continued therapy in a patient not responding within this 
time period. 
 
Based on the high inter-subject variability observed, accumulation in a subset of patients with 
carcinoid syndrome cannot be excluded. Therefore, intake of higher doses is not recommended (see 
section 5.2). 
 
Missed doses  
In the event of a missed dose, patients should take their subsequent dose at the next scheduled time 
point. Patients should not take a double dose to make up for a missed dose. 
 
Elderly (65 years of age and above) 
No specific dose recommendations are available for elderly patients (see section 5.2). 
 



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Renal impairment 
No change in dose is required in patients with mild, moderate or severe renal impairment; who are not 
requiring dialysis (see section 5.2). As a precautionary measure, it is recommended that patients with 
severe renal impairment will be monitored for signs of reduced tolerability. 
 
The use of Xermelo is not recommended in patients with end-stage renal disease requiring dialysis 
(eGFR < 15 mL/min requiring dialysis) because efficacy and safety of Xermelo in these patients has 
not been established.  
 
Hepatic impairment 
In patients with mild hepatic impairment (Child Pugh score A), it may be necessary to reduce the dose 
to 250 mg twice daily according to tolerability. In patients with moderate hepatic impairment (Child 
Pugh score B), it may be necessary to reduce the dose to 250 mg once daily according to tolerability. 
The use of telotristat is not recommended in patients with severe hepatic impairment (Child Pugh 
score C) (see section 5.2). 
 
Paediatric population 
There is no relevant use of telotristat in the paediatric population in the indication of carcinoid 
syndrome. 
 
Method of administration  
Oral use 
Xermelo should be taken with food (see sections 5.1 and 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Hepatic enzymes elevations 
Elevations in hepatic enzymes were observed in clinical trials (see section 4.8). Laboratory monitoring 
of hepatic enzymes prior to and during telotristat therapy is recommended as clinically indicated. In 
patients with hepatic impairment, continuous monitoring for adverse events and worsening of liver 
function is recommended. 
Patients who develop symptoms suggestive of hepatic dysfunction should have liver enzymes tested 
and telotristat should be discontinued if liver injury is suspected. 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-evaluated. 
 
Depressive disorders 
Depression, depressed mood and decreased interest have been reported in clinical trials and from post-
marketing in some patients treated with telotristat (see section 4.8). 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, total lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 



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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 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. 
 
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 safety events.  
 
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 machines 
 
Telotristat has minor influence on the ability to drive and use machines. Fatigue may occur following 
administration of telotristat (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 



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The most commonly reported adverse reactions in patients treated with telotristat were abdominal pain 
(26%), gamma-glutamyl transferase increased (11%) and fatigue (10%). They were generally of mild 
or moderate intensity. The most frequently reported adverse reaction leading to discontinuation of 
telotristat was abdominal pain in 7.1% of patients (5/70). 
 
Tabulated list of adverse reactions 
Adverse reactions reported in a pooled safety dataset of 70 patients with carcinoid syndrome receiving 
telotristat ethyl 250 mg tid in combination with SSA therapy in placebo-controlled clinical trials are 
listed in Table 1. Adverse reactions are listed by MedDRA body system organ class and by frequency 
using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon 
(≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be 
estimated from the available data). Within each frequency grouping, adverse reactions are presented in 
order of decreasing seriousness  
 
Table 1 - Adverse reactions reported in patients treated with Xermelo 

System organ class Very common Common Uncommon 
Metabolism and 
nutrition disorders 

 Decreased appetite  

Psychiatric disorders  Depression, depressed 
mood 

 

Nervous system 
disorders 

 Headache  

Gastrointestinal 
disorders 

Abdominal paina, 
nausea 

Abdominal distension, 
Constipation,  
Flatulence 

Faecalomac, intestinal 
obstruction 

Hepatobiliary 
disorders 

Gamma-
glutamyltransferase 
increasedb 

Alanine aminotransferase 
increased (ALT),  
Aspartate 
aminotransferase increased 
(AST), 
Blood alkaline 
phosphatase increased 
(ALP) 

 

General disorders 
and administration 
site conditions 

Fatigue Oedema peripheral,  
Pyrexia 

 

a Abdominal pain (including upper and lower abdominal pain) 
b Gamma-glutamyl transferase increased (including preferred terms of gamma-glutamyl transferase 
increased, gamma-glutamyl transferase, and liver function test abnormal / hepatic enzyme increased 
for which gamma-glutamyl transferase was increased). 
c Faecaloma has only been observed in a clinical study at a dosage of 500mg tid (twice the 
recommended dose). 
 
Description of selected adverse reactions 
Hepatic enzymes elevations 
Elevations in ALT >3 × upper limit of normal (ULN) or ALP>2 ULN have been reported in patients 
receiving therapy with telotristat, most cases being reported at a higher dose (500 mg). These have not 
been associated with concomitant elevations in total serum bilirubin. The increases were largely 
reversible on dose interruption or reduction, or recovered whilst maintaining treatment at the same 
dose. For clinical management of elevated hepatic enzymes, see section 4.4. 
 
Gastrointestinal disorders 
The most frequently reported adverse event in patients receiving telotristat ethyl 250 mg tid was 
abdominal pain (25.7%; 18/70) versus placebo (19.7%; 14/71). Abdominal distension was reported in 
7.1% of patients (5/70) receiving telotristat ethyl 250 mg tid, versus 4.2% in the placebo group (3/71). 
Flatulence was seen in 5.7% of patients (4/70) and 1.4% (1/71) in the telotristat ethyl 250 mg and 
placebo groups, respectively. Most events were mild or moderate and did not limit study treatment.  



