Safety of tacrolimus during lactation: an exploratory retrospective analysis in a small Japanese cohort

他克莫司在哺乳期的安全性:一项针对日本小型队列的探索性回顾性分析

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Abstract

BACKGROUND: Tacrolimus is a calcineurin inhibitor immunosuppressant widely used in organ transplantation and the management of autoimmune diseases. Tacrolimus is generally considered to be safe for women who are breastfeeding; however, pharmacokinetic differences related to genetic background have been reported, and clinical data focusing on Japanese women during lactation remain scarce. As such, this study evaluated the safety of tacrolimus in Japanese women diagnosed with autoimmune diseases during breastfeeding. METHODS: This exploratory retrospective analysis was conducted at a single tertiary care hospital in Japan. Participants were divided into 2 groups: breastfeeding mothers prescribed tacrolimus (n = 6); and breastfeeding mothers who did not receive tacrolimus (control group; n = 12). Most infants were primarily breastfed. Between January 2011 and June 2018, maternal characteristics and adverse events in infants from birth to the 1-month checkup were collected from medical records and “plan-sheets for lactation” completed at approximately 28 weeks’ gestation. RESULTS: All mothers in the tacrolimus group received a daily tacrolimus dose of 3 mg throughout the observation period. The adverse events observed in the tacrolimus group included jaundice (n = 5), rashes (n = 3), vomiting (n = 3), head hematoma (n = 2), minor skin lesion (n = 1), and respiratory failure (n = 1). All adverse events were non-serious and the infants recovered uneventfully. The Isobe Neonatal Withdrawal Syndrome score was 0 in all evaluated infants in the tacrolimus group during the first month after birth. All 6 mother-infant pairs in the tacrolimus group continued breastfeeding and maternal medication through the 1-month postpartum checkup. A significantly higher incidence of vomiting was observed in the tacrolimus group compared with the control group. CONCLUSION: Preliminary observations in this small Japanese cohort revealed no serious adverse events in breastfed infants during the first month, but larger studies are required to confirm safety.

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