telotristat ethyl

Therapeutic Classification: antidiarrheals

Pharmacologic Classification: tryptophan hydroxylase inhibitors

Indications ⬆ ⬇

REMS

Carcinoid syndrome diarrhea uncontrolled by treatment with somatostatin analog (in combination with somatostatin analog).

Action ⬆ ⬇

Inhibits tryptophan hydroxylase, which reduces production of serotonin and subsequent motility and inflammation in GI tract.

Therapeutic effects:

Reduced frequency of carcinoid syndrome diarrhea.

Pharmacokinetics ⬆ ⬇

Absorption: Absorption ↑ with food (especially high-fat meal).

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Telotristat ethyl is metabolized via hydrolysis to active metabolite (telotristat); telotristat is further metabolized in the liver; primarily excreted in feces.

Half-Life: Telotristat ethyl: 0.6 hr; telotristat: 5 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.5–2 hr (telotristat ethyl); 1–3 hr (telotristat)	8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Moderate or severe hepatic impairment.

Use Cautiously in:

End-stage renal disease requiring dialysis;
Mild hepatic impairment;
OB: Safety not established in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant; closely monitor infant for constipation;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema

GI: nausea, abdominal pain, CONSTIPATION, ↓appetite, flatulence, ↑liver enzymes

Neuro: headache, depression

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

May ↓ levels and effectiveness of CYP3A4 substrates, including midazolam; may need to ↑ dose of CYP3A4 substrate.
May ↓ levels and effectiveness of CYP2B6 substrates, including bupropion and efavirenz; may need to ↑ dose of CYP2B6 substrate.
Octreotide (short-acting) may ↓ levels of telostriat; administer short-acting octreotide ≥30 min before telostriat.

Route/Dosage ⬆ ⬇

PO (Adults ): 250 mg 3 times daily.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Assess bowel status prior to and periodically during therapy. Monitor for development of constipation and/or severe, persistent, or worsening abdominal pain. Discontinue telotristat ethyl if severe constipation or severe, persistent, or worsening abdominal pain occur.
Assess patient for signs of angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing); may occur at any time during therapy. Discontinue medication and provide supportive care.

Implementation ⬆ ⬇

PO: Administer 3 times daily with food. If used in conjunction with octreotide, administer octreotide at least 30 min after telotristat ethyl.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take telotristat ethyl as directed. If a dose is missed, omit and take next regularly scheduled dose; do not take 2 doses at same time.
Advise patient to discontinue telotristat ethyl if severe constipation occurs.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. If breastfeeding during therapy, monitor infant for constipation.

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Pronunciation ⬇

Classifications ⬆ ⬇