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Constipation was reported in 5.7% of patients (4/70) in the telotristat ethyl 250 mg group and in 4.2% 
of patients (3/71) in the placebo group. Serious constipation was observed in 3 patients treated with a 
higher dose (500 mg) in the overall safety population (239 patients). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms  
There is limited clinical experience with telotristat overdose in humans. Gastrointestinal disorders 
including nausea, diarrhoea, abdominal pain and vomiting have been reported in healthy subjects 
taking a single dose of 1,500 mg in a phase 1 study.  
 
Management  
Treatment of an overdose should include general symptomatic management. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other alimentary tract and metabolism products: Various alimentary tract 
and metabolism products, ATC code: A16AX15 
 
Mechanism of action 
Both the prodrug (telotristat ethyl) and its active metabolite (telotristat) are inhibitors of L-tryptophan 
hydroxylases (TPH1 and TPH2, the rate limiting steps in serotonin biosynthesis). Serotonin plays a 
critical role in regulating several major physiological processes, including secretion, motility, 
inflammation, and sensation of the gastrointestinal tract, and is over-secreted in patients with carcinoid 
syndrome. Through inhibition of peripheral TPH1, telotristat reduces the production of serotonin, thus 
alleviating symptoms associated with carcinoid syndrome. 
 
Pharmacodynamic effects 
In Phase 1 studies, dosing with telotristat ethyl in healthy subjects (dose range: 100 mg once daily to 
500 mg tid) produced statistically significant reductions from baseline in whole blood serotonin and 
24-hour urinary 5-hydroxyindoleacetic acid (u5-HIAA) compared with placebo.  
In patients with carcinoid syndrome, telotristat resulted in reductions in u5-HIAA (refer to Table 3 for 
TELESTAR and information provided for TELECAST). Statistically significant reductions in 
u5-HIAA were seen for telotristat ethyl 250 mg tid compared with placebo in both Phase 3 studies. 
 
Clinical efficacy and safety 
The efficacy and safety of telotristat for the treatment of carcinoid syndrome in patients with 
metastatic neuroendocrine tumours who were receiving SSA therapy was established in a 12-week 
double-blind, placebo-controlled, randomised, multicentre phase 3 trial in adult patients, which 
included a 36-week extension during which all patients were treated with open-label telotristat 
(TELESTAR Study). 
 
A total of 135 patients were evaluated for efficacy. The mean age was 64 years (range 37 to 88 years), 
52% were male and 90% were white. All patients had well-differentiated metastatic neuroendocrine 
tumours and carcinoid syndrome. They were on SSA therapy and had ≥4 daily BM.  
 
The study included a 12-week double-blind treatment (DBT) period, in which patients initially 
received placebo (n=45), telotristat ethyl 250 mg (n=45) or a higher dose (telotristat ethyl 500 mg; 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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n=45) tid. During the study, patients were allowed to use rescue medication (short-acting SSA 
therapy) and anti-diarrhoeals for symptomatic relief but were required to be on stable-dose long-acting 
SSA therapy for the duration of the DBT period. Xermelo was taken within 15 minutes before, or 
within 1 hour after food. 
 
Table 2: BM response (TELESTAR Study) 

 Parameter Placebo Telotristat ethyl 250 mg tid  

BMs/day at baseline  
Number of patients  45 45 
Baseline mean (SD) 5.2 (1.35) 6.1 (2.07) 

Primary endpoint: 
change from baseline 
in BMs/day averaged 
over 12 weeks  

Number of patients  45 45 

Change averaged 
over 12 weeks: mean 
(SD) 

˗0.6 (0.83) ˗1.4 (1.37) 

ANCOVAa 

Least Square mean 
difference 

--- -0.6 

97.5% CL for 
difference --- -1.16, -0.06 

p value --- 0.01 
Percentage of 
patients with durable 
responseb  

Number of patients  45 45 

Responder, n (%) 9 (20.0) 20 (44.4)c 

BM = bowel movement; CL=confidence limit; tid=three times daily; SD=standard deviation. 
a. Analysis of covariance including treatment group and urinary 5-HIAA stratification at 

randomisation as fixed effects, and the baseline number of BM as a fixed covariate. 
b. Defined as the proportion of responders with ≥30% reduction in daily number of BMs for ≥50% 

of time over the DBT period.  
c. p=0.01 

 
When the full effect of telotristat is observed (during the last 6 weeks of the DBT period) the 
proportion of responders with at least 30% BM reduction was 51% (23/45) in the 250 mg group versus 
22% (10/45) in the placebo group (post-hoc analysis). 
 
In the 12-week DBT period of the study, average weekly reductions in BM frequency on telotristat 
were observed as early as 3 weeks, with the greatest reductions occurring during the last 6 weeks of 
the DBT period, compared with placebo (refer to Figure 1).  
 



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Figure 1 – Mean change from baseline in BMs by study week during the DBT period, Intent-to-
Treat Population 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The proportions of patients reporting reductions from baseline in daily BM frequency (averaged over 
12 weeks) were: 
- Patients with a mean reduction of at least 1 BM per day: 66.7% (telotristat ethyl 250 mg) and 

31.1% (placebo); 
- Patients with a mean reduction of at least 1.5 BM per day: 46.7% (telotristat ethyl 250 mg) and 

20.0% (placebo); 
- Patients with a mean reduction of at least 2 BM per day: 33.3% (telotristat ethyl 250 mg) and 

4.4% (placebo). 
 
