Evidence map›Paper›PMID 23620168›Full record

ReviewDrug safety2013

Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives.

Rashmi R Shah, Joel Morganroth, Devron R Shah

Abstract readReview
PubMed Publisher
In one paragraph

Review in Drug safety, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 6 pooled it
10.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 6 syntheses or guidelines pooled it, 241 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Acidifying agents impact erlotinib and gefitinib pharmacokinetic parameters and elevate liver enzymes in Wistar rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025
    Article
  19. Survival impact and safety comparison of pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A meta-analysis.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2025
    Article
  20. Review

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Rashmi R ShahRashmi Shah Consultancy Ltd, 8 Birchdale, Gerrards Cross, Buckinghamshire, SL9 7JA, UK. clinical.safety@hotmail.co.uk
Joel Morganroth
Devron R Shah
21c Consultancy (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The introduction of small-molecule tyrosine kinase inhibitors (TKIs) in clinical oncology has transformed the treatment of certain forms of cancers. As of 31 March 2013, 18 such agents have been approved by the US Food and Drug Administration (FDA), 15 of these also by the European Medicines Agency (EMA), and a large number of others are in development or under regulatory review. Unexpectedly, however, their use has been found to be associated with serious toxic effects on a number of vital organs including the liver. Drug-induced hepatotoxicity has resulted in withdrawal from the market of many widely used drugs and is a major public health issue that continues to concern all the stakeholders. This review focuses on hepatotoxic potential of TKIs. The majority of TKIs approved to date are reported to induce hepatic injury. Five of these (lapatinib, pazopanib, ponatinib, regorafenib and sunitinib) are sufficiently potent in this respect as to require a boxed label warning. Onset of TKI-induced hepatotoxicity is usually within the first 2 months of initiating treatment, but may be delayed, and is usually reversible. Fatality from TKI-induced hepatotoxicity is uncommon compared to hepatotoxic drugs in other classes but may lead to long-term consequences such as cirrhosis. Patients should be carefully monitored for TKI-induced hepatotoxicity, the management of which requires individually tailored reappraisal of the risk/benefit. The risk is usually manageable by dose adjustment or a switch to a suitable alternative TKI. Confirmation of TKI-induced hepatotoxicity can present challenges in the presence of hepatic metastasis and potential drug interactions. Its diagnosis in a patient with TKI-sensitive cancer requires great care if therapy with the TKI suspected to be causal is to be modified or interrupted as a result. Post-marketing experience with drugs such as imatinib, lapatinib and sorafenib suggests that the hepatotoxic safety of all the TKIs requires diligent surveillance.

Indexed as

AnimalsChemical and Drug Induced Liver InjuryHumansLiverProtein Kinase InhibitorsProtein-Tyrosine KinasesProtein Kinase InhibitorsProtein-Tyrosine Kinases

Identifiers

PMID23620168
OpenAlexW2065902287

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.