5/17. Telotristyl ethyl -(XERMELO)-@- (Feb 2017) to treat carcinoid syndrome diarrhea stro-intestinal product
Drug Name:5/17. Telotristyl ethyl -(XERMELO)-@- (Feb 2017) to treat carcinoid syndrome diarrhea stro-intestinal product
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
CYP3A4 Substrates (e.g., midazolam): Efficacy of concomitant drugs may be
decreased; monitor for suboptimal efficacy and consider increasing the dose
of the concomitant drug.
Indication:
BRIEF SUMMARY
TELOTRISTYL ethyl- (Feb 20170
Indn- To treat carciniod syndrome diarrhea
Comp- Tablets: 250 mg telotristat ethyl The recommended dosage of Xermelo in adult patients is 250 mg three times daily for patients whose diarrhea is inadequately controlled by a SSA therapy.
ADR- Most common adverse reactions (.5%) are nausea, headache, increased GGT,
depression, flatulence, decreased appetite, peripheral edema, and pyrexia.
CI- None.
WARNINGS-
Constipation:
Xermelo reduces bowel movement frequency; monitor patients for constipation
and/or severe persistent or worsening abdominal pain.
Discontinue Xermelo if severe constipation or abdominal pain develops.
Pat Infn-
1.If they experience severe constipation or severe persistent or worsening
abdominal pain, to discontinue Xermelo and contact their healthcare provider.
2.To take Xermelo with food.
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U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 5
Name of the Drug- XERMELO
Active Ingredient- Telotristat Ethyl Pharmacological Classification-
To treat carciniod syndrome diarrhea
Date of Approval- 02-28-2017
(Ref- FDA approved List 2017)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
XERMELO safely and effectively. See full prescribing information for XERMELO.
XERMELO (telotristat ethyl) tablets, for oral use
Initial U.S. Approval: 2017
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (.5%) are nausea, headache, increased GGT,
depression, flatulence, decreased appetite, peripheral edema, and pyrexia.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Constipation:
Xermelo reduces bowel movement frequency; monitor patients for constipation
and/or severe persistent or worsening abdominal pain.
Discontinue Xermelo if severe constipation or abdominal pain develops.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
Xermelo is a tryptophan hydroxylase inhibitor indicated for the treatment of
carcinoid syndrome diarrhea in combination with somatostatin analog (SSA)
therapy in adults inadequately controlled by SSA therapy.
DOSAGE AND ADMINISTRATION
The recommended dosage of Xermelo in adult patients is 250 mg three times
daily for patients whose diarrhea is inadequately controlled by a SSA therapy.
1.Take Xermelo with food.
2.When short-acting octreotide is used in combination with Xermelo, administer
short-acting octreotide at least 30 minutes after administering Xermelo.
3.Discontinue Xermelo if severe constipation develops.
DOSAGE FORMS AND STRENGTHS
Tablets: 250 mg telotristat ethyl
Patient Information:
PATIENT COUNSELING INFORMATION
Advise patients:
1.If they experience severe constipation or severe persistent or worsening
abdominal pain, to discontinue Xermelo and contact their healthcare provider.
2.To take Xermelo with food.
3.When short-acting octreotide is used in combination with Xermelo,
administer short-acting octreotide at least 30 minutes after administering Xermelo.
4.If a dose is missed, take the next dose at the regular time.
Do not take 2 doses at the same time to make up for a missed dose.
Distributed by:
Lexicon Pharmaceuticals, Inc.
8800 Technology Forest Place
The Woodlands, TX 77381
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Telotristat, the active metabolite of telotristat ethyl, is an inhibitor of tryptophan
hydroxylase, which mediates the rate limiting step in serotonin biosynthesis.
The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase is
29 times higher than that of telotristat ethyl. Serotonin plays a role in mediating
secretion, motility, inflammation, and sensation of the gastrointestinal tract,
and is over-produced in patients with carcinoid syndrome.
Through inhibition of tryptophan hydroxylase, telotristat and telotristat ethyl
reduce the production of peripheral serotonin, and the frequency of carcinoid
syndrome diarrhea.