Table 3: u5-HIAA excretion at baseline and week 12 (TELESTAR Study) 

 Parameter Placebo Telotristat ethyl  250 mg tid  
u5-HIAA excretion 
(mg/24 hours) at 
baseline  

Number of Patients 44 42 

Baseline Meana (SD) 81.0 (161.01) 92.6 (114.90) 

Percent change from 
baseline in u5-HIAA 
excretion (mg/24 
hours) at week 12 

Number of Patients 28 32 
Percent Change at 
Week 12: Mean (SD) 14.4 (57.80) -42.3 (41.96) 

Estimate of Treatment 
Difference (95% CL)b --- 

-53.4 c 
(-69.32, -38.79) 

CL=confidence limit; tid=three times daily; SD=standard deviation; u5-HIAA = urinary 
5--hydroxyindoleacetic acid. 
a. Baseline data based on all patients with data at baseline. 
b. Statistical tests used a blocked 2-sample Wilcoxon Rank Sum statistic (van Elteren test) 

stratified by the u5-HIAA stratification at randomization. CLs were based on the Hodges-
Lehmann estimator of the median paired difference. 

c. p<0.001   
 
There was no significant difference between treatment groups for the endpoints of flushing and 
abdominal pain. 
 
A post-hoc analysis showed that the average number of daily short-acting SSA injections used for 
rescue therapy over the 12-week DBT period was 0.3 and 0.7 in the telotristat ethyl 250 mg and 
placebo groups, respectively. 
 

0 1 2 3 4 5 6 7 8 9 10 11 12

Study week

-2.50

-2.25

-2.00

-1.75

-1.50

-1.25

-1.00

-0.75

-0.50

-0.25

0.00

in
 B

ow
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 M
ov

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C
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om

 B
as

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(a

nd
 9

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 C

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Telotristat Ethyl 250mgPlacebo

               
 ,  p

Note: This figure plots the arithmetic mean and 95% confidence limits (CL) (based on normal approximation) of the change
from Baseline in the number of daily bowel movements (counts/day) averaged at each week.



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A pre-specified patient exit interview substudy was conducted to assess relevance and clinical 
meaningfulness of symptom improvements in 35 patients. Questions were asked to blinded 
participants to further characterise the degree of change experienced during the trial. There were 
12 patients who were “very satisfied”, and all of them were on telotristat. The proportions of patients 
who were “very satisfied” were 0/9 (0%) on placebo, 5/9 (56%) on telotristat ethyl 250 mg tid and 
7/15 (47%) on a higher dose of telotristat ethyl. 
 
Overall, 18 patients (13.2%) prematurely discontinued from the study during the DBT Period, 
7 patients in the placebo group, 3 in the telotristat ethyl 250 mg group and 8 in the higher dose group. 
At the conclusion of the 12-week DBT period, 115 patients (85.2%) entered the 36-week open-label 
extension period, where all patients were titrated to receive a higher dose of telotristat ethyl (500 mg) 
tid.  
 
In a phase 3 study of similar design (TELECAST), a total of 76 patients were evaluated for efficacy. 
The mean age was 63 years (range 35 to 84 years), 55% were male and 97% were white. 
All patients had well-differentiated metastatic neuroendocrine tumour with carcinoid syndrome. Most 
patients (92.1%) had fewer than 4 BM per day and all except 9 were treated by SSA therapy.  
 
The primary endpoint was the percent change from Baseline in u5-HIAA at Week 12. The mean 
u5-HIAA excretion at baseline was 69.1 mg/24hours in the 250 mg group (n=17) and 
84.8 mg/24 hours in the placebo group (n=22). The percent change from baseline in u5-HIAA 
excretion at week 12 was +97.7% in the placebo group versus -33.2% in the 250 mg group. 
 
The mean number of daily BM at baseline was 2.2 and 2.5 respectively in the placebo (n=25) and 
250 mg group (n=25). The change from baseline in daily BM averaged over 12 weeks was +0.1 and  
-0.5 in the placebo and 250 mg groups respectively. Telotristat ethyl 250 mg showed that stool 
consistency, as measured by Bristol Stool Form Scale, was improved compared with placebo. There 
were 40% patients (10/25) with durable response (as defined in Table2) in the telotristat ethyl 250 mg 
group, versus 0% in the placebo group (0/26) (p=0.001). 
 
The long-term safety and tolerability of telotristat was evaluated in a nonpivotal (nonrandomized), 
phase 3, multicentre, open-label, long-term extension study. Patients having participated in any 
Xermelo phase 2 or phase 3 carcinoid syndrome study were eligible to enter the study at the same dose 
level and regimen as identified in their original study, for at least 84 weeks of treatment. No new 
significant safety signals were identified.  
The secondary objective of this study was to evaluate changes in patients’ quality of life (QOL) 
through Week 84. QOL was generally stable over the course of the study. 
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
telotristat in all subsets of the paediatric population in the treatment of carcinoid syndrome (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of telotristat ethyl and its active metabolite have been characterised in healthy 
volunteers and patients with carcinoid syndrome.  
 
Absorption 
After oral administration to healthy volunteers, telotristat ethyl was rapidly absorbed, and almost 
completely converted to its active metabolite. Peak plasma levels of telotristat ethyl were achieved in 
0.53 to 2.00 hours and those of the active metabolite in 1.50 to 3.00 hours after oral administration.  
Following administration of a single 500 mg dose of telotristat ethyl (twice the recommended dose) 
under fasted conditions in healthy subjects, the mean Cmax and AUC0-inf were 4.4 ng/mL and 
6.23 ng•hr/mL, respectively for telotristat ethyl. The mean Cmax and AUC0-inf were 610 ng/mL and 
2320 ng•hr/mL, respectively for telotristat. 
 



