Vitrakvi 20mg/ml Solution
It is used to treat cancer.
Drug Class
Antineoplastic agent
Pharmacologic Class
Tyrosine Kinase Inhibitor; TRK inhibitor
Pregnancy Category
Not available
FDA Approved
Nov 2018
DEA Schedule
Not Controlled
Overview
What is this medicine?
Vitrakvi is a medicine used to treat certain cancers that have a specific genetic change called an NTRK gene fusion. This medicine works by blocking signals that help cancer cells grow and spread.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most out of your medication, follow these steps:
Take your medication exactly as directed by your doctor. Read all the information provided with your prescription and follow the instructions carefully.
You can take this medication with or without food.
If you're taking a liquid dose, measure it carefully using the measuring device that comes with the medication. If one isn't provided, ask your pharmacist for a device to measure your dose accurately.
Continue taking your medication as instructed by your doctor or healthcare provider, even if you're feeling well.
What to Do If You Vomit After Taking a Dose
If you vomit after taking a dose, don't repeat the dose. Instead, take your next dose at the usual time.
Storing and Disposing of Your Medication
To keep your medication effective and safe:
Store it in the refrigerator, but do not freeze it.
For 50 mL bottles, discard any unused medication 31 days after opening the bottle.
For 100 mL bottles, discard any unused medication 90 days after opening the bottle.
Missing a Dose
If you miss a dose, take it as soon as you remember. However:
If it's less than 6 hours until your next scheduled dose, skip the missed dose and take the next one at the usual time.
* Do not take two doses at the same time or take extra doses.
To ensure you get the most out of your medication, follow these steps:
Take your medication exactly as directed by your doctor. Read all the information provided with your prescription and follow the instructions carefully.
You can take this medication with or without food.
If you're taking a liquid dose, measure it carefully using the measuring device that comes with the medication. If one isn't provided, ask your pharmacist for a device to measure your dose accurately.
Continue taking your medication as instructed by your doctor or healthcare provider, even if you're feeling well.
What to Do If You Vomit After Taking a Dose
If you vomit after taking a dose, don't repeat the dose. Instead, take your next dose at the usual time.
Storing and Disposing of Your Medication
To keep your medication effective and safe:
Store it in the refrigerator, but do not freeze it.
For 50 mL bottles, discard any unused medication 31 days after opening the bottle.
For 100 mL bottles, discard any unused medication 90 days after opening the bottle.
Missing a Dose
If you miss a dose, take it as soon as you remember. However:
If it's less than 6 hours until your next scheduled dose, skip the missed dose and take the next one at the usual time.
* Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take Vitrakvi exactly as prescribed by your doctor.
- You can take Vitrakvi with or without food.
- Do not eat grapefruit or drink grapefruit juice while taking Vitrakvi, as it can increase the amount of medicine in your body.
- Do not stop taking Vitrakvi or change your dose without talking to your doctor.
- Store the oral solution in the refrigerator. Do not freeze.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
100 mg orally twice daily
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
100 mg/m² orally twice daily, up to a maximum of 100 mg per dose
Adolescent:
100 mg/m² orally twice daily, up to a maximum of 100 mg per dose
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed
Moderate:
No dose adjustment needed
Severe:
No dose adjustment needed
Dialysis:
Not studied; consider close monitoring
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A)
Moderate:
Reduce dose by 50% (Child-Pugh B)
Severe:
Reduce dose by 75% (Child-Pugh C)
Pharmacology
Mechanism of Action
Larotrectinib is a selective inhibitor of the tropomyosin receptor kinases (TRK), specifically TRKA, TRKB, and TRKC. These kinases are encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively. Chromosomal rearrangements involving these NTRK genes can result in oncogenic TRK fusion proteins that are constitutively active, leading to uncontrolled cell growth and survival. Larotrectinib binds to the ATP-binding site of these TRK fusion proteins, inhibiting their kinase activity and downstream signaling pathways (e.g., MAPK, PI3K/AKT), thereby leading to tumor cell apoptosis and inhibition of tumor growth.
Pharmacokinetics
Absorption:
Bioavailability:
Not available
Tmax:
1 hour (oral solution)
FoodEffect:
High-fat meal decreases Cmax by 35% and AUC by 17%. Can be taken with or without food.
