VINDESINE sulfaat

Vindesine kan een invloed hebben op de vruchtbaarheid van de vrouw [SKP Eldisine 08 2018].

De bestaande informatie over het gebruik van vindesine bij zwangere vrouwen volstaat niet om de eventuele toxiciteit ervan te beoordelen. Op basis van de farmacologische activiteit is het mogelijk dat de substantie toxisch is bij gebruik tijdens de zwangerschap [SKP Eldisine 08 2018].

Bij dierproeven is het geneesmiddel schadelijk gebleken [SKP Eldisine 08 2018].

Zie eerste trimester.

Geen specifieke informatie beschikbaar.

Het NTP-rapport vermeldt één blootstelling gedurende het 3de trimester. De moeder bracht een baby zonder afwijkingen ter wereld [NTP 2013; Schaefer et al. 2015]. Zie ook eerste trimester.

Geen specifieke informatie beschikbaar.

Geen specifieke informatie beschikbaar.

Geen specifieke informatie beschikbaar.

Geen specifieke informatie beschikbaar.

Geen specifieke informatie beschikbaar.

L?

Er bestaan geen gegevens betreffende de mogelijke uitscheiding van vindesine in de moedermelk. Op basis van de farmacologische activiteit is het mogelijk dat de substantie toxisch is bij gebruik tijdens de borstvoeding [SKP Eldisine 08 2018].

Geen specifieke informatie beschikbaar.

Beperkte humane gegevens wijzen op mogelijke verlaging vruchtbaarheid bij mannen.

Geen specifieke informatie beschikbaar.

Geen specifieke informatie beschikbaar over de overgang via het sperma.

Geen specifieke informatie beschikbaar.

Hale, Medications and Mothers´Milk, 17th Edition, 2017

Wetenschappelijke bijsluiter (SKP Samenvatting van de Kenmerken van het Product)

Briggs G, Freeman R, Yaffe S. Drugs in Pregnancy and Lactation, 10th edition, Philadelphia 2015;

Schaefer, Drugs during pregnancy and lactation, 3th Edition, 2015

National Toxicology Program, NTP Monograph

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

Summary

Exposure to vincristine is documented for 226 pregnancies and 228 conceptuses, including 1 case with 2 singleton pregnancies and 2 sets of twins. Overall, the apparent rate of major malformations among all vincristine-exposed offspring, regardless of the nature of the malformations or the gestational stage at exposure, was 2% (5/204 conceptuses, based on 196 liveborn infants and examination of the fetuses of 4 induced abortions, 3 stillbirths, and 1 maternal/fetal death) (Table 78). 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 4 liveborn infants with exposure to  vincristine during the first trimester. The cranial and skeletal malformations as well as hydrocephalus observed in 3 infants gestationally exposed to vincristine polytherapy were also observed in developmental toxicity studies of vincristine administered during organogenesis to rats and mice. Thus, the apparent rate of major malformations following exposure to vincristine during  the first trimester was 10% (4/42 conceptuses, based on 39 liveborn infants and  examination of the fetuses of 2 induced abortions and 1 maternal/ fetal death). Major malformations were observed in 1 liveborn infant exposed to vincristine in the second and third trimesters: bilateral syndactyly of digits 2 and 3 (Van  Calsteren et al. 2010a). However, syndactyly in this infant was not likely caused by vincristine polytherapy because it  was administered on gestation week 26, after the active period of skeletal development in the first trimester. Thus, the adjusted rate of major malformations following exposure to vincristine in the second and/or third trimester only was 0% (0/159 conceptuses, based on 154 liveborn infants and examination of the fetuses of 2 induced abortions and 3  stillbirths). No major malformations were reported in 1 liveborn infant for which timing of exposure was not specified.

Follow-up

Follow-up evaluations were reported for 143 children ranging in age from 8 weeks to 19 years; age at follow- up was not specified for 5 children (Khurshid and Saleem 1978, Willemse et al. 1990, Bergstrom and Altman 1998, Seamon et al. 2009). Normal growth and development were reported for all but 5 children who had delayed development or depressed growth. One child had a mild delay in motor skills at 14 months (Lam 2006), and 2 children had speech delays at 18 months (Achtari and Hohlfeld 2000) or at 4.3 years old (Cardonick et al. 2010). One child had normal Denver Developmental Screening test results, but his growth was in the third percentile at 13.5 months (Doney et al. 1979). At 26 months, another child’s body weight was <10th percentile, and the child had a constant cold (Gulati et al. 1986); however, the infant’s immune function test and complete blood count were normal. In addition, 1 child with normal growth and development at age 2 years tested HIV positive; her mother was HIV positive (Okechukwu and Ross 1998).

Cytotoxische geneesmiddelen toegediend binnen de 10 dagen na conceptie geven een alles-of-niets effect. De organogenese start vanaf de 10de dag en is na 8 weken een feit. Toedienen van cytostatica in deze periode verhoogt de kans op misvormingen sterk. Wanneer één cytostaticum wordt toegediend wordt de kans op misvormingen op 7 tot 17% geschat. Deze kans verhoogt met 25% bij combinatietherapie. Vermijden van foliumzuur-antagonisten vermindert de kans op misvormingen met 6%.

Conclusie : chemotherapie is tegenaangewezen gedurende het eerste trimester [Dekrem et al. 2013].

Geen specifieke informatie beschikbaar.