VITRAKVI (Larotrectinib)
Selective TRK inhibitor for NTRK gene fusion-positive solid tumors
VITRAKVI (larotrectinib) is a targeted cancer therapy that treats solid tumors driven by NTRK gene fusions. As a selective TRK inhibitor, it blocks the abnormal proteins that fuel tumor growth regardless of where the cancer originated. Approved for both adults and children, VITRAKVI represents a landmark in tumor-agnostic oncology treatment.
Quick Facts
Key Takeaways
- VITRAKVI targets NTRK gene fusion-positive solid tumors regardless of cancer type or patient age, making it one of the first truly tumor-agnostic therapies.
- An NTRK gene fusion test is mandatory before starting treatment — only patients with confirmed fusions are eligible for VITRAKVI.
- The standard adult dose is 100 mg taken orally twice daily; children's doses are calculated by body surface area.
- Common side effects include fatigue, dizziness, nausea, and elevated liver enzymes — regular blood monitoring is required during treatment.
- Grapefruit and grapefruit juice must be avoided during treatment as they increase drug levels in the body.
What Is VITRAKVI and What Is It Used For?
VITRAKVI contains the active substance larotrectinib, a highly selective inhibitor of tropomyosin receptor kinase (TRK) proteins. It is indicated for the treatment of adult and pediatric patients who have solid tumors that display a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. This genetic alteration leads to the production of abnormal TRK fusion proteins, which can trigger cells to multiply uncontrollably and form cancerous tumors.
What makes VITRAKVI unique in oncology is its tumor-agnostic approach. Rather than targeting cancer based on where it originates in the body, VITRAKVI targets the specific molecular driver — the NTRK gene fusion — regardless of the tumor type. This means it can be used to treat a wide range of cancers, including lung cancer, thyroid cancer, salivary gland tumors, soft tissue sarcomas, and many others, as long as the NTRK fusion is present.
VITRAKVI is prescribed when the tumor has advanced locally or spread to other parts of the body (metastasized), or when surgical removal would likely result in severe complications. Additionally, the medicine is only used when there is no satisfactory alternative treatment available. Before prescribing VITRAKVI, your oncologist will arrange for specialized molecular testing — such as next-generation sequencing (NGS) or fluorescence in situ hybridization (FISH) — to confirm the presence of an NTRK gene fusion in your tumor.
How Does VITRAKVI Work?
In patients whose cancer harbors an NTRK gene fusion, the fusion event causes two genes to join abnormally. This produces a chimeric TRK fusion protein that is permanently activated, sending continuous growth signals to the cancer cell. Under normal circumstances, TRK proteins play a role in the nervous system, but when an NTRK gene fuses with another gene, the resulting protein drives cancer progression.
VITRAKVI works by selectively binding to and blocking all three TRK fusion proteins — TRKA, TRKB, and TRKC. By inhibiting these proteins, VITRAKVI interrupts the signaling pathways that promote tumor cell proliferation and survival. This can slow or halt cancer growth and, in many cases, cause significant tumor shrinkage. In clinical trials, VITRAKVI demonstrated an overall response rate of approximately 75% across a wide range of NTRK fusion-positive tumor types, with durable responses lasting months to years in many patients.
The selectivity of larotrectinib for TRK proteins is a significant advantage. Because it has minimal activity against other kinases, VITRAKVI tends to have a more favorable side effect profile compared to less selective kinase inhibitors. This selectivity also contributes to its efficacy, as the drug can potently block the specific target driving the cancer.
What Should You Know Before Taking VITRAKVI?
Contraindications
VITRAKVI must not be taken if you have a known hypersensitivity (allergy) to larotrectinib or any of the other ingredients in the formulation. Allergic reactions may include skin rash, swelling, or difficulty breathing. If you experience any signs of an allergic reaction after taking VITRAKVI, seek medical attention immediately and do not take any further doses until you have consulted your prescribing physician.
