DAUNORUBICINE

Hale, Medications and Mothers´Milk, 15th Edition, 2012

 

Briggs G, Freeman R, Yaffe S.Drugs in Pregnancy and Lactation, 9th edition, Philadelphia 2011;

 

 

Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy. US Department of Health and Human Services, May 2013, 234 pages.

 

 

 

In utero exposure to daunorubicin was documented for 107 pregnancies (108 conceptuses, including 1 set of twins). Overall, the apparent rate of major malformations among all daunorubicin-exposed offspring, regardless of the nature of the malformations or the gestational stage at exposure, was 5% (4/85 conceptuses, based on 77 liveborn infants and examination of the fetus of 2 induced abortuses, 1 spontaneous abortus, 4 stillbirths, and 1 maternal/fetal death) (Table 43). As a point of reference, the prevalence of major malformations in the general population of the US is 3% (Correa et al. 2007). Major malformations were observed in only 1 liveborn infant following gestational exposure to daunorubicin, cytarabine, and vincristine in the first trimester (Artlich et al. 1994); the malformations included hypoplastic thumbs on each hand, a variety of cranial defects and hypoplasia, and a small ostium, secundum-type atrial defect. The skeletal malformations observed were consistent with malformations observed in other human conceptuses exposed to cytarabine polytherapy as well as with developmental toxicity studies of cytarabine in laboratory animals (see Section 5.12.3). Similarly, aberrant cardiac development has been documented in developmental toxicity studies of daunorubicin in laboratory animals. Thus, the apparent rate of major malformations following exposure to daunorubicin during the first trimester was 20% (1/5 conceptuses, based on 4 liveborn infants and examination of the fetus of 1 maternal and fetal death). Major malformations were observed in 3 liveborn infants following exposure to daunorubicin in the second and/or third trimester only. However, it was unlikely that exposure to daunorubicin in the second trimester was the cause of Down syndrome (Roy et al. 1989) or polydactyly in an infant with a family history of polydactyly (Volkenandt et al. 1987), or hypospadias following third-trimester exposure (De Carolis et al. 2006). Thus, the adjusted apparent rate of major malformations following exposure to daunorubicin in the second and/or third trimester only was 0% (0/75 conceptuses, based on 68 liveborn infants and examination of the fetus of 2 induced abortuses, 1 spontaneous abortus, and 4 stillbirths). No major malformations were observed in the 5 liveborn infants exposed to daunorubicin for which timing of exposure was not specified (0/5 conceptuses, based on 5 liveborn infants). There were a few other notable pregnancy outcomes following gestational exposure to daunorubicin. The apparent rate of spontaneous abortion following exposure to daunorubicin during the first trimester was 50% (4/8 conceptuses, not including terminations of pregnancy (9 conceptuses) or maternal/fetal deaths (1 conceptus). It has been hypothesized that acute leukemia during pregnancy may increase the risk of spontaneous fetal loss (Brenner et al. 2012). Daunorubicin is reported to cause cardiotoxicity in adult cancer patients administered the drug. Fetal tachycardia was reported in 1 singleton pregnancy (Garcia et al. 1999), and 1 newborn was treated for congestive heart failure (Okun et al. 1979).

 

 

Follow-up evaluations were available for 52 infants ranging in age from 2 months to 29 years. Normal growth and development were observed in all but 2 children. At 13 months, 1 child had normal fine motor skills and social development, but was underweight with slightly delayed motor milestones (Artlich et al. 1994). Failure to thrive was reported for another infant, who did not begin to gain weight until 3 months of age (Garcia et al. 1999). Of note, the newborn treated for cardiac arrest had normal growth and development at age 1 year.