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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: December 5, 2017.



Dasatinib is a selective tyrosine kinase receptor inhibitor that is used in the therapy of chronic myelogenous leukemia (CML) positive for the Philadelphia chromosome. Dasatinib is commonly associated with transient elevations in serum aminotransferase levels during treatment, but with only rare instances of clinically apparent acute liver injury.


Dasatinib is an orally available, small molecule inhibitor of the unique BCR-ABL tyrosine kinase receptor, which is the product of a fusion gene resulting from the translocation between chromosomes 9 and 22 that underlies the Philadelphia chromosome of chronic myelogenous leukemia (CML). The abnormal tyrosine kinase receptor is constitutively expressed and causes abnormal cell growth and proliferation. Inhibition of the enzyme can lead to dramatic reversal of progression of leukemia and is highly effective, although limited by the development of tumor resistance caused by mutations in the kinase. Dasatinib is actually a multi-kinase inhibitor and also has activity against scr, c-Kit and ephrin receptors, among others. Dasatanib received approval for use in the United States in 2006 and is one of five such specific inhibitors of BCR-ABL approved for clinical use, the others being imatinib [2001], nilotinib [2007], bosutinib [2012] and ponatinib [2012]. Dasatinib is available in tablets of 20, 50, 70, 80, 100 and 140 mg under the brand name Sprycel. Current indications are for treatment of Philadelphia chromosome-positive CML in the chronic, accelerated or blast phase usually after failure of a previous treatment. It is also approved for use in adutls with Philadelphia chromcsome-positive acute lymphoblastic leukemia. The typical dose is 100 to 140 mg daily. Common side effects include bone marrow suppression, fluid retention, diarrhea, headache, muscle cramps, arthralgias, fatigue, dyspnea, cough, pleural effusions and rash. Rare, but potentially severe side effects include bone marrow suppression, QTc prolongation, heart failure and pulmonary artery hypertension.


In large clinical trials, elevations in serum aminotransferase levels during dasatinib therapy occurred in up to 50% of patients, but were usually mild and self-limited. Elevations above 5 times the upper limit of normal (ULN) occurred in 1% to 9% of patients and generally responded to dose adjustment or temporary discontinuation and restarting at a lower dose, which is recommended if liver test results are markedly elevated (ALT or AST persistently greater than 5 times ULN or bilirubin more than 3 times ULN). While episodes of marked serum aminotransferase elevations with symptoms have been reported, there have been no published reports of clinically apparent liver injury with jaundice attributed to dasatinib therapy. Certainly other tyrosine kinase receptor inhibitors used in the therapy of CML such as imatinib, nilotinib and ponatinib have been associated with cases of acute liver injury with jaundice. With these agents, the liver injury typically arises after several months of therapy and the pattern of serum enzyme elevations is typically hepatocellular. Immunoallergic features (rash, fever and eosinophilia) and autoantibody formation are usually not present.

Reactivation of hepatitis B has been reported with dasatinib as well as imatinib and nilotinib therapy. Reactivation typically occurs in an HBsAg positive person treated with the tyrosine kinase inhibitor for 3 to 6 months, presenting with jaundice, marked serum aminotransferase elevations and an increase in HBV DNA levels. Reactivation of hepatitis B can be severe and fatal instances have been reported after imatinib and nilotinib therapy. Screening of patients for HBsAg and anti-HBc is sometimes recommended before starting cancer chemotherapy and those with HBsAg offered prophylaxis with oral antiviral agents, such as lamivudine, tenofovir or entecavir.

Likelihood score: D (possible cause of clinically apparent liver injury).

Mechanism of Injury

Dasatinib is metabolized in the liver largely through the CYP 3A4 pathway and liver injury may be related to production of a toxic intermediate. Because of this pathway of metabolism, dasatinib is susceptible to drug-drug interactions when used with agents that induce or inhibit CYP 3A4.

Outcome and Management

Serum aminotransferase elevations above 5 times the upper limit of normal (if confirmed) should lead to dose reduction or temporary cessation. In some situations, therapy can be restarted, particularly with concurrent prednisone (10 to 20 mg daily). In patients with clinically apparent liver injury and jaundice, restarting therapy should be done with caution. There does not appear to be cross reactivity with other tyrosine kinase inhibitors and switching to another tyrosine kinase receptor inhibitor may be the most appropriate approach. No cases of acute liver failure have occurred in patients receiving dasatinib, but instances have been reported with imatinib, nilotinib and ponatinib.

Drug Class: Antineoplastic Agents, Protein Kinase Inhibitors

Other Drugs in the Subclass, Chronic Myeloid Leukemia Agents: Bosutinib, Imatinib, Nilotinib, Omacetaxine, Ponatinib



Dasatinib – Sprycel®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Dasatinib 863127-77-9 C22-H26-Cl-N7-O2-S.H2-O
Dasatinib chemical structure


References updated: 05 December 2017

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    (Review of hepatotoxicity published in 1999 before the availability of dasatinib and the tyrosine kinase inhibitors).
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