Vitrakvi 25mg Capsules

Larotrectinib is a highly selective, central nervous system (CNS) active, oral tropomyosin receptor kinase (TRK) inhibitor. It targets TRK fusion proteins (TRKA, TRKB, and TRKC), which are oncogenic drivers in various solid tumors. By inhibiting the kinase activity of these fusion proteins, larotrectinib blocks downstream signaling pathways (e.g., MAPK/ERK, PI3K/AKT) that promote cell proliferation and survival, leading to tumor regression.

Serious Side Effects: Seek Medical Help Right Away

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 immediately or seek medical attention:

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 can increase the risk of infection. If you experience signs of infection, such as fever, chills, or sore throat, contact your doctor immediately.

Other Possible Side Effects

Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild 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:

Constipation
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Dizziness
Drowsiness
Fatigue
Weakness
Trouble sleeping
Cough
Headache
Stuffy nose
Weight gain
Back pain
Muscle pain
Joint pain
Muscle weakness
Pain in the arms or legs

Reporting Side Effects

This list is not exhaustive, and you may experience other 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 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, can 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. To ensure your safety, it is crucial to discuss all your medications (prescription or OTC, natural products, vitamins) and health conditions with your doctor and pharmacist. Before starting, stopping, or changing the dose of any medication, consult with your doctor to confirm that it is safe to do so in conjunction with this medication.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Until you are aware of how this drug affects you, avoid operating a vehicle and engaging in other activities that require alertness. As directed by your doctor, regular blood tests will be necessary 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. Be aware that this drug may increase the risk of fractures; discuss this risk with your doctor to understand the implications.

When administering this medication to children, exercise caution, as the risk of certain side effects may be higher in this population. Additionally, this drug may affect fertility, making it more challenging to conceive; discuss this potential effect 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 could become pregnant, it is crucial to use effective birth control methods during treatment and for a specified period after the final dose. Consult your doctor to determine the recommended duration of birth control use. In the event of a pregnancy, notify your doctor immediately.

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): May increase larotrectinib exposure, increasing risk of adverse reactions. Avoid coadministration or reduce larotrectinib dose.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): May decrease larotrectinib exposure, reducing efficacy. Avoid coadministration.

• Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem, verapamil): May increase larotrectinib exposure. Monitor for adverse reactions.
• Moderate CYP3A4 inducers (e.g., efavirenz, bosentan): May decrease larotrectinib exposure. Monitor for reduced efficacy.

• Substrates of CYP3A4 (e.g., midazolam, simvastatin): Larotrectinib is a weak inhibitor of CYP3A4 in vitro, but clinical significance is likely minimal. Monitor for increased exposure of sensitive CYP3A4 substrates if coadministered.

• Dizziness
• Ataxia (difficulty with coordination)
• Paresthesia (numbness or tingling)
• Fatigue
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Musculoskeletal pain
• Weight gain
• Elevated liver enzymes (symptoms like dark urine, yellow skin/eyes, severe nausea/vomiting)

Larotrectinib can cause fetal harm when administered to a pregnant woman. Based on animal studies, it may cause adverse developmental effects. Advise pregnant women of the potential risk to a 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 3 months after the last dose.

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

Larotrectinib is approved for pediatric patients with NTRK gene fusion-positive solid tumors. Dosing is based on body surface area (BSA) for younger children and fixed dose for adolescents with BSA ≥ 1.0 m². Monitor growth and development in pediatric patients as growth plate abnormalities were observed in juvenile animals.

No overall differences in safety or effectiveness were observed between elderly patients (≥65 years) and younger patients. No specific dose adjustment is required based on age alone.

• Larotrectinib is a tumor-agnostic therapy, meaning its use is based on the presence of an NTRK gene fusion, not the tumor's origin.
• It is crucial to confirm the presence of an NTRK gene fusion using a validated diagnostic test before initiating treatment.
• Neurological adverse events, particularly dizziness and ataxia, are common and can impact quality of life; monitor patients closely and consider dose modifications if severe.
• Weight gain is a common side effect; monitor patient weight and provide dietary counseling if needed.
• Liver enzyme elevations are possible; regular monitoring of LFTs is essential.
• Larotrectinib has demonstrated CNS activity and can be effective in patients with brain metastases.
• Counsel patients on potential drug interactions, especially with strong CYP3A4 inhibitors and inducers, and grapefruit products.

• Entrectinib (another TRK inhibitor, also approved for NTRK fusion-positive tumors)
• Chemotherapy (traditional cytotoxic agents, depending on tumor type)
• Radiation therapy (depending on tumor type and stage)
• Surgery (depending on tumor type and stage)
• Other targeted therapies or immunotherapies (if other actionable mutations or biomarkers are present)

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 consult with your pharmacist. If you have any questions or concerns about this 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 seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.