Dosing & Uses
Dosage Forms & Strengths
tablet
- 250mg
Carcinoid Syndrome Diarrhea
Indicated in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy
250 mg PO TID
Also, see Administration
Dosing Modifications
Renal impairment:
- Mild, moderate, or severe renal impairment not requiring dialysis: No dosage adjustment necessary
- End-stage renal disease requiring dialysis (eGFR< 15 mL/min/1.73 m²): Not studied
Hepatic impairment:
- Mild (Child-Pugh A): No dosage adjustment necessary; however, additional monitoring of associated adverse reactions (eg, constipation) recommended
- Moderate (Child-Pugh Class B) to severe (Child-Pugh C): Not recommended
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (2)
- doravirine
telotristat ethyl will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.
- lonafarnib
telotristat ethyl will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.
Serious - Use Alternative (18)
- avapritinib
telotristat ethyl will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- entrectinib
telotristat ethyl will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fedratinib
telotristat ethyl will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.
- finerenone
telotristat ethyl will decrease the level or effect of finerenone by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.
- infigratinib
telotristat ethyl will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lefamulin
telotristat ethyl will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.
- lemborexant
telotristat ethyl will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lorlatinib
telotristat ethyl will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with moderate CYP3A inducers. If unable to avoid, monitor ALT, AST, and bilirubin as recommended.
- lurbinectedin
telotristat ethyl will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pemigatinib
telotristat ethyl will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pretomanid
telotristat ethyl will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of pretomanid with strong or moderate CYP3A4 inducers.
- rimegepant
telotristat ethyl will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- selumetinib
telotristat ethyl will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- siponimod
telotristat ethyl will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.
- tazemetostat
telotristat ethyl will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voclosporin
telotristat ethyl will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voxelotor
telotristat ethyl will decrease the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with moderate or strong CYP3A4 inducers. If unable to avoid coadministration, increase voxelotor dose (see Dosage Modifications).
- zanubrutinib
telotristat ethyl will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (37)
- alfentanil
telotristat ethyl will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- alpelisib
telotristat ethyl will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- buprenorphine subdermal implant
telotristat ethyl will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.
- buprenorphine, long-acting injection
telotristat ethyl will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.
- bupropion
telotristat ethyl will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Consider increasing dosage of interacting drug, if necessary
- carbamazepine
telotristat ethyl will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- clonidine
telotristat ethyl will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- colchicine
telotristat ethyl will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- cyclosporine
telotristat ethyl will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- diazepam intranasal
telotristat ethyl, diazepam intranasal. Other (see comment). Use Caution/Monitor. Comment: Coadministration may either increase or decrease diazepam elimination.
- dihydroergotamine
telotristat ethyl will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- disopyramide
telotristat ethyl will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- efavirenz
telotristat ethyl will decrease the level or effect of efavirenz by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Consider increasing dosage of interacting drug, if necessary
- elagolix
telotristat ethyl will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erdafitinib
telotristat ethyl will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If a moderate CYP3A4 inducer must be coadministered, administer 8-mg/day dose initially, with potential to increase to 9 mg/day based on serum phosphate levels on Days 14-21 and tolerability. If a moderate CYP3A4 inducer must be coadministered after the initial dose increase period based on serum phosphate levels and tolerability, increase erdafitinib dose up to 9 mg. When a moderate inducer discontinued, continue erdafitinib at same dose, in absence of drug-related toxicity.
- ergotamine
telotristat ethyl will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- ethosuximide
telotristat ethyl will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- everolimus
telotristat ethyl will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- fentanyl
telotristat ethyl will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- isavuconazonium sulfate
telotristat ethyl will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levamlodipine
telotristat ethyl will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.
- midazolam
telotristat ethyl will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- naldemedine
telotristat ethyl will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Simulation using physiologically-based pharmacokinetic modeling suggests that concomitant use of moderated CYP3A4 inducers decrease exposure to naldemedine. The clinical consequence of this decreased exposure is unknown.
- octreotide
octreotide decreases levels of telotristat ethyl by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administer short-acting octreotide at least 30 minutes after telotristat ethyl.