Distribution:
Vd:
91 L (oral solution)
ProteinBinding:
70%
CnssPenetration:
Yes
Elimination:
HalfLife:
4.9 hours (oral solution)
Clearance:
Not available
ExcretionRoute:
Feces (96%), urine (1%)
Unchanged:
34% (in feces)
Pharmacodynamics
OnsetOfAction:
Not available
PeakEffect:
Not available
DurationOfAction:
Not available
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of low calcium levels, such as:
+ Muscle cramps or spasms
+ Numbness and tingling
+ Seizures
Signs of a urinary tract infection (UTI), including:
+ Blood in the urine
+ Burning or pain when passing urine
+ Frequent or urgent need to urinate
+ Fever
+ Lower stomach pain
+ Pelvic pain
Confusion
Memory problems or loss
Depression or other mood changes
Trouble speaking
Bone pain
Difficulty walking
Falls
Changes in balance
Shakiness
Swelling in the arms or legs
Shortness of breath
Low white blood cell counts, which may increase the risk of infection. If you experience signs of infection, such as fever, chills, or sore throat, contact your doctor right away.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you notice any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Dizziness
Drowsiness
Fatigue
Weakness
Trouble sleeping
Cough
Headache
Stuffy nose
Weight gain
Back pain
Joint pain
Muscle pain
Neck pain
Muscle weakness
* Pain in the arms or legs
Reporting Side Effects
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of low calcium levels, such as:
+ Muscle cramps or spasms
+ Numbness and tingling
+ Seizures
Signs of a urinary tract infection (UTI), including:
+ Blood in the urine
+ Burning or pain when passing urine
+ Frequent or urgent need to urinate
+ Fever
+ Lower stomach pain
+ Pelvic pain
Confusion
Memory problems or loss
Depression or other mood changes
Trouble speaking
Bone pain
Difficulty walking
Falls
Changes in balance
Shakiness
Swelling in the arms or legs
Shortness of breath
Low white blood cell counts, which may increase the risk of infection. If you experience signs of infection, such as fever, chills, or sore throat, contact your doctor right away.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you notice any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Dizziness
Drowsiness
Fatigue
Weakness
Trouble sleeping
Cough
Headache
Stuffy nose
Weight gain
Back pain
Joint pain
Muscle pain
Neck pain
Muscle weakness
* Pain in the arms or legs
Reporting Side Effects
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe dizziness or problems with balance
- Numbness or tingling in your hands or feet (paresthesia)
- Severe fatigue or weakness
- Yellowing of your skin or the whites of your eyes (jaundice)
- Dark urine or light-colored stools
- Severe nausea, vomiting, or stomach pain
- Unexplained weight gain or swelling
- Vision changes
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. Certain medications, such as those used to treat HIV, infections, or seizures, may interact with this drug.
* If you are breastfeeding. You should not breastfeed while taking this medication and for 1 week after your last dose.
Please note that this is not an exhaustive list of all potential interactions or health concerns. To ensure your safety, it is crucial to discuss all of your medications (prescription and OTC), natural products, vitamins, and health problems with your doctor and pharmacist. They will help determine whether it is safe for you to take this medication with your existing treatments and health conditions. Never start, stop, or change the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. Certain medications, such as those used to treat HIV, infections, or seizures, may interact with this drug.
* If you are breastfeeding. You should not breastfeed while taking this medication and for 1 week after your last dose.
Please note that this is not an exhaustive list of all potential interactions or health concerns. To ensure your safety, it is crucial to discuss all of your medications (prescription and OTC), natural products, vitamins, and health problems with your doctor and pharmacist. They will help determine whether it is safe for you to take this medication with your existing treatments and health conditions. Never start, stop, or change the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Until you understand how this drug affects you, avoid operating a vehicle and engaging in other activities that require alertness. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to discuss any concerns or questions with your doctor.
To minimize potential interactions, avoid consuming grapefruit and grapefruit juice while taking this medication. Additionally, be aware that this drug may increase the risk of fractures. Discuss this risk with your doctor to understand the potential implications.
When administering this medication to children, exercise caution, as they may be more susceptible to certain side effects. Furthermore, this drug may affect fertility, making it more challenging to conceive. Discuss this potential effect with your doctor.
Due to the risk of harm to an unborn baby, a pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you or your partner may become pregnant, it is crucial to use effective birth control methods while taking this medication and for a specified period after the final dose. Consult your doctor to determine the recommended duration of birth control use. If pregnancy occurs, notify your doctor immediately.
To minimize potential interactions, avoid consuming grapefruit and grapefruit juice while taking this medication. Additionally, be aware that this drug may increase the risk of fractures. Discuss this risk with your doctor to understand the potential implications.
When administering this medication to children, exercise caution, as they may be more susceptible to certain side effects. Furthermore, this drug may affect fertility, making it more challenging to conceive. Discuss this potential effect with your doctor.
