Vitrakvi 100mg Capsules

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 and drive cell proliferation and survival in various tumor types. Larotrectinib inhibits the kinase activity of these TRK fusion proteins, leading to inhibition of downstream signaling pathways (e.g., MAPK/ERK, PI3K/AKT) and ultimately inducing tumor cell apoptosis and growth inhibition.

Urgent Side Effects: Seek Medical Help Right Away

While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:

Signs of an allergic reaction: 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, or swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes
Signs of low calcium levels: muscle cramps or spasms, numbness and tingling, or seizures
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain
Feeling confused
Memory problems or loss
Depression or other mood changes
Trouble speaking
Bone pain
Trouble walking
Falls
Change 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

Most people do not experience significant side effects, but some may occur. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention if they bother you or do not go away:

Constipation, diarrhea, stomach pain, upset stomach, vomiting, or decreased appetite
Feeling dizzy, sleepy, tired, or weak
Trouble sleeping
Cough
Headache
Stuffy nose
Weight gain
Back, muscle, or joint pain
Muscle weakness
Pain in 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.

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 you experienced, including any symptoms that occurred.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This medication can interact with various drugs, such as those used to treat HIV, infections, or seizures.
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 problems that may affect your use of this medication. To ensure your safety, it is crucial to:

Inform your doctor and pharmacist about all your medications (prescription and OTC), natural products, vitamins, and health problems.
Verify that it is safe to take this medication with all your other medications and health conditions.
Never start, stop, or change the dose of any medication without first consulting your doctor.

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. As directed by your doctor, undergo regular blood tests and discuss the results with them.

To minimize potential interactions, avoid consuming grapefruit and grapefruit juice while taking this medication. Be aware that this drug may increase the risk of fractures; therefore, consult your doctor to discuss this potential risk.

When administering this medication to children, exercise caution, as they may be more susceptible to certain side effects. Additionally, this drug may affect fertility, making it more challenging to conceive. Discuss this possibility with your doctor.

Due to the potential harm this medication can cause 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 birth control during treatment 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.

• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): May significantly decrease larotrectinib exposure, leading to reduced efficacy. Avoid co-administration.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): May significantly increase larotrectinib exposure, leading to increased adverse reactions. Reduce larotrectinib dose by 50% if co-administered.

• Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil): May decrease larotrectinib exposure. Consider alternative agents or monitor for reduced efficacy.
• Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem, verapamil, fluconazole): May increase larotrectinib exposure. Consider reducing larotrectinib dose by 25% if co-administered.

• Dizziness
• Gait disturbance/ataxia
• Paresthesia (numbness, tingling)
• Cognitive impairment (e.g., memory impairment, confusion)
• Musculoskeletal pain (arthralgia, myalgia)
• Fatigue
• Nausea/Vomiting
• Diarrhea
• Constipation
• Elevated liver enzymes (jaundice, dark urine, right upper quadrant pain)
• Fever

Vitrakvi can cause fetal harm when administered to a pregnant woman. Based on animal studies, larotrectinib may cause embryo-fetal toxicity. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose.

It is not known whether larotrectinib or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with Vitrakvi and for 1 month after the last dose.

Vitrakvi is approved for pediatric patients with TRK fusion-positive solid tumors. Dose is based on Body Surface Area (BSA) for pediatric patients. Neurological adverse reactions and musculoskeletal adverse reactions (e.g., arthralgia, myalgia) are common in pediatric patients. Growth and development should be monitored.

No specific dose adjustment is required for geriatric patients. Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

• Larotrectinib was the first tumor-agnostic therapy approved by the FDA for solid tumors with NTRK gene fusions, regardless of tumor type.
• It is crucial to confirm the presence of an NTRK gene fusion using a validated diagnostic test (e.g., NGS) before initiating therapy.
• While generally well-tolerated, neurological adverse events (dizziness, ataxia, paresthesia) are common and require careful monitoring and potential dose modification.
• Hepatotoxicity can occur; regular monitoring of liver function tests is important.
• Larotrectinib is a substrate of CYP3A4, making drug-drug interactions with strong CYP3A4 inhibitors and inducers clinically significant and requiring dose adjustments.
• Due to its high cost, patient assistance programs and insurance coverage verification are essential.

• Entrectinib (another TRK inhibitor, also approved for NTRK fusion-positive solid tumors)
• Other targeted therapies or chemotherapy regimens depending on the specific tumor type and patient characteristics if NTRK fusion is not present or if resistance develops.

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't 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 seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.