Tacrolimus as Basic Immunosuppression in Pregnancy After Renal Transplantation. A Single-Center Experience

García-Donaire, José Antonio; Acevedo, Mercedes; Gutiérrez, M.; Manzanera, M.; Oliva, Elena; Gutiérrez, Eduardo; Andrés, Amado; Morales, J. M.

doi:10.1016/j.transproceed.2005.09.124

Cited by 25 publications

(12 citation statements)

References 2 publications

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“…Our major findings suggest that pregnancy can result in lower whole blood tacrolimus concentrations but no significant change in unbound concentrations if no adjustment in dosage is made. In the clinical setting, although approaches differ, some providers routinely adjust the tacrolimus dosage during pregnancy to maintain target whole blood trough concentrations, 46, 47 without considering possible changes in unbound tacrolimus, since these are not measured in clinical practice. Challenges in measuring unbound tacrolimus concentrations include avoiding plastics in all procedures due to extensive binding of tacrolimus to plastics, separating plasma and plasma water at 37° C due to temperature dependent binding and using a highly sensitive and specific assay to detect the extremely low concentrations of the unbound drug.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Tacrolimus During Pregnancy

Zheng¹,

Easterling²,

Umans³

et al. 2012

Therapeutic Drug Monitoring

105

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Background Information on the pharmacokinetics of tacrolimus during pregnancy is limited to case reports despite the increasing number of pregnant women being prescribed tacrolimus for immunosuppression. Methods Blood, plasma and urine samples were collected over one steady-state dosing interval from women treated with oral tacrolimus during early to late pregnancy (n = 10) and postpartum (n = 5). Total and unbound tacrolimus as well as metabolite concentrations in blood and plasma were assayed by a validated LC/MS/MS method. A mixed effect linear model was used for comparison across gestational age and using postpartum as the reference group. Results The mean oral clearance (CL/F) based on whole blood tacrolimus concentration was 39% higher during mid- and late-pregnancy compared to postpartum (47.4 ± 12.6 vs. 34.2 ± 14.8 L/h, P < 0.03). Tacrolimus free fraction increased by 91% in plasma (fP) and by 100% in blood (fB) during pregnancy (P = 0.0007 and 0.002, respectively). Increased fP was inversely associated with serum albumin concentration (r = − 0.7, P = 0.003), which decreased by 27% during pregnancy. Pregnancy related changes in fP and fB contributed significantly to the observed gestational increase in tacrolimus whole blood CL/F (r2 = 0.36 and 0.47 respectively, P < 0.01). In addition, tacrolimus whole blood CL/F was inversely correlated with both hematocrit and red blood cell counts, suggesting that binding of tacrolimus to erythrocytes restricts its availability for metabolism. Treating physicians increased tacrolimus dosages in study participants during pregnancy by an average of 45% in order to maintain tacrolimus whole blood trough concentrations in the therapeutic range. This led to striking increases in unbound tacrolimus trough concentrations and unbound AUC, by 112% and 173%, respectively during pregnancy (P = 0.02 and 0.03, respectively). Conclusions Tacrolimus pharmacokinetics are altered during pregnancy. Dose adjustment to maintain whole blood tacrolimus concentration in the usual therapeutic range during pregnancy increases circulating free drug concentrations, which may impact clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Tacrolimus During Pregnancy

Zheng¹,

Easterling²,

Umans³

et al. 2012

Therapeutic Drug Monitoring

105

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“…Data on a large number of pregnancies exposed to cyclosporine have not shown a significant increase in major birth defect risk [106][107][108] . There are less data available on tacrolimus use during pregnancy; however, more than 200 pregnancies have been documented, indicating no teratogenic risk [109][110][111][112][113] . An increased risk of fetal growth restriction, preterm delivery, and preeclampsia has been observed in pregnancies exposed to cyclosporine and tacrolimus [108,113,114] .…”

Section: Immunosuppressants and Anti-inflammatory Drugsmentioning

confidence: 99%

Safety of Drugs during Pregnancy and Breastfeeding in Cystic Fibrosis Patients

Panchaud

Paolo²,

Koutsokera³

et al. 2016

Respiration

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Health management of cystic fibrosis (CF) patients should be maximized during pregnancy and breastfeeding because of its significant impact on the maternal and newborn outcomes. Thus, numerous drugs will have to be continued during pregnancy and lactation. Most of the drugs representing CF treatment lines cross the placenta or are excreted into human milk. Research addressing the risks and benefits of drugs used in CF patients during pregnancy and lactation is often incomplete or challenged by limited methodology, which often leads to conflicting or inconclusive results. Yet, potential treatment benefits for CF pregnant patients most often outbalance potential risks for the unborn child.

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“…Une augmentation des fentes palatines, des retards de croissance et des pertes foetales ont été décrits lors de l'utilisation de doses importantes au long cours. • Tacrolimus (Prograf®) : il est foetotoxique chez l'animal mais les données publiées chez la femme enceinte exposées au tacrolimus ne mettent pas en évidence d'augmentation des malformations [18]. Ces données sont rassurantes, elles ne retrouvent pas d'effet tératogène ou malformatif [17].…”

Section: Immunosuppresseursunclassified

“…• Ciclosporine (Sandimmun®, Néoral®) : de nombreuses grossesses sous ciclosporine ont été rapportées dans la littérature. Peu de grossesses ont été menées sous Cellcept® mais de nombreuses malformations ont été retrouvées après exposition : syndrome polymalformatif (fentes labio-narinaires et palatines, microtie, atrésie du conduit auditif externe) [18]. Un risque accru de retard de croissance intra-utérin et un faible poids de naissance ont été décrits, mais il est difficile d'incriminer exclusivement le médicament (rôle de nombreux facteurs).…”

Section: Immunosuppresseursunclassified

Néphropathies

Chauvet¹

2014

Pathologies Maternelles Et Grossesse

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Tacrolimus as Basic Immunosuppression in Pregnancy After Renal Transplantation. A Single-Center Experience

Cited by 25 publications

References 2 publications

Pharmacokinetics of Tacrolimus During Pregnancy

Pharmacokinetics of Tacrolimus During Pregnancy

Safety of Drugs during Pregnancy and Breastfeeding in Cystic Fibrosis Patients

Néphropathies

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