Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
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 studies 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         Very common                     Common                      Uncommon class
Metabolism and                               Decreased appetite nutrition disorders
Psychiatric                                  Depression, depressed mood disorders
Nervous system                               Headache disorders
Gastrointestinal      Abdominal paina,       Abdominal distension,            Faecalomac, intestinal disorders             nausea                 constipation,                    obstruction flatulence
Hepatobiliary         Gamma-                 Alanine aminotransferase disorders             glutamyltransferase increased (ALT),
increasedb             aspartate aminotransferase increased (AST),
blood alkaline phosphatase increased (ALP)
General disorders     Fatigue                Oedema peripheral,
and administration                           Pyrexia site conditions 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 dose of 500 mg 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.
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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/