VITRAKVI should only be prescribed by or under the supervision of physicians experienced in the administration of anticancer medicines. A confirmed NTRK gene fusion must be established using a validated test before initiating treatment. Using VITRAKVI without confirmed NTRK fusion status is not recommended, as the drug specifically targets this molecular alteration.
Warnings and Precautions
VITRAKVI may cause elevated levels of the liver enzymes ALT (alanine aminotransferase), AST (aspartate aminotransferase), and bilirubin in the blood. Your oncologist will order blood tests before starting treatment and at regular intervals during therapy to monitor your liver function. If significant liver enzyme elevations are detected, your doctor may reduce the dose, temporarily halt treatment, or discontinue VITRAKVI permanently, depending on the severity.
VITRAKVI can affect the nervous system. Contact your doctor immediately if you experience dizziness, tingling, numbness, or a burning sensation in the hands and feet, or difficulty walking normally. Your doctor may need to adjust your dose or pause treatment.
Patients should be monitored for neurological side effects, including dizziness and peripheral neuropathy (nerve damage causing tingling, numbness, or pain in the extremities). These effects may require dose modifications. Dizziness is a very common side effect, while signs of neurotoxicity such as difficulty walking are less frequent but require prompt medical evaluation.
Pregnancy and Breastfeeding
VITRAKVI should not be used during pregnancy because its effects on the developing fetus are unknown. If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before taking this medicine. Women of childbearing potential must use effective contraception during treatment and for at least one month after the last dose. If you are using hormonal contraceptives, you must also use a barrier method (such as a condom), as VITRAKVI may reduce the effectiveness of hormonal contraception.
Breastfeeding must be discontinued during treatment and for at least 3 days after the last dose, as it is not known whether larotrectinib passes into breast milk. Men who have sexual partners of childbearing potential should also use effective contraception during treatment and for at least one month after the final dose.
Driving and Operating Machinery
VITRAKVI can cause dizziness and fatigue, which may impair your ability to drive, cycle, or operate machinery. If you experience these effects, refrain from these activities until the symptoms resolve. Discuss with your healthcare team whether it is safe for you to drive while on treatment.
Do not eat grapefruit or drink grapefruit juice while taking VITRAKVI. Grapefruit inhibits the CYP3A4 enzyme that metabolizes larotrectinib, which can increase drug levels in your body and raise the risk of side effects.
How Does VITRAKVI Interact with Other Drugs?
Larotrectinib is primarily metabolized by the liver enzyme CYP3A4 and to a lesser extent by other enzymes. Any drug that strongly inhibits or induces CYP3A4 can significantly affect larotrectinib blood levels, potentially increasing toxicity or reducing efficacy. Additionally, VITRAKVI itself can affect the metabolism of other drugs, which may alter their effectiveness or safety.
It is essential to inform your oncologist, pharmacist, or nurse about all medications you are currently taking, have recently taken, or plan to take. This includes prescription drugs, over-the-counter medicines, herbal remedies, and dietary supplements. Your healthcare team can then assess whether dose adjustments are necessary.
Major Interactions
The following drugs have significant interactions with VITRAKVI and require careful management. Strong CYP3A4 inhibitors can substantially increase larotrectinib levels in the blood, raising the risk of adverse effects. Conversely, strong CYP3A4 inducers can dramatically reduce larotrectinib levels, potentially rendering the treatment ineffective.