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In patients with carcinoid syndrome on long-acting SSA therapy, there was also a rapid conversion of 
telotristat ethyl to its active metabolite. A high variability (% CV range of 18% to 99%) in telotristat 
ethyl and its active metabolite parameters was observed within the overall PK. The mean PK 
parameters for telotristat ethyl and the active metabolite appeared unchanged between week 24 and 
week 48, suggesting the achievement of steady-state conditions at or prior to week 24.  
 
Food effect 
In a food effect study administration of telotristat ethyl 500 mg with a high-fat meal resulted in higher 
exposure to the parent compound (Cmax, AUC0-tlast, and AUC0-∞ being 112%, 272%, and 264% higher, 
respectively compared with the fasted state) and its active metabolite (Cmax, AUC0-tlast, and AUC0-∞, 
47%, 32%, and 33% higher, respectively compared with the fasted state).  
 
Distribution 
Both telotristat ethyl and its active metabolite are > 99% bound to human plasma proteins. 
 
Biotransformation 
After oral administration, telotristat ethyl undergoes hydrolysis via carboxylesterases to its active and 
major metabolite. The only metabolite of telotristat (active metabolite) representing consistently 
> 10% of total plasma drug-related material was its oxidative decarboxylated deaminated metabolite, 
LP-951757. Systemic exposure to LP-951757 was about 35% of the systemic exposure to telotristat 
(active metabolite) in the mass balance study. LP-951757 was pharmacologically inactive at TPH1 in 
vitro.  
 
Interactions 
Cytochromes 
CYP2B6  
In vitro telotristat (active metabolite) caused a concentration dependent increase in CYP2B6 mRNA 
levels (>2-fold increase and > 20% of the positive control, with a maximum observed effect similar to 
the positive control), suggesting possible CYP2B6 induction (see section 4.5). 
 
CYP3A4 
Telotristat ethyl and its active metabolite were not shown to be inducers of CYP3A4 at systemically 
relevant concentrations, based on in vitro findings. The potential of telotristat ethyl as an inducer of 
CYP3A4 was not assessed at concentrations expectable at the intestinal level, due to its low solubility 
in vitro. 
In vitro telotristat ethyl engages in an allosteric interaction with CYP3A4 resulting at the same time in 
a reduced conversion of midazolam to 1’-OH-MDZ, and increased conversion to 4-OH-MDZ. 
 
In an in vivo clinical drug-drug interaction (DDI) study with midazolam (a sensitive CYP3A4 
substrate), following administration of multiple doses of telotristat ethyl, the systemic exposure to 
concomitant midazolam was significantly decreased (see section 4.5). When 3 mg midazolam was 
coadministered orally after 5-day treatment with telotristat ethyl 500 mg tid (twice the recommended 
dose), the mean Cmax, and AUC0-inf for midazolam were decreased by 25%, and 48%, respectively, 
compared with administration of midazolam alone. The mean Cmax, and AUC0-inf for the active 
metabolite, 1’-hydroxymidazolam, were also decreased by 34%, and 48%, respectively.  
 
Other CYPs 
Based on in vitro findings, no clinically-relevant interaction is expected with other cytochromes P450. 
 
Carboxylesterases  
The IC50 of the inhibition of loperamide on the metabolism of telotristat ethyl by CES2 was 5.2 µM 
(see section 4.5). 
In vitro, telotristat ethyl inhibited CES2 with an IC50 approximately of 0.56 μM. 
 
Transporters  
 
P-glycoprotein (P-gp) and Multi-drug Resistance associated Protein 2 (MRP-2) 



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In vitro telotristat ethyl inhibited P-gp, but its active metabolite did not at the clinically relevant 
concentrations. 
Telotristat ethyl inhibited MRP2-mediated transport (98% inhibition).  
In a specific clinical DDI study, the Cmax and AUC of fexofenadine (a P-gp and MRP-2 substrate) 
increased by 16% when a single 180 mg dose of fexofenadine was co-administered orally with a dose 
of telotristat ethyl 500 mg administered tid (twice the recommended dose) for 5 days. Based on the 
small increase observed, clinically meaningful interactions with P-gp and MRP-2 substrates are 
unlikely. 
 
Breast Cancer Resistance Protein (BCRP) 
In vitro telotristat ethyl inhibited BCRP (IC50 = 20 µM), but its active metabolite telotristat did not 
show any significant inhibition of BCRP activity (IC50 > 30 µM). The potential for in vivo drug 
interaction via inhibition of BCRP is considered low. 
 
Other transporters 
Based on in vitro findings, no clinically-relevant interaction is expected with other transporters.  
 
Short-acting octreotide 
A study examining the effect of short-acting octreotide (3 doses of 200◦micrograms given 8◦hours 
apart) on the single dose pharmacokinetics of Xermelo in normal healthy volunteers showed an 83% 
and 81% decrease in Cmax and AUC of telotristat ethyl and telotristat, respectively (see section 4.5). 
Reduced exposures were not observed in a 12◦week double-blind, placebo-controlled, randomised, 
multicentre clinical trial in adult patients with carcinoid syndrome on long-acting SSA therapy. 
 
Pharmacokinetic/pharmacodynamic relationship(s) 
 
Acid Reducers 
Concomitant use of telotristat etiprate (Xermelo, the hippurate salt of telotristat ethyl) with acid-
reducers (omeprazole and famotidine) showed that the AUC of telotristat ethyl was increased 2-3 fold, 
while the AUC of the active metabolite (telotristat) was not changed. Since telotristat ethyl is rapidly 
converted to its active metabolite, which is > 25× more active than telotristat ethyl, no dose 
adjustments are required when using Xermelo with acid reducers. 
 
