Pharmacology and pharmacovigilance of protein kinase inhibitors

Khouri, Charles; Mahé, Julien; Caquelin, Laura; Locher, Clara; Despas, Fabien

doi:10.1016/j.therap.2021.11.004

Cited by 2 publications

(2 citation statements)

References 90 publications

(95 reference statements)

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“…A fluid retention signal was observed with the five studied TKIs. Fluid retention resulting in anasarca, ascites, and pleural or pericardial effusion is described in the SmPC of the BCR-ABL TKIs and has been extensively reported in the literature [ 23 , 24 , 25 , 26 ]. Several mechanisms have been suggested, including the inhibition of PDGFR [ 26 ] and alterations of focal adhesions and adherent junctions related to the inhibition of SRC-related kinases [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding nilotinib, cardiovascular events including peripheral artery occlusion disease, ischemic heart disease, basilar artery stenosis, and ischemic cerebrovascular disease have been reported in phase III trials, such as the ENESTnd study (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients), but renal artery stenosis has not been reported yet and is not described in the SmPC [ 4 , 38 ]. However, the rapid evolution of atherosclerosis in this context has led to recommendations regarding ponatinib and nilotinib prescription in patients with pre-existent atherosclerotic risk factors [ 23 ]. Altogether, these observations underline the vascular risk associated with ponatinib and nilotinib.…”

Section: Discussionmentioning

confidence: 99%

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Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase®, the WHO Pharmacovigilance Database

Cellier

Bourneau‐Martin

Abbara

et al. 2023

Cancers

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Background: Alongside their BCR-ABL specificity, TKIs used in chronic myeloid leukemia also target other tyrosine kinases expressed in the kidney such as PDGFR, c-KIT, SRC, and VEGFR, which may result in specific renal adverse drug reaction (ADR). To evaluate the renal safety profile in real-life conditions, a case/non-case study was performed on VigiBase®, the WHO global safety database. Methods: From 7 November 2001 to 2 June 2021, all cases in which the involvement of imatinib, dasatinib, nilotinib, bosutinib, and ponatinib was suspected in the occurrence of renal ADR were extracted from VigiBase®. Disproportionality analyses were assessed using the reporting odds ratio. Results: A total of 1409 cases were included. Imatinib accounts for half of the reported cases. A signal of disproportionate reporting (SDR) of renal failure and fluid retention was found for the five TKIs. Only dasatinib and nilotinib were related to an SDR for nephrotic syndrome. Nilotinib and ponatinib were related to an SDR for renal artery stenosis, while dasatinib was related to an SDR for thrombotic microangiopathy. No SDR for tubulointerstitial nephritis was observed. Conclusion: This study identified a new safety signal, nephrotic syndrome, for nilotinib and highlights the importance of post-marketing safety surveillance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase®, the WHO Pharmacovigilance Database

Cellier

Bourneau‐Martin

Abbara

et al. 2023

Cancers

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Protein Kinase Inhibitors Indicated for Lung Cancer: Pharmacodynamics, Pharmacokinetics, Adverse Drug Reactions, and Evaluation in Clinical Trials

Bordet,

Dongay,

Zelmat

et al. 2024

Journal of Clinical Pharmacy and Therapeutics

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WhatIs Known and Objective. Anti‐EGFR (epidermal growth factor receptor) drugs are indicated for non‐small‐cell lung cancer (NSCLC). This review summarises the information available to date on the first anti‐EGFRs granted market authorisation: erlotinib TARCEVA®, gefitinib IRESSA®, afatinib GIOTRIF®, dacomitinib VIZIMPRO®, and osimertinib TAGRISSO®. Methods. A literature search was conducted in the PubMed database including studies published in English using the terms gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib. Furthermore, bibliographies of selected references were also studied for relevant articles. Clinical trial (CT) data were extracted from clinicaltrials.gov (ongoing trials and adverse events (AEs)). Assessment of AEs for these drugs was conducted using global pharmacovigilance data from VigiBase®. Results and Discussion. Erlotinib and gefitinib are first‐generation anti‐EGFR drugs, able to bind competitively and reversibly to the ATP‐ (adenosine triphosphate‐) binding site of the EGFR exon 19 and exon 21 mutations. Afatinib and dacomitinib are second‐generation anti‐EGFRs able to bind covalently and irreversibly to the ATP site and inhibit EGFR and HER (human epidermal growth factor receptor) such as HER2 and HER4 enzyme activity. Osimertinib is a third‐generation PKI and overcomes the EGFR T790M gatekeeper mutation through covalent binding at the ATP site. Medical interactions with these drugs are reported, notably with cytochrome P450 inducers or inhibitors. The most reported AEs in CTs are cutaneous reactions and gastrointestinal disorders. The occurrence of cutaneous reactions is less reported with third generation than with first‐ and second‐generation anti‐EGFR drugs. These results are consistent with the results from the VigiBase® global pharmacovigilance database. What Is New and Conclusion. This review summarises current knowledge regarding five anti‐EGFRs in the literature. The third‐generation anti‐EGFR appears to be more effective than the first and second generations and is indicated as first‐line therapy. This trial is registered with NCT01523587, NCT01466660, NCT01774721, NCT01360554, and NCT02296125.

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Pharmacology and pharmacovigilance of protein kinase inhibitors

Cited by 2 publications

References 90 publications

Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase®, the WHO Pharmacovigilance Database

Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase®, the WHO Pharmacovigilance Database

Protein Kinase Inhibitors Indicated for Lung Cancer: Pharmacodynamics, Pharmacokinetics, Adverse Drug Reactions, and Evaluation in Clinical Trials

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