| Drug | Used For | Interaction Type | Effect |
|---|---|---|---|
| Itraconazole, Voriconazole | Fungal infections | Strong CYP3A4 inhibitor | Increases VITRAKVI levels |
| Ketoconazole | Cushing's syndrome | Strong CYP3A4 inhibitor | Increases VITRAKVI levels |
| Clarithromycin, Telithromycin | Bacterial infections | Strong CYP3A4 inhibitor | Increases VITRAKVI levels |
| Atazanavir, Ritonavir, Saquinavir | HIV infection | Strong CYP3A4 inhibitor | Increases VITRAKVI levels |
| Rifampicin | Tuberculosis | Strong CYP3A4 inducer | Decreases VITRAKVI levels |
| Phenytoin, Carbamazepine, Phenobarbital | Epilepsy | Strong CYP3A4 inducer | Decreases VITRAKVI levels |
| St. John's Wort | Mild depression (herbal) | Strong CYP3A4 inducer | Decreases VITRAKVI levels |
Other Important Interactions
VITRAKVI can also affect the blood levels of drugs that are substrates of CYP3A4 or CYP2C8 enzymes. If you are taking any of the following medications, your doctor may need to monitor you more closely or adjust doses:
| Drug | Used For | Potential Effect |
|---|---|---|
| Cyclosporine, Sirolimus, Tacrolimus | Organ transplant rejection prevention | Altered immunosuppressant levels |
| Fentanyl, Alfentanil | Pain management | Altered opioid levels |
| Quinidine | Abnormal heart rhythm | Altered quinidine levels |
| Warfarin | Blood clot prevention | Altered anticoagulant effect |
| Repaglinide, Tolbutamide | Diabetes (blood sugar lowering) | Altered blood sugar levels |
| Pimozide | Involuntary movements | Altered pimozide levels |
| Dihydroergotamine, Ergotamine | Migraine | Altered ergot levels |
| Statins | High cholesterol | Altered statin levels |
| Hormonal contraceptives | Birth control | Reduced contraceptive effectiveness |
| Omeprazole | Stomach acid reduction | Altered omeprazole levels |
What Is the Correct Dosage of VITRAKVI?
Always take VITRAKVI exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor, pharmacist, or nurse for clarification. Your oncologist will determine the appropriate dose based on your individual circumstances, including your age, body size, and how well you tolerate the treatment.
Adults (18 years and older)
Standard Adult Dose
The recommended dose is 100 mg twice daily (1 capsule of 100 mg, or 4 capsules of 25 mg, taken in the morning and evening). This should be continued for as long as your doctor determines it is beneficial. Your doctor will monitor your response and may adjust the dose if needed due to side effects.
Children and Adolescents
Pediatric Dose
The dose for children and adolescents is calculated based on body surface area (determined by height and weight). Your child's oncologist will calculate the appropriate dose. The maximum recommended dose is 100 mg twice daily. An oral solution formulation is available for patients who cannot swallow capsules.
Elderly Patients
No specific dose adjustments are required for elderly patients based on age alone. However, elderly patients may be more susceptible to certain side effects, and your doctor will monitor you closely and adjust the dose if necessary based on tolerability and any co-existing health conditions.
How to Take VITRAKVI
VITRAKVI capsules should be swallowed whole with a glass of water. Do not open, chew, or crush the capsules, as the contents have a very bitter taste. The capsules can be taken with or without food at approximately the same times each day. Maintaining a consistent schedule helps ensure steady drug levels in the body.
- Take your doses approximately 12 hours apart (e.g., morning and evening).
- Set reminders on your phone or use a pill organizer to help maintain your schedule.
- If you experience nausea, taking VITRAKVI with a light meal may help.
- Store capsules in their original container to protect from moisture.
Missed Dose
If you miss a dose of VITRAKVI, do not take a double dose to make up for it. Similarly, if you vomit after taking the medicine, do not take a replacement dose. Simply take your next scheduled dose at the usual time. Consistent adherence to the dosing schedule is important for treatment success, so try to avoid missing doses whenever possible.
Overdose
If you accidentally take more VITRAKVI than prescribed, contact your doctor, pharmacist, or go to the nearest hospital emergency department immediately. Take the medicine packaging and this information with you so that healthcare professionals can identify the product and dose taken. There is no specific antidote for larotrectinib overdose, and treatment would focus on managing symptoms and providing supportive care.
Do not stop taking VITRAKVI without first discussing it with your doctor. It is important to continue treatment for as long as your oncologist recommends. Stopping treatment prematurely could allow the cancer to grow again.
What Are the Side Effects of VITRAKVI?
Like all medicines, VITRAKVI can cause side effects, although not everybody gets them. Most side effects are mild to moderate in severity and can often be managed with dose adjustments or supportive care. Your oncologist will monitor you regularly for side effects and adjust treatment as needed.
