Larotrectinib

(LAR-oh-TREK-ti-nib)

Brand Name(s): Vitrakvi® (vi-trak-vee)

Larotrectinib is the generic name for the trade name drug Vitrakvi®. In some cases, health care professionals may use the trade name Vitrakvi® when referring to the generic drug name larotrectinib.

Drug Type: Larotrectinib is a targeted therapy. Larotrectinib is classified as a "Tropomyosin Receptor Kinase Inhibitor" (for more details, see "How Larotrectinib Works" below).

What Larotrectinib Is Used For

• Treatment of solid tumors that express neurotrophic receptor tyrosine kinase (NTRK) gene fusions

Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How Larotrectinib Is Given

• Larotrectinib comes in capsules (25 mg and 100 mg) and as an oral solution.
• Take larotrectinib exactly as your healthcare provider tells you.
• Your healthcare provider may stop treatment or change your dose of larotrectinib if you have side effects. Do not change your dose or stop taking larotrectinib unless your healthcare provider tells you.
• Larotrectinib should be taken by mouth, with or without food.
• Larotrectinib is usually taken by mouth two times a day.
• Swallow larotrectinib capsules whole with water. Do not chew or crush the capsules.
• Ask your doctor or pharmacist to show you how to correctly measure and give a dose of larotrectinib oral solution.
• Always use the oral syringes provided with larotrectinib to make sure that you correctly measure the prescribed dose. Each oral syringe may be used over a 7-day period. Do not use a household teaspoon to measure the dose.
• If a dose is missed, take it as soon as you remember unless your next scheduled dose is due within 6 hours. Do not take extra doses.
• If vomiting occurs after taking a dose of lartrectinib, wait and take the next dose at the scheduled time.
• Avoid grapefruit, grapefruit juice, and supplements that contain grapefruit extract while taking larotrectinib. Grapefruit products may increase the amount of larotrectinib.
• The amount of larotrectinib that you will receive depends on many factors including your general health, or other health problems, and other medications you are taking.

Side Effects

Important things to remember about the side effects of larotrectinib:

• Most people do not experience all of the side effects listed.
• Side effects are often predictable in terms of their onset and duration.
• There are many options to help minimize or prevent side effects.
• There is no relationship between the presence or severity of side effects and the effectiveness of the medication.
• Side effects may be quite manageable. There are many options to minimize or prevent the side effects of larotrectinib.

The following side effects are common (occurring in greater than 30%) for patients taking larotrectinib:

• Neurotoxicity which could include symptoms such as an acutely disturbed state of mind (delirium), difficulty speaking or unclear speech (dysarthria), dizziness, difficulty walking (gait disturbance), and abnormal sensations such as tingling, prickling, chilling, burning or numbness (paresthesia) - most commonly occurs within the first 3 months of treatment. You should not perform tasks requiring mental alertness (such as driving or operating heavy machinery) if you are experiencing any neurotoxicity.
• Low red blood cell counts. This can put you at increased risk for anemia.
• Fatigue
• Low albumin (hypoalbuminemia)
• Increased liver enzymes (hepatotoxicity) - most commonly occurs at 2 months of treatment. Your doctor will monitor your liver function closely while taking larotrectinib. These return to normal once treatment is stopped.

These are less common side effects (occurring in 10-29%) for patients receiving larotrectinib:

• Low white blood cell counts (neutropenia). This can put you at increased risk for infection.
• Fever
• Increased swelling (edema) in your extremities (like feet, ankles, and hands)
• Shortness of breath
• High blood pressure (hypertension)
• Headache
• Weight gain
• Nausea and vomiting
• Constipation
• Diarrhea
• Abdominal pain
• Decreased Appetite
• Joint pain (arthralgia), muscle pain (myalgia), back pain and limb pain
• Muscle weakness (myasthenia)
• Cough and nasal congestion

Not all side effects are listed above. Some that are rare (occurring in less than about 10% of patients) are not listed here. However, you should always inform your health care provider if you experience any unusual symptoms.

