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THE ONLY TRK* INHIBITOR WITH BOTH CAPSULES AND AN ORAL SOLUTION1

AVAILABLE IN CAPSULES AND AN ORAL SOLUTION1

Graphic of a capsule medication and text of 100mg and 25mg

100-mg and 25-mg
capsules1

Graphic of a dropper measuring 20mg/ml oral solution

20-mg/mL oral
solution1

Graphic of a plate with a fork and knife and text of Vitrakvi® (larotrectinib) can be taken with or without food

VITRAKVI® can be taken with or without food1

Graphic of a strawberry indicating that pre-mixed oral solution will be available in strawberry flavor

Pre-mixed oral solution is available in strawberry flavor.1,a

*TRK, tropomyosin receptor kinase.

aAvailable in the 2x50-mL solution only.1

VITRAKVI is taken twice daily1

Adult1

100 mg taken orally twice daily until disease progression or until unacceptable toxicity occurs.

Pediatric1

  • Recommended dosage in pediatric patients with body surface area of ≥1.0 m2: 100 mg taken orally twice daily until disease progression or until unacceptable toxicity
  • Recommended dosage in pediatric patients with body surface area <1.0 m2: 100 mg/m2 taken orally twice daily until disease progression or until unacceptable toxicity

VITRAKVI CAPSULES OR ORAL SOLUTION MAY BE USED INTERCHANGEABLY.1

RECOMMENDED DOSE REDUCTIONS FOR ADVERSE REACTIONS1

Table showcasing recommended dose reductions for adverse reactions during treatment
Dose reduction chart

For Grade 2 and higher liver function test abnormalities, refer to the Recommended Dose Modifications for Hepatotoxicity table below.1

  • For all other Grade 3 or 4 adverse reactions1:
    • Withhold VITRAKVI until adverse reaction resolves or improves to baseline or Grade 1. Resume at the next dose modification if resolution occurs within 4 weeks
    • Permanently discontinue VITRAKVI if an adverse reaction does not resolve within 4 weeks
  • Permanently discontinue VITRAKVI in patients who are unable to tolerate VITRAKVI after 3 dose modifications1

For CTCAE Grade 2 ALT and/or AST elevation, monitor liver function frequently as clinically indicated to establish whether a dose interruption or reduction is required.1

bPediatric patients on 25 mg/m2 orally twice daily should remain on this dose even if body surface area becomes >1.0 m2 during the treatment. Maximum dose should be 25 mg/m2 orally twice daily at the third dose modification.1

Recommended Dose Modifications for Hepatotoxicity1

Table showcasing recommended dose modifications for hepatotoxicity during treatment

cGrading defined by NCI-CTCAE version 4.03.1

dULN, upper limit of normal.

Dosage modifications for coadministration with strong or moderate CYP3A4 inhibitors1

  • Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. If coadministration of a strong CYP3A4 inhibitor cannot be avoided, reduce the VITRAKVI dose by 50%. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the VITRAKVI dose taken prior to initiating the CYP3A4 inhibitor
  • For coadministration with moderate CYP3A4 inhibitors, monitor for adverse reactions more frequently and reduce the dosage based on severity

Dosage modifications for coadministration with strong or moderate CYP3A4 inducers1

  • Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. If coadministration of a strong CYP3A4 inducer cannot be avoided, double the VITRAKVI dose. After the inducer has been discontinued for 3 to 5 elimination half-lives, resume the VITRAKVI dose that was used prior to initiating the CYP3A4 inducer. For coadministration with moderate CYP3A4 inducers, modify dose as recommended

Dosage modifications for patients with hepatic impairment1

  • Reduce the starting dose of VITRAKVI by 50% in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment

Learn About NTRK Testing

Reference

  • VITRAKVI [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; November 2023. Return to content
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Indication

VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that:

  • have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation,
  • are metastatic or where surgical resection is likely to result in severe morbidity, and
  • have no satisfactory alternative treatments or that have progressed following treatment.

Select patients for therapy based on an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

Warning and Precautions

  • Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances.

    In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients.

    Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification and 20% required dose interruption.

    Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients.

    Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification and 5% required dose interruption.

    Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption.

    Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

  • Skeletal Fractures: Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients.

    Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures.

  • Hepatotoxicity: Hepatotoxicity including drug induced liver injury (DILI) has been reported in patients taking VITRAKVI.

    In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) of patients.

    There have been reports in adult patients from clinical studies and post-marketing cases of Grade ≥ 2 increases in ALT and/or AST with increases in bilirubin ≥ 2 x ULN.

    Obtain liver function tests (ALT, AST, ALP and bilirubin) before initiation of VITRAKVI and monitor every 2 weeks during the first two months of treatment, then monthly thereafter, or more frequently following the occurrence of Grade 2 or greater AST or ALT elevation. Temporarily withhold, reduce the dose, or permanently discontinue VITRAKVI based on severity.

  • Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.

Adverse Reactions

  • The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased AST (52%), increased ALT (45%), anemia (42%), musculoskeletal pain (42%), fatigue (36%), hypoalbuminemia (36%), neutropenia (36%), increased alkaline phosphatase (34%), cough (32%), leukopenia (28%), constipation (27%), diarrhea (27%), dizziness (27%), hypocalcemia (25%), nausea (25%), vomiting (25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%).

Drug Interactions

  • Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs. For coadministration with moderate CYP3A4 inhibitors, monitor for adverse reactions more frequently and reduce the dosage based on severity. For coadministration with moderate CYP3A4 inducers, modify dose as recommended.

Use in Specific Populations

  • Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.

For important risk and use information about VITRAKVI, please see the full Prescribing Information.

You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

For Bayer products, you can report these directly to Bayer by clicking here.

© 2024 Bayer. All rights reserved. Bayer, the Bayer Cross, and VITRAKVI are registered trademarks of Bayer, and Access Services by Bayer is a trademark of Bayer. All other trademarks are the property of their respective owners.

 

This site is intended for US audiences only.

Site last updated on 10/2024

© 2024 Bayer. All rights reserved. Bayer, the Bayer Cross, and VITRAKVI are registered trademarks of Bayer, and Access Services by Bayer is a trademark of Bayer. All other trademarks are the property of their respective owners.

 

This site is intended for US audiences only.

 

Site last updated on 10/2024