Telotristat

What is Telotristat?

• Telotristat (Xermelo) is a tryptophan hydroxylase inhibitor used for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (lanreotide, octreotide, pasinreotide) (SSA) therapy.

Telotristat

Telotristat ethyl

What are the uses of this medicine?

• Telotristat (Xermelo) is used for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy (eg: lanreotide, octreotide, pasinreotide)

How does this medicine work?

• Telotristat (tel oh' tri stat) is an oral small molecule inhibitor of tryptophan hydroxylase, an enzyme that is responsible for the rate-limiting step in serotonin (5-hydroxtryptamine) synthesis.
• Serotonin is a neuroactive signaling molecule that is produced in excess by some neuroendocrine tumors and causes the symptoms of carcinoid syndrome (flushing, diarrhea, abdominal pain and heart valvular complications).
• Carcinoid syndrome is typically treated with somatostatin analogues that inhibit the growth of neuroendocrine tumors.
• However, treatment with somatostatin analogues (such as octreotide, lanreotide and pasireotide) does not always control symptoms of carcinoid syndrome, particularly the diarrhea and abdominal discomfort.
• Telotristat does not decrease the neuroendocrine tumor size or growth but lowers the peripheral synthesis of serotonin which leads to decreased plasma levels.
• In several small, prelicensure clinical trials, telotristat therapy was associated with a decrease in diarrhea in at least half of treated patients with carcinoid syndrome, with residual diarrheal symptoms despite stable doses of somatostatin analogues.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• a history of a hypersensitivity reaction to telotristat.

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Be sure to mention any of the following:

• CYP3A4 substrates (e.g., midazolam)
• CYP2B6 substrates (e.g., bupropion, efavirenz)
• short-acting octreotide

• If treatment with short-acting octreotide is needed in combination with Xermelo, administer short-acting octreotide at least 30 minutes after administration of Xermelo.

Is this medicine FDA approved?

• Telotristat was approved for this indication in the United States in 2017 and is available in tablets of 250 mg under the brand name Xermelo.

How should this medicine be used?

Recommended dosage:

• The recommended dosage of Xermelo in adult patients is 250 mg three times daily for patients whose diarrhea is inadequately controlled by SSA therapy.

Administration:

• Telotristat comes as a tablet to take by mouth.
• It is usually taken with food three times a day.
• Take telotristat at around the same times every day.
• When short-acting octreotide is used in combination with Xermelo, administer short-acting octreotide at least 30 minutes after administering Xermelo.
• 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.
• Discontinue Xermelo if severe constipation develops.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 250 mg telotristat ethyl

This medicine is available in fallowing brand namesː

• Xermelo

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea, headache, increased GGT, depression, flatulence, decreased appetite, peripheral edema, and pyrexia.

Less common side effects may include:

• increased alkaline phosphatase, increased alanine aminotransferase, and increased aspartate aminotransferase.
• Fecaloma
• intestinal obstruction
• angioedema
• pruritis, rash

What special precautions should I follow?

• Xermelo reduces bowel movement frequency and may lead to constipation. Discontinue Xermelo if severe constipation or severe persistent or worsening abdominal pain develops.
• When short-acting octreotide is used in combination with Xermelo, administer short-acting octreotide at least 30 minutes after administering Xermelo.
• 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.
• If you are having surgery, including dental surgery, tell the doctor or dentist that you are taking telotristat.
• Telotristat is associated with modest rate of minor serum enzyme elevations during therapy but has not been linked to cases of clinically apparent [[]]liver injury.
• 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. Monitor the breastfed infant for symptoms of constipation.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• If overdose occurs, symptomatic management is indicated.

Can this medicine be used in pregnancy?

• There are no human data with Xermelo use in pregnant women to inform a drug-associated risk.

Can this medicine be used in children?

• The safety and effectiveness of Xermelo in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• telotristat ethyl (free base) which is equivalent to 328 mg telotristat etiprate.

Inactive ingredients:

• colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, lactose anhydrous, macrogol/PEG, magnesium stearate, polyvinyl alcohol [part hydrolyzed], talc and titanium dioxide.

Who manufactures and distributes this medicine?

Distributed by:

• TerSera Therapeutics LLC, Deerfield, IL

What should I know about storage and disposal of this medication?

• Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Antidiarrheal agents

Antidiarrheal agents include bulk forming agents, hydroscopic agents, bile acid resins, bismuth, inhibitors of intestinal motility, non-absorbed antibiotics and hormones. Bulk forming agents include methylcellulose; hydroscopic agents include pectin and kaolin; bile acid resins are cholestyramine, colestipol and colesevalam; inhibitors of intestinal motility include opioids such as diphenoxylate and loperamide. Antibiotics include rifamycin and rifaximin which are non-absorbed and are used for travelers' diarrhea. Hormones with antidiarrheal activity include octretide and somatostatin. Most antidiarrheal agents are active locally in the small intestine and colon and are largely not absorbed. Some, however, have been implicated in rare causes of liver injury (senna, cascara, cholestyramine). Telotristat is a relatively new agent that inhibits the synthesis of serotonin and is used specifically for the diarrhea of carcinoid syndrome.

• Cholestyramine
• Colesevelam
• Colestipol
• Crofelemer
• Difenoxin
• Diphenoxylate
• Kaolin
• Loperamide
• Methylcellulose
• Octreotide
• Pectin
• Rifamycin
• Rifaximin
• Somatostatin
• Telotristat

Antiemetics are a diverse group of medications that act at different points in the pathways that regulate nausea and vomiting. These include antihistamines, anticholinergic agents, phenothiazines, serotonin type 3 receptor blockers, centrally acting benzamides, cannabinoid receptor agonists, substance P antagonists and miscellaneous.

Anticholinergic Agents

• Hyoscyamine, Methscopolamine, Scopolamine

Antihistamines

• Cyclizine, Dimenhydrinate, Hydroxyzine, Meclizine, and Promethazine

Cannabinoid Receptor Agonists

• Dronabinol, Nabilone, Tetrahydrocannabinol
• Phenothiazines [See Antipsychotic Agents]
• Chlorpromazine, Prochlorperazine

Serotonin 5-HT3 Receptor Antagonists

• Alosetron, Dolasetron, Granisetron, Ondansetron, Palonosetron

Substance P/Neurokinin 1 Receptor Antagonists

• Aprepitant, Fosaprepitant, Rolapitant

Miscellaneous

• Dexamethasone, Metoclopramide, Trimethobenzamide

Acid peptic disease/antiulcer agents that include antacids, the histamine type 2 receptor blockers (H2 blockers), and the proton pump inhibitors (PPIs). These agents are some of the most commonly taken medications and are very well tolerated, most being available both by prescription and over-the-counter. While many of these drugs are approved for use in duodenal and gastric ulcer disease, their major use is for acid reflux and indigestion.

Histamine H2 Receptor Antagonists (H2 Blockers) Cimetidine, Famotidine, Nizatidine, Ranitidine

Proton Pump Inhibitors

• Dexlansoprazole, Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole

Cathartics, laxatives or agents for constipation include bulk forming agents, osmotic agents, stool wetting agents, nonspecific stimulants, prokinetic agents and agents that increase fluid secretion. Many of these therapies are not systemically absorbed and none are considered particularly hepatotoxic. Naldemedine and naloxegol are opioid antagonists and are used to treat the constipation associated with opioid use.

• Bisacodyl
• Cascara Sagrada
• Castor Oil
• Docusate
• Fiber, Bran
• Lactulose
• Magnesium Sulfate
• Methylcellulose
• Naldemedine (Opioid Antagonist)
• Naloxegol (Opioid Antagonist)
• Plecanatide (for Chronic Idiopathic Constipation)
• Prucalopride (for Chronic Idiopathic Constipation)
• Senna

Inflammatory bowel disease encompasses several disorders, most commonly ulcerative colitis and Crohn colitis. Agents can be classified as 5-aminosalicyclic acid (5-ASA) based agents, immunosuppressive drugs, antitumor necrosis factor agents, corticosteroids, antibiotics and miscellaneous.

5-Aminosalicyclic Acid (5-ASA) Derivatives

• Balsalazide, Mesalamine, Olsalazine, Sulfasalazine

Immunosuppressive Agents

• Azathioprine, Mercaptopurine, Methotrexate

Tumor Necrosis Factor Antagonists

• Adalimumab, Certolizumab, Golimumab, Infliximab

Miscellaneous

• Metronidazole, Natalizumab, Vedolizumab

Irritable Bowel Syndrome Agents Antimuscarinics/Antispasmodics [See Anticholinergic agents

• Dicyclomine, Glycopyrrolate, Hyoscyamine, Methscopolamine

Prokinetic Agents - See Serotonin 5-ht4 receptor agonists Alosetron, Cisapride, Domperidone, Linaclotide, Lubiprostone, Metoclopramide, Plecanatide, Prucalopride, Tegaserod

Other

• Eluxadoline

• Dailymed label info on Telotristat
• FDA Telotristat

Telotristat Resources
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