When to Contact Your Doctor or Health Care Provider

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Fever of 100.4º F (38º C) or higher, chills (possible signs of infection)
• Shortness of breath, wheezing, difficulty breathing, closing up of the throat, swelling of facial features, hives (possible allergic reaction)

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

• Nausea (interferes within ability to eat and unrelieved with prescribed medication)
• Vomiting (vomiting more than 4-5 times in a 24-hour period)
• Diarrhea (4-6 episodes) in a 24-hour period)
• Constipation unrelieved by laxative use
• Extreme fatigue (unable to carry on self-care activities)
• Yellowing of the skin or eyes, light-colored stools, dark urine, and/or stomach pain
• Swelling of the arms, legs, feet or ankles
• Sudden weight gain
• Signs of infection such as fever, chills or sore throat
• Difficulty speaking, confusion, memory impairment, tremors, or frequent episodes of dizziness or falls
• A burning, numbness, or tingling feeling that is not normal
• Signs of high blood pressure such as a severe headache or dizziness, passing out, or changes in eyesight

Always inform your health care provider if you experience any unusual symptoms.

Precautions

• Before starting larotrectinib treatment, make sure you tell your doctor about any other medications you taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.)
• Avoid taking St. John's wort, eating grapefruit or drinking grapefruit juice during treatment with larotrectinib.
• Do not drive or operate heavy machinery until you know how larotrectinib affects you.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Larotrectinib can harm your unborn baby. You should not become pregnant during treatment with larotrectinib.
• Your doctor may do a pregnancy test before you start treatment with larotrectinib.
• For men and women: Use effective birth control (contraception) during treatment and for at least 1 week after the final dose of larotrectinib.
• Talk to your doctor about birth control methods that may be right for you.
• Do not breast feed while taking lartrectinib and for 1 week after the final larotrectinib dose.

Self-Care Tips

• Stay hydrated. Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
• You may be at risk of infection so try to avoid crowds or people with colds, and report any other signs of infection immediately to your health care provider.
• Wash your hands often.
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.
• Follow instructions for anti-diarrhea medication as prescribed by your health care professional (if necessary).
• Eat foods that may help reduce diarrhea (see managing side effects - diarrhea).
• Keep your bowels moving. Your health care provider may prescribe a stool softener to help prevent constipation that may be caused by this medicine (see managing side effects - constipation)
• You may experience drowsiness or dizziness; avoid driving or engaging in tasks that require alertness until your response to the drug is known.
• Acetaminophen or ibuprofen may help relieve discomfort from fever, headache and/or generalized aches and pains. However, be sure to talk with your doctor before taking it.
• Avoid sun exposure. Wear SPF 30 (or higher) sunblock and protective clothing.
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. You should discuss this with your doctor.
• Get plenty of rest.
• Maintain good nutrition.
• Remain active as you are able. Gentle exercise is encouraged such as a daily walk.
• If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and Testing While Taking Larotrectinib

You will be checked regularly by your doctor while you are taking larotrectinib, to monitor side effects and check your response to therapy. Periodic blood work will be obtained to monitor side effects and check your response to therapy. Periodic blood work will be obtained to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver) will also be ordered by your doctor.

How Larotrectinib Works

Targeted therapy is the result of about 100 years of research dedicated to understanding the differences between cancer cells and normal cells. To date, cancer treatment has focused primarily on killing rapidly dividing cells because on feature of cancer cells is that they divide rapidly. Unfortunately, some of our normal cells divide rapidly too, causing multiple side effects.

Targeted therapy is about identifying other features of cancer cells. Scientists look for specific differences in the cancer cells and the normal cells. This information is used to create a targeted therapy to attack the cancer cells without damaging the normal cells, thus leading to fewer side effects. Each type of targeted therapy works a little bit differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells.

There are different types of targeted therapies, defined in three broad categories. Some targeted therapies focus in the internal components and function of the cancer cell. The targeted therapies use small molecules that can get into the cell and disrupt the function of the cells, causing them to die. There are several types of targeted therapy that focus on the inner parts of the cells. Other targeted therapies target receptors that are on the outside of the cell. Therapies that target receptors are also known as monoclonal antibodies. Anti-angiogenesis inhibitors target the blood vessels that supply oxygen to the cells, ultimately causing the cells to starve.

Researchers agree that targeted therapies are not a replacement for traditional therapies. they may best be used in combination with traditional therapies. More research is needed to identify which cancers may be best treated with targeted therapies and to identify additional targets for more types of cancer.

Larotrectinib is a targeted therapy that targets and binds to tropomycin receptor kinase (TRK) proteins found on the surface of the cell. Tumor cells may overexpress TRK proteins or develop constantly active TRK proteins. By binding to these proteins larotrectinib blocks an important pathway that promotes tumor cell division and survival.

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.