2. Pharmacodynamics
In healthy subjects, telotristat ethyl 500 mg three times daily (twice the recommended
dosage) for 14 days decreased whole blood serotonin and 24-hour urinary
5-hydroxyindolacetic acid (5HIAA) from baseline.
A decrease in 24-hour u5-HIAA was observed as early as after 5 days of treatment.
In patients with metastatic neuroendocrine tumors and carcinoid syndrome diarrhea,
24-hour u5HIAA decreased from baseline following 6 and 12 weeks of treatment
with Xermelo 250 mg three times a day, whereas placebo did not decrease u5-HIAA.
3. Pharmacokinetics
Absorption
After a single oral dose of telotristat ethyl to healthy subjects, telotristat ethyl was
absorbed and metabolized to its active metabolite, telotristat.
Peak plasma concentrations of telotristat ethyl were achieved within 0.5 to 2 hours,
and those of telotristat within 1 to 3 hours. Plasma concentrations thereafter declined
in a biphasic manner. Following administration of a single 500 mg dose of telotristat ethyl (twice the recommended dosage) under fasted conditions in healthy subjects,
the mean C max and AUC 0-inf were 4.4 ng/mL and 6.23 ng•hr/mL, respectively
for telotristat ethyl.
The mean C max and AUC 0-inf were 610 ng/mL and 2320 ng•hr/mL, respectively for
telotristat. Peak plasma concentrations and AUC of telotristat ethyl and telotristat
appeared to be dose proportional following administration of a single dose of telotristat
ethyl in the range of 100 mg (0.4 times the lowest recommended dose to
1000 mg [4 times the highest recommended dose]) under fasted conditions.
Following multiple-dose administration of telotristat ethyl 500 mg three times daily,
there was negligible accumulation at steady state for both telotristat ethyl and telotristat.
Food Effect
Administration of a single 500 mg dose of Xermelo (twice the recommended dose)
with food resulted in higher exposure to both telotristat ethyl and telotristat.
The systemic exposure to telotristat ethyl, was significantly increased following
administration with a high-fat meal, with Cmax , and AUC0-inf being
112%, and 264% higher, respectively compared to the fasted state.
Following administration of a single 500 mg dose of telotristat ethyl
under the fed conditions in healthy subjects, the mean C max and AUC 0-inf were
10.5 ng/mL and 21.6 ng•hr/mL, respectively for telotristat ethyl.
The Cmax and AUC0-inf values for telotristat were also increased by 47% and 33%,
respectively, with a high-fat meal compared to the fasted state.
The mean C max and AUC 0inf were 908 ng/mL and 2980 ng•hr/mL, respectively
for telotristat under the fed condition
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no human data with Xermelo use in pregnant women to inform a
drug-associated risk. In animal reproduction studies, no effects on embryo-fetal
development were observed with the administration of oral telotristat ethyl to rats
during organogenesis at doses up to 750 mg/kg/day (approximately 9 times
the exposure at the RHD [recommended human dose]).
Treatment of pregnant rabbits with oral telotristat ethyl during organogenesis
produced maternal toxicity and post-implantation loss at doses of 250 mg/kg/day
or higher (approximately 15 times the exposure at the RHD), and reduced
fetal weight at 500 mg/kg/day (approximately 33 times the exposure at the RHD).
2. Lactation
Risk Summary
There are no data on the presence of telotristat ethyl in human or animal milk,
the effects on the breastfed infant, or the effects on milk production.
The effects of local gastrointestinal and systemic exposure to telotristat ethyl
on breastfed infants are unknown.
The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for Xermelo and any potential adverse effects
on the breastfed infant from Xermelo or from the underlying maternal condition.
Clinical Considerations
Monitor the breastfed infant for symptoms of constipation.
3. Pediatric Use
The safety and effectiveness of Xermelo in pediatric patients have not been established.
4. Geriatric Use
Of 45 patients in a clinical trial of Xermelo, 19 (42%) patients were 65 years of age
and over. No overall differences in safety or effectiveness were observed between
these patients and younger patients, and other reported clinical experience has not
identified differences in responses between the elderly and younger patients
but greater sensitivity of some older individuals cannot be ruled out.
