Larotrectinib belongs to a group of cancer-fighting medications called protein kinase inhibitors. It works by recognizing certain types of cancer cells and blocking the action of chemicals that cause them to divide and grow. This may slow down or stop cancers from growing and dividing.

This medication may be used for solid (cancerous) tumours that have spread to other parts of the body (metastasized) or for which surgery is not appropriate, or that have a specific genetic change known as Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion, and there are no other satisfactory treatments available.

Larotrectinib has been granted a notice of compliance with conditions (NOC/c) by Health Canada. This means that Health Canada has approved this medication to be marketed based on promising evidence of effectiveness, but additional results of studies are needed to verify its effectiveness. An NOC/c is used to allow access to products that are used to treat or prevent serious, life-threatening, or severely debilitating illness.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

The usual adult dose of larotrectinib is 100 mg taken by mouth, twice a day.

Doses for children are based on the child's body size, specifically the body surface area (BSA). The recommended dose for children is 100 mg per square metre of body surface area and will be calculated by your child's doctor. The maximum dose for children is 100 mg taken twice a day.

Larotrectinib may be taken with food or on an empty stomach. Swallow the capsules whole with some fluid. Do not open, crush, chew, or dissolve the capsules to take them.

Use an oral syringe to measure each dose of the liquid, as this gives a more accurate measurement than household teaspoons.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

If you vomit after taking a dose, take your next dose at the regularly scheduled time. Do not replace the vomited dose.

Store the capsule form of this medication at room temperature in its original package, protect it from light and moisture, and keep it out of the reach of children. The oral solution should be stored in the refrigerator. Do not freeze. Discard the bottle 30 days after opening.

Capsule

25 mg
Each white opaque, hard gelatin capsule (size 2) with blue printing of "BAYER" cross and "25 mg" on the body of capsule, contains 25 mg of larotrectinib. Nonmedicinal ingredients: gelatin printing ink (shellac, FD&C Blue No. 2 Aluminum Lake, titanium dioxide, propylene glycol, ammonia solution, dimethicone), and titanium dioxide.

100 mg
Each white opaque, hard gelatin capsule (size 0) with blue printing of "BAYER" cross and "100 mg" on the body of capsule, contains 100 mg of larotrectinib. Nonmedicinal ingredients: gelatin printing ink (shellac, FD&C Blue No. 2 Aluminum Lake, titanium dioxide, propylene glycol, ammonia solution, dimethicone), and titanium dioxide.

Oral Solution

20 mg/mL
Each mL of citrus-berry flavoured, clear yellow to orange liquid solution contains 20 mg of larotrectinib. Nonmedicinal ingredients: bitterness masking flavour (propylene glycol, natural flavour), taste modifier flavour (propylene glycol, glycerol, natural flavour), hydroxypropyl betadex, natural bitterness masking type flavour (glycerol, natural flavor ingredients), natural masking type flavour (glycerol, natural flavour ingredients), Ora-SweetÒ (purified water, sucrose, glycerol, sorbitol, citric acid, sodium dihydrogen phosphate, flavouring and preservative agents methylparahydroxybenzoate and potassium sorbate), purified water, and sodium citrate.

Do not take this medication if you are allergic to larotrectinib or any ingredients of the medication.

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal pain
• constipation
• cough
• diarrhea
• dizziness
• fatigue
• fever
• headache
• loss of appetite
• muscle and joint aches or pain
• nausea
• shortness of breath
• stuffy nose
• swelling or pain in the arms, legs, hands, or feet
• vomiting
• weakness
• weight gain

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• anxiety
• balance problems
• change in mental status, ability to concentrate
• difficulty walking normally
• memory problems
• numbness or tingling in hands and feet
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• tremor

Stop taking the medication and seek immediate medical attention if any of the following occur:

• delirium
• symptoms of blood infection (e.g., high fever, shaking, chills, weakness, fast heartbeat, fast breathing)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Drowsiness/reduced alertness: Larotrectinib may cause drowsiness or dizziness, affecting your ability to drive or operate machinery. Avoid driving, operating machinery, or performing other potentially hazardous tasks until you have determined how you are affected by this medication.

Kidney function: Kidney disease or reduced kidney function may cause this medication to build up in the body, causing side effects. If you have kidney problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.

Liver function: Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. People taking larotrectinib may also have changes in liver function that produce abnormal liver test results. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. Women of childbearing age who are taking larotrectinib and women whose partners are taking larotrectinib, should use an effective method of birth control, such as condoms, during treatment and for at least 1 month after stopping the medication. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: It is not known if larotrectinib passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Women using this medication are advised to not breast-feed while taking the medication and for 1 week after their last dose.

Children: The safety and effectiveness of using this medication have not been established for infants less than one month of age.

There may be an interaction between larotrectinib and any of the following:

• antiarrhythmics (e.g., amiodarone, dronedarone, propafenone, quinidine)
• apalutamide
• aprepitant
• "azole" antifungals (e.g., fluconazole, ketoconazole, voriconazole)
• benzodiazepines (e.g., alprazolam, chlordiazepoxide, clonazepam, diazepam, triazolam)
• bosentan
• carbamazepine
• carvedilol
• cobicistat
• conivaptan
• cyclosporine
• deferasirox
• diltiazem
• dihydroergotamine
• diltiazem
• dronedarone
• elagolix
• eliglustat
• enzalutamide
• fentanyl
• flibanserin
• grapefruit juice
• hepatitis C antivirals (letermovir, velpatasvir)
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine, nevirapine)
• HIV protease inhibitors (e.g., darunavir, indinavir, ritonavir, saquinavir)
• lemborexant
• lomitapide
• lumacaftor and ivacaftor
• macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
• mifepristone
• mitotane
• modafinil
• osmeritinib
• phenobarbital
• phenytoin
• pimozide
• primidone
• protein kinase inhibitors (e.g., bosutinib, crizotinib, dabrafenib, lapatinib)
• quinine
• rifabutin
• rifampin
• St. John's wort
• sarilumab
• siltuximab
• sirolimus
• "statin" anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
• tacrolimus
• tocilizumab
• verapamil

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.