Due to the risk of harm to an unborn baby, a pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you or your partner may become pregnant, it is crucial to use effective birth control methods while taking this medication and for a specified period after the final dose. Consult your doctor to determine the recommended duration of birth control use. If pregnancy occurs, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Exacerbation of known adverse reactions (e.g., severe dizziness, liver enzyme elevations, neurological symptoms)
What to Do:
There is no specific antidote for Vitrakvi overdose. Management should be supportive and directed at treating the symptoms. Call 1-800-222-1222 (Poison Control) or seek immediate medical attention.
Drug Interactions
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice)
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort)
Moderate Interactions
- Moderate CYP3A4 inhibitors
- Moderate CYP3A4 inducers
Minor Interactions
- P-glycoprotein (P-gp) substrates (e.g., digoxin, dabigatran)
- Sensitive CYP3A4 substrates (e.g., midazolam, oral contraceptives)
Monitoring
Baseline Monitoring
Liver function tests (ALT, AST, bilirubin)
Rationale: To establish baseline and monitor for hepatotoxicity
Timing: Prior to initiation of treatment
Neurological assessment
Rationale: To establish baseline and monitor for neurological adverse reactions (e.g., dizziness, gait disturbance)
Timing: Prior to initiation of treatment
Growth and development assessment
Rationale: To establish baseline and monitor for potential effects on growth in pediatric patients
Timing: Prior to initiation of treatment (pediatric patients)
Routine Monitoring
Liver function tests (ALT, AST, bilirubin)
Frequency: Every 2 weeks for the first month, then monthly for 3 months, then periodically as clinically indicated
Target: Within normal limits or stable
Action Threshold: Grade 3 or 4 elevation, or persistent Grade 2 elevation; consider dose modification or interruption
Neurological assessment
Frequency: Periodically, as clinically indicated
Target: Stable neurological function
Action Threshold: New or worsening neurological symptoms (e.g., dizziness, gait disturbance, paresthesia); consider dose modification or interruption
Growth and development
Frequency: Periodically
Target: Normal growth trajectory
Action Threshold: Significant deviation from growth curve; consider consultation with endocrinologist
Tumor response
Frequency: As per standard oncology practice (e.g., every 8-12 weeks)
Target: Stable disease, partial response, or complete response
Action Threshold: Disease progression
Symptom Monitoring
- Dizziness
- Gait disturbance
- Paresthesia (numbness/tingling)
- Fatigue
- Nausea
- Vomiting
- Constipation
- Diarrhea
- Elevated liver enzymes (symptoms like yellowing of skin/eyes, dark urine)
- Muscle pain
- Weight gain
- Vision changes
Special Patient Groups
Pregnancy
Based on animal studies, Vitrakvi can cause fetal harm. It is not recommended for use during pregnancy. Females of reproductive potential should use effective contraception during treatment and for at least 1 month after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 1 month after the last dose.
Trimester-Specific Risks:
First Trimester:
Potential for embryo-fetal toxicity based on animal data.
Second Trimester:
Potential for embryo-fetal toxicity based on animal data.
Third Trimester:
Potential for embryo-fetal toxicity based on animal data.
Lactation
It is not known if larotrectinib is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with Vitrakvi and for 1 month after the last dose.
Infant Risk:
High (potential for serious adverse reactions)
Pediatric Use
Vitrakvi is approved for pediatric patients. Monitor for growth and development, as well as neurological adverse reactions (e.g., dizziness, gait disturbance). Dose is based on body surface area.
Geriatric Use
No specific dose adjustment is needed for geriatric patients. The incidence of adverse reactions was generally similar to younger adults, though some adverse reactions (e.g., dizziness) may be more common or severe in older patients.
Clinical Information
Clinical Pearls
- Vitrakvi is the first FDA-approved TRK inhibitor for solid tumors with NTRK gene fusion, regardless of tumor type or location.
- Requires molecular testing (e.g., NGS) to confirm the presence of an NTRK gene fusion before initiation.
- The oral solution formulation is particularly useful for pediatric patients or those who have difficulty swallowing capsules.
- Neurological adverse events, such as dizziness and gait disturbance, are common and may require dose modification or interruption.
- Liver enzyme elevations can occur and require regular monitoring.
- Patients should be advised to avoid grapefruit and St. John's Wort due to potential drug interactions.
Alternative Therapies
- Entrectinib (another TRK inhibitor)
- Standard chemotherapy regimens (depending on tumor type)
- Radiation therapy
- Surgical resection
Cost & Coverage
Average Cost:
Extremely high (e.g., $15,000 - $20,000+) per 100 mL bottle (20 mg/mL)
Insurance Coverage:
Specialty Tier (requires prior authorization, often with patient assistance programs)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it is a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.