Elimination 
Following a single 500 mg oral dose of 14C-telotristat ethyl, approximately 93% of the dose was 
recovered. The majority was eliminated in the faeces. 
 
Telotristat ethyl and telotristat have a low renal elimination following oral administration (less than 
1% of the dose recovered from the urine).  
Following a single oral 250 mg dose of telotristat ethyl to heathy volunteers, urine concentrations of 
telotristat ethyl were close to or below the limit of quantification (<0.1 ng/mL). The renal clearance of 
telotristat was 0.126 L/h.  
 
The apparent half-life of telotristat ethyl in normal healthy volunteers following a single 500 mg oral 
dose 14C-telotristat ethyl was approximately 0.6 hour and that of its active metabolite was 5 hours. 
Following administration of 500 mg tid, the apparent terminal half-life was approximately 11 hours. 
 
Linearity/non-linearity 
In patients treated at 250 mg tid, a slight accumulation of telotristat levels was observed with a median 
accumulation ratio based on AUC0-4h of 1.55 [minimum, 0.25; maximum, 5.00; n=11; week 12], with a 
high inter-subject variability (%CV = 72%). In patients treated at 500 mg tid (twice the recommended 
dose), a median accumulation ratio based on AUC0-4h of 1.095 (minimum, 0.274; maximum, 11.46; 
n=16; week 24) was observed, with a high inter-subject variability (%CV = 141.8%).  
Based on the high inter-subject variability observed, accumulation in a subset of patients with CS 
cannot be excluded. 
 
Special populations 



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Elderly 
The influence of age on the pharmacokinetics of telotristat ethyl and its active metabolite has not been 
conclusively evaluated. No specific study has been performed in the elderly population.  
 
Renal impairment 
A study was conducted to investigate the impact of renal impairment on the pharmacokinetics of a 
single dose of telotristat ethyl 250 mg. Eight subjects with severe to moderate renal impairment not 
requiring dialysis [eGFR ≤ 33 mL/min at screening and ≤40 mL/min at the day prior to dosing] and 
eight healthy to mildly impaired subjects [eGFR ≥88 mL/min at screening and ≥83 mL/min at the day 
prior to dosing] were included in this study. 
In the subjects with severe to moderate renal impairment, an increase (1.3- fold) in peak exposure 
Cmax of telotristat ethyl and an increase (<1.52- fold) in plasma exposure (AUC) and Cmax of its 
active metabolite telotristat was observed compared to healthy to mildly impaired subjects.  
Variability of the main plasma telotristat PK parameters was higher in subjects with severe to 
moderate renal impairment, with CV% ranging from 53.3% for Cmax to 77.3% for AUC as compared 
to 45.4% for Cmax and 39.7% for AUC in healthy to mildly impaired subjects, respectively. 
 
Administration of a single dose of 250 mg was well tolerated in subjects with severe to moderate renal 
impairment.  
 
Overall, severe to moderate renal impairment did not result in a clinically meaningful change in the 
PK profile or safety of telotristat ethyl and its metabolite telotristat. Therefore, dose adjustment does 
not appear necessary in patients with mild, moderate or severe renal impairment; who are not requiring 
dialysis. Given the high variability observed, it is recommended as a precautionary measure that 
patients with severe renal impairment will be monitored for signs of reduced tolerability. 
 
The efficacy and safety in patients with end-stage renal disease who require dialysis (eGFR < 15 
mL/min/1.73 m² requiring dialysis) has not been established. 
 
Hepatic impairment 
A hepatic impairment study was conducted in subjects with mild and moderate hepatic impairment 
and in healthy subjects. At a single dose of 500 mg, exposures to the parent compound and its active 
metabolite (based on AUC0-last) were higher in patients with mild hepatic impairment (2.3- and 2.4-
fold, respectively) and in patients with moderate hepatic impairment (3.2- and 3.5-fold, respectively) 
compared with healthy subjects. Administration of a single dose of 500 mg was well tolerated. A 
reduction in dose may be necessary in patients with mild or moderate hepatic impairment (respectively 
Child Pugh score A and B) based on tolerability (see section 4.2). 
 
A further hepatic impairment study was conducted in subjects with severe hepatic impairment and in 
healthy subjects. At a single dose of 250 mg, exposure to the parent compound (AUCt and Cmax) was 
increased 317.0% and 529.5%, respectively, and to the active metabolite (AUCt, AUCinf, and Cmax) 
497%, 500%, and 217%, respectively, for subjects with severe hepatic impairment compared to 
subjects with normal hepatic function. In addition, the half-life of the active metabolite was increased, 
i.e. the mean half life was 16.0 hours in subjects with severe hepatic impairment compared to 5.47 
hours in healthy subjects. Based on these findings, the use of telotristat etiprate is not recommended in 
patients with severe hepatic impairment (Child Pugh score C) (see section 4.2). 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeat dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and 
development.  
 
In rats decrease in brain serotonin (5-HT) was observed at doses≥1,000 mg/kg/day of telotristat 
etiprate per os. Brain 5-HIAA levels were unchanged at all doses of telotristat ethyl examined. This is 



13 

approximately 14 times the human exposure (AUC total) at the maximum recommended human dose 
(MRHD) of 750 mg/day for the active metabolite LP-778902. 
 
