Side Effects of tepotinib: A Synthesis of Findings from 4 Studies

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Original Abstract of the Article

Major findings

Tepotinib is a potent inhibitor of c-Met, which has been approved for use in Japan for the treatment of patients with non-small cell lung cancer (NSCLC) harboring an MET exon 14 skipping alteration who have progressed after platinum-based therapy. 4 To identify the generation of iminium intermediates in its metabolism, practical and in silico approaches were used to screen for the metabolic profile and reactive intermediates of tepotinib. 4 Understanding the bioactive center and structural alerts in the tepotinib structure has helped in making targeted modifications to improve its safety. 4

Reason for side effects

The generation of iminium intermediates in the metabolic pathway of tepotinib may provide an explanation for its adverse reactions. 4 As proposed by the DEREK software and a Xenosite reactivity model, the piperidine ring is considered a structural alert for toxicity, which was confirmed by practical experiments. 4 Steric hindrance or isosteric replacement at the α-carbon of the piperidine ring stops the bioactivation sequence, which was confirmed using the DEREK software. 4

Common side effects

Hepatotoxicity

Use of the antithyroid drugs (ATDs) thiamazole (MMI) and propylthiouracil (PTU) is associated with a high frequency of side effects. 1 When patients experience side effects with one (the 1st) ATD, it is usually discontinued and another is administered (the 2nd ATD). 1 We investigated side effects associated with the 1st and 2nd ATDs, and found hepatotoxicity to be one of them. 1 .

Cutaneous reactions

Use of the antithyroid drugs (ATDs) thiamazole (MMI) and propylthiouracil (PTU) is associated with a high frequency of side effects. 1 When patients experience side effects with one (the 1st) ATD, it is usually discontinued and another is administered (the 2nd ATD). 1 We investigated side effects associated with the 1st and 2nd ATDs, and found cutaneous reactions to be one of them. 1 .

Side effects countermeasures

Countermeasures for Hepatotoxicity

Hepatotoxicity is a common side effect associated with the use of antithyroid drugs (ATDs). 1 Many of the side effects of ATDs are known to be dose-dependent. 1 Therefore, it is important to reduce the dose of ATDs to prevent side effects such as hepatotoxicity. 1 It is also important to monitor liver function by performing regular blood tests. 1

Countermeasures for Cutaneous reactions

Cutaneous reactions are a common side effect associated with the use of antithyroid drugs (ATDs). 1 Many of the side effects of ATDs are known to be dose-dependent. 1 Therefore, it is important to reduce the dose of ATDs to prevent side effects such as cutaneous reactions. 1 Also, if cutaneous reactions occur, treatments such as steroid cream may be effective. 1

Comparison between studies

Common points of the studies

All these studies are investigating the side effects associated with the use of specific drugs. 4 1 Also, all these studies are looking for ways to reduce the side effects of drugs. 4 1

Differences between the studies

These studies vary in the drugs they are investigating. 4 1 Also, the research methods used in the studies differ. 4 1

Points to note for application to real life

The findings of these studies can be helpful for the treatment of patients using tepotinib or antithyroid drugs. 4 1 However, these studies do not apply to everyone. 4 1 Therefore, it is important for patients receiving treatment to discuss with their doctors and determine the appropriate course of treatment. 4 1

Limitations of current research

These studies do not apply to everyone. 4 1 Therefore, the findings of these studies cannot be applied to everyone. 4 1 These studies are also focused on specific drugs. 4 1 Therefore, we cannot learn about the side effects of other drugs from these studies. 4 1

Future directions for research

The information obtained from these studies could help in the development of safer and more effective treatments. 4 1 Therefore, it is necessary to further investigate the side effects of these drugs. 4 1 It is also necessary to investigate the side effects of other drugs. 4 1 Furthermore, new methods need to be developed to reduce the side effects of drugs. 4 1

Conclusion

Tepotinib and antithyroid drugs are effective drugs for the treatment of certain cancers and thyroid diseases. 4 1 However, these drugs can cause side effects such as hepatotoxicity and cutaneous reactions. 4 1 Therefore, it is important to discuss with your doctor and determine the appropriate course of treatment when using these drugs. 4 1 Also, new methods need to be developed to reduce the side effects of these drugs. 4 1

Literature analysis of 4 papers
Positive Content
3
Neutral Content
1
Negative Content
0
Article Type
1
0
2
1
4
1.

Hepatotoxicity and cutaneous reactions after antithyroid drug administration.

Author: OtsukaFumiko, NohJaeduk Y, ChinoToshiko, ShimizuTaeko, MukasaKoji, ItoKunihiko, ItoKoichi, TaniyamaMatsuo

Antithyroid drug side effects

This study investigated side effects associated with the first and second antithyroid drugs (ATDs) used in patients. The study highlights the high frequency of side effects associated with thiamazole (MMI) and propylthiouracil (PTU).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

Influence of the anti-oestrogens tamoxifen and letrozole on thyroid function in women with early and advanced breast cancer: A systematic review.

Author: MarinaDjordje, RasmussenÅse Krogh, Buch-LarsenKristian, GillbergLinn, AnderssonMichael, SchwarzPeter

BC recurrence
Thyroid function

Tamoxifen and letrozole are anti-oestrogens used to prevent breast cancer recurrence. While their side effects are well-documented, their impact on thyroid function is less clear. This review explores the potential effects of tamoxifen and letrozole on thyroid function and their contribution to weight gain observed in breast cancer patients.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Achievements in Hypothyroidism Treatment with Herbal Medicine: A Systematic Review of Randomized Controlled Trials.

Author: JavidiNajmeh, KhorasaniZahra Mazloum, SalariRoshanak, NiroumandShabnam, YousefiMahdi

Hypothyroidism treatment

Hypothyroidism is a common condition that can cause health problems, especially in older adults. While medications are used to treat hypothyroidism, they can have side effects. Herbal remedies are being explored as a potential treatment for hypothyroidism that can regulate thyroid hormones and reduce side effects.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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