Lacteal Secretion, Fetal and Maternal Tissue Distribution of Dasatinib in Rats

Data published and informations acquired in terms of fertility, conception, pregnancy, pregnancy outcome and illness control for all the approved TKIs will be reviewed, as well as suggest how to manage a planned and/or unplanned pregnancy/conception. Literature search methodology included examination of PubMed index, meeting presentations, and updated Investigator's brochures and data files of TKIs companies. Expert commentary: Male patients trying to conceive apparently have no limitation in the use of TKIs, while effective contraception should be encouraged in all female patients due to the risk of fetal complications after drug exposure. In a female patient pregnancy should be planned and TKI therapy discontinued, while individual risks need to be considered when an unplanned pregnancy occurs.

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“…In rats, dasatinib was observed to be teratogenic, extensively distributed in maternal tissues, and secreted into milk [17].…”

Section: Dasatinibmentioning

confidence: 99%

Management of pregnant chronic myeloid leukemia patients

Abruzzese

Trawinska

Fabritiis

et al. 2016

Expert Review of Hematology

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“…Embryo-foetal defects seen included skeletal malformations at multiple sites (scapula, humerus, femur, radius, ribs and clavicle), reduced ossification (sternum, vertebrae, pelvis and hyoid body), oedema and microhepatia [4]. It is not known whether dasatinib is secreted in human milk, but from animal studies, dasatinib was found to be excreted into milk in female rats [6].…”

Section: Dasatinibmentioning

confidence: 99%

Managing pregnancy in chronic myeloid leukaemia

2015

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Over the past decade, we have witnessed significant advances in knowledge of the biology and treatment of chronic myeloid leukaemia (CML). The development of molecular-targeted therapy with tyrosine kinase inhibitors (TKIs) has fundamentally changed the outcome of this disease. Treatment with TKIs is now the standard of care in patients with CML and has dramatically improved long-term survival in the majority of patients. Patients who achieve major molecular response (MMR) after 2 years of treatment with imatinib have survival rates comparable to those of the general population. The success of TKIs has led to durable molecular response and possibility of normal life expectancies, such that it is now timely to address quality of life aspects such as fertility, pregnancy and family planning. Pregnancy in CML presents specific management and therapeutic challenges for the patient and the physician. Despite the recent treatment advances, we still have limited data on the safety of TKIs in pregnancy and its effect on fertility. However, there is a cause for concern and heightened awareness following the occurrence of a constellation of rare congenital malformations and spontaneous abortions in association with imatinib therapy. When a patient becomes pregnant whilst receiving TKI therapy, the difficulty lies in balancing the risk to the foetus of continuing therapy versus the risk to the patient of treatment interruption and potentially losing optimal disease response. All couples should be counselled on the risks associated with pregnancy whilst receiving TKI therapy. This is an essential aspect in patient care and frequently not emphasized enough by physicians. At the time of diagnosis, fertility preservation should be discussed with both male and female patients of childbearing potential. They should be made aware of fertility options which are available such as semen cryopreservation, ovarian or oocyte retrieval and storage and embryo cryopreservation in view of the potential detrimental effect of TKIs on fertility and gonadal function. The recommendation given to patients planning pregnancy differs according to their disease response to TKI therapy, which is the most important prognostic factor in CML.

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“…75 Dasatinib, a dual BCR-ABL/src kinase inhibitor crosses the placenta and leads to considerable levels in fetal plasma. 81 In the first trimester, dasatinib has been reported to cause fetal hydrops and severe fetal bicytopenia, 76 but normal pregnancies have also been reported. 74,[77][78][79] HC is a cytotoxic agent that inhibits RNA synthesis and is commonly used for cytoreduction in newly diagnosed CML, prior to therapy with TKI.…”

Section: Chronic Leukemias Chronic Myeloid Leukemiamentioning

confidence: 99%

How I treat leukemia during pregnancy

Milojković

Apperley

2014

Blood

123

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Leukemia in pregnancy remains a challenging therapeutic prospect. The prevalence is low at ∼1 in 10 000 pregnancies, and as a result data are limited to small retrospective series and case reports, rendering evidence-based recommendations for management strategies difficult. The management of the leukemias in pregnancy requires close collaboration with obstetric and neonatology colleagues as both the maternal and fetal outcomes must be taken into consideration. The decision to introduce or delay chemotherapy must be balanced against the impact on maternal and fetal survival and morbidity. Invariably, acute leukemia diagnosed in the first trimester necessitates intensive chemotherapy that is likely to induce fetal malformations. As delaying treatment in this situation is usually inappropriate, counseling with regard to termination of pregnancy is often essential.For chronic disease and acute leukemia diagnosed after the second trimester, therapeutic termination of the pregnancy is not inevitable and often, standard management approaches similar to those in nongravid patients can be used. Here, the management of the acute and chronic leukemias will be addressed. (Blood. 2014;123(7):974-984)

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Lacteal Secretion, Fetal and Maternal Tissue Distribution of Dasatinib in Rats

Cited by 48 publications

References 26 publications

Management of pregnant chronic myeloid leukemia patients

Management of pregnant chronic myeloid leukemia patients

Managing pregnancy in chronic myeloid leukaemia

How I treat leukemia during pregnancy

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