In a 26-week repeat-dose toxicity study in rats a No-Observed Adverse Effect Level (NOAEL) of 
50 mg/kg/day was determined. This is approximately 0.4 times the human exposure (AUC total) at 
MRHD of 750 mg/day for the active metabolite LP-778902. At doses of 200 and 500 mg/kg/day 
degeneration/necrosis in the nonglandular and/or glandular portions of the stomach and/or increased 
protein droplets in the glandular portions were observed. The microscopic changes in the 
gastrointestinal tract reversed with a 4-week recovery period. Relevance of these gastrointestinal 
findings to humans is unknown.  
 
In dogs decreases in brain 5-HT and 5-HIAA levels were observed at dose of 200 mg/kg/day and 
30 mg/kg/day of telotristat etiprate per os, respectively. This is approximately 21 times the human 
exposure (AUC total) at MRHD of 750 mg/day for the active metabolite LP-778902. No decrease in 
brain 5-HT and 5-HIAA levels were observed after intravenous application of active metabolite. The 
clinical significance of the decrease in brain 5-HIAA with or without a concomitant decrease in brain 
5-HT is unknown.  
 
In a 39-week repeat-dose toxicity study in dogs NOAEL of 300 mg/kg/day was determined. Clinical 
signs were limited to increase in frequency of liquid faeces at all doses. This is approximately 20 times 
the human exposure (AUC total) at MRHD of 750 mg/day for the active metabolite LP-778902. 
 
The carcinogenic potential of telotristat etiprate was studied in transgenic mice (26 weeks) and rats 
(104 weeks). These studies confirmed that telotristat did not increase the incidence of tumours in both 
species and sexes, at doses corresponding to an exposure of approximately 10- to 15-fold and 2- to 
4.5-fold the human exposure to the active metabolite at the MRHD in mice and rats, respectively. 
 
In rats, there were no adverse effects on male and female fertility. Prenatal development in rats and 
rabbits was affected by increased prenatal lethality (increased early and late resorptions), while no 
adverse effects were noted on postnatal development in rats. The NOAEL for parental / maternal / 
prenatal and postnatal toxicity is 500 mg/kg/day in rats corresponding to 3 to 4 times the estimated 
human exposure (AUC0-24) of the active metabolite LP-778902 at the MRHD. In rabbits the NOAEL 
for maternal and prenatal toxicity is 125 mg/kg/d corresponding to 1.5 to 4 times the estimated human 
exposure (AUC0-24) of the active metabolite LP-778902 at the MRHD. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Lactose anhydrous 
Hydroxypropylcellulose  
Croscarmellose sodium 
Magnesium stearate 
Silica, colloidal anhydrous 
 
Film-coating 
Poly(vinyl alcohol) (partially hydrolysed) (E1203) 
Titanium dioxide (E171) 
Macrogol 3350 (E1521) 
Talc (E553b) 
 
6.2 Incompatibilities 
 
Not applicable. 
 



14 

6.3 Shelf life 
 
4 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container  
 
PVC/PCTFE/PVC/Al blister 
The blisters are packaged in a carton.  
 
Pack sizes of 90 and 180 tablets. Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Ipsen Pharma  
65 quai Georges Gorse 
92100 Boulogne-Billancourt 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1224/001 
EU/1/17/1224/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 18 September 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
  

http://www.ema.europa.eu/


15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 



16 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
BEAUFOUR IPSEN INDUSTRIE 
RUE ETHE VIRTON 
DREUX 
28100 
France 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and 
any subsequent updates published on the European medicines web-portal. 
The marketing authorisation holder (MAH) shall submit the first PSUR for this medicinal product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing 
authorisation and any agreed subsequent updates of the RMP. 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 

 

  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



19 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xermelo 250 mg film-coated tablets 
telotristat ethyl 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains telotristat etiprate equivalent to 250 mg telotristat ethyl. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 film-coated tablets 
180 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



20 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste should be disposed of in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Ipsen Pharma 
65 quai Georges Gorse 
92100 Boulogne-Billancourt 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1224/001 
EU/1/17/1224/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
xermelo 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC {number}  
SN {number}  
NN {number}  
 
  



21 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xermelo 250 mg film-coated tablets 
telotristat ethyl 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Ipsen Pharma 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 

  



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



23 

Package leaflet: Information for the patient 
 

Xermelo 250 mg film-coated tablets 
telotristat ethyl  

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Xermelo is and what it is used for  
2. What you need to know before you take Xermelo  
3. How to take Xermelo  
4. Possible side effects  
5. How to store Xermelo  
6. Contents of the pack and other information 
 
 
1. What Xermelo is and what it is used for 
 
What Xermelo is 
This medicine contains the active substance telotristat ethyl.  
 
What Xermelo is used for 
This medicine is used in adults with a condition called ‘carcinoid syndrome’. This is when a tumour, 
called a ‘neuroendocrine tumour’, releases a substance called serotonin into your bloodstream.  
 
Your doctor will prescribe this medicine if your diarrhoea is not well controlled with injections of 
other medicines called ‘somatostatin analogues’ (lanreotide or octreotide). You should keep having 
injections of these other medicines when taking Xermelo. 
 
How Xermelo works 
When the tumour releases too much serotonin into your bloodstream you can get diarrhoea.  
This medicine works by reducing the amount of serotonin made by the tumour. It will reduce your 
diarrhoea.  
 
 
2. What you need to know before you take Xermelo  
 
Do not take Xermelo 
- if you are allergic to telotristat or any of the other ingredients of this medicine (listed in 
section 6). 
 
Warnings and precautions  
Talk to your doctor or pharmacist before taking Xermelo: 
• if you have liver problems. This is because this medicine is not recommended for use in patients 

with severe liver problems. Your doctor may decide to decrease your daily dose of Xermelo in 



24 

cases where your liver problems are considered mild or moderate. Your doctor will also monitor 
your liver. 