Contact your doctor immediately if you experience: dizziness (very common), tingling, numbness or a burning sensation in your hands and feet, or difficulty walking normally (common). These may be signs of nervous system problems that may require dose reduction or treatment interruption.
Very Common
May affect more than 1 in 10 patients
- Anemia (low red blood cells) — you may appear pale and experience heart palpitations
- Neutropenia and leukopenia (low white blood cells) — flu-like symptoms including fever
- Nausea or vomiting
- Diarrhea
- Constipation
- Muscle pain (myalgia)
- Fatigue
- Dizziness
- Increased liver enzymes (ALT, AST) in blood tests
- Weight gain
Common
May affect up to 1 in 10 patients
- Thrombocytopenia (low platelets) — you may bruise or bleed more easily
- Taste changes (dysgeusia)
- Muscle weakness
- Peripheral neuropathy — tingling, numbness or burning sensation in hands and feet
- Difficulty walking normally (gait disturbance)
- Elevated alkaline phosphatase in blood tests (very common in children)
Not Known
Frequency cannot be estimated from available data
- Liver problems — combination of fatigue, upper right abdominal pain, loss of appetite, nausea or vomiting, yellowing of skin or eyes, easy bruising or bleeding, and dark urine
Managing Side Effects
Many of the side effects of VITRAKVI can be managed effectively. Your oncology team will provide guidance on supportive measures. For nausea, anti-emetic medications can be prescribed. Fatigue may improve with regular light exercise and adequate rest. If you develop liver enzyme elevations, your doctor will decide whether to continue, modify, or discontinue treatment based on the severity of the abnormality.
Neurotoxicity, including peripheral neuropathy and dizziness, is an important side effect to watch for. In clinical studies, neurological events led to dose modifications in a minority of patients. Most neurological side effects resolved or improved after dose reduction or treatment interruption. Report any new neurological symptoms to your oncologist promptly, as early intervention can prevent worsening.
Regular blood tests are essential during VITRAKVI treatment. These tests monitor your blood cell counts (red blood cells, white blood cells, and platelets) and liver function. Based on these results, your doctor may adjust your dose, recommend supportive treatments, or temporarily pause therapy if needed.
Reporting Side Effects
Reporting suspected adverse reactions after authorization of the medicine is important. It allows continued monitoring of the benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected side effects to their national pharmacovigilance authority, such as the FDA MedWatch program (USA), the MHRA Yellow Card Scheme (UK), or the EMA EudraVigilance system (EU).
How Should You Store VITRAKVI?
Keep this medicine out of the sight and reach of children at all times. VITRAKVI capsules do not require any special storage conditions. Store them at room temperature in their original container to protect from moisture. Do not use the capsules after the expiry date printed on the carton and bottle label after "EXP." The expiry date refers to the last day of that month.
Before taking VITRAKVI, visually inspect the capsules. Do not use any capsule that appears damaged, discolored, or shows signs of deterioration. If you notice any abnormality, return the affected capsules to your pharmacist and request a replacement.
Dispose of unused or expired medicines properly. Do not throw them in household waste or flush them down the drain, as this can harm the environment. Ask your pharmacist about proper disposal methods for anticancer medications, as special handling may be required. Many pharmacies and hospitals have take-back programs for unused medicines.
What Does VITRAKVI Contain?
The active substance in VITRAKVI is larotrectinib, supplied as larotrectinib sulfate. Each VITRAKVI 25 mg capsule contains 25 mg of larotrectinib, and each VITRAKVI 100 mg capsule contains 100 mg of larotrectinib.
Inactive Ingredients
The capsule shell is composed of gelatin and titanium dioxide (E 171). The printing ink on the capsules contains shellac (bleached, dewaxed), indigo carmine aluminum lake (E 132), titanium dioxide (E 171), propylene glycol (E 1520), and dimethicone 1000.
