Xermelo

Xermelo is used to treat carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults whose diarrhea is inadequately controlled by SSA therapy alone. It is taken as a tablet three times a day.

Carcinoid syndrome diarrhea is a rare condition that occurs when neuroendocrine tumors release excessive serotonin into the bloodstream. This excess serotonin overstimulates the digestive tract, causing rapid intestinal movement, poor water and electrolyte absorption, and frequent, watery bowel movements.

Once in the body, Xermelo (telotristat ethyl) is converted into its active form, telotristat, which blocks tryptophan hydroxylase, the key enzyme responsible for serotonin production. This decreases bowel movement frequency and improves diarrhea.

Xermelo (telotristat ethyl) gained FDA approval on February 28, 2017. There is no generic.

Xermelo at a glance

Xermelo (telotristat ethyl) is a tryptophan hydroxylase inhibitor. It works by blocking tryptophan hydroxylase, the key enzyme responsible for making serotonin. Serotonin controls several gut functions, including fluid secretion, movement, inflammation, and sensation, and excess levels can cause frequent, watery bowel movements. By reducing serotonin production, Xermelo decreases the frequency of bowel movements and improves diarrhea.

In the Phase 3 TELESTAR trial (NCT01677910), 135 people with carcinoid syndrome who still had 4 or more bowel movements a day despite somatostatin analog (SSA) therapy were studied over 12 weeks. Xermelo reduced bowel movements more than placebo:

• Xermelo 250 mg three times daily (the approved dose): about 1.7 fewer bowel movements per day
• Placebo: about 0.9 fewer bowel movements per day.

A higher dose of 500 mg three times daily was also studied (about 2.1 fewer bowel movements per day), but this higher dose is not approved. The recommended dose is 250 mg three times daily.

Take Xermelo as 1 tablet (250 mg), three times a day, every day.

• Take it with a meal or a snack. Food increases your body's ability to absorb Xermelo.
• If you also use short-acting octreotide, take the octreotide at least 30 minutes after your Xermelo dose.
• Xermelo comes in a monthly pack with weekly blister packs. Keep the tablets in the original packaging until you are ready to use them.
• Stop taking Xermelo and call your healthcare provider if you develop severe constipation.

TerSera NurseSupport provides one-on-one assistance through Clinical Nurse Educators who can help you understand Xermelo, connect with advocacy resources, and learn about carcinoid syndrome diarrhea and nutrition management.

What happens if I miss a dose?

Skip the missed dose and take your next dose at the regular scheduled time. Do not take 2 doses at the same time to make up for a missed dose.

What happens if I take too much Xermelo?

Tell your healthcare provider, seek emergency medical attention, or call Poison Control at 1-800-222-1222.

Do not take Xermelo if you have had a hypersensitivity (allergic) reaction to telotristat. Such reactions have included angioedema (swelling), rash, and itching (pruritus).

Before taking Xermelo, tell your healthcare provider about all your medical conditions, including if you:

• Have liver disease or a history of liver problems
• Have any drug allergies
• Have constipation
• Are pregnant or plan to become pregnant. It is not known if Xermelo will affect an unborn baby.
• Are breastfeeding or plan to breastfeed. It is not known if Xermelo passes into breast milk. If you breastfeed, watch your baby for constipation.

Xermelo is not approved for use by anyone younger than 18 years.

Xermelo and liver or kidney problems

Xermelo is not recommended for people with moderate or severe liver impairment (Child-Pugh B or C), because levels of the drug in the body are much higher in these patients. No dose change is needed for mild liver impairment (Child-Pugh A), but closer monitoring for side effects such as constipation is recommended.

No dose adjustment is needed for mild, moderate, or severe kidney (renal) impairment in people not on dialysis. There is no information for people with end-stage kidney disease who need dialysis.

Common side effects

The most common side effects of Xermelo (occurring in at least 5% of people and more often than with placebo) are:

• Nausea
• Headache
• Increased liver enzyme (gamma-glutamyl transferase, or GGT)
• Depression (including depressed mood and decreased interest)
• Swelling of the hands and feet (peripheral edema)
• Flatulence (gas)
• Decreased appetite
• Fever (pyrexia).

In a separate study of people with fewer than 4 bowel movements a day, abdominal pain and constipation were also reported more often than with placebo.

Serious side effects

Xermelo may cause the following serious side effects:

• Severe constipation. Xermelo reduces the frequency of bowel movements and can cause constipation, which can be serious. Serious complications, including intestinal obstruction, intestinal perforation, and fecaloma (a hard mass of stool), have been reported. Stop taking Xermelo and tell your healthcare provider if you develop constipation or severe, persistent, or worsening abdominal pain.
• Allergic reactions. Get emergency medical help if you have signs of an allergic reaction to Xermelo, such as hives, rash, itching, difficulty breathing, or swelling of your face, lips, tongue, or throat (angioedema).

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adult dose for carcinoid syndrome diarrhea:

• 250 mg orally 3 times a day, with food.
• When short-acting octreotide is used in combination with Xermelo, give the short-acting octreotide at least 30 minutes after Xermelo.
• Discontinue Xermelo if severe constipation develops.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Xermelo can change the levels of some other medicines in your body, which may make them less effective. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products. Key interactions include:

• CYP3A4 substrates (for example, midazolam): Xermelo may lower their levels and make them less effective. Your doctor may need to monitor your response or adjust the dose of the other drug.
• CYP2B6 substrates (for example, bupropion, efavirenz): Xermelo may lower their levels and make them less effective. Your doctor may need to monitor your response or adjust the dose of the other drug.
• Short-acting octreotide: taking it at the same time lowers the amount of Xermelo in your body. If you need short-acting octreotide, take it at least 30 minutes after your Xermelo dose.

Other drugs may also interact with Xermelo. This is not a complete list.

The cost of Xermelo depends on your insurance coverage and whether you qualify for a co-pay card or assistance program.

• TerSera SupportSource helps eligible patients access Xermelo through co-pay cards for commercially insured patients (reducing out-of-pocket costs) and referrals to independent financial assistance foundations.
• A Patient Assistance Program offers free medication to qualifying uninsured patients who demonstrate financial need. Restrictions apply, and beneficiaries of government-funded programs are not eligible.

For more information, see Xermelo Prices, Coupons, Copay Cards & Patient Assistance.

• Store at room temperature, around 77 degrees Fahrenheit (25 degrees Celsius).
• Acceptable temperature range: 59 to 86 degrees Fahrenheit (15 to 30 degrees Celsius).
• Keep the tablets in the original packaging until ready to use.

Active ingredient: 250 mg telotristat ethyl (free base), equivalent to 328 mg telotristat etiprate.

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, lactose anhydrous, macrogol/PEG, magnesium stearate, polyvinyl alcohol (partially hydrolyzed), talc, and titanium dioxide.

Available as 250 mg tablets, dispensed in a monthly case that holds four weekly packs (21 tablets per weekly pack, 84 tablets for 28 days of therapy).

Xermelo is distributed by TerSera Therapeutics LLC, Deerfield, IL 60015.