Carcinoid syndrome diarrhea: Oral: 250 mg 3 times daily
Missed dose: If a dose is missed, administer the next dose at the regularly scheduled time; do not take 2 doses at the same time.
Mild to severe impairment: No dosage adjustment necessary.
End-stage renal disease requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild impairment (Child-Pugh class A): No dosage adjustment necessary; additional monitoring for adverse reactions recommended.
Moderate to severe hepatic impairment (Child-Pugh class B and C): Use not recommended.
Refer to adult dosing.
Gastrointestinal toxicity: Discontinue for severe constipation or for development of severe, persistent or worsening abdominal pain
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Xermelo: 250 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Xermelo: 250 mg
Administer with food. If used in combination with short-acting octreotide, administer octreotide at least 30 minutes after telotristat ethyl. Rescue octreotide (short-acting) and antidiarrheals were allowed and unrestricted in a clinical study (Kulke 2017).
Carcinoid syndrome diarrhea: Treatment of carcinoid syndrome diarrhea (in combination with somatostatin analog therapy) in adults with symptoms inadequately controlled by somatostatin analog therapy
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (11%)
Gastrointestinal: Nausea (13%)
1% to 10%:
Cardiovascular: Peripheral edema (7%)
Central nervous system: Depression (9%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (9%)
Gastrointestinal: Decreased appetite (7%), flatulence (7%), abdominal pain (≥5%), constipation (≥5%)
Hepatic: Increased serum alkaline phosphatase (<5%), increased serum ALT (<5%), increased serum AST (<5%)
Miscellaneous: Fever (7%)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to telotristat ethyl or any component of the formulation.
Concerns related to adverse effects:
• Gastrointestinal toxicity: Constipation has been reported in clinical trials. Although rarely serious, some events resulted in hospitalization, intestinal perforation or bowel obstruction (these events occurred at a dose higher than the recommended dose). Patients with advanced carcinoid tumors may be at risk for altered gastrointestinal tract wall integrity; monitor closely for constipation and/or severe, persistent, or worsening abdominal pain. Discontinue for severe constipation and/or the development of severe persistent or worsening abdominal pain.
Disease-related concerns:
• Hepatic impairment: Additional monitoring for GI effects (eg, constipation) recommended in patients with mild impairment. Use not recommended in moderate to severe impairment.
Induces CYP3A4 (weak)
Capecitabine: Telotristat Ethyl may decrease serum concentrations of the active metabolite(s) of Capecitabine. Risk C: Monitor therapy
CarBAMazepine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
Irinotecan Products: Telotristat Ethyl may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
Octreotide: May decrease the serum concentration of Telotristat Ethyl. Management: Administer short-acting octreotide at least 30 minutes after administration of telotristat ethyl and monitor for decreased telotristat ethyl efficacy. Risk D: Consider therapy modification
Prasugrel: Telotristat Ethyl may decrease serum concentrations of the active metabolite(s) of Prasugrel. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification
Administration with food results in higher exposure to telotristat ethyl and telotristat.
Adverse events were observed in some animal reproduction studies.
It is not known if telotristat ethyl is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Breastfed infants should be monitored for constipation.
Monitor for symptoms of constipation and/or severe, persistent, or worsening abdominal pain
Telotristat ethyl is a small molecule inhibitor of tryptophan hydroxylase (TPH). TPH converts tryptophan to 5-hydroxytryptophan and ultimately to serotonin, and is the rate-limiting enzyme in serotonin synthesis (Kulke 2017). Decreased production of peripheral serotonin by telotristat ethyl results in a reduction in the frequency of carcinoid syndrome diarrhea.
Distribution: The high molecular weight and acidic moieties of telotristat ethyl inhibit the compound from crossing the blood brain barrier (Kulke 2017).
Protein binding: >99%
Metabolism: Telotristat ethyl is hydrolyzed via carboxylesterases to the metabolite telotristat (active); telotristat is further metabolized.
Half-life elimination: Telotristat ethyl: ~0.6 hours; Telotristat: ~5 hours
Time to peak: Telotristat ethyl: 0.5 to 2 hours; Telotristat: 1 to 3 hours
Excretion: Feces (~93%); urine (<1%)
Hepatic function impairment: Telotristat ethyl systemic exposure (AUC0-last) increased 2.3-, 3.2-, and 4-fold, respectively, and telotristat (active metabolite) systemic exposure (AUC0-last) increased 2.4-, 3.5-, and 5-fold, respectively, in patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) impairment compared to patients with normal hepatic function.
Tablets (Xermelo Oral)
250 mg (per each): $113.32
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
