{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:05:49Z","timestamp":1792058749486,"version":"4.4.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>Objective: To review the pharmacology, pharmacokinetics, clinical trials, adverse effects, and formulary considerations of ponatinib, a pan-tyrosine kinase inhibitor (TKI). Data Sources: A literature search of articles published between January 1966 and June 2013 was performed using PubMed with the following search terms: ponatinib, AP24534, and Iclusig. ARIAD Pharmaceuticals, Inc, was contacted for unpublished information. Other sources included American Society of Hematology abstracts, the Food and Drug Administration Center for Drug Evaluation and Research Web site, and clinicaltrials.gov . Study Selection\/Data Extraction: Included articles and abstracts were published in English and contain information about ponatinib, particularly in the treatment of chronic myeloid leukemia (CML) or Philadelphia chromosome\u2013positive (Ph+) acute lymphoblastic leukemia (ALL). Data Synthesis: Following the phase II PACE trial, ponatinib was approved for the treatment of patients with chronic-phase (CP), accelerated-phase (AP), or blast-phase (BP) CML or Ph+ ALL who have become intolerant or resistant to previous therapy. Unlike other BCR-ABL TKIs, ponatinib was designed to overcome the T315I mutation. At 15.3 months, 46% of patients with CP-CML achieved a complete cytogenetic response, and 34% achieved a major molecular response. Complete hematologic responses occurred in 47% of patients with AP-CML, 21% with BP-CML, and 34% with Ph+ ALL after 1 year. Severe toxicities included myelosuppression, hepatotoxicity, pancreatitis, and arterial thrombosis. Conclusions: Ponatinib is a potent TKI that can overcome several resistance mechanisms in previously treated patients with CML and Ph+ ALL. Ponatinib should be reserved for patients who have failed first-line therapy, have the T315I mutation, or have progressed.<\/jats:p>","DOI":"10.1177\/1060028013501144","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T13:56:59Z","timestamp":1405432619000},"page":"1540-1546","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":46,"title":["Ponatinib"],"prefix":"10.1177","volume":"47","author":[{"given":"Caitlin L.","family":"Shamroe","sequence":"first","affiliation":[{"name":"Louisiana State University Health, Shreveport, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Comeau","sequence":"additional","affiliation":[{"name":"Louisiana State University Health, Shreveport, LA, USA"},{"name":"University of Louisiana at Monroe College of Pharmacy, Shreveport, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,11,21]]},"reference":[{"key":"bibr1-1060028013501144","first-page":"2267","volume-title":"Devita, Hellman, and Rosenberg\u2019s Cancer: Principles and Practice of Oncology","author":"Druker BJ","year":"2007","edition":"8"},{"key":"bibr2-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023001"},{"key":"bibr3-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V114.22.1126.1126"},{"key":"bibr4-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-358135"},{"key":"bibr5-1060028013501144","first-page":"180","volume-title":"World Health Organization of Tumours of Haematopoietic and Lymphoid Tissues","author":"Vardiman JW","year":"2008","edition":"4"},{"key":"bibr6-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062867"},{"key":"bibr7-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-009-0046-y"},{"key":"bibr8-1060028013501144","unstructured":"National Comprehensive Cancer Network. Chronic myelogenous leukemia. www.nccn.org\/professionals\/physicians_gls\/pdf\/cml.pdf. Accessed March 1, 2013."},{"key":"bibr9-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404320"},{"key":"bibr10-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2008.26.15_suppl.7019"},{"key":"bibr11-1060028013501144","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11891"},{"key":"bibr12-1060028013501144","unstructured":"National Comprehensive Cancer Network. Acute lymphoblastic leukemia. www\/nccn\/org\/professionals\/physicians_gls\/pdf\/all.pdf. Accessed April 24, 2013."},{"key":"bibr13-1060028013501144","unstructured":"FDA\/CEDR resources page. http:\/\/www.accessdata.fda.gov\/scripts\/cder\/drugsatfda\/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed February 29, 2013."},{"key":"bibr14-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2010.01054.x"},{"key":"bibr15-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1021\/jm901443h"},{"key":"bibr16-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.09.028"},{"key":"bibr17-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.01.023"},{"key":"bibr18-1060028013501144","unstructured":"FDA\/CEDR resources page. http:\/\/www.accessdata.fda.gov\/scripts\/cder\/drugsatfda\/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed February 29, 2013."},{"key":"bibr19-1060028013501144","unstructured":"Iclusig (Ponatinib) [product information]. Cambridge, MA: ARIAD Pharmaceuticals, Inc; 2012."},{"key":"bibr20-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205127"},{"key":"bibr21-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V120.21.163.163"},{"key":"bibr22-1060028013501144","unstructured":"ClinicalTrials.gov; M D Anderson Cancer Center. Hyper-CVAD and ponatinib in Ph-positive and\/or BCR-ABL positive acute lymphoblastic leukemia (ALL). http:\/\/www.clinicaltrials.gov\/show\/NCT01424982 NLM Identifier: NCT01424982. Accessed July 31, 2013."},{"key":"bibr23-1060028013501144","unstructured":"ClinicalTrials.gov; Gruppo Italiano Malattie Ematologiche dell\u2019Adulto. Phase II Front-line treatment of Philadelphia positive (Ph+)\/BCR-ABL positive acute lymphoblastic leukemia (ALL) with AP24534 (Ponatinib), a new potent tyrosine kinase inhibitor (TKI): a phase II exploratory multicentric study in patients more than 60 years old or unfit for a program of intensive chemotherapy and stem cell transplantation. http:\/\/www.clinicaltrials.gov\/show\/NCT01641107 NLM Identifier: NCT01641107. Accessed March 6, 2013."},{"key":"bibr24-1060028013501144","unstructured":"ClinicalTrials.gov; ARIAD Pharmaceuticals. Ponatinib in newly diagnosed chronic myeloid leukemia (CML) (EPIC). http:\/\/www.clinicaltrials.gov\/show\/NCT01650805 NLM Identifier: NCT01650805. Accessed March 6, 2013."},{"key":"bibr25-1060028013501144","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V120.21.915.915"},{"key":"bibr26-1060028013501144","unstructured":"Iclusig (ponatinib): indication and important safety information. Cambridge, MA: ARIAD Pharmaceuticals, Inc; 2013."},{"key":"bibr27-1060028013501144","unstructured":"Red book Micromedex. Ponatinib. http:\/\/www.micromedexsolutions.com.ezproxy.ttuhsc.edu\/micromedex2\/librarian\/ND_T\/evidencexpert\/ND_PR\/evidencexpert\/CS\/DA7C16\/ND_AppProduct\/evidencexpert\/DUPLICATIONSHIELDSYNC\/8B9372\/ND_PG\/evidencexpert\/ND_B\/evidencexpert\/ND_P\/evidencexpert\/PFActionId\/evidencexpert.ShowRedBookSearchResultsForActiveIngredient?SearchTerm=Ponatinib+Hydrochloride. Accessed March 11, 2013."},{"key":"bibr28-1060028013501144","unstructured":"Red book Micromedex. Imatinib. http:\/\/www.micromedexsolutions.com.ezproxy.ttuhsc.edu\/micromedex2\/librarian\/ND_T\/evidencexpert\/ND_PR\/evidencexpert\/CS\/C7FD77\/ND_AppProduct\/evidencexpert\/DUPLICATIONSHIELDSYNC\/8C6C96\/ND_PG\/evidencexpert\/ND_B\/evidencexpert\/ND_P\/evidencexpert\/PFActionId\/evidencexpert.ShowRedBookSearchResultsForActiveIngredient?SearchTerm=Imatinib+Mesylate. 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