- pimozide
telotristat ethyl will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- quinidine
telotristat ethyl will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- quinine
telotristat ethyl will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- ripretinib
telotristat ethyl will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability
- sirolimus
telotristat ethyl will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- stiripentol
telotristat ethyl will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor closely if stiripentol is coadministered with a moderate CYP3A4 inducer.
- sufentanil SL
telotristat ethyl decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.
- tacrolimus
telotristat ethyl will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- theophylline
telotristat ethyl will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- tinidazole
telotristat ethyl will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tivozanib
telotristat ethyl will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- triazolam
telotristat ethyl will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
- ubrogepant
telotristat ethyl will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is recommended with concomitant use of ubrogepant and moderate and weak CYP3A4 inducers. (see Dosage Modifications)
Minor (0)
Adverse Effects
>10%
Nausea (13%)
Headache (11%)
1-10%
Increased GGT (9%)
Depression (9%)
Peripheral edema (7%)
Flatulence (7%)
Decreased appetite (7%)
Pyrexia (7%)
Abdominal pain (5%)
Constipation (5%)
Increased alkaline phosphatase (<5%)
Increased ALT and AST (<5%)
Warnings
Contraindications
None
Cautions
Reduces bowel movement frequency; monitor for development of constipation and/or severe, persistent, or worsening abdominal pain; discontinue if severe constipation or severe persistent or worsening abdominal pain develops
Drug interaction overview
- Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates
- Short-acting octreotide decreases telotristat Cmax and AUC by 79% and 68%, respectively; administer octreotide at least 30 minutes after telotristat ethyl (also see Administration)
Pregnancy
Pregnancy
There are no human data in pregnant women to inform a drug-associated risk
Animal studies
- No effects on embryo-fetal development were observed with administration of telotristat ethyl to rats during organogenesis at doses up to 750 mg/kg/day (~9 times the exposure at recommended human dose [RHD])
- Treatment of pregnant rabbits during organogenesis produced maternal toxicity and postimplantation loss at doses of ≥250 mg/kg/day (~15 times the exposure at the RHD), and reduced fetal weight at 500 mg/kg/day (~33 times the exposure at the RHD)
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
If administered to a breastfeeding woman, monitor infant for constipation
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Telotristat, the active metabolite of telotristat ethyl, inhibits tryptophan hydroxylase, which mediates the rate-limiting step in serotonin biosynthesis
Serotonin plays a role in mediating secretion, motility, inflammation, and sensation of the GI tract, and is overproduced in patients with carcinoid syndrome
In vitro inhibitory potency of telotristat towards tryptophan hydroxylase is 29 times higher than that of telotristat ethyl
Absorption
Peak plasma time: 1 hr (telotristat ethyl); 2 hr (telotristat)
Peak plasma concentration: 7 ng/mL (telotristat ethyl); 900 ng/mL (telotristat)
AUC: 22 ng·hr/mL (telotristat ethyl); 3000 ng·hr/mL (telotristat)
Administration with food significantly increases systemic exposure of telotristat ethyl and telotristat
Distribution
Protein bound: >99% (both telotristat ethyl and telotristat)
P-gp substrate
Metabolism
Telotristat ethyl undergoes hydrolysis via carboxylesterases to telotristat, its active metabolite
Telotristat is further metabolized
Telotristat ethyl and telotristat are not substrates for CYP enzymes
Elimination
Half-life: 0.6 hr (telotristat ethyl); 5 hr (telotristat)
Total clearance: 2.7 L/hr (telotristat ethyl); 152 L/hr (telotristat)
Excretion: <0.4% urine; 92.8% feces
Administration
Oral Administration
Take with food
When used in combination with short-acting octreotide, administer short-acting octreotide at least 30 minutes after telotristat ethyl
Discontinue if severe constipation develops
Missed dose
- 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
Storage
Store at controlled room temperature (25°C [77°F])
Excursions permitted to 15-30°C (59-86°F)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Xermelo oral - | 250 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
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