Tyrosine Kinase in Pediatric Growth

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The use of tyrosine kinase inhibitor (TKI) therapy has become more common in pediatric patients in the last few years. This trend is likely to continue as more TKIs are approved and the list of conditions for which TKIs have clinical utility expands. Imatinib (Gleevec™) is a tyrosine kinase inhibitor that is specifically indicated for Philadelphia positive chronic myelogenous leukemia (PHÆCML). Dasatinib (Sprycel™) and nilotinib (Tasigna™) are TKIs indicated for CML patients who are no longer benefitting from, or did not tolerate, other treatments including imatinib.

OBJECTIVE:The objective of this study was to determine whether there is evidence of growth retardation as an adverse drug experience for TKIs.

METHODS:The FDA Adverse Event Reporting System (FAERS) was reviewed for currently posted data from 4th quarter 2012 until 1st quarter 2014 for individuals ≤ 18 years of age. The most recent update of the FAERs data was in October of 2014. These are sponsor, patient and physician reported events. A search for approximate matches to the drug names using the generalized Levenshtein edit distance using the R and SAS™ 9.3 was used to search for patterns in the adverse experiences. These AEs were grouped by Preferred Term(PT), and the ranking of growth related AEs was conducted relative to other PTs.

RESULTS:Of 574 self-reported adverse experiences reported for imatinib from 2012-2014, there were 12 (2.1%) cases of growth retardation. Growth retardation was the 5th most commonly occurring AE. Of 594 self-reported adverse experiences for dasatinib from 2012-2104, no cases of growth retardation occurred. Likewise, of 25 self-reported AEs for nilotinib, none were growth related.

CONCLUSION:There appears to be some evidence of growth retardation in imatinib patients, and none for dasatinib patients. Not enough AEs have yet been reported for nilotinib to judge whether growth is also retarded in these patients.


Presented at the 116th American Society for Clinical Pharmacology and Therapeutics Annual Meeting, Atlanta, GA.