Acute Myeloid Leukemia (AML) Medication

Updated: Jul 26, 2023
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Medication Summary

Medications used for the treatment of acute myeloid leukemia (AML) cause severe bone marrow depression. Only physicians specifically trained in their use should use these agents. In addition, access to appropriate supportive care (ie, blood banking) is required.



Class Summary

Antineoplastic agents are used for induction or consolidation therapy. These agents inhibit cell growth and differentiation. They include cytarabine, daunorubicin, idarubicin, and mitoxantrone.

Azacitidine (Vidaza, Onureg)

Azacitidine is a pyrimidine nucleoside analog of cytidine. It interferes with nucleic acid metabolism. It exerts antineoplastic effects by DNA hypomethylation and direct cytotoxicity on abnormal hematopoietic bone marrow cells. Hypomethylation may restore normal function to genes critical for cell differentiation and proliferation. Nonproliferative cells are largely insensitive to azacitidine. The IV formulation is indicated to treat myelodysplastic syndromes (MDSs) and is FDA approved for all 5 MDS subtypes. The new oral formulation is approved for acute myeloid leukemia in adults who achieved first complete remission following intensive induction chemotherapy who are not able to complete intensive curative therapy.   


Cytarabine is an antimetabolite specific for cells in the S-phase of the cell cycle. It acts through inhibition of DNA polymerase and cytosine incorporation into DNA and RNA.

Daunorubicin (Cerubidine)

Daunorubicin is a topoisomerase-II inhibitor. It inhibits DNA and RNA synthesis by intercalating between DNA base pairs.


Idarubicin is a topoisomerase-II inhibitor. It inhibits cell proliferation by inhibiting DNA and RNA polymerase.


Mitoxantrone inhibits cell proliferation by intercalating DNA. It inhibits topoisomerase II.

Arsenic trioxide

Arsenic trioxide is used in patients with relapsed acute promyelocytic leukemia (APL). Its mechanism of action is not completely understood. Arsenic trioxide causes morphologic changes and DNA fragmentation that are characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML-RAR alpha.


Fludarabine contains fludarabine phosphate, a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-b-D-arabinofuranosyladenine (ara-A), that enters the cell and is phosphorylated to form the active metabolite 2-fluoro-ara-ATP, which inhibits DNA synthesis. It is also incorporated into RNA, causing inhibition of RNA and protein synthesis; however, its primary effect may result from activation of apoptosis. It is also relatively resistant to deamination by adenosine deaminase.

The dosage may be decreased or delayed based on evidence of hematologic or nonhematologic toxicity. Physicians should consider delaying or discontinuing the drug if neurotoxicity occurs. The optimal duration of treatment is not clearly established. It is recommended that 3 additional cycles of fludarabine be administered following the achievement of maximal response, and then the drug should be discontinued.


Cyclophosphamide is a cyclic polypeptide that suppresses some humoral activity. It is chemically related to nitrogen mustards and is activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type of reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.

It is biotransformed by cytochrome P450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. The interaction of phosphoramide mustard with DNA is considered cytotoxic.

When cyclophosphamide is used in autoimmune diseases, the mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

In high doses, it affects B cells by inhibiting clonal expansion and suppression of the production of immunoglobulins. With long-term, low-dose therapy, it affects T-cell functions.


Cladribine is a synthetic antineoplastic agent for continuous IV infusion. The enzyme deoxycytidine kinase phosphorylates this compound into an active 5+-triphosphate derivative, which, in turn, brakes DNA strands and inhibits DNA synthesis. It disrupts cell metabolism, causing death to resting and dividing cells.

Decitabine (Dacogen)

Decitabine is a hypomethylating agent believed to exert antineoplastic effects by incorporating into DNA and inhibiting methyltransferase, resulting in hypomethylation. Hypomethylation in neoplastic cells may restore normal function to genes critical for cellular control of differentiation and proliferation. Decitabine is indicated for myelodysplastic syndromes (MDSs), including previously treated and untreated, de novo, and secondary MDSs of all French-American-British (FAB) subtypes (ie, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia) and International Prognostic Scoring System (IPSS) groups intermediate-1 risk, intermediate-2 risk, and high risk.

