daunorubicin
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Leucemias agudas dentro de regímenes de inducción y consolidación autorizados. No corresponde a daunorrubicina/citarabina liposomal.
Contraindicaciones
Absolutas
- Hipersensibilidad; infecciones graves; mielosupresión persistente; insuficiencia hepática o renal grave; insuficiencia cardiaca o cardiomiopatía grave; lactancia. Incluye Child-Pugh C, TFG <10 ml/min o creatinina >7,9 mg/dl, cardiopatía grave o arritmia significativa y haber alcanzado el máximo acumulado.
Advertencias clínicas
- Controla el hemograma antes de cada ciclo y durante el nadir. No administres fuera de un protocolo oncológico especializado; la mielosupresión puede causar infección o hemorragia mortal. — CIMA/AEMPS, ficha técnica 46427
- Calcula la exposición acumulada previa a antraciclinas y evalúa la función ventricular antes y durante el tratamiento. La cardiomiopatía e insuficiencia cardiaca pueden aparecer durante el tratamiento o años después. — CIMA/AEMPS, ficha técnica 46427
- Administra solo por una vía intravenosa permeable. Detén inmediatamente ante sospecha de extravasación: es vesicante y puede causar necrosis grave. — CIMA/AEMPS, ficha técnica 46427
- Controla hemograma, función renal/hepática, médula, ECG/LVEF y síndrome de lisis tumoral. Evita vacunas vivas. — CIMA/AEMPS, ficha técnica 46427
- Existe riesgo de leucemia secundaria, habitualmente con latencia de 1 a 3 años, especialmente con otros antineoplásicos que dañan el ADN o radioterapia. La radioterapia mediastínica puede aumentar la cardiotoxicidad y la daunorrubicina puede causar reacciones locales de recuerdo de radiación. — CIMA/AEMPS, ficha técnica 46427
Interacciones medicamentosas
- SeveraOtros cardiotóxicos o mielosupresores
Mecanismo: Pueden aumentar la cardiotoxicidad y mielosupresión.
Recomendación: Usa solo combinaciones del protocolo y vigila corazón y hemograma.
CIMA/AEMPS, ficha técnica 46427
- SeveraMetotrexato, hepatotóxicos, ácido acetilsalicílico y vacunas vivas
Mecanismo: Pueden aumentar hepatotoxicidad, sangrado o infección vacunal.
Recomendación: Evita vacunas vivas y aspirina en trombocitopenia; vigila estrechamente con metotrexato u otros hepatotóxicos.
CIMA/AEMPS, ficha técnica 46427
Embarazo y lactancia
El embarazo y la lactancia están contraindicados. Las mujeres deben usar anticoncepción durante el tratamiento y al menos 27 semanas después; los hombres, durante el tratamiento y al menos 14 semanas después.
Bibliografía reciente (PubMed)
The first 5 decades of research in acute myeloid leukemia (AML) were dominated by the cytarabine plus anthracyclines backbone, with advances in strategies including allogeneic hematopoietic stem cell transplantation, high-dose cytarabine, supportive care measures, and targeted therapies for the subset of patients with acute promyelocytic leukemia. Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 (liposomal encapsulation of cytarabine:daunorubicin at a molar ratio of 5:1); glasdegib (hedgehog inhibitor); and recently revumenib (menin inhibitor; approved November 2024). Oral decitabine-cedazuridine, which is approved as a bioequivalent alternative to parenteral hypomethylating agents in myelodysplastic syndrome, can be used for the same purpose in AML. Menin inhibitors, CD123 antibody-drug conjugates, and other antibodies targeting CD123, CD33, and other surface markers are showing promising results. Herein, the authors review the frontline and later line therapies in AML and discuss important research directions.
Patients with acute myeloid leukaemia (AML) positive for internal tandem duplication (ITD) mutations of FLT3 have poor outcomes. Quizartinib, an oral, highly potent, selective, type 2 FLT3 inhibitor, plus chemotherapy showed antitumour activity with an acceptable safety profile in patients with FLT3-ITD-positive newly diagnosed AML. The aim of the study was to compare the effect of quizartinib versus placebo on overall survival in patients with FLT3-ITD-positive newly diagnosed AML aged 18-75 years. We conducted a randomised, double-blind, placebo-controlled, phase 3 trial comparing quizartinib and placebo in combination with chemotherapy in induction and consolidation, followed by quizartinib or placebo single-agent continuation, in patients with FLT3-ITD-positive newly diagnosed AML at 193 hospitals and clinics in 26 countries in Europe; North America; and Asia, Australia, and South America. Patients aged 18-75 years were eligible. Patients were randomly assigned (1:1) to the quizartinib group or the placebo group by an independent biostatistician through an interactive web and voice response system, stratified by region, age, and white blood cell count at diagnosis. Patients, investigators, funders, and contract research organisations were masked to treatments assigned. Induction therapy comprised a standard 7 + 3 induction regimen of cytarabine 100 mg/m2 per day (or 200 mg/m2 per day allowed if institutional or local standard) by continuous intravenous infusion from day 1 to day 7 and anthracycline (daunorubicin 60 mg/m2 per day or idarubicin 12 mg/m2 per day) by intravenous infusion on days 1, 2, and 3, then quizartinib 40 mg orally or placebo once per day, starting on day 8, for 14 days. Patients with complete remission or complete remission with incomplete neutrophil or platelet recovery received standard consolidation with high-dose cytarabine plus quizartinib (40 mg per day orally) or placebo, allogeneic haematopoietic cell transplantation (allo-HCT), or bo
The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor). Other targeted therapies (menin inhibitors, CD123 antibody-drug conjugates) are showing promising results. To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions. Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy, especially anthracyclines such as daunorubicin.[1] It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence. Based on the 27-hour half-life of the active metabolite daunorubicinol a minimum of 6 days would be required before resuming nursing. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[2] Women who receive chemotherapy during pregnancy are more likely to have difficulty
Therapy-related acute myeloid leukemia (t-AML), defined as AML arising from prior cytotoxic, radiation, or immunosuppressive therapy for an unrelated disease, accounts for 7 %-8 % of AML cases and primarily occurs in elderly patients. t-AML is associated with an increased probability of adverse cytogenetics and shortened survival compared with de novo AML. Factors predicting poorer prognosis in t-AML include older age, unfavorable karyotype, presence of certain mutations, poor performance status, and poor bone marrow reserve. Few clinical studies have focused specifically on patients with t-AML, and the choice of induction therapy for t-AML is thus typically based on subset analyses of larger studies or on extrapolation. In patients deemed fit, t-AML treatment can involve CPX-351 (liposomal daunorubicin and cytarabine) or conventional chemotherapy, ideally followed by hematopoietic cell transplantation. Patients who are not candidates for intensive therapy may benefit from lower-intensity therapies. Additional agents and combination regimens are being evaluated in clinical studies.