Appearance and Pack Size
VITRAKVI 25 mg: White, opaque, hard gelatin capsules (18 mm long × 6 mm wide), marked with the Bayer cross and "25 mg" in blue printing ink on the capsule body.
VITRAKVI 100 mg: White, opaque, hard gelatin capsules (22 mm long × 7 mm wide), marked with the Bayer cross and "100 mg" in blue printing ink on the capsule body.
Each carton contains one child-resistant plastic bottle with 56 hard gelatin capsules. The child-resistant closure is an important safety feature — always ensure the bottle is properly closed after each use, and store the medicine well out of children's reach.
Frequently Asked Questions About VITRAKVI
VITRAKVI (larotrectinib) is used to treat solid tumors in adults and children that have a specific genetic alteration called an NTRK gene fusion. It is prescribed when the cancer has advanced or spread, when surgery would cause serious complications, and when no satisfactory treatment alternative exists. An NTRK gene fusion test must be performed before starting treatment. VITRAKVI is unique because it targets the molecular driver of the cancer rather than the organ where the cancer originated.
The most common side effects (affecting more than 1 in 10 patients) include fatigue, dizziness, nausea, vomiting, constipation, diarrhea, anemia (low red blood cells), increased liver enzymes (ALT and AST), muscle pain (myalgia), and weight gain. Most side effects are mild to moderate in severity and can be managed with dose adjustments or supportive medications. Regular blood tests help monitor for these effects.
VITRAKVI works by selectively blocking TRK fusion proteins. In patients whose cancer is caused by an NTRK gene fusion, the body produces abnormal TRK fusion proteins that drive uncontrolled cell growth and cancer progression. VITRAKVI specifically inhibits all three types of TRK proteins (TRKA, TRKB, and TRKC), interrupting the signaling that promotes tumor growth. This can slow or stop the cancer and may cause tumors to shrink significantly.
Yes, VITRAKVI is approved for use in both children and adults. The dose for children and adolescents is calculated based on body surface area (determined by height and weight). The maximum recommended dose is 100 mg twice daily. An oral solution formulation is available for patients who cannot swallow capsules, making it suitable for younger children. Clinical trials included pediatric patients from infancy onwards.
You must avoid eating grapefruit or drinking grapefruit juice while taking VITRAKVI. Grapefruit contains compounds that inhibit the CYP3A4 enzyme responsible for metabolizing larotrectinib, which can increase the drug's concentration in your bloodstream and raise the risk of side effects. VITRAKVI capsules can be taken with or without food, and no other specific dietary restrictions apply. Always consult your oncology team if you have questions about diet during treatment.
An NTRK (neurotrophic tyrosine receptor kinase) gene fusion occurs when an NTRK gene becomes abnormally joined to another unrelated gene, creating an oncogenic driver. This fusion produces an abnormal TRK fusion protein that signals cells to grow uncontrollably. NTRK fusions are identified through specialized molecular testing, including next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), or immunohistochemistry (IHC). Your oncologist will arrange the appropriate test using a tumor biopsy sample.
References
This article is based on the following peer-reviewed sources and regulatory documents:
- European Medicines Agency (EMA). VITRAKVI (larotrectinib) — Summary of Product Characteristics. Last updated 2024. Available from: EMA EPAR — VITRAKVI.
- Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378(8):731-739. doi:10.1056/NEJMoa1714448.
- Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21(4):531-540. doi:10.1016/S1470-2045(19)30856-3.
- U.S. Food and Drug Administration (FDA). FDA approves larotrectinib for solid tumors with NTRK gene fusions. FDA Drug Approvals and Databases. 2018.
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd List, 2023. Geneva: WHO; 2023.
- European Society for Medical Oncology (ESMO). ESMO Clinical Practice Guidelines: Molecular testing and targeted therapy in NTRK fusion-positive tumors. Ann Oncol. 2023.
- Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731-747. doi:10.1038/s41571-018-0113-0.
- British National Formulary (BNF). Larotrectinib. NICE Evidence Services. Last updated 2024.
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, composed of specialist physicians in oncology and clinical pharmacology. Our editorial process follows international standards:
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