Cytarabine/daunorubicin liposomal (Vyxeos)

Fixed-dose combination of liposomal bound cytarabine and daunorubicin that delivers the 2 medications in a 5:1 molar ratio. The combination has been shown to have synergistic effects at killing leukemia cells in vitro and in murine models. It is indicated for newly diagnosed therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC).

Gemtuzumab (Mylotarg)

Gemtuzumab ozogamicin is an antibody-drug conjugate. The antibody portion of gemtuzumab binds to CD33, an antigen expressed on the surface of leukemic blasts in more than 80% of AML patients. Binding results in the formation of a complex that is internalized. Upon internalization, the drug that is covalently attached to the antibody, a calicheamicin derivative, is released inside the lysosomes of the myeloid cell. The released calicheamicin drerivative binds to DNA in the minor groove resulting in DNA double strand breaks and cell death.       


Antineoplastics, Tyrosine Kinase Inhibitor

Class Summary

Tyrosine kinase inhibitors that target FLT3 mutations have been approved by the FDA to treat AML.

Midostaurin (Rydapt)

Midostaurin and its major active metabolites inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. It is indicated in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by an FDA-approved test.

Gilteritinib (Xospata)

Gilteritinib inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). It inhibits FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3. It is indicated for adults with AML with a FLT3 mutation who have relapsed or are refractory.

Quizartinib (Vanflyta)

Quizartinib and its active metabolite (AC886) inhibit FLT3 kinase activity. This prevents autophosphorylation of the receptor, thereby inhibiting downstream FLT3 receptor signaling and blocking FLT3-internal tandem duplication (ITD)-dependent cell proliferation. It is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for treatment of adult patients with newly diagnosed AML that is FLT3 ITD-positive.


Antineoplastics, Hedgehog Pathway Inhibitor

Class Summary

Smoothen (SMO) inhibition of Hedgehog (Hh) signaling impacts tumor biology by disrupting the regulation of cancer stem cell survival. This may inhibit development of drug resistance and prevent relapse.

Glasdegib (Daurismo)

Inhibits the SMO receptor, a transmembrane protein involved in Hh signal transduction, thereby disrupting the Hh pathway. It is indicated for newly diagnosed AML in adults aged 75 years or older, or adults who have comorbidities that preclude use of intensive induction chemotherapy in combination with low-dose cytarabine.


Bcl-2 Inhibitor

Class Summary

Overexpression of Bcl-2 has been demonstrated in AML cells, where it mediates tumor cell survival and has been associated with resistance to chemotherapeutic agents.

Venetoclax (Venclexta)

Selective inhibitor of the B-cell lymphoma 2 (Bcl-2) regulator protein, an antiapoptotic protein. Venetoclax helps restore the process of apoptosis by binding directly to Bcl-2 protein. It is indicated for newly diagnosed AML in adults aged 75 years or older, or adults who have comorbidities that preclude use of intensive induction chemotherapy. It is used in combination with azacytidine, or decitabine, or low-dose cytarabine.


IDH Inhibitors

Class Summary

Clinical trials of inhibitors of isocitrate dehydrogenase (IDH) demonstrated decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH mutated AML.

Enasidenib (Idhifa)

Enasidenib is a small molecule inhibitor of IDH-2 enzyme. Enasidenib targets mutant IDH2 variants (ie, R140Q, R172S, and R172K) at ~40-fold lower concentrations than the wild-type enzyme in vitro. It is indicated for adults with relapsed or refractory IDH2-mutated AML.

Ivosidenib (Tibsovo)

IDH1 inhibitor; inhibits selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro. In blood samples from patients with AML with mutated IDH1, ivosidenib decreased 2-HG levels ex vivo, reduced blast counts, and increased percentages of mature myeloid cells. It is indicated for patients with susceptible IDH1 mutations who have relapsed or refractory AML. It is also indicated for newly-diagnosed IDH1-mutated AML in patients aged 75 y or older, or patients who have comorbidities that preclude use of intensive induction chemotherapy.

Olutasidenib (Rezlidhia)

Olutasidenib is an oral IDH1 inhibitor indicated for relapsed and/or refractory acute myeloid leukemia with a confirmed IDH1 mutation (mIDH1+ R/R AML).