• if you have end-stage kidney disease or are on dialysis. This is because this medicine has not been 
tested in patients with end-stage kidney disease, requiring dialysis.  

 
Look out for side effects 
Tell your doctor straight away if you notice any of the following signs and symptoms that suggest that 
your liver may not be working properly: 
• feeling or being sick (unexplained nausea or vomiting), abnormally dark urine, yellow skin or eyes, 

pain in the upper right belly.  
Your doctor will do blood tests to check your liver and will decide whether you should keep taking 
this medicine. 
 
Talk to your doctor or pharmacist: 
• if you feel down, depressed, or if you feel you have no interest or take any pleasure in doing your 

normal activities, whilst taking this medicine 
• if you have signs of constipation, as telotristat reduces the number of your bowel movements. 

 
Tests 
• Your doctor may carry out blood tests before you start taking this medicine and while you are 

taking it. This is to check that your liver is working normally. 
 
Children and adolescents 
This medicine is not recommended in patients below 18 years old. This is because the medicine has 
not been tested in this age group. 
 
Other medicines and Xermelo 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This is because Xermelo can affect the way some other medicines work, or other medicines 
can affect the way Xermelo works. This could mean that your doctor needs to change the dose(s) that 
you take. You should tell your doctor about every medicine. This includes:  
• medicines for diarrhoea. Xermelo and these medicines reduce the number of your bowel 

movements and taken together, they can cause severe constipation. Your doctor may need to 
change the dose of your medicines.  

• medicines used to treat epilepsy, such as valproic acid. 
• medicines used to treat your neuroendocrine tumour, such as sunitinib or everolimus. 
• medicines to treat depression, such as bupropion or sertraline. 
• medicines used to avoid transplant rejection, such as cyclosporine. 
• medicines used to lower cholesterol levels, such as simvastatin. 
• oral contraceptives, such as ethinyloestradiol.  
• medicines used to treat high blood pressure, such as amlodipine. 
• medicines used to treat some types of cancers, such as irinotecan, capecitabine and flutamide. 
• medicines used to reduce the chance of a blood clot forming, such as prasugrel. 
• octreotide. If you need treatment with octreotide subcutaneous injections, you should have your 

injection at least 30 minutes after taking Xermelo. 
 
Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you might be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.  
You should not take this medicine if you are pregnant or might become pregnant. It is not known how 
telotristat may affect the baby.  
Women should use effective methods of contraception while taking this medicine. 
You should not breast-feed if you are taking Xermelo, as this medicine may be passed on to your 
baby.  
 



25 

Driving and using machines 
Telotristat may have a small effect on your ability to drive or use any tools or machines. If you feel 
tired, you should wait until you feel better before driving or using any tools or machines. 
 
Xermelo contains lactose 
Xermelo contains lactose (a type of sugar). If you have been told by your doctor that you have 
intolerance to some sugars, contact your doctor before taking this medicine. 
 
 
3. How to take Xermelo 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 
How much to take 
The recommended dose is one tablet (250 mg) three times a day. The maximum dose of Xermelo is 
750 mg in 24 hours. 
Your doctor will decide for how long you should take Xermelo. 
If you have liver problems, your doctor may decide to reduce your daily dose of Xermelo. 
 
Taking this medicine 
• Always take this medicine with a meal or some food.  
• You should keep having injections of somatostatin analogues (lanreotide or octreotide) when taking 

Xermelo. 
 
If you take more Xermelo than you should 
You may feel sick or be sick, have diarrhoea or stomach ache. Talk to a doctor. Take the medicine 
pack with you.  
 
If you forget to take Xermelo 
If you forget to take a dose, take your next dose when it is due, skipping the missed dose. 
Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking Xermelo 
Do not stop taking Xermelo without talking with your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor immediately if you notice any of the following side effects: 
• feeling or being sick, abnormally dark urine, yellow skin or eyes, pain in the upper right belly. 

These may be signs that your liver is not working properly. This might also be shown by changes 
in your blood test results, such as an increase of liver enzymes: gamma-glutamyl transferase (very 
common, may affect more than 1 in 10 people), transaminases and blood alkaline phosphatase 
(common, may affect up to 1 in 10 people). 

 
Other side effects 
Tell your doctor, pharmacist or nurse if you notice any of the following side effects: 
 
Very common side effects (may affect more than 1 in 10 people):  
• Belly (abdominal) pain 
• Feeling tired or weak (fatigue) 
• Feeling sick (nausea) 



26 

 
Common side effects (may affect up to 1 in 10 people):  
• Wind 
• Fever 
• Headache  
• Constipation  
• Swollen stomach 
• Decreased appetite 
• Swelling (build-up of fluid in the body) 
• Depression, you may experience decreased self-esteem, lack of motivation, sadness or low mood 
 
Uncommon side effects (may affect up to 1 in 100 people): 

• Impacted stools (bowel obstruction, faecaloma), you may experience, constipation, watery 
diarrhoea, pale skin (anaemia), nausea, vomiting, weight loss, back pain or stomach pains 
particularly after eating or a reduction in passing water (urination).  
 
Tell your doctor immediately if you experience any of the following side effects: 

• Breathing problems, rapid heartbeat, fever, incontinence (uncontrollable urination), confusion, 
dizziness or agitation.  

