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TERMS OF USE

General Conditions of use

Access to and use of this website are subject to the following conditions. Please do not use this website unless you agree with these conditions. This website has been developed by the Bayer Pharma AG, BHC Global Corporate Communications (hereinafter to be referred to as BAYER) and is administrated by the same. We reserve the right to discontinue or to make partial or complete modifications to this website or to the General Conditions of Use, to our General Terms and Conditions, and to our Conditions of Sale and Delivery. Please note that we may make such changes at our own discretion and without prior announcement. We must therefore ask you, next time you visit this website, to view the conditions again and to note any changes or amendments that may have been made.

 

Surrender of use and benefit

All details, documents and illustrations published on this website are the sole property of BAYER. Any permission to use the same is granted on the proviso that the relevant copyright note is displayed on all copies, that such details are only used for personal purposes, that they are not exploited commercially, that the details are not modified in any way and that all illustrations gained from the website are only used in conjunction with the accompanying text.

 

Trademarks and Copyright

All trademarks on this website are the property of Bayer, unless otherwise noted or in any other way perceivable as third party rights. Any unauthorized use of these trademarks or other materials is expressly prohibited and constitutes a violation of copyright, trademark law or other industrial property rights.

 

Limited liability

BAYER has compiled the detailed information provided on this website from internal and external sources to the best of its knowledge and belief, using professional diligence. We endeavor to expand and update this range of information on an ongoing basis. The information on this website is purely for the purpose of presenting BAYER and its products and services. However, no representation is made or warranty given, either expressly or tacitly, for the completeness or correctness of the information on this website. In particular, we must ask you to be aware that this information may no longer be up to date. We therefore recommend that you check any information you obtain from this website prior to using it in whatever form. Advice given on this website does not exempt you from conducting your own checks on our latest advice - particularly our safety datasheets and technical specifications - and on our products, with a view to their suitability for the intended processes and purposes. Should you require any advice or instructions concerning our products or services, please contact us directly. Users of this website declare that they agree to access the website and its content at their own risk. Neither BAYER nor third parties involved in the writing, production or transmission of this website can be held liable for damage or injury resulting from access or the impossibility of access or from the use or impossibility of use of this website or from the fact that you have relied on information given on this website.

 

Websites of third-party vendors/links

This website contains links/references to third-party websites. By providing such links, BAYER does not give its approval to their contents. Neither does BAYER accept any responsibility for the availability or the contents of such websites or any liability for damage or injury resulting from the use of such contents, of whatever form. Links to other websites are provided to website users merely for the sake of convenience. Users access such websites at their own risk.

 

Details supplied by yourself

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International users

This website is checked, operated and updated by BAYER at Berlin, Germany. This website is intended to provide information to an international audience outside the USA and UK. BAYER gives no guarantee that the details presented on this website are also correct in places outside the USA and UK, and, in particular, that products and services will be available with the same appearance, in the same sizes or on the same conditions. Should you call up this website from a place outside the USA and UK or download contents from such a place, please note that it is your own responsibility to ensure that you act in compliance with local legislation applicable in that place.

 

Products mentioned on this website may come in different packaging, in different package sizes, or with different lettering or markings, depending on the country.

 

In the USA business is conducted by the Bayer Corporation and/or Bayer Pharma AG, BHC Global Corporate Communications. Customers in the USA are requested to address to one of these entities.

 

Sale of BAYER Products

Our products are sold in accordance with the current version of our General Conditions of Sale and Delivery.

 

Applicable law

Any legal claims or lawsuits in conjunction with this website or its use are subject to the interpretation of the laws of the Federal Republic of Germany, except for the provisions of international private law and the Hague Convention relating to a Uniform Law on the International Sale of Goods of July 1, 1964 and in the UN Sales Convention of April 11, 1980.

 

Forward-Looking Statements

This website may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

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.

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.