 
Tell your doctor, pharmacist or nurse if you notice any of the side effects listed above. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Xermelo 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP. 
The expiry date refers to the last day of that month. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Xermelo contains  
• The active substance is telotristat ethyl. Each tablet contains telotristat etiprate equivalent to 

250 mg telotristat ethyl. 
• The other ingredients are: lactose anhydrous (see section 2 under ‘Xermelo contains lactose’), 

hydroxypropylcellulose, croscarmellose sodium, magnesium stearate, colloidal anhydrous silica, 
poly(vinyl alcohol) (partially hydrolysed) (E1203), titanium dioxide (E171), macrogol 3350 
(E1521) and talc (E553b).  

 
What Xermelo looks like and contents of the pack 
The tablets are white to off-white, film-coated and oval shaped. Each tablet is approximately 17 mm 
long by 7.5 mm wide with ‘T-E’ debossed on one side and ‘250’ debossed on the other. The tablets are 
packaged in a PVC/PCTFE/PVC/Al blister. The blisters are packaged in a carton. 
 
Cartons of 90 and 180 tablets. Not all pack sizes may be marketed. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


27 

 
Marketing Authorisation Holder  
Ipsen Pharma 
65 quai Georges Gorse 
92100 Boulogne-Billancourt 
France 
 
Manufacturer 
Beaufour Ipsen Industrie 
Rue Ethé Virton 
28100 Dreux 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien, 
Luxembourg/Luxemburg  
Ipsen NV 
Guldensporenpark 87 
B-9820 Merelbeke  
België/Belgique/Belgien 
Tél/Tel: + 32 - 9 - 243 96 00 
 

Latvija  
Ipsen Pharma pārstāvniecība Latvijā 
Kalnciema iela 33-5 
Rīga  
LV 1046 
Tel: +371 67622233 
 

България 
Pharmaswiss EOOD 
16, Troyanski Prohod Street 
Floor 3, Office 8, Lagera 
1612 Sofia 
Teл.: +359 28952 110 
 

Lietuva 
Ipsen Pharma SAS Lietuvos filialas  
T. Narbuto g. 5, 
08105 Vilnius 
Tel: + 370 700 33305 
 

Česká republika  
Ipsen Pharma, s.r.o.  
Olbrachtova 2006/9, 
140 00 Praha 4 
Tel: + 420 242 481 821 
 

Magyarország 
IPSEN Pharma Hungary Kft. 
Váci út 33 IX. em. 
1134 Budapest 
Tel.: +36-1-555-5930 
 

Danmark, Norge, Suomi/Finland, Sverige, 
Ísland 
Institut Produits Synthèse (IPSEN) AB 
Kista Science Tower  
Färögatan 33 
SE- 164 51 Kista  
Sverige/Ruotsi/Svíþjóð  
Tlf/Puh/Tel/Sími: +46 8 451 60 00 
 

Nederland 
Ipsen Farmaceutica B.V.  
Taurusavenue 33b 
2132 LS Hoofddorp  
Tel: + 31 (0) 23 554 1600 
 
 

Deutschland, Österreich  
Ipsen Pharma GmbH 
Einsteinstraße 174  
D-81677 München 
Tel.: +49 89 262043289 
 

Polska 
Ipsen Poland Sp. z o.o. 
Al. Jana Pawła II 29 
00-867 Warszawa 
Tel.: + 48 22 653 68 00 
 
 

Eesti 
CentralPharma Communications OÜ 
Selise 26 - 11 
13522 Tallinn 

Portugal  
Ipsen Portugal - Produtos Farmacêuticos S.A. 
Alameda Fernão Lopes, n° 16A–1°B 
1495 - 190 Algés 



28 

Estonia 
Tel: +372 6015540 
 

Portugal 
Tel: + 351 - 21 - 412 3550 
 

Ελλάδα, Κύπρος, Malta 
Ipsen Μονοπρόσωπη EΠΕ 
Αγ. Δημητρίου 63 Άλιμος 
GR-17456 Αθήνα 
Ελλάδα 
Τηλ: + 30 - 210 - 984 3324 
 

România 
Ipsen Pharma România SRL 
Sectorul 1, Strada Grigore Alexandrescu nr. 59, 
Etaj 1 
Bucureşti, 010623 
Tel: + 40 21 231 27 20 
 

España 
Ipsen Pharma, S.A. 
Torre Realia, Plaza de Europa, 41-43  
08908 L’Hospitalet de Llobregat  
Barcelona 
Tel: + 34 936 858 100 
 

Slovenija  
Pharmaswiss d.o.o. 
Brodišče 32 
SI-1236 Trzin 
Tel: +386 1 236 47 00  
 
 

France, Hrvatska 
Ipsen Pharma 
65 quai Georges Gorse 
92100 Boulogne-Billancourt  
France 
Tél: + 33 1 58 33 50 00 
 

Slovenská republika 
Ipsen Pharma, organizačná zložka 
Zámocká 3 
SK-811 01 Bratislava  
Slovenská republika 
Tel: + 420 242 481 821  
 

Ireland 
Ipsen Pharmaceuticals Ltd.  
Blanchardstown Industrial Park  
Blanchardstown 
IRL-Dublin 15 
Tel: +353-1-809-8256 
 

United Kingdom 
Ipsen Ltd. 
190 Bath Road  
Slough, Berkshire SL1 3XE 
United Kingdom 
Tel: + 44 (0)1753 - 62 77 00 

Italia 
Ipsen SpA 
Via del Bosco Rinnovato n. 6 
Milanofiori Nord Palazzo U7 
20090 Assago (MI) 
Tel: + 39 - 02 - 39 22 41 
 

 

   
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site:  
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
 
 
 
 
 

http://www.ema.europa.eu/

	ANNEX I
	SUMMARY OF PRODUCT CHARACTERISTICS
	ANNEX II
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	ANNEX III
	A. LABELLING
	B